INTRODUCTION — Bipolar disorder causes a person to experience periods of mania (feeling excessively elated, impulsive, irritable, or irrational) or hypomania (a milder form of mania), and may also cause a person to experience periods of major depression (feeling excessively sad).
Bipolar disorder can lead to significant illness and even death by suicide if untreated or treated incorrectly. A number of effective treatment options are available.
CAUSE — Research has helped clarify the complex biologic basis of bipolar disorder, although the exact cause is still uncertain. Studies suggest that it results from an imbalance of neurochemicals in the brain, including serotonin, norepinephrine, and dopamine. These neurochemicals allow cells to communicate with each other and play an essential role in all brain functions, including movement, sensation, memory, and emotions.
People with a family history of bipolar disorder are at increased risk of developing the condition. This is thought to be the result of changes in genes, which are passed down from parents to children. Results of gene research indicate that there are probably multiple genes affected in persons with bipolar disorder.
SYMPTOMS
Mania — Mania causes a person to feel abnormally and persistently elated, irritable, hyperactive, impulsive, and irrational. These feelings last at least one week, and may be severe enough to require hospitalization. The mania of bipolar disorder is not caused by other medical illnesses or drug abuse. Other symptoms may include: Feelings of superiority and grandiosity Decreased need for sleep, restlessness Talking excessively Racing thoughts Short attention span Inappropriate laughing or joking Inappropriate spending sprees or sexual activity
Mania often causes a person to have difficulty maintaining relationships with friends and family, and can interfere with work or other responsibilities. During a manic episode, a person's moods can change rapidly from euphoria to depression or irritability.
Hypomania — Hypomania is less severe than mania, but causes a significant change in mood that is abnormal for the patient. Hypomania lasts for at least four days, but is usually briefer than manic episodes. Hypomania does not seriously impair a person's ability to function, and some people actually function better during a hypomanic episode. Hypomania does not require hospitalization, but is generally treated with medications because it may lead to a manic or depressive episode.
Depression — People with major depression experience significant sadness and difficulty functioning. They are typically depressed most of the day and may have little or no interest in any activity. Other symptoms may include one or more of the following: Significant weight loss or gain Changes in sleep patterns, including insomnia or excessive sleeping Change in activity level (including sluggishness, reduced activity, or agitation) Fatigue or loss of energy Feelings of worthlessness or guilt Difficulty concentrating and making decisions Recurring thoughts of death or suicide
To be considered major depression, a patient must have at least five symptoms on a daily or nearly daily basis for at least two weeks. In addition, symptoms must not be caused solely by a medical condition, drug abuse, medications, or the loss of a loved one. (See "Patient information: Depression in adults").
Bipolar disorder — Bipolar disorder usually presents in one of two ways: Bipolar I disorder causes at least one manic episode, often with episodes of depression Bipolar II disorder causes at least one hypomanic episode and one or more episodes of major depression.
Bipolar I disorder affects men and women equally; bipolar II disorder is more common in women. Most people develop the first symptoms of biplar disorder between 15 and 30 years of age. Newly diagnosed mania is uncommon in children and in adults over the age of 65.
People with bipolar disorder typically have cycles of relapse (when depression and/or mania occur) and remissions (when symptoms improve or resolve), often in an alternating pattern. Ninety percent of individuals who have one manic episode have another within five years. Ninety percent of individuals with bipolar disorder must be hospitalized in a psychiatric facility at least once, and two-thirds have two or more hospitalizations in their lifetime. Patients with bipolar II disorder are much more likely to have symptoms of depression than hypomania or mixed symptoms.
Alcohol, drugs, and suicide in bipolar disorder — Alcohol and drug abuse occur in more than 60 percent of people with bipolar disorder. The risk of suicide also is higher in people with bipolar disorder than in people with other psychiatric illnesses (including depression).
Suicide is often the result of feeling hopeless, and is more likely in patients with severe symptoms who must be hospitalized for treatment. Family members or friends of a person with bipolar disorder should consider any mention of suicide a serious threat, and should immediately contact a healthcare provider.
DIAGNOSIS — There is no one blood or imaging test that can determine if a person has bipolar disorder. The diagnosis is based upon a comprehensive medical and psychologic history and physical examination. Bipolar disorder can be confused with a number of other medical and psychiatric conditions. Laboratory testing may be performed to rule out other diagnoses.
TREATMENT OF MANIA — Treatment during an episode of mania focuses on managing symptoms and ensuring the patient's safety. In the early phase of mania (called the acute phase), a patient may be psychotic or display such poor judgment that they are at risk of injuring themselves or others. Hospitalization may be necessary until symptoms are controlled. Treatment of mania continues until symptoms completely resolve and the patient is able to function, although many patients are maintained on medications indefinitely to prevent a recurrence of mania symptoms.
Medications are the primary treatment for mania, and a number of medications are available. It is not usually possible to know which medication will be the most effective and cause the fewest side effects, and it may be necessary to try several medications before finding the best one. A person who responds well to one medication is likely to respond well to that treatment during future episodes.
Mood stabilizers — Mood stabilizing medications, such as lithium carbonate, lamotrigine, valproate, and carbamazepine, are often used in the treatment of mania or hypomania. Medications used for treatment of mania (and depression) are thought to cause changes in chemicals in the brain that affect mood. All of these medications are similarly effective, and the choice is often made based upon a patient's previous history, side effects, and any underlying medical illnesses.
Lithium — Lithium has been used for many years for the treatment of mania. It is usually taken two to three times per day. Common side effects include frequent urination, tremor, loose stools, and weight gain. Longer term complications include the potential for kidney or thyroid dysfunction (hypothyroidism).
Blood testing to measure the lithium level and kidney and thyroid function is usually done every 6 to 12 months once the lithium dose has been stabilized. Lithium can cause serious illness if an overdose is taken or if abnormal kidney function prevents the body from eliminating the drug. This can occur if the patient becomes severely dehydrated or uses medications such as nonsteroidal antiinflammatory drugs (eg, aspirin, ibuprofen, naproxen sodium) or an ACE inhibitor (used to treat high blood pressure).
While taking lithium, patients should talk to their healthcare provider before using any over the counter medications. Patients should give a complete list of prescription and nonprescription medications to their provider at every visit.
Valproate — Valproate is a medication occasionally used for patients with seizures, although it is also effective in stabilizing the mood of patients with mania. It may be used instead of or in combination with lithium. Common side effects include weight gain, nausea, vomiting, hair loss, easy bruising, and tremor. Liver failure and low platelet count (a type of blood cell) have rarely been associated with valproate use. Blood testing to monitor liver function and platelet count are usually done to monitor for these complications.
Carbamezapine — Carbamepazine was originally developed for prevention of seizures, but is also now used for treatment of bipolar disorder. It is usually taken twice per day. The most common side effects include nausea, vomiting, diarrhea, low sodium level, rash, itching, low white blood cell count, and fluid retention. Blood testing to monitor the carbamazepine level, liver function, and blood counts is recommended every 6 to 12 months.
Lamotrigine — Lamotrigine was also developed for seizure disorders, but may be particularly effective for depression in bipolar disorder. Routine blood tests are not needed for monitoring. Significant interactions with other medications can occur, and patients should be sure that all healthcare providers have an updated list of both prescription and nonprescription medication. An infrequent but serious and potentially life threatening rash (called Stevens-Johnson syndrome) can occur early in treatment.
Antipsychotics — Antipsychotic medications may be used alone or in combination with a mood stabilizer in patients with acute mania. Older antipsychotic medications (eg, haloperidol (Haldol®)) can cause bothersome involuntary movements (eg, tongue thrusting, tremors, restlessness). Atypical antipsychotics such as olanzapine (Zyprexa®), risperidone (Risperdal®), and quetiapine (Seroquel®) have a smaller risk of these side effects, but are more likely to cause weight gain, glucose intolerance, diabetes mellitus, and hyperlipidemia. Clozapine (Clozaril®) may be particularly effective in patients who do not respond to other mood stabilizers or antipsychotics, but it is associated with the potential for a dangerous decrease in the number of white blood cells. The newer atypical antipsychotics ziprasidone (Geodon®) and aripiprazole (Abilify®) appear to be as effective as other atypical antipsychotics, but without the risk of weight gain and diabetes. There is not as much experience with these medications, and there may be long-term risks or complications that are unknown.
TREATMENT OF DEPRESSION
Medications — During the initial phase of bipolar depression, an antidepressant medication is usually the best option for treatment. However, antidepressants may cause manic episodes, and are generally used only in the initial phase of bipolar depression in combination with a mood stabilizer. There are several types of antidepressants, each of which works slightly differently. Selective serotonin reuptake inhibitors (eg, fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), and escitalopram (Lexapro®)) Bupropion (Wellbutrin®) Monoamine oxidase inhibitors (tranylcypromine (Parnate®) and phenelzine (Nardil®).
Tricyclic antidepressants (eg, imipramine (Tofranil®), amitriptyline (Elavil®), desipramine (Norpramin®), nortriptyline (Pamelor®), and clomipramine (Anafranil®)) are more likely to cause mania than the medications mentioned above, and as a result are rarely used in patients with bipolar disorder.
ELECTROCONVULSIVE THERAPY (ECT) — During electroconvulsive therapy (ECT), an electrical current is passed through the brain, triggering a seizure. For unknown reasons, the seizure helps to restore the normal balance of neurochemicals in the brain. ECT is especially effective for people with severe, life-threatening depression or mania that has not responded to medication.
ECT can be used in pregnant women and in those who cannot tolerate antidepressant or mood stabilizing medications, and is especially useful for those who need a treatment that begins working rapidly.
Patients who undergo ECT are given general anesthesia (medication is given to induce sleep and prevent pain). The heart and breathing rate, oxygen levels, and blood pressure are carefully monitored before, during, and after treatment is given. Side effects of this therapy include brief confusion and memory loss. Although ECT has been negatively portrayed in the media, this therapy often provides rapid and dramatic relief of symptoms and has few side effects.
MAINTENANCE THERAPY
Medications — Once the acute symptoms of mania or depression are resolved, treatment focuses on preventing their recurrence and maintaining remission. At least one year of medication is recommended for all people who have suffered a manic episode; lifetime treatment with a mood stabilizer is often recommended for patients who have had three or more manic episodes.
Psychotherapy (counseling) — Although medications are the treatment of choice for bipolar disorder, counseling and talk therapy have an important role in treatment, particularly once an acute episode has passed. Treatment may include individual counseling as well as education, marital and family therapy, and treatment of substance abuse. Therapy may help patients to stick with their medication regimen, thereby decreasing the risk of relapse and the need for hospitalization.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Mental Health
(www.nimh.nih.gov/)
Depression and Bipolar Support Alliance (DBSA)
(www.DBSAlliance.org)
National Mental Health Association
(www.nmha.org)
National Alliance for the Mentally Ill
(www.nami.org/)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Keck, PE Jr, McElroy, SL. Outcome in the pharmacologic treatment of bipolar disorder. J Clin Psychopharmacol 1996; 16:15S.
2. Keck, PE Jr, McElroy, SL, Arnold, LM. Bipolar disorder. Med Clin North Am 2001; 85:645.
3. Gijsman, HJ, Geddes, JR, Rendell, JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 2004; 161:1537.
4. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002; 159:1.
5. Müller-Oerlinghausen, B, Berghöfer, A, Bauer, M. Bipolar disorder. Lancet 2002; 359:241.
Sunday, October 21, 2007
Bipolar disorder
INTRODUCTION — Bipolar disorder causes a person to experience periods of mania (feeling excessively elated, impulsive, irritable, or irrational) or hypomania (a milder form of mania), and may also cause a person to experience periods of major depression (feeling excessively sad).
Bipolar disorder can lead to significant illness and even death by suicide if untreated or treated incorrectly. A number of effective treatment options are available.
CAUSE — Research has helped clarify the complex biologic basis of bipolar disorder, although the exact cause is still uncertain. Studies suggest that it results from an imbalance of neurochemicals in the brain, including serotonin, norepinephrine, and dopamine. These neurochemicals allow cells to communicate with each other and play an essential role in all brain functions, including movement, sensation, memory, and emotions.
People with a family history of bipolar disorder are at increased risk of developing the condition. This is thought to be the result of changes in genes, which are passed down from parents to children. Results of gene research indicate that there are probably multiple genes affected in persons with bipolar disorder.
SYMPTOMS
Mania — Mania causes a person to feel abnormally and persistently elated, irritable, hyperactive, impulsive, and irrational. These feelings last at least one week, and may be severe enough to require hospitalization. The mania of bipolar disorder is not caused by other medical illnesses or drug abuse. Other symptoms may include: Feelings of superiority and grandiosity Decreased need for sleep, restlessness Talking excessively Racing thoughts Short attention span Inappropriate laughing or joking Inappropriate spending sprees or sexual activity
Mania often causes a person to have difficulty maintaining relationships with friends and family, and can interfere with work or other responsibilities. During a manic episode, a person's moods can change rapidly from euphoria to depression or irritability.
Hypomania — Hypomania is less severe than mania, but causes a significant change in mood that is abnormal for the patient. Hypomania lasts for at least four days, but is usually briefer than manic episodes. Hypomania does not seriously impair a person's ability to function, and some people actually function better during a hypomanic episode. Hypomania does not require hospitalization, but is generally treated with medications because it may lead to a manic or depressive episode.
Depression — People with major depression experience significant sadness and difficulty functioning. They are typically depressed most of the day and may have little or no interest in any activity. Other symptoms may include one or more of the following: Significant weight loss or gain Changes in sleep patterns, including insomnia or excessive sleeping Change in activity level (including sluggishness, reduced activity, or agitation) Fatigue or loss of energy Feelings of worthlessness or guilt Difficulty concentrating and making decisions Recurring thoughts of death or suicide
To be considered major depression, a patient must have at least five symptoms on a daily or nearly daily basis for at least two weeks. In addition, symptoms must not be caused solely by a medical condition, drug abuse, medications, or the loss of a loved one. (See "Patient information: Depression in adults").
Bipolar disorder — Bipolar disorder usually presents in one of two ways: Bipolar I disorder causes at least one manic episode, often with episodes of depression Bipolar II disorder causes at least one hypomanic episode and one or more episodes of major depression.
Bipolar I disorder affects men and women equally; bipolar II disorder is more common in women. Most people develop the first symptoms of biplar disorder between 15 and 30 years of age. Newly diagnosed mania is uncommon in children and in adults over the age of 65.
People with bipolar disorder typically have cycles of relapse (when depression and/or mania occur) and remissions (when symptoms improve or resolve), often in an alternating pattern. Ninety percent of individuals who have one manic episode have another within five years. Ninety percent of individuals with bipolar disorder must be hospitalized in a psychiatric facility at least once, and two-thirds have two or more hospitalizations in their lifetime. Patients with bipolar II disorder are much more likely to have symptoms of depression than hypomania or mixed symptoms.
Alcohol, drugs, and suicide in bipolar disorder — Alcohol and drug abuse occur in more than 60 percent of people with bipolar disorder. The risk of suicide also is higher in people with bipolar disorder than in people with other psychiatric illnesses (including depression).
Suicide is often the result of feeling hopeless, and is more likely in patients with severe symptoms who must be hospitalized for treatment. Family members or friends of a person with bipolar disorder should consider any mention of suicide a serious threat, and should immediately contact a healthcare provider.
DIAGNOSIS — There is no one blood or imaging test that can determine if a person has bipolar disorder. The diagnosis is based upon a comprehensive medical and psychologic history and physical examination. Bipolar disorder can be confused with a number of other medical and psychiatric conditions. Laboratory testing may be performed to rule out other diagnoses.
TREATMENT OF MANIA — Treatment during an episode of mania focuses on managing symptoms and ensuring the patient's safety. In the early phase of mania (called the acute phase), a patient may be psychotic or display such poor judgment that they are at risk of injuring themselves or others. Hospitalization may be necessary until symptoms are controlled. Treatment of mania continues until symptoms completely resolve and the patient is able to function, although many patients are maintained on medications indefinitely to prevent a recurrence of mania symptoms.
Medications are the primary treatment for mania, and a number of medications are available. It is not usually possible to know which medication will be the most effective and cause the fewest side effects, and it may be necessary to try several medications before finding the best one. A person who responds well to one medication is likely to respond well to that treatment during future episodes.
Mood stabilizers — Mood stabilizing medications, such as lithium carbonate, lamotrigine, valproate, and carbamazepine, are often used in the treatment of mania or hypomania. Medications used for treatment of mania (and depression) are thought to cause changes in chemicals in the brain that affect mood. All of these medications are similarly effective, and the choice is often made based upon a patient's previous history, side effects, and any underlying medical illnesses.
Lithium — Lithium has been used for many years for the treatment of mania. It is usually taken two to three times per day. Common side effects include frequent urination, tremor, loose stools, and weight gain. Longer term complications include the potential for kidney or thyroid dysfunction (hypothyroidism).
Blood testing to measure the lithium level and kidney and thyroid function is usually done every 6 to 12 months once the lithium dose has been stabilized. Lithium can cause serious illness if an overdose is taken or if abnormal kidney function prevents the body from eliminating the drug. This can occur if the patient becomes severely dehydrated or uses medications such as nonsteroidal antiinflammatory drugs (eg, aspirin, ibuprofen, naproxen sodium) or an ACE inhibitor (used to treat high blood pressure).
While taking lithium, patients should talk to their healthcare provider before using any over the counter medications. Patients should give a complete list of prescription and nonprescription medications to their provider at every visit.
Valproate — Valproate is a medication occasionally used for patients with seizures, although it is also effective in stabilizing the mood of patients with mania. It may be used instead of or in combination with lithium. Common side effects include weight gain, nausea, vomiting, hair loss, easy bruising, and tremor. Liver failure and low platelet count (a type of blood cell) have rarely been associated with valproate use. Blood testing to monitor liver function and platelet count are usually done to monitor for these complications.
Carbamezapine — Carbamepazine was originally developed for prevention of seizures, but is also now used for treatment of bipolar disorder. It is usually taken twice per day. The most common side effects include nausea, vomiting, diarrhea, low sodium level, rash, itching, low white blood cell count, and fluid retention. Blood testing to monitor the carbamazepine level, liver function, and blood counts is recommended every 6 to 12 months.
Lamotrigine — Lamotrigine was also developed for seizure disorders, but may be particularly effective for depression in bipolar disorder. Routine blood tests are not needed for monitoring. Significant interactions with other medications can occur, and patients should be sure that all healthcare providers have an updated list of both prescription and nonprescription medication. An infrequent but serious and potentially life threatening rash (called Stevens-Johnson syndrome) can occur early in treatment.
Antipsychotics — Antipsychotic medications may be used alone or in combination with a mood stabilizer in patients with acute mania. Older antipsychotic medications (eg, haloperidol (Haldol®)) can cause bothersome involuntary movements (eg, tongue thrusting, tremors, restlessness). Atypical antipsychotics such as olanzapine (Zyprexa®), risperidone (Risperdal®), and quetiapine (Seroquel®) have a smaller risk of these side effects, but are more likely to cause weight gain, glucose intolerance, diabetes mellitus, and hyperlipidemia. Clozapine (Clozaril®) may be particularly effective in patients who do not respond to other mood stabilizers or antipsychotics, but it is associated with the potential for a dangerous decrease in the number of white blood cells. The newer atypical antipsychotics ziprasidone (Geodon®) and aripiprazole (Abilify®) appear to be as effective as other atypical antipsychotics, but without the risk of weight gain and diabetes. There is not as much experience with these medications, and there may be long-term risks or complications that are unknown.
TREATMENT OF DEPRESSION
Medications — During the initial phase of bipolar depression, an antidepressant medication is usually the best option for treatment. However, antidepressants may cause manic episodes, and are generally used only in the initial phase of bipolar depression in combination with a mood stabilizer. There are several types of antidepressants, each of which works slightly differently. Selective serotonin reuptake inhibitors (eg, fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), and escitalopram (Lexapro®)) Bupropion (Wellbutrin®) Monoamine oxidase inhibitors (tranylcypromine (Parnate®) and phenelzine (Nardil®).
Tricyclic antidepressants (eg, imipramine (Tofranil®), amitriptyline (Elavil®), desipramine (Norpramin®), nortriptyline (Pamelor®), and clomipramine (Anafranil®)) are more likely to cause mania than the medications mentioned above, and as a result are rarely used in patients with bipolar disorder.
ELECTROCONVULSIVE THERAPY (ECT) — During electroconvulsive therapy (ECT), an electrical current is passed through the brain, triggering a seizure. For unknown reasons, the seizure helps to restore the normal balance of neurochemicals in the brain. ECT is especially effective for people with severe, life-threatening depression or mania that has not responded to medication.
ECT can be used in pregnant women and in those who cannot tolerate antidepressant or mood stabilizing medications, and is especially useful for those who need a treatment that begins working rapidly.
Patients who undergo ECT are given general anesthesia (medication is given to induce sleep and prevent pain). The heart and breathing rate, oxygen levels, and blood pressure are carefully monitored before, during, and after treatment is given. Side effects of this therapy include brief confusion and memory loss. Although ECT has been negatively portrayed in the media, this therapy often provides rapid and dramatic relief of symptoms and has few side effects.
MAINTENANCE THERAPY
Medications — Once the acute symptoms of mania or depression are resolved, treatment focuses on preventing their recurrence and maintaining remission. At least one year of medication is recommended for all people who have suffered a manic episode; lifetime treatment with a mood stabilizer is often recommended for patients who have had three or more manic episodes.
Psychotherapy (counseling) — Although medications are the treatment of choice for bipolar disorder, counseling and talk therapy have an important role in treatment, particularly once an acute episode has passed. Treatment may include individual counseling as well as education, marital and family therapy, and treatment of substance abuse. Therapy may help patients to stick with their medication regimen, thereby decreasing the risk of relapse and the need for hospitalization.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Mental Health
(www.nimh.nih.gov/)
Depression and Bipolar Support Alliance (DBSA)
(www.DBSAlliance.org)
National Mental Health Association
(www.nmha.org)
National Alliance for the Mentally Ill
(www.nami.org/)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Keck, PE Jr, McElroy, SL. Outcome in the pharmacologic treatment of bipolar disorder. J Clin Psychopharmacol 1996; 16:15S.
2. Keck, PE Jr, McElroy, SL, Arnold, LM. Bipolar disorder. Med Clin North Am 2001; 85:645.
3. Gijsman, HJ, Geddes, JR, Rendell, JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 2004; 161:1537.
4. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002; 159:1.
5. Müller-Oerlinghausen, B, Berghöfer, A, Bauer, M. Bipolar disorder. Lancet 2002; 359:241.
Bipolar disorder can lead to significant illness and even death by suicide if untreated or treated incorrectly. A number of effective treatment options are available.
CAUSE — Research has helped clarify the complex biologic basis of bipolar disorder, although the exact cause is still uncertain. Studies suggest that it results from an imbalance of neurochemicals in the brain, including serotonin, norepinephrine, and dopamine. These neurochemicals allow cells to communicate with each other and play an essential role in all brain functions, including movement, sensation, memory, and emotions.
People with a family history of bipolar disorder are at increased risk of developing the condition. This is thought to be the result of changes in genes, which are passed down from parents to children. Results of gene research indicate that there are probably multiple genes affected in persons with bipolar disorder.
SYMPTOMS
Mania — Mania causes a person to feel abnormally and persistently elated, irritable, hyperactive, impulsive, and irrational. These feelings last at least one week, and may be severe enough to require hospitalization. The mania of bipolar disorder is not caused by other medical illnesses or drug abuse. Other symptoms may include: Feelings of superiority and grandiosity Decreased need for sleep, restlessness Talking excessively Racing thoughts Short attention span Inappropriate laughing or joking Inappropriate spending sprees or sexual activity
Mania often causes a person to have difficulty maintaining relationships with friends and family, and can interfere with work or other responsibilities. During a manic episode, a person's moods can change rapidly from euphoria to depression or irritability.
Hypomania — Hypomania is less severe than mania, but causes a significant change in mood that is abnormal for the patient. Hypomania lasts for at least four days, but is usually briefer than manic episodes. Hypomania does not seriously impair a person's ability to function, and some people actually function better during a hypomanic episode. Hypomania does not require hospitalization, but is generally treated with medications because it may lead to a manic or depressive episode.
Depression — People with major depression experience significant sadness and difficulty functioning. They are typically depressed most of the day and may have little or no interest in any activity. Other symptoms may include one or more of the following: Significant weight loss or gain Changes in sleep patterns, including insomnia or excessive sleeping Change in activity level (including sluggishness, reduced activity, or agitation) Fatigue or loss of energy Feelings of worthlessness or guilt Difficulty concentrating and making decisions Recurring thoughts of death or suicide
To be considered major depression, a patient must have at least five symptoms on a daily or nearly daily basis for at least two weeks. In addition, symptoms must not be caused solely by a medical condition, drug abuse, medications, or the loss of a loved one. (See "Patient information: Depression in adults").
Bipolar disorder — Bipolar disorder usually presents in one of two ways: Bipolar I disorder causes at least one manic episode, often with episodes of depression Bipolar II disorder causes at least one hypomanic episode and one or more episodes of major depression.
Bipolar I disorder affects men and women equally; bipolar II disorder is more common in women. Most people develop the first symptoms of biplar disorder between 15 and 30 years of age. Newly diagnosed mania is uncommon in children and in adults over the age of 65.
People with bipolar disorder typically have cycles of relapse (when depression and/or mania occur) and remissions (when symptoms improve or resolve), often in an alternating pattern. Ninety percent of individuals who have one manic episode have another within five years. Ninety percent of individuals with bipolar disorder must be hospitalized in a psychiatric facility at least once, and two-thirds have two or more hospitalizations in their lifetime. Patients with bipolar II disorder are much more likely to have symptoms of depression than hypomania or mixed symptoms.
Alcohol, drugs, and suicide in bipolar disorder — Alcohol and drug abuse occur in more than 60 percent of people with bipolar disorder. The risk of suicide also is higher in people with bipolar disorder than in people with other psychiatric illnesses (including depression).
Suicide is often the result of feeling hopeless, and is more likely in patients with severe symptoms who must be hospitalized for treatment. Family members or friends of a person with bipolar disorder should consider any mention of suicide a serious threat, and should immediately contact a healthcare provider.
DIAGNOSIS — There is no one blood or imaging test that can determine if a person has bipolar disorder. The diagnosis is based upon a comprehensive medical and psychologic history and physical examination. Bipolar disorder can be confused with a number of other medical and psychiatric conditions. Laboratory testing may be performed to rule out other diagnoses.
TREATMENT OF MANIA — Treatment during an episode of mania focuses on managing symptoms and ensuring the patient's safety. In the early phase of mania (called the acute phase), a patient may be psychotic or display such poor judgment that they are at risk of injuring themselves or others. Hospitalization may be necessary until symptoms are controlled. Treatment of mania continues until symptoms completely resolve and the patient is able to function, although many patients are maintained on medications indefinitely to prevent a recurrence of mania symptoms.
Medications are the primary treatment for mania, and a number of medications are available. It is not usually possible to know which medication will be the most effective and cause the fewest side effects, and it may be necessary to try several medications before finding the best one. A person who responds well to one medication is likely to respond well to that treatment during future episodes.
Mood stabilizers — Mood stabilizing medications, such as lithium carbonate, lamotrigine, valproate, and carbamazepine, are often used in the treatment of mania or hypomania. Medications used for treatment of mania (and depression) are thought to cause changes in chemicals in the brain that affect mood. All of these medications are similarly effective, and the choice is often made based upon a patient's previous history, side effects, and any underlying medical illnesses.
Lithium — Lithium has been used for many years for the treatment of mania. It is usually taken two to three times per day. Common side effects include frequent urination, tremor, loose stools, and weight gain. Longer term complications include the potential for kidney or thyroid dysfunction (hypothyroidism).
Blood testing to measure the lithium level and kidney and thyroid function is usually done every 6 to 12 months once the lithium dose has been stabilized. Lithium can cause serious illness if an overdose is taken or if abnormal kidney function prevents the body from eliminating the drug. This can occur if the patient becomes severely dehydrated or uses medications such as nonsteroidal antiinflammatory drugs (eg, aspirin, ibuprofen, naproxen sodium) or an ACE inhibitor (used to treat high blood pressure).
While taking lithium, patients should talk to their healthcare provider before using any over the counter medications. Patients should give a complete list of prescription and nonprescription medications to their provider at every visit.
Valproate — Valproate is a medication occasionally used for patients with seizures, although it is also effective in stabilizing the mood of patients with mania. It may be used instead of or in combination with lithium. Common side effects include weight gain, nausea, vomiting, hair loss, easy bruising, and tremor. Liver failure and low platelet count (a type of blood cell) have rarely been associated with valproate use. Blood testing to monitor liver function and platelet count are usually done to monitor for these complications.
Carbamezapine — Carbamepazine was originally developed for prevention of seizures, but is also now used for treatment of bipolar disorder. It is usually taken twice per day. The most common side effects include nausea, vomiting, diarrhea, low sodium level, rash, itching, low white blood cell count, and fluid retention. Blood testing to monitor the carbamazepine level, liver function, and blood counts is recommended every 6 to 12 months.
Lamotrigine — Lamotrigine was also developed for seizure disorders, but may be particularly effective for depression in bipolar disorder. Routine blood tests are not needed for monitoring. Significant interactions with other medications can occur, and patients should be sure that all healthcare providers have an updated list of both prescription and nonprescription medication. An infrequent but serious and potentially life threatening rash (called Stevens-Johnson syndrome) can occur early in treatment.
Antipsychotics — Antipsychotic medications may be used alone or in combination with a mood stabilizer in patients with acute mania. Older antipsychotic medications (eg, haloperidol (Haldol®)) can cause bothersome involuntary movements (eg, tongue thrusting, tremors, restlessness). Atypical antipsychotics such as olanzapine (Zyprexa®), risperidone (Risperdal®), and quetiapine (Seroquel®) have a smaller risk of these side effects, but are more likely to cause weight gain, glucose intolerance, diabetes mellitus, and hyperlipidemia. Clozapine (Clozaril®) may be particularly effective in patients who do not respond to other mood stabilizers or antipsychotics, but it is associated with the potential for a dangerous decrease in the number of white blood cells. The newer atypical antipsychotics ziprasidone (Geodon®) and aripiprazole (Abilify®) appear to be as effective as other atypical antipsychotics, but without the risk of weight gain and diabetes. There is not as much experience with these medications, and there may be long-term risks or complications that are unknown.
TREATMENT OF DEPRESSION
Medications — During the initial phase of bipolar depression, an antidepressant medication is usually the best option for treatment. However, antidepressants may cause manic episodes, and are generally used only in the initial phase of bipolar depression in combination with a mood stabilizer. There are several types of antidepressants, each of which works slightly differently. Selective serotonin reuptake inhibitors (eg, fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), and escitalopram (Lexapro®)) Bupropion (Wellbutrin®) Monoamine oxidase inhibitors (tranylcypromine (Parnate®) and phenelzine (Nardil®).
Tricyclic antidepressants (eg, imipramine (Tofranil®), amitriptyline (Elavil®), desipramine (Norpramin®), nortriptyline (Pamelor®), and clomipramine (Anafranil®)) are more likely to cause mania than the medications mentioned above, and as a result are rarely used in patients with bipolar disorder.
ELECTROCONVULSIVE THERAPY (ECT) — During electroconvulsive therapy (ECT), an electrical current is passed through the brain, triggering a seizure. For unknown reasons, the seizure helps to restore the normal balance of neurochemicals in the brain. ECT is especially effective for people with severe, life-threatening depression or mania that has not responded to medication.
ECT can be used in pregnant women and in those who cannot tolerate antidepressant or mood stabilizing medications, and is especially useful for those who need a treatment that begins working rapidly.
Patients who undergo ECT are given general anesthesia (medication is given to induce sleep and prevent pain). The heart and breathing rate, oxygen levels, and blood pressure are carefully monitored before, during, and after treatment is given. Side effects of this therapy include brief confusion and memory loss. Although ECT has been negatively portrayed in the media, this therapy often provides rapid and dramatic relief of symptoms and has few side effects.
MAINTENANCE THERAPY
Medications — Once the acute symptoms of mania or depression are resolved, treatment focuses on preventing their recurrence and maintaining remission. At least one year of medication is recommended for all people who have suffered a manic episode; lifetime treatment with a mood stabilizer is often recommended for patients who have had three or more manic episodes.
Psychotherapy (counseling) — Although medications are the treatment of choice for bipolar disorder, counseling and talk therapy have an important role in treatment, particularly once an acute episode has passed. Treatment may include individual counseling as well as education, marital and family therapy, and treatment of substance abuse. Therapy may help patients to stick with their medication regimen, thereby decreasing the risk of relapse and the need for hospitalization.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Mental Health
(www.nimh.nih.gov/)
Depression and Bipolar Support Alliance (DBSA)
(www.DBSAlliance.org)
National Mental Health Association
(www.nmha.org)
National Alliance for the Mentally Ill
(www.nami.org/)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Keck, PE Jr, McElroy, SL. Outcome in the pharmacologic treatment of bipolar disorder. J Clin Psychopharmacol 1996; 16:15S.
2. Keck, PE Jr, McElroy, SL, Arnold, LM. Bipolar disorder. Med Clin North Am 2001; 85:645.
3. Gijsman, HJ, Geddes, JR, Rendell, JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 2004; 161:1537.
4. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002; 159:1.
5. Müller-Oerlinghausen, B, Berghöfer, A, Bauer, M. Bipolar disorder. Lancet 2002; 359:241.
Bipolar disorder
INTRODUCTION — Bipolar disorder causes a person to experience periods of mania (feeling excessively elated, impulsive, irritable, or irrational) or hypomania (a milder form of mania), and may also cause a person to experience periods of major depression (feeling excessively sad).
Bipolar disorder can lead to significant illness and even death by suicide if untreated or treated incorrectly. A number of effective treatment options are available.
CAUSE — Research has helped clarify the complex biologic basis of bipolar disorder, although the exact cause is still uncertain. Studies suggest that it results from an imbalance of neurochemicals in the brain, including serotonin, norepinephrine, and dopamine. These neurochemicals allow cells to communicate with each other and play an essential role in all brain functions, including movement, sensation, memory, and emotions.
People with a family history of bipolar disorder are at increased risk of developing the condition. This is thought to be the result of changes in genes, which are passed down from parents to children. Results of gene research indicate that there are probably multiple genes affected in persons with bipolar disorder.
SYMPTOMS
Mania — Mania causes a person to feel abnormally and persistently elated, irritable, hyperactive, impulsive, and irrational. These feelings last at least one week, and may be severe enough to require hospitalization. The mania of bipolar disorder is not caused by other medical illnesses or drug abuse. Other symptoms may include: Feelings of superiority and grandiosity Decreased need for sleep, restlessness Talking excessively Racing thoughts Short attention span Inappropriate laughing or joking Inappropriate spending sprees or sexual activity
Mania often causes a person to have difficulty maintaining relationships with friends and family, and can interfere with work or other responsibilities. During a manic episode, a person's moods can change rapidly from euphoria to depression or irritability.
Hypomania — Hypomania is less severe than mania, but causes a significant change in mood that is abnormal for the patient. Hypomania lasts for at least four days, but is usually briefer than manic episodes. Hypomania does not seriously impair a person's ability to function, and some people actually function better during a hypomanic episode. Hypomania does not require hospitalization, but is generally treated with medications because it may lead to a manic or depressive episode.
Depression — People with major depression experience significant sadness and difficulty functioning. They are typically depressed most of the day and may have little or no interest in any activity. Other symptoms may include one or more of the following: Significant weight loss or gain Changes in sleep patterns, including insomnia or excessive sleeping Change in activity level (including sluggishness, reduced activity, or agitation) Fatigue or loss of energy Feelings of worthlessness or guilt Difficulty concentrating and making decisions Recurring thoughts of death or suicide
To be considered major depression, a patient must have at least five symptoms on a daily or nearly daily basis for at least two weeks. In addition, symptoms must not be caused solely by a medical condition, drug abuse, medications, or the loss of a loved one. (See "Patient information: Depression in adults").
Bipolar disorder — Bipolar disorder usually presents in one of two ways: Bipolar I disorder causes at least one manic episode, often with episodes of depression Bipolar II disorder causes at least one hypomanic episode and one or more episodes of major depression.
Bipolar I disorder affects men and women equally; bipolar II disorder is more common in women. Most people develop the first symptoms of biplar disorder between 15 and 30 years of age. Newly diagnosed mania is uncommon in children and in adults over the age of 65.
People with bipolar disorder typically have cycles of relapse (when depression and/or mania occur) and remissions (when symptoms improve or resolve), often in an alternating pattern. Ninety percent of individuals who have one manic episode have another within five years. Ninety percent of individuals with bipolar disorder must be hospitalized in a psychiatric facility at least once, and two-thirds have two or more hospitalizations in their lifetime. Patients with bipolar II disorder are much more likely to have symptoms of depression than hypomania or mixed symptoms.
Alcohol, drugs, and suicide in bipolar disorder — Alcohol and drug abuse occur in more than 60 percent of people with bipolar disorder. The risk of suicide also is higher in people with bipolar disorder than in people with other psychiatric illnesses (including depression).
Suicide is often the result of feeling hopeless, and is more likely in patients with severe symptoms who must be hospitalized for treatment. Family members or friends of a person with bipolar disorder should consider any mention of suicide a serious threat, and should immediately contact a healthcare provider.
DIAGNOSIS — There is no one blood or imaging test that can determine if a person has bipolar disorder. The diagnosis is based upon a comprehensive medical and psychologic history and physical examination. Bipolar disorder can be confused with a number of other medical and psychiatric conditions. Laboratory testing may be performed to rule out other diagnoses.
TREATMENT OF MANIA — Treatment during an episode of mania focuses on managing symptoms and ensuring the patient's safety. In the early phase of mania (called the acute phase), a patient may be psychotic or display such poor judgment that they are at risk of injuring themselves or others. Hospitalization may be necessary until symptoms are controlled. Treatment of mania continues until symptoms completely resolve and the patient is able to function, although many patients are maintained on medications indefinitely to prevent a recurrence of mania symptoms.
Medications are the primary treatment for mania, and a number of medications are available. It is not usually possible to know which medication will be the most effective and cause the fewest side effects, and it may be necessary to try several medications before finding the best one. A person who responds well to one medication is likely to respond well to that treatment during future episodes.
Mood stabilizers — Mood stabilizing medications, such as lithium carbonate, lamotrigine, valproate, and carbamazepine, are often used in the treatment of mania or hypomania. Medications used for treatment of mania (and depression) are thought to cause changes in chemicals in the brain that affect mood. All of these medications are similarly effective, and the choice is often made based upon a patient's previous history, side effects, and any underlying medical illnesses.
Lithium — Lithium has been used for many years for the treatment of mania. It is usually taken two to three times per day. Common side effects include frequent urination, tremor, loose stools, and weight gain. Longer term complications include the potential for kidney or thyroid dysfunction (hypothyroidism).
Blood testing to measure the lithium level and kidney and thyroid function is usually done every 6 to 12 months once the lithium dose has been stabilized. Lithium can cause serious illness if an overdose is taken or if abnormal kidney function prevents the body from eliminating the drug. This can occur if the patient becomes severely dehydrated or uses medications such as nonsteroidal antiinflammatory drugs (eg, aspirin, ibuprofen, naproxen sodium) or an ACE inhibitor (used to treat high blood pressure).
While taking lithium, patients should talk to their healthcare provider before using any over the counter medications. Patients should give a complete list of prescription and nonprescription medications to their provider at every visit.
Valproate — Valproate is a medication occasionally used for patients with seizures, although it is also effective in stabilizing the mood of patients with mania. It may be used instead of or in combination with lithium. Common side effects include weight gain, nausea, vomiting, hair loss, easy bruising, and tremor. Liver failure and low platelet count (a type of blood cell) have rarely been associated with valproate use. Blood testing to monitor liver function and platelet count are usually done to monitor for these complications.
Carbamezapine — Carbamepazine was originally developed for prevention of seizures, but is also now used for treatment of bipolar disorder. It is usually taken twice per day. The most common side effects include nausea, vomiting, diarrhea, low sodium level, rash, itching, low white blood cell count, and fluid retention. Blood testing to monitor the carbamazepine level, liver function, and blood counts is recommended every 6 to 12 months.
Lamotrigine — Lamotrigine was also developed for seizure disorders, but may be particularly effective for depression in bipolar disorder. Routine blood tests are not needed for monitoring. Significant interactions with other medications can occur, and patients should be sure that all healthcare providers have an updated list of both prescription and nonprescription medication. An infrequent but serious and potentially life threatening rash (called Stevens-Johnson syndrome) can occur early in treatment.
Antipsychotics — Antipsychotic medications may be used alone or in combination with a mood stabilizer in patients with acute mania. Older antipsychotic medications (eg, haloperidol (Haldol®)) can cause bothersome involuntary movements (eg, tongue thrusting, tremors, restlessness). Atypical antipsychotics such as olanzapine (Zyprexa®), risperidone (Risperdal®), and quetiapine (Seroquel®) have a smaller risk of these side effects, but are more likely to cause weight gain, glucose intolerance, diabetes mellitus, and hyperlipidemia. Clozapine (Clozaril®) may be particularly effective in patients who do not respond to other mood stabilizers or antipsychotics, but it is associated with the potential for a dangerous decrease in the number of white blood cells. The newer atypical antipsychotics ziprasidone (Geodon®) and aripiprazole (Abilify®) appear to be as effective as other atypical antipsychotics, but without the risk of weight gain and diabetes. There is not as much experience with these medications, and there may be long-term risks or complications that are unknown.
TREATMENT OF DEPRESSION
Medications — During the initial phase of bipolar depression, an antidepressant medication is usually the best option for treatment. However, antidepressants may cause manic episodes, and are generally used only in the initial phase of bipolar depression in combination with a mood stabilizer. There are several types of antidepressants, each of which works slightly differently. Selective serotonin reuptake inhibitors (eg, fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), and escitalopram (Lexapro®)) Bupropion (Wellbutrin®) Monoamine oxidase inhibitors (tranylcypromine (Parnate®) and phenelzine (Nardil®).
Tricyclic antidepressants (eg, imipramine (Tofranil®), amitriptyline (Elavil®), desipramine (Norpramin®), nortriptyline (Pamelor®), and clomipramine (Anafranil®)) are more likely to cause mania than the medications mentioned above, and as a result are rarely used in patients with bipolar disorder.
ELECTROCONVULSIVE THERAPY (ECT) — During electroconvulsive therapy (ECT), an electrical current is passed through the brain, triggering a seizure. For unknown reasons, the seizure helps to restore the normal balance of neurochemicals in the brain. ECT is especially effective for people with severe, life-threatening depression or mania that has not responded to medication.
ECT can be used in pregnant women and in those who cannot tolerate antidepressant or mood stabilizing medications, and is especially useful for those who need a treatment that begins working rapidly.
Patients who undergo ECT are given general anesthesia (medication is given to induce sleep and prevent pain). The heart and breathing rate, oxygen levels, and blood pressure are carefully monitored before, during, and after treatment is given. Side effects of this therapy include brief confusion and memory loss. Although ECT has been negatively portrayed in the media, this therapy often provides rapid and dramatic relief of symptoms and has few side effects.
MAINTENANCE THERAPY
Medications — Once the acute symptoms of mania or depression are resolved, treatment focuses on preventing their recurrence and maintaining remission. At least one year of medication is recommended for all people who have suffered a manic episode; lifetime treatment with a mood stabilizer is often recommended for patients who have had three or more manic episodes.
Psychotherapy (counseling) — Although medications are the treatment of choice for bipolar disorder, counseling and talk therapy have an important role in treatment, particularly once an acute episode has passed. Treatment may include individual counseling as well as education, marital and family therapy, and treatment of substance abuse. Therapy may help patients to stick with their medication regimen, thereby decreasing the risk of relapse and the need for hospitalization.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Mental Health
(www.nimh.nih.gov/)
Depression and Bipolar Support Alliance (DBSA)
(www.DBSAlliance.org)
National Mental Health Association
(www.nmha.org)
National Alliance for the Mentally Ill
(www.nami.org/)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Keck, PE Jr, McElroy, SL. Outcome in the pharmacologic treatment of bipolar disorder. J Clin Psychopharmacol 1996; 16:15S.
2. Keck, PE Jr, McElroy, SL, Arnold, LM. Bipolar disorder. Med Clin North Am 2001; 85:645.
3. Gijsman, HJ, Geddes, JR, Rendell, JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 2004; 161:1537.
4. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002; 159:1.
5. Müller-Oerlinghausen, B, Berghöfer, A, Bauer, M. Bipolar disorder. Lancet 2002; 359:241.
Bipolar disorder can lead to significant illness and even death by suicide if untreated or treated incorrectly. A number of effective treatment options are available.
CAUSE — Research has helped clarify the complex biologic basis of bipolar disorder, although the exact cause is still uncertain. Studies suggest that it results from an imbalance of neurochemicals in the brain, including serotonin, norepinephrine, and dopamine. These neurochemicals allow cells to communicate with each other and play an essential role in all brain functions, including movement, sensation, memory, and emotions.
People with a family history of bipolar disorder are at increased risk of developing the condition. This is thought to be the result of changes in genes, which are passed down from parents to children. Results of gene research indicate that there are probably multiple genes affected in persons with bipolar disorder.
SYMPTOMS
Mania — Mania causes a person to feel abnormally and persistently elated, irritable, hyperactive, impulsive, and irrational. These feelings last at least one week, and may be severe enough to require hospitalization. The mania of bipolar disorder is not caused by other medical illnesses or drug abuse. Other symptoms may include: Feelings of superiority and grandiosity Decreased need for sleep, restlessness Talking excessively Racing thoughts Short attention span Inappropriate laughing or joking Inappropriate spending sprees or sexual activity
Mania often causes a person to have difficulty maintaining relationships with friends and family, and can interfere with work or other responsibilities. During a manic episode, a person's moods can change rapidly from euphoria to depression or irritability.
Hypomania — Hypomania is less severe than mania, but causes a significant change in mood that is abnormal for the patient. Hypomania lasts for at least four days, but is usually briefer than manic episodes. Hypomania does not seriously impair a person's ability to function, and some people actually function better during a hypomanic episode. Hypomania does not require hospitalization, but is generally treated with medications because it may lead to a manic or depressive episode.
Depression — People with major depression experience significant sadness and difficulty functioning. They are typically depressed most of the day and may have little or no interest in any activity. Other symptoms may include one or more of the following: Significant weight loss or gain Changes in sleep patterns, including insomnia or excessive sleeping Change in activity level (including sluggishness, reduced activity, or agitation) Fatigue or loss of energy Feelings of worthlessness or guilt Difficulty concentrating and making decisions Recurring thoughts of death or suicide
To be considered major depression, a patient must have at least five symptoms on a daily or nearly daily basis for at least two weeks. In addition, symptoms must not be caused solely by a medical condition, drug abuse, medications, or the loss of a loved one. (See "Patient information: Depression in adults").
Bipolar disorder — Bipolar disorder usually presents in one of two ways: Bipolar I disorder causes at least one manic episode, often with episodes of depression Bipolar II disorder causes at least one hypomanic episode and one or more episodes of major depression.
Bipolar I disorder affects men and women equally; bipolar II disorder is more common in women. Most people develop the first symptoms of biplar disorder between 15 and 30 years of age. Newly diagnosed mania is uncommon in children and in adults over the age of 65.
People with bipolar disorder typically have cycles of relapse (when depression and/or mania occur) and remissions (when symptoms improve or resolve), often in an alternating pattern. Ninety percent of individuals who have one manic episode have another within five years. Ninety percent of individuals with bipolar disorder must be hospitalized in a psychiatric facility at least once, and two-thirds have two or more hospitalizations in their lifetime. Patients with bipolar II disorder are much more likely to have symptoms of depression than hypomania or mixed symptoms.
Alcohol, drugs, and suicide in bipolar disorder — Alcohol and drug abuse occur in more than 60 percent of people with bipolar disorder. The risk of suicide also is higher in people with bipolar disorder than in people with other psychiatric illnesses (including depression).
Suicide is often the result of feeling hopeless, and is more likely in patients with severe symptoms who must be hospitalized for treatment. Family members or friends of a person with bipolar disorder should consider any mention of suicide a serious threat, and should immediately contact a healthcare provider.
DIAGNOSIS — There is no one blood or imaging test that can determine if a person has bipolar disorder. The diagnosis is based upon a comprehensive medical and psychologic history and physical examination. Bipolar disorder can be confused with a number of other medical and psychiatric conditions. Laboratory testing may be performed to rule out other diagnoses.
TREATMENT OF MANIA — Treatment during an episode of mania focuses on managing symptoms and ensuring the patient's safety. In the early phase of mania (called the acute phase), a patient may be psychotic or display such poor judgment that they are at risk of injuring themselves or others. Hospitalization may be necessary until symptoms are controlled. Treatment of mania continues until symptoms completely resolve and the patient is able to function, although many patients are maintained on medications indefinitely to prevent a recurrence of mania symptoms.
Medications are the primary treatment for mania, and a number of medications are available. It is not usually possible to know which medication will be the most effective and cause the fewest side effects, and it may be necessary to try several medications before finding the best one. A person who responds well to one medication is likely to respond well to that treatment during future episodes.
Mood stabilizers — Mood stabilizing medications, such as lithium carbonate, lamotrigine, valproate, and carbamazepine, are often used in the treatment of mania or hypomania. Medications used for treatment of mania (and depression) are thought to cause changes in chemicals in the brain that affect mood. All of these medications are similarly effective, and the choice is often made based upon a patient's previous history, side effects, and any underlying medical illnesses.
Lithium — Lithium has been used for many years for the treatment of mania. It is usually taken two to three times per day. Common side effects include frequent urination, tremor, loose stools, and weight gain. Longer term complications include the potential for kidney or thyroid dysfunction (hypothyroidism).
Blood testing to measure the lithium level and kidney and thyroid function is usually done every 6 to 12 months once the lithium dose has been stabilized. Lithium can cause serious illness if an overdose is taken or if abnormal kidney function prevents the body from eliminating the drug. This can occur if the patient becomes severely dehydrated or uses medications such as nonsteroidal antiinflammatory drugs (eg, aspirin, ibuprofen, naproxen sodium) or an ACE inhibitor (used to treat high blood pressure).
While taking lithium, patients should talk to their healthcare provider before using any over the counter medications. Patients should give a complete list of prescription and nonprescription medications to their provider at every visit.
Valproate — Valproate is a medication occasionally used for patients with seizures, although it is also effective in stabilizing the mood of patients with mania. It may be used instead of or in combination with lithium. Common side effects include weight gain, nausea, vomiting, hair loss, easy bruising, and tremor. Liver failure and low platelet count (a type of blood cell) have rarely been associated with valproate use. Blood testing to monitor liver function and platelet count are usually done to monitor for these complications.
Carbamezapine — Carbamepazine was originally developed for prevention of seizures, but is also now used for treatment of bipolar disorder. It is usually taken twice per day. The most common side effects include nausea, vomiting, diarrhea, low sodium level, rash, itching, low white blood cell count, and fluid retention. Blood testing to monitor the carbamazepine level, liver function, and blood counts is recommended every 6 to 12 months.
Lamotrigine — Lamotrigine was also developed for seizure disorders, but may be particularly effective for depression in bipolar disorder. Routine blood tests are not needed for monitoring. Significant interactions with other medications can occur, and patients should be sure that all healthcare providers have an updated list of both prescription and nonprescription medication. An infrequent but serious and potentially life threatening rash (called Stevens-Johnson syndrome) can occur early in treatment.
Antipsychotics — Antipsychotic medications may be used alone or in combination with a mood stabilizer in patients with acute mania. Older antipsychotic medications (eg, haloperidol (Haldol®)) can cause bothersome involuntary movements (eg, tongue thrusting, tremors, restlessness). Atypical antipsychotics such as olanzapine (Zyprexa®), risperidone (Risperdal®), and quetiapine (Seroquel®) have a smaller risk of these side effects, but are more likely to cause weight gain, glucose intolerance, diabetes mellitus, and hyperlipidemia. Clozapine (Clozaril®) may be particularly effective in patients who do not respond to other mood stabilizers or antipsychotics, but it is associated with the potential for a dangerous decrease in the number of white blood cells. The newer atypical antipsychotics ziprasidone (Geodon®) and aripiprazole (Abilify®) appear to be as effective as other atypical antipsychotics, but without the risk of weight gain and diabetes. There is not as much experience with these medications, and there may be long-term risks or complications that are unknown.
TREATMENT OF DEPRESSION
Medications — During the initial phase of bipolar depression, an antidepressant medication is usually the best option for treatment. However, antidepressants may cause manic episodes, and are generally used only in the initial phase of bipolar depression in combination with a mood stabilizer. There are several types of antidepressants, each of which works slightly differently. Selective serotonin reuptake inhibitors (eg, fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), and escitalopram (Lexapro®)) Bupropion (Wellbutrin®) Monoamine oxidase inhibitors (tranylcypromine (Parnate®) and phenelzine (Nardil®).
Tricyclic antidepressants (eg, imipramine (Tofranil®), amitriptyline (Elavil®), desipramine (Norpramin®), nortriptyline (Pamelor®), and clomipramine (Anafranil®)) are more likely to cause mania than the medications mentioned above, and as a result are rarely used in patients with bipolar disorder.
ELECTROCONVULSIVE THERAPY (ECT) — During electroconvulsive therapy (ECT), an electrical current is passed through the brain, triggering a seizure. For unknown reasons, the seizure helps to restore the normal balance of neurochemicals in the brain. ECT is especially effective for people with severe, life-threatening depression or mania that has not responded to medication.
ECT can be used in pregnant women and in those who cannot tolerate antidepressant or mood stabilizing medications, and is especially useful for those who need a treatment that begins working rapidly.
Patients who undergo ECT are given general anesthesia (medication is given to induce sleep and prevent pain). The heart and breathing rate, oxygen levels, and blood pressure are carefully monitored before, during, and after treatment is given. Side effects of this therapy include brief confusion and memory loss. Although ECT has been negatively portrayed in the media, this therapy often provides rapid and dramatic relief of symptoms and has few side effects.
MAINTENANCE THERAPY
Medications — Once the acute symptoms of mania or depression are resolved, treatment focuses on preventing their recurrence and maintaining remission. At least one year of medication is recommended for all people who have suffered a manic episode; lifetime treatment with a mood stabilizer is often recommended for patients who have had three or more manic episodes.
Psychotherapy (counseling) — Although medications are the treatment of choice for bipolar disorder, counseling and talk therapy have an important role in treatment, particularly once an acute episode has passed. Treatment may include individual counseling as well as education, marital and family therapy, and treatment of substance abuse. Therapy may help patients to stick with their medication regimen, thereby decreasing the risk of relapse and the need for hospitalization.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Mental Health
(www.nimh.nih.gov/)
Depression and Bipolar Support Alliance (DBSA)
(www.DBSAlliance.org)
National Mental Health Association
(www.nmha.org)
National Alliance for the Mentally Ill
(www.nami.org/)
[1-5]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Keck, PE Jr, McElroy, SL. Outcome in the pharmacologic treatment of bipolar disorder. J Clin Psychopharmacol 1996; 16:15S.
2. Keck, PE Jr, McElroy, SL, Arnold, LM. Bipolar disorder. Med Clin North Am 2001; 85:645.
3. Gijsman, HJ, Geddes, JR, Rendell, JM, et al. Antidepressants for bipolar depression: a systematic review of randomized, controlled trials. Am J Psychiatry 2004; 161:1537.
4. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry 2002; 159:1.
5. Müller-Oerlinghausen, B, Berghöfer, A, Bauer, M. Bipolar disorder. Lancet 2002; 359:241.
Alzheimer's disease
INTRODUCTION — Alzheimer's disease (AD) is a form of dementia, a group of disorders characterized by a decrease in the overall level of cognitive (mental) functioning, especially memory. In addition to memory deficits, people with Alzheimer's disease may have behavioral disturbances and experience generalized physical and mental decline. This combination eventually prevents a person from functioning independently in day-to-day life.
Alzheimer's disease accounts for 60 to 80 percent of all cases of dementia among the elderly. About four million Americans have Alzheimer's disease now, and close to three million Americans are caring for relatives or friends who have it. There is striking variety in presentation and severity of symptoms and signs, often leading to underrecognition. Currently available medical treatments can be of help in controlling the mental and behavioral symptoms of the disease but leave much to be desired in many cases. Meanwhile, ongoing research has made major advances in understanding the underlying causes of this kind of dementia. This research holds great promise for developing treatments to slow down and hopefully delay the onset or even prevent Alzheimer's disease.
CAUSES — Scientists have not yet been able to determine exactly why and how Alzheimer's disease develops. Researchers have determined that the brains of patients with AD develop deposits of a protein called beta amyloid (these deposits are also known as plaques), and that people also develop disorganized masses of protein fibers within the brain cells known as neurofibrillary tangles.
In addition, Alzheimer's disease is associated with the death of nerve cells (neurons) in important parts of the brain. Currently, these changes to the brain can only be seen during autopsy after a patient's death, but researchers are working to develop ways of imaging these brain changes in living patients.
RISK FACTORS — A risk factor is not necessarily the cause of a particular condition, but merely something that helps predict it. Some risk factors can indeed cause a particular illness. As an example, we know that smoking can cause lung cancer. The relationship between other risk factors and specific diseases is more complicated, and in many cases scientists do not know if there is any causal relationship involved or not. They just know that people who have a particular risk factor are for some reason also more likely to get a particular disease.
Age — The biggest risk factor for Alzheimer's disease is age: the older you are, the more likely you are to develop Alzheimer's disease. As an example, one large study found that among people ages 65 to 69, less than 1 percent of people develop AD per year [1]. For people ages 70 to 74, the incidence was 1 percent, and for people ages 75 to 79, 2 percent. The number affected by Alzheimer's is more than 3 percent among people ages 80 to 84, and to more than 8 percent among those 85 and over.
Family history — Having a close family member with Alzheimer's disease increases the chances of developing it yourself. People with a first-degree relative, such as a parent or sibling, with Alzheimer's disease have a 10 to 30 percent chance of developing the disorder. The risk is probably higher if the family member developed Alzheimer's disease at a younger age and lower if the family member did not get Alzheimer's disease until late in life [2].
Scientists have discovered a particular gene increases a person's risk of developing Alzheimer's. But even among individuals with this gene, only about one-half develop Alzheimer's by age 90, suggesting that other factors are also involved [3]. It is possible to test for this gene in family members of patients with Alzheimer's disease, but this test is currently recommended only for people involved in a research study.
SYMPTOMS
Normal changes versus Alzheimer's — Many people worry that memory problems are caused by early Alzheimer's disease. Normal age-related changes usually cause minor difficulties in short term memory and a slowed ability to learn and process information. These changes are usually mild and do not worsen over time, nor should they interfere with a person's day-to-day functioning.
Early changes — The earliest symptoms of Alzheimer's disease are gradual and often subtle. Many patients and their families first notice difficulty remembering recent events or information. Other changes can include one or more of the following: Confusion Difficulties with language (eg, not being able to find the right words for things) Difficulty with concentration and reasoning Problems with complex tasks like paying bills or balancing a checkbook Problems with orientation or spatial ability (eg, getting lost in a familiar place)
Later changes — As Alzheimer's disease progresses, a person's ability to think clearly continues to decline, and personality and behavioral symptoms are more likely to appear. These can include: Increased anger, hostility, and/or suspicion Aggression and physical violence Hallucinations Delusions Wandering Increased number of physical accidents
The number of symptoms and speed with which symptoms progress can vary widely from one person to the next. In some people, severe dementia occurs within five years of the diagnosis; for others, the process can take more than 10 years. Most people with Alzheimer's disease do not die from the disease itself, but instead die from a secondary illness such as pneumonia, urinary tract infection, or complications of a fall.
DIAGNOSIS — There is no single medical or laboratory test that can determine if a person has Alzheimer's disease. Instead, a healthcare provider must make the diagnosis based upon information gathered from the patient and family, and upon the results of tests that measure mental functioning.
The provider will want to know about the patient's recent history: the nature of any mental changes or memory loss, behavioral changes, any medical conditions or illnesses, and any medications the patient has been taking. A complete physical check-up and blood work may be done at this time.
It is important to rule out other possible causes for a patient's mental difficulties. These can include medications or other medical conditions. As examples, both delirium and depression have symptoms similar to those of Alzheimer's disease and may occur in patients with dementia.
The provider will also need to rule out other forms of dementia before diagnosing Alzheimer's disease. These include vascular dementia (changes caused by blood vessel abnormalities), dementia caused by Parkinson's disease, dementia related to alcohol or medications, and other conditions.
To get a sense of how the patient is functioning mentally, the doctor will probably administer a brief test such as the Mini-Mental State Exam, or MMSE. This is the most widely used test to assess a person's ability to think and remember. It takes about seven minutes to complete and evaluates a range of mental functions, including being able to state today's day, month, and year to being able to remember a short list of words or write a full sentence spontaneously.
TREATMENT — Although scientists are learning more about Alzheimer's disease all the time, currently there is no cure. There are a number of medications that may help to control some of the symptoms of Alzheimer's disease. Research suggests that treatments to prevent and even cure the condition may be available in the not too distant future.
Safety issues — A major issue in managing individuals with Alzheimer's disease is safety. Because many patients do not realize that their mental functioning is impaired, they try to continue their day-to-day activities as usual. This can lead to physical danger, and caregivers must help to avoid situations that can threaten the safety of the patient or others.
Driving — Driving is often one of the first safety issues that arises. This is often difficult to face because driving represents independence for many people. Although people with Alzheimer's disease do not have more car accidents than others during the first year after diagnosis, the risk of crashes more than doubles after the first year. It is best to discuss the issue of driving early.
There may be significant resistance to stopping driving since the patient may not realize that he or she has impairments in mental functioning or reaction time. But all patients with Alzheimer's disease will eventually reach the point where driving is dangerous to themselves and others. The healthcare provider and family must work together to determine when a patient needs to stop driving.
Most states do not have specific regulations or restrictions on driving for patients with dementia, although some do provide roadside testing and other ways of evaluating an individual's ability to drive safely. Even if a person with newly diagnosed, mild Alzheimer's disease is still able to drive, the appropriateness of driving needs to be reassessed every six months, with the expectation that driving will eventually no longer be possible.
Cooking — Cooking is another area in which dementia can lead to serious safety concerns. Symptoms such as distractibility, forgetfulness, and difficulty in following directions can lead to burns, fires, or other injuries. Many providers recommend that patients be taught early how to use a microwave oven, which poses fewer dangers than stove-top cooking.
Wandering — As dementia progresses, some patients with Alzheimer's disease begin to wander. Because restlessness, distractibility, and memory problems are common, a person who wanders may easily become lost. Identification bracelets can help ensure that a lost wanderer gets home. The Alzheimer's Association provides a "safe return" program with ID tags and 24-hour assistance (www.alz.org/we_can_help_safe_return.asp).
Regular exercise may decrease the restlessness that may lead to wandering. For patients that continue to wander, alarm systems are available that alert caretakers when the wearer goes too far from home.
Falls — For all types of dementia, including Alzheimer's disease, falls eventually become a safety concern. As an example, one study in Sweden found that among people over age 75, those with cognitive impairment were twice as likely to suffer from hip fractures as those with no impairment [4]. Caregivers should assess the physical environment in the home to eliminate potential hazards such as loose electrical cords, slippery rugs, and so forth.
Aggressive behavior — One of the most difficult issues for caregivers and Alzheimer's patients is aggressive behavior. Fortunately, this behavior is not common. However, many family members are reluctant to report a patient's aggressive behavior. In some cases, the behavior becomes physically abusive as dementia progresses. In addition, some caregivers become so frustrated that they themselves begin to behave abusively.
Family members should discuss any concerns regarding aggressive behavior with a healthcare provider, and arrange for help if necessary. Medications are available to help control behavioral difficulties in patients with Alzheimer's and also to help with mental functioning (see "Treatment of behavioral symptoms" below).
Medications — Although there are no medications available that cure Alzheimer's disease, several drugs have been developed to help control symptoms of the disease. These include medications to manage memory and cognitive impairments as well as behavioral problems. In addition, research shows promise for developing treatments to modify the course of the disease and possibly delay or even prevent it.
Treatment of the memory disturbance — There are four drugs currently available for treating memory disturbances in Alzheimer's disease. All work by decreasing the release of a chemical called cholinesterase, allowing more of a chemical called acetylcholine to be active in the nervous system. People with Alzheimer's disease have declining levels of acetylcholine in the brain. Donepezil (Aricept®) is taken once a day, usually 5 mg per day for four weeks and then increased to 10 mg per day. Clinical studies have shown that donepezil can slow memory loss in some patients with mild to moderate Alzheimer's disease [5]. Side effects, including diarrhea, nausea, and vomiting, should be monitored. Rivastigmine (Exelon®) is a cholinesterase inhibitor that helps some patients with mild to moderate disease. This drug has side effects similar to those produced by donepezil, and appears to be similarly effective. It is usually started at a dose of 1.5 mg twice per day and gradually increased to 6 mg twice per day. Galantamine (Reminyl®) is used in patients with mild to moderate Alzheimer's disease to slow the loss of mental abilities and the decline in a patient's ability to perform normal daily activities.. Memantine (Namenda®) is a unique medication that works differently than cholinesterase inhibitors. It may function to protect the brain from further damage caused by AD. It has shown promise in treating persons with moderate to severe AD. Dizziness is the most common side effect, and aggression and hallucinations may worsen in some patients. It is sometimes used along with a cholinesterase inhibitor.
Typically, one of these drugs will be tried for a period of about eight weeks while the patient is monitored for side effects and response. If there is no improvement, the drug is usually stopped (with the exception of memantine, which may be continued due to the possible protective benefits). Sometimes a patient will decline after the drug is stopped; if this happens, the drug may be started again. The drugs can be taken for as long as needed in people who benefit from their use.
It is important to have realistic expectations about the potential benefits of these drugs. As mentioned, none of them cures the disease, and over time most people will continue to have a decline in function. When these drugs are effective, the hope is that this decline will be sufficiently slowed so that patients and their families will have an improved quality of life for a longer period.
Treatment of behavioral symptoms — The behavioral symptoms of Alzheimer's disease are often more troubling than the cognitive symptoms. Even in mild cases, agitation, anxiety, and irritability can occur and generally worsen as the disease advances.
Before a patient is treated for these behavioral problems, the provider must be sure that the problem is not caused by another illness or medications. If AD is determined to be the sole cause, a combination of medication and behavioral therapy may be helpful.
Problems such as wandering, hoarding or hiding objects, withdrawal, and socially inappropriate behavior often improve more with behavioral therapy than medications. Other problems, such as agitation, aggression, delusions, and hallucinations may be more responsive to medications. Because these latter behaviors are often the reason for putting an Alzheimer's patient into a nursing home, most providers try to control these problems as soon as they appear.
Delusions are common in patients with dementia, occurring in up to 30 percent of those with advanced disease. Paranoid delusions are particularly distressing to both the patients and the caregivers: these often include beliefs that someone has invaded the house, that family members have been replaced by impostors, that spouses have been unfaithful, or that personal possessions have been stolen. If these delusions are troublesome, antipsychotic medications can be prescribed to help control them.
In choosing a medication, the side effects must be considered. Some medications can worsen mental processes and cause sedation, while others may cause unacceptable side effects such as muscle tremors, tics, rigidity, etc.
The choice of medications for troublesome delusions and hallucinations is complex. Providers typically begin these drugs at the lowest effective dose to minimize side effects. Depression — Depression is a problem that sometimes occurs in people with dementia. Depression is not always present throughout the course of dementia. It can be difficult to diagnose because other behavioral changes occur that have similar symptoms. (See "Patient information: Depression in adults").
If depression is suspected in a person with Alzheimer's disease, the first step may be to try an antidepressant medication. A group of medications known as selective serotonin reuptake inhibitors, or SSRIs, are usually preferred. SSRIs include fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), and escitalopram (Lexapro®). These medications are often helpful, but may be needed lifelong.
Other antidepressants, such as venlafaxine, duloxetine mirtazapine, and bupropion may also be effective, but have not been well studied in people with Alzheimer's disease.
Although tricyclic antidepressants have been studied for years and in low doses generally have a good safety profile, they are no longer recommended as first line agents in the treatment of people with dementia who have with depression because they may cause increased side effects. It is not necessary to stop a tricyclic antidepressant if it is working well.
Other treatments, such as behavioral therapy may also be recommended for depression. Behavioral therapy involves changing the environment that produces the depression (eg, encouraging exercise, socialization). Behavioral changes are believed to lead to changes in thoughts and emotions. Anxiety and aggression — These problems can be caused by a number of factors, including: Confusion or misunderstanding Frightening or paranoid delusions Depression Sleep disorders Medical conditions such as difficulty urinating or severe constipation
The best treatment for these symptoms depends upon what triggers them. As an example, a person who becomes aggressive during periods of confusion might best be treated through behavioral therapy, while someone who becomes aggressive during delusions might require medication.
Studies of older antipsychotic medications (haloperidol, thioridazine, thiothixene, chlorpromazine, trifluoperazine and acetophenazine) concluded that there was no clear evidence of benefit for these agents in patients with dementia [6]. One review concluded that haloperidol may help control aggression, but not other neuropsychiatric manifestations of dementia [7].
A newer class of medications known as atypical neuroleptics (aripiprazole, olanzapine, quetiapine, and risperidone) have been the medications of choice for treating hallucinations in patients with dementia. However, use of these medications for the treatment of behavioral problems in elderly patients with dementia is associated with an increased risk of death [8].
Nonetheless, the benefit of atypical neuroleptics often still outweigh their risks when treatment of hallucinations and delusions is necessary. Because there are no other medications that are effective, some experts continue to use them cautiously, after informing the patient and family about the potential risks. Sleep problems — Patients with sleep disorders may benefit from both medication and behavior changes: for example, limiting daytime naps, increasing physical activity, avoiding evening consumption of caffeine and alcohol, as well as a sleeping medication. However, sleeping pills also will worsen confusion.
Medications typically used to ease agitation and sleeping difficulties include the antidepressant trazodone (Desyrel) and the mood stabilizer carbamazepine (Epitol, Tegretol). Benzodiazepines such as alprazolam (Xanax) and diazepam (Valium) are not generally recommended for people with Alzheimer's disease because of their side effects (sedation).
Treatments that may be effective — A number of therapies have been studied in patients with Alzheimer's disease, including some that may alter the course of the dementia, not just treat the symptoms.
Vitamin E and selegiline — Reports of the effectiveness of vitamin E (alpha-tocopherol) have appeared in the popular press and research findings suggest that vitamin E may slow the progression of Alzheimer's disease. Another substance believed to help slow the condition is the drug selegiline (Eldepryl). In a study that compared vitamin E, selegiline, and a combination of the two, the two treatments were equally effective, and no advantage was seen in the group that took both [9].
There were some problems with the methods of this study, making it difficult to know for sure if vitamin E is beneficial in preventing or slowing the progression of AD. Nevertheless, this trial was the first to show a benefit of any therapy for delaying the progression of Alzheimer's disease. Some clinicians recommend that people with Alzheimer's disease take 1000 IU of vitamin E twice daily; this has fewer side effects and is less expensive than selegiline.
There is growing concern regarding the increased risk of death related to use of vitamin E supplements. Vitamin E is appropriate only for patients with AD or at high risk of developing AD (ie, those who have more than one family member with AD) who lack significant heart disease. We do not recommend vitamin E for the routine prevention of AD or other types of dementia.
Estrogen — Estrogen has been studied as a treatment that might slow the course of Alzheimer's disease. However, the most recent and well-controlled studies have shown no beneficial effects [10-12].
Nonsteroidal antiinflammatory drugs — Research with nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, naproxen, and indomethacin has been inconclusive. So far, there is no evidence that these drugs can help treat Alzheimer's disease. NSAIDs should not be used for the treatment or prevention of dementia.
Ginkgo biloba — The herbal supplement ginkgo biloba has also been studied in patients with Alzheimer's disease and shown some promise in reducing mental decline [13]. The use of ginkgo is appealing since it has few side effects. However, we do not recommend the use of ginkgo because there is little evidence that it is effective and because it's production is not regulated; it is considered to be a dietary supplement, which means that the dose and ingredients can vary from pill to pill and bottle to bottle.
FUTURE TREATMENT AND PREVENTION — A number of research projects are currently underway to study how Alzheimer's develops and progresses over time. This kind of research holds considerable promise for treatment of AD symptoms, changing the course of AD, and even preventing it.
Some research is aimed at discovering more about the amyloid-beta plaques that develop in the brains of Alzheimer's patients, and how to prevent or even remove them. The protein tangles that are characteristic of Alzheimer's are another target of research, with the first goal being to figure out whether these tangles actually contribute to the disease or are a result of it, perhaps caused by the amyloid-beta plaques.
Animal research has shown that vaccines made from the amyloid-beta proteins may be able to slow the progression of brain damage in Alzheimer's and possibly even reverse it [14-16]. This kind of research will not yield results for treating humans for years, but the findings so far are promising.
The best hope may be to discover risk factors for Alzheimer's disease. Simply delaying the age of onset could significantly reduce the burden of the illness for patients, families, and other caregivers.
LIFE WITH ALZHEIMER'S — Being diagnosed with Alzheimer's disease can be overwhelming for both patients and their loved ones. However, the diagnosis does not mean that life is over.
For patients — It is important for people with early Alzheimer's disease to care for their physical and mental health. This means getting regular checkups, taking medications if needed, eating a healthy diet, exercising regularly, getting enough sleep, and avoiding activities that may be risky.
It may be helpful to talk to a counselor or social worker to discuss feelings of frustration, anger, loneliness, or depression. All of these feelings are normal, and dealing with these feelings can help a person to feel more in control of their wellbeing. Support groups are also available for patients and families to discuss these issues with other people dealing with similar problems.
Another issue to consider is how to tell family and friends about the diagnosis of Alzheimer's disease. Explaining the disease can help others to understand what to expect and how they can help, now and in the future. This can be especially helpful for children and grandchildren, who may not be familiar with the condition.
Patients may live alone in the early stages of Alzheimer's, but often need help with tasks such as housekeeping, cooking, transportation, and paying bills. If possible, ask a friend or family member for help to develop plans to deal with these and other issues as the condition progresses. In addition, patients and their loved ones should discuss preferences regarding issues that are likely to become important as AD worsens, including health insurance, where the patient will live, and the financial resources to pay for care. A number of resources are available to assist in this type of planning. (See "Where to get more information" below).
For caregivers — Alzheimer's disease is a debilitating disease that can impose an enormous burden on patients and families or other caregivers. People with Alzheimer's disease become less able to care for themselves as the disease progresses. Some tips that may help caregivers create a positive environment include the following: Make a daily plan and prepare to be flexible if needed. Focus on the process, not the end result. Try to be patient when responding to repetitive questions, behaviors, or statements. This type of behavior is common, and often is the result of feeling insecure or nervous. Use memory aids such as writing out a list of daily activities, phone numbers, and instructions for usual tasks (ie, the telephone, microwave, etc). Establish calm nighttime routines to manage behavioral problems, which are often worst at night. Leave a night light on in the patient's bedroom. Avoid major changes to the home environment. Employ safety measures in the home, such as locks on medicine cabinets, keep furniture in the same place to prevent falls, remove electrical appliances from the bathroom, install grab bars in the bathroom, and set the water heater at or below 120ºF. Help the patient perform personal care as they are willing and able. It is not necessary to bathe every day, although a healthcare provider should be notified if the patient develops sores in the mouth or genitals related to hygiene problems (eg, urinary incontinence, ill-fitting dentures). Speak slowly, present only one idea at a time, and be patient when waiting for responses. Encourage physical activity and exercise. A daily walk can help prevent physical decline and improve behavioral problems [17]. Consider respite care. Respite care can provide a needed break for family and can strengthen the family's ability to provide care in the future. This is offered in many communities in the form of in-home care or adult day care. Caregiving can be an all-consuming experience. Be sure to take time for yourself, take care of your own medical problems, and arrange for breaks when you need them.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Neurological Disorders and Stroke
(www.ninds.nih.gov)
National Institute of Mental Health
(www.nimh.nih.gov)
Administration on Aging (Department of Health and Human Services)
(www.aoa.dhhs.gov)
The American Geriatrics Society
(www.americangeriatrics.org)
Alzheimer's Association
(www.alz.org)
Alzheimer's Disease Education and Referral (ADEAR) Center (National Institute on Aging)
(www.nia.nih.gov/alzheimers)
Eldercare Locator (Administration on Aging)
(www.eldercare.gov)
Family Caregiver Alliance
(www.caregiver.org)
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Hebert, LE, Scherr, PA, Beckett, LA. Age-specific incidence of Alzheimer's disease in a community population. JAMA 1995; 273:1354.
2. Silverman, JM, Smith, CJ, Marin, DB, et al. Familial patterns of risk in very late-onset Alzheimer disease. Arch Gen Psychiatry 2003; 60:190.
3. Henderson, AS, Easteal, S, Jorm, AF. Apolipoprotein E allele epsilon 4, dementia, and cognitive decline in a population sample. Lancet 1995; 346:1387.
4. Guo, Z, Wills, P, Viitanen, M, et al. Cognitive impairment, drug use, and the risk of hip fracture in persons over 75 years old: A community-based prospective study. Am J Epidemiol 1998; 148:887.
5. Rogers, SL, Farlow, MR, Doody, RS, et al. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group [see comments]. Neurology 1998; 50:136.
6. Sink, KM, Holden, KF, Yaffe, K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA 2005; 293:596.
7. Lonergan, E, Luxenberg, J, Colford, J. Haloperidol for agitation in dementia. Cochrane Database Syst Rev 2002; :CD002852.
8. Lee, PE, Gill, SS, Freedman, M, et al. Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. BMJ 2004; 329:75.
9. Sano, M, Ernesto, C, Thomas, RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study [see comments]. N Engl J Med 1997; 336:1216.
10. Shumaker, SA, Legault, C, Thal, L, et al. Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women: The Women's Health Initiative Memory Study: A Randomized Controlled Trial. JAMA 2003; 289:2651.
11. Shumaker, SA, Legault, C, Kuller, L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004; 291:2947.
12. Espeland, MA, Rapp, SR, Shumaker, SA, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004; 291:2959.
13. Le Bars, PL, Katz, MM, Berman, N, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. JAMA 1997; 278:1327.
14. Schenk, D, Barbour, R, Dunn, W, et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse [see comments]. Nature 1999; 400:173.
15. Weiner, HL, Lemere, CA, Maron, R, et al. Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease. Ann Neurol 2000; 48:567.
16. Morgan, D, Diamond, DM, Gottschall, PE, et al. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 2000; 408:982.
17. Teri, L. Gibbons, LE, McCurry, SM., et al. Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. JAMA 2003; 290:2015.
Alzheimer's disease accounts for 60 to 80 percent of all cases of dementia among the elderly. About four million Americans have Alzheimer's disease now, and close to three million Americans are caring for relatives or friends who have it. There is striking variety in presentation and severity of symptoms and signs, often leading to underrecognition. Currently available medical treatments can be of help in controlling the mental and behavioral symptoms of the disease but leave much to be desired in many cases. Meanwhile, ongoing research has made major advances in understanding the underlying causes of this kind of dementia. This research holds great promise for developing treatments to slow down and hopefully delay the onset or even prevent Alzheimer's disease.
CAUSES — Scientists have not yet been able to determine exactly why and how Alzheimer's disease develops. Researchers have determined that the brains of patients with AD develop deposits of a protein called beta amyloid (these deposits are also known as plaques), and that people also develop disorganized masses of protein fibers within the brain cells known as neurofibrillary tangles.
In addition, Alzheimer's disease is associated with the death of nerve cells (neurons) in important parts of the brain. Currently, these changes to the brain can only be seen during autopsy after a patient's death, but researchers are working to develop ways of imaging these brain changes in living patients.
RISK FACTORS — A risk factor is not necessarily the cause of a particular condition, but merely something that helps predict it. Some risk factors can indeed cause a particular illness. As an example, we know that smoking can cause lung cancer. The relationship between other risk factors and specific diseases is more complicated, and in many cases scientists do not know if there is any causal relationship involved or not. They just know that people who have a particular risk factor are for some reason also more likely to get a particular disease.
Age — The biggest risk factor for Alzheimer's disease is age: the older you are, the more likely you are to develop Alzheimer's disease. As an example, one large study found that among people ages 65 to 69, less than 1 percent of people develop AD per year [1]. For people ages 70 to 74, the incidence was 1 percent, and for people ages 75 to 79, 2 percent. The number affected by Alzheimer's is more than 3 percent among people ages 80 to 84, and to more than 8 percent among those 85 and over.
Family history — Having a close family member with Alzheimer's disease increases the chances of developing it yourself. People with a first-degree relative, such as a parent or sibling, with Alzheimer's disease have a 10 to 30 percent chance of developing the disorder. The risk is probably higher if the family member developed Alzheimer's disease at a younger age and lower if the family member did not get Alzheimer's disease until late in life [2].
Scientists have discovered a particular gene increases a person's risk of developing Alzheimer's. But even among individuals with this gene, only about one-half develop Alzheimer's by age 90, suggesting that other factors are also involved [3]. It is possible to test for this gene in family members of patients with Alzheimer's disease, but this test is currently recommended only for people involved in a research study.
SYMPTOMS
Normal changes versus Alzheimer's — Many people worry that memory problems are caused by early Alzheimer's disease. Normal age-related changes usually cause minor difficulties in short term memory and a slowed ability to learn and process information. These changes are usually mild and do not worsen over time, nor should they interfere with a person's day-to-day functioning.
Early changes — The earliest symptoms of Alzheimer's disease are gradual and often subtle. Many patients and their families first notice difficulty remembering recent events or information. Other changes can include one or more of the following: Confusion Difficulties with language (eg, not being able to find the right words for things) Difficulty with concentration and reasoning Problems with complex tasks like paying bills or balancing a checkbook Problems with orientation or spatial ability (eg, getting lost in a familiar place)
Later changes — As Alzheimer's disease progresses, a person's ability to think clearly continues to decline, and personality and behavioral symptoms are more likely to appear. These can include: Increased anger, hostility, and/or suspicion Aggression and physical violence Hallucinations Delusions Wandering Increased number of physical accidents
The number of symptoms and speed with which symptoms progress can vary widely from one person to the next. In some people, severe dementia occurs within five years of the diagnosis; for others, the process can take more than 10 years. Most people with Alzheimer's disease do not die from the disease itself, but instead die from a secondary illness such as pneumonia, urinary tract infection, or complications of a fall.
DIAGNOSIS — There is no single medical or laboratory test that can determine if a person has Alzheimer's disease. Instead, a healthcare provider must make the diagnosis based upon information gathered from the patient and family, and upon the results of tests that measure mental functioning.
The provider will want to know about the patient's recent history: the nature of any mental changes or memory loss, behavioral changes, any medical conditions or illnesses, and any medications the patient has been taking. A complete physical check-up and blood work may be done at this time.
It is important to rule out other possible causes for a patient's mental difficulties. These can include medications or other medical conditions. As examples, both delirium and depression have symptoms similar to those of Alzheimer's disease and may occur in patients with dementia.
The provider will also need to rule out other forms of dementia before diagnosing Alzheimer's disease. These include vascular dementia (changes caused by blood vessel abnormalities), dementia caused by Parkinson's disease, dementia related to alcohol or medications, and other conditions.
To get a sense of how the patient is functioning mentally, the doctor will probably administer a brief test such as the Mini-Mental State Exam, or MMSE. This is the most widely used test to assess a person's ability to think and remember. It takes about seven minutes to complete and evaluates a range of mental functions, including being able to state today's day, month, and year to being able to remember a short list of words or write a full sentence spontaneously.
TREATMENT — Although scientists are learning more about Alzheimer's disease all the time, currently there is no cure. There are a number of medications that may help to control some of the symptoms of Alzheimer's disease. Research suggests that treatments to prevent and even cure the condition may be available in the not too distant future.
Safety issues — A major issue in managing individuals with Alzheimer's disease is safety. Because many patients do not realize that their mental functioning is impaired, they try to continue their day-to-day activities as usual. This can lead to physical danger, and caregivers must help to avoid situations that can threaten the safety of the patient or others.
Driving — Driving is often one of the first safety issues that arises. This is often difficult to face because driving represents independence for many people. Although people with Alzheimer's disease do not have more car accidents than others during the first year after diagnosis, the risk of crashes more than doubles after the first year. It is best to discuss the issue of driving early.
There may be significant resistance to stopping driving since the patient may not realize that he or she has impairments in mental functioning or reaction time. But all patients with Alzheimer's disease will eventually reach the point where driving is dangerous to themselves and others. The healthcare provider and family must work together to determine when a patient needs to stop driving.
Most states do not have specific regulations or restrictions on driving for patients with dementia, although some do provide roadside testing and other ways of evaluating an individual's ability to drive safely. Even if a person with newly diagnosed, mild Alzheimer's disease is still able to drive, the appropriateness of driving needs to be reassessed every six months, with the expectation that driving will eventually no longer be possible.
Cooking — Cooking is another area in which dementia can lead to serious safety concerns. Symptoms such as distractibility, forgetfulness, and difficulty in following directions can lead to burns, fires, or other injuries. Many providers recommend that patients be taught early how to use a microwave oven, which poses fewer dangers than stove-top cooking.
Wandering — As dementia progresses, some patients with Alzheimer's disease begin to wander. Because restlessness, distractibility, and memory problems are common, a person who wanders may easily become lost. Identification bracelets can help ensure that a lost wanderer gets home. The Alzheimer's Association provides a "safe return" program with ID tags and 24-hour assistance (www.alz.org/we_can_help_safe_return.asp).
Regular exercise may decrease the restlessness that may lead to wandering. For patients that continue to wander, alarm systems are available that alert caretakers when the wearer goes too far from home.
Falls — For all types of dementia, including Alzheimer's disease, falls eventually become a safety concern. As an example, one study in Sweden found that among people over age 75, those with cognitive impairment were twice as likely to suffer from hip fractures as those with no impairment [4]. Caregivers should assess the physical environment in the home to eliminate potential hazards such as loose electrical cords, slippery rugs, and so forth.
Aggressive behavior — One of the most difficult issues for caregivers and Alzheimer's patients is aggressive behavior. Fortunately, this behavior is not common. However, many family members are reluctant to report a patient's aggressive behavior. In some cases, the behavior becomes physically abusive as dementia progresses. In addition, some caregivers become so frustrated that they themselves begin to behave abusively.
Family members should discuss any concerns regarding aggressive behavior with a healthcare provider, and arrange for help if necessary. Medications are available to help control behavioral difficulties in patients with Alzheimer's and also to help with mental functioning (see "Treatment of behavioral symptoms" below).
Medications — Although there are no medications available that cure Alzheimer's disease, several drugs have been developed to help control symptoms of the disease. These include medications to manage memory and cognitive impairments as well as behavioral problems. In addition, research shows promise for developing treatments to modify the course of the disease and possibly delay or even prevent it.
Treatment of the memory disturbance — There are four drugs currently available for treating memory disturbances in Alzheimer's disease. All work by decreasing the release of a chemical called cholinesterase, allowing more of a chemical called acetylcholine to be active in the nervous system. People with Alzheimer's disease have declining levels of acetylcholine in the brain. Donepezil (Aricept®) is taken once a day, usually 5 mg per day for four weeks and then increased to 10 mg per day. Clinical studies have shown that donepezil can slow memory loss in some patients with mild to moderate Alzheimer's disease [5]. Side effects, including diarrhea, nausea, and vomiting, should be monitored. Rivastigmine (Exelon®) is a cholinesterase inhibitor that helps some patients with mild to moderate disease. This drug has side effects similar to those produced by donepezil, and appears to be similarly effective. It is usually started at a dose of 1.5 mg twice per day and gradually increased to 6 mg twice per day. Galantamine (Reminyl®) is used in patients with mild to moderate Alzheimer's disease to slow the loss of mental abilities and the decline in a patient's ability to perform normal daily activities.. Memantine (Namenda®) is a unique medication that works differently than cholinesterase inhibitors. It may function to protect the brain from further damage caused by AD. It has shown promise in treating persons with moderate to severe AD. Dizziness is the most common side effect, and aggression and hallucinations may worsen in some patients. It is sometimes used along with a cholinesterase inhibitor.
Typically, one of these drugs will be tried for a period of about eight weeks while the patient is monitored for side effects and response. If there is no improvement, the drug is usually stopped (with the exception of memantine, which may be continued due to the possible protective benefits). Sometimes a patient will decline after the drug is stopped; if this happens, the drug may be started again. The drugs can be taken for as long as needed in people who benefit from their use.
It is important to have realistic expectations about the potential benefits of these drugs. As mentioned, none of them cures the disease, and over time most people will continue to have a decline in function. When these drugs are effective, the hope is that this decline will be sufficiently slowed so that patients and their families will have an improved quality of life for a longer period.
Treatment of behavioral symptoms — The behavioral symptoms of Alzheimer's disease are often more troubling than the cognitive symptoms. Even in mild cases, agitation, anxiety, and irritability can occur and generally worsen as the disease advances.
Before a patient is treated for these behavioral problems, the provider must be sure that the problem is not caused by another illness or medications. If AD is determined to be the sole cause, a combination of medication and behavioral therapy may be helpful.
Problems such as wandering, hoarding or hiding objects, withdrawal, and socially inappropriate behavior often improve more with behavioral therapy than medications. Other problems, such as agitation, aggression, delusions, and hallucinations may be more responsive to medications. Because these latter behaviors are often the reason for putting an Alzheimer's patient into a nursing home, most providers try to control these problems as soon as they appear.
Delusions are common in patients with dementia, occurring in up to 30 percent of those with advanced disease. Paranoid delusions are particularly distressing to both the patients and the caregivers: these often include beliefs that someone has invaded the house, that family members have been replaced by impostors, that spouses have been unfaithful, or that personal possessions have been stolen. If these delusions are troublesome, antipsychotic medications can be prescribed to help control them.
In choosing a medication, the side effects must be considered. Some medications can worsen mental processes and cause sedation, while others may cause unacceptable side effects such as muscle tremors, tics, rigidity, etc.
The choice of medications for troublesome delusions and hallucinations is complex. Providers typically begin these drugs at the lowest effective dose to minimize side effects. Depression — Depression is a problem that sometimes occurs in people with dementia. Depression is not always present throughout the course of dementia. It can be difficult to diagnose because other behavioral changes occur that have similar symptoms. (See "Patient information: Depression in adults").
If depression is suspected in a person with Alzheimer's disease, the first step may be to try an antidepressant medication. A group of medications known as selective serotonin reuptake inhibitors, or SSRIs, are usually preferred. SSRIs include fluoxetine (Prozac®), sertraline (Zoloft®), paroxetine (Paxil®), citalopram (Celexa®), and escitalopram (Lexapro®). These medications are often helpful, but may be needed lifelong.
Other antidepressants, such as venlafaxine, duloxetine mirtazapine, and bupropion may also be effective, but have not been well studied in people with Alzheimer's disease.
Although tricyclic antidepressants have been studied for years and in low doses generally have a good safety profile, they are no longer recommended as first line agents in the treatment of people with dementia who have with depression because they may cause increased side effects. It is not necessary to stop a tricyclic antidepressant if it is working well.
Other treatments, such as behavioral therapy may also be recommended for depression. Behavioral therapy involves changing the environment that produces the depression (eg, encouraging exercise, socialization). Behavioral changes are believed to lead to changes in thoughts and emotions. Anxiety and aggression — These problems can be caused by a number of factors, including: Confusion or misunderstanding Frightening or paranoid delusions Depression Sleep disorders Medical conditions such as difficulty urinating or severe constipation
The best treatment for these symptoms depends upon what triggers them. As an example, a person who becomes aggressive during periods of confusion might best be treated through behavioral therapy, while someone who becomes aggressive during delusions might require medication.
Studies of older antipsychotic medications (haloperidol, thioridazine, thiothixene, chlorpromazine, trifluoperazine and acetophenazine) concluded that there was no clear evidence of benefit for these agents in patients with dementia [6]. One review concluded that haloperidol may help control aggression, but not other neuropsychiatric manifestations of dementia [7].
A newer class of medications known as atypical neuroleptics (aripiprazole, olanzapine, quetiapine, and risperidone) have been the medications of choice for treating hallucinations in patients with dementia. However, use of these medications for the treatment of behavioral problems in elderly patients with dementia is associated with an increased risk of death [8].
Nonetheless, the benefit of atypical neuroleptics often still outweigh their risks when treatment of hallucinations and delusions is necessary. Because there are no other medications that are effective, some experts continue to use them cautiously, after informing the patient and family about the potential risks. Sleep problems — Patients with sleep disorders may benefit from both medication and behavior changes: for example, limiting daytime naps, increasing physical activity, avoiding evening consumption of caffeine and alcohol, as well as a sleeping medication. However, sleeping pills also will worsen confusion.
Medications typically used to ease agitation and sleeping difficulties include the antidepressant trazodone (Desyrel) and the mood stabilizer carbamazepine (Epitol, Tegretol). Benzodiazepines such as alprazolam (Xanax) and diazepam (Valium) are not generally recommended for people with Alzheimer's disease because of their side effects (sedation).
Treatments that may be effective — A number of therapies have been studied in patients with Alzheimer's disease, including some that may alter the course of the dementia, not just treat the symptoms.
Vitamin E and selegiline — Reports of the effectiveness of vitamin E (alpha-tocopherol) have appeared in the popular press and research findings suggest that vitamin E may slow the progression of Alzheimer's disease. Another substance believed to help slow the condition is the drug selegiline (Eldepryl). In a study that compared vitamin E, selegiline, and a combination of the two, the two treatments were equally effective, and no advantage was seen in the group that took both [9].
There were some problems with the methods of this study, making it difficult to know for sure if vitamin E is beneficial in preventing or slowing the progression of AD. Nevertheless, this trial was the first to show a benefit of any therapy for delaying the progression of Alzheimer's disease. Some clinicians recommend that people with Alzheimer's disease take 1000 IU of vitamin E twice daily; this has fewer side effects and is less expensive than selegiline.
There is growing concern regarding the increased risk of death related to use of vitamin E supplements. Vitamin E is appropriate only for patients with AD or at high risk of developing AD (ie, those who have more than one family member with AD) who lack significant heart disease. We do not recommend vitamin E for the routine prevention of AD or other types of dementia.
Estrogen — Estrogen has been studied as a treatment that might slow the course of Alzheimer's disease. However, the most recent and well-controlled studies have shown no beneficial effects [10-12].
Nonsteroidal antiinflammatory drugs — Research with nonsteroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, naproxen, and indomethacin has been inconclusive. So far, there is no evidence that these drugs can help treat Alzheimer's disease. NSAIDs should not be used for the treatment or prevention of dementia.
Ginkgo biloba — The herbal supplement ginkgo biloba has also been studied in patients with Alzheimer's disease and shown some promise in reducing mental decline [13]. The use of ginkgo is appealing since it has few side effects. However, we do not recommend the use of ginkgo because there is little evidence that it is effective and because it's production is not regulated; it is considered to be a dietary supplement, which means that the dose and ingredients can vary from pill to pill and bottle to bottle.
FUTURE TREATMENT AND PREVENTION — A number of research projects are currently underway to study how Alzheimer's develops and progresses over time. This kind of research holds considerable promise for treatment of AD symptoms, changing the course of AD, and even preventing it.
Some research is aimed at discovering more about the amyloid-beta plaques that develop in the brains of Alzheimer's patients, and how to prevent or even remove them. The protein tangles that are characteristic of Alzheimer's are another target of research, with the first goal being to figure out whether these tangles actually contribute to the disease or are a result of it, perhaps caused by the amyloid-beta plaques.
Animal research has shown that vaccines made from the amyloid-beta proteins may be able to slow the progression of brain damage in Alzheimer's and possibly even reverse it [14-16]. This kind of research will not yield results for treating humans for years, but the findings so far are promising.
The best hope may be to discover risk factors for Alzheimer's disease. Simply delaying the age of onset could significantly reduce the burden of the illness for patients, families, and other caregivers.
LIFE WITH ALZHEIMER'S — Being diagnosed with Alzheimer's disease can be overwhelming for both patients and their loved ones. However, the diagnosis does not mean that life is over.
For patients — It is important for people with early Alzheimer's disease to care for their physical and mental health. This means getting regular checkups, taking medications if needed, eating a healthy diet, exercising regularly, getting enough sleep, and avoiding activities that may be risky.
It may be helpful to talk to a counselor or social worker to discuss feelings of frustration, anger, loneliness, or depression. All of these feelings are normal, and dealing with these feelings can help a person to feel more in control of their wellbeing. Support groups are also available for patients and families to discuss these issues with other people dealing with similar problems.
Another issue to consider is how to tell family and friends about the diagnosis of Alzheimer's disease. Explaining the disease can help others to understand what to expect and how they can help, now and in the future. This can be especially helpful for children and grandchildren, who may not be familiar with the condition.
Patients may live alone in the early stages of Alzheimer's, but often need help with tasks such as housekeeping, cooking, transportation, and paying bills. If possible, ask a friend or family member for help to develop plans to deal with these and other issues as the condition progresses. In addition, patients and their loved ones should discuss preferences regarding issues that are likely to become important as AD worsens, including health insurance, where the patient will live, and the financial resources to pay for care. A number of resources are available to assist in this type of planning. (See "Where to get more information" below).
For caregivers — Alzheimer's disease is a debilitating disease that can impose an enormous burden on patients and families or other caregivers. People with Alzheimer's disease become less able to care for themselves as the disease progresses. Some tips that may help caregivers create a positive environment include the following: Make a daily plan and prepare to be flexible if needed. Focus on the process, not the end result. Try to be patient when responding to repetitive questions, behaviors, or statements. This type of behavior is common, and often is the result of feeling insecure or nervous. Use memory aids such as writing out a list of daily activities, phone numbers, and instructions for usual tasks (ie, the telephone, microwave, etc). Establish calm nighttime routines to manage behavioral problems, which are often worst at night. Leave a night light on in the patient's bedroom. Avoid major changes to the home environment. Employ safety measures in the home, such as locks on medicine cabinets, keep furniture in the same place to prevent falls, remove electrical appliances from the bathroom, install grab bars in the bathroom, and set the water heater at or below 120ºF. Help the patient perform personal care as they are willing and able. It is not necessary to bathe every day, although a healthcare provider should be notified if the patient develops sores in the mouth or genitals related to hygiene problems (eg, urinary incontinence, ill-fitting dentures). Speak slowly, present only one idea at a time, and be patient when waiting for responses. Encourage physical activity and exercise. A daily walk can help prevent physical decline and improve behavioral problems [17]. Consider respite care. Respite care can provide a needed break for family and can strengthen the family's ability to provide care in the future. This is offered in many communities in the form of in-home care or adult day care. Caregiving can be an all-consuming experience. Be sure to take time for yourself, take care of your own medical problems, and arrange for breaks when you need them.
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Neurological Disorders and Stroke
(www.ninds.nih.gov)
National Institute of Mental Health
(www.nimh.nih.gov)
Administration on Aging (Department of Health and Human Services)
(www.aoa.dhhs.gov)
The American Geriatrics Society
(www.americangeriatrics.org)
Alzheimer's Association
(www.alz.org)
Alzheimer's Disease Education and Referral (ADEAR) Center (National Institute on Aging)
(www.nia.nih.gov/alzheimers)
Eldercare Locator (Administration on Aging)
(www.eldercare.gov)
Family Caregiver Alliance
(www.caregiver.org)
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. Hebert, LE, Scherr, PA, Beckett, LA. Age-specific incidence of Alzheimer's disease in a community population. JAMA 1995; 273:1354.
2. Silverman, JM, Smith, CJ, Marin, DB, et al. Familial patterns of risk in very late-onset Alzheimer disease. Arch Gen Psychiatry 2003; 60:190.
3. Henderson, AS, Easteal, S, Jorm, AF. Apolipoprotein E allele epsilon 4, dementia, and cognitive decline in a population sample. Lancet 1995; 346:1387.
4. Guo, Z, Wills, P, Viitanen, M, et al. Cognitive impairment, drug use, and the risk of hip fracture in persons over 75 years old: A community-based prospective study. Am J Epidemiol 1998; 148:887.
5. Rogers, SL, Farlow, MR, Doody, RS, et al. A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease. Donepezil Study Group [see comments]. Neurology 1998; 50:136.
6. Sink, KM, Holden, KF, Yaffe, K. Pharmacological treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA 2005; 293:596.
7. Lonergan, E, Luxenberg, J, Colford, J. Haloperidol for agitation in dementia. Cochrane Database Syst Rev 2002; :CD002852.
8. Lee, PE, Gill, SS, Freedman, M, et al. Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. BMJ 2004; 329:75.
9. Sano, M, Ernesto, C, Thomas, RG, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study [see comments]. N Engl J Med 1997; 336:1216.
10. Shumaker, SA, Legault, C, Thal, L, et al. Estrogen Plus Progestin and the Incidence of Dementia and Mild Cognitive Impairment in Postmenopausal Women: The Women's Health Initiative Memory Study: A Randomized Controlled Trial. JAMA 2003; 289:2651.
11. Shumaker, SA, Legault, C, Kuller, L, et al. Conjugated equine estrogens and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004; 291:2947.
12. Espeland, MA, Rapp, SR, Shumaker, SA, et al. Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study. JAMA 2004; 291:2959.
13. Le Bars, PL, Katz, MM, Berman, N, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. JAMA 1997; 278:1327.
14. Schenk, D, Barbour, R, Dunn, W, et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse [see comments]. Nature 1999; 400:173.
15. Weiner, HL, Lemere, CA, Maron, R, et al. Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease. Ann Neurol 2000; 48:567.
16. Morgan, D, Diamond, DM, Gottschall, PE, et al. A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 2000; 408:982.
17. Teri, L. Gibbons, LE, McCurry, SM., et al. Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. JAMA 2003; 290:2015.
Tuesday, October 16, 2007
Preventing complications in diabetes mellitus
INTRODUCTION — Diabetes mellitus is a chronic condition that can lead to complications over time. These complications include: Coronary heart disease, which can lead to a heart attack Cerebrovascular disease, which can lead to stroke Retinopathy (disease of the eye), which can lead to blindness Nephropathy (disease of the kidney), which can lead to kidney failure and the need for dialysis Neuropathy (disease of the nerves), which can lead to, among other things, ulceration of the foot requiring amputation
Many of these complications produce no symptoms in the early stages, and most can be prevented or minimized with a combination of regular medical care and blood glucose monitoring.
CONTROLLING BLOOD SUGAR — The long-term complications of diabetes result from the effects of hyperglycemia (elevated blood glucose levels) on blood vessels. Two important studies, the Diabetes Control and Complications Trial (DCCT) in patients with type 1 diabetes and the United Kingdom Prospective Diabetes Study (UKPDS) in patients with type 2 diabetes, found that patients with lower blood glucose values had fewer complications than those with higher values.
Thus, keeping blood sugars close to normal can help prevent the long-term complications of diabetes mellitus. However, there are some risks associated with tight control, particularly an increased risk of hypoglycemia (low blood sugar).
Monitoring blood sugar levels — Monitoring blood sugars with finger sticks at home can indicate how well diabetes is controlled and serves as a guide to adjusting therapy. (See "Patient information: Self-blood glucose monitoring"). For most patients, a target for fasting blood glucose and for blood glucose levels before each meal is 80-120 mg/dl (4.4 to 6.6 mmol/L); however, these targets may need to be individualized for a patient by their doctor or health care team.
A blood test called A1C is also used to monitor blood sugar control; the result provides an average of blood glucose levels during the previous one to three months. An A1C of 7 percent or less is recommended; this corresponds to an average blood glucose of 150 mg/dL (8.3 mmol/L, show figure 1). The target may be somewhat higher in people who are older or who have other conditions that increase the risks associated with hypoglycemia. Patients who are unable to reach this goal can be reassured that even small decreases in A1C lowers the risk of diabetes-related complications to some degree.
The combination of A1C and fingerstick blood sugars provides information about the average blood sugar as well as daily fluctuations in blood sugar.
Type 1 diabetes — Blood sugar control in type 1 diabetes requires some form of insulin, which can be given with insulin injections, an insulin pump, or a combination of inhaled insulin and insulin injections. Most healthcare providers recommend intensive insulin therapy, which requires frequent injections, inhaled insulin, or use of an insulin pump and blood glucose monitoring. (See "Patient information: Diabetes type 1: Insulin treatment").
Intensive insulin therapy increases the risk of low blood glucose, is more expensive than traditional insulin therapy, and requires that patients monitor their blood glucose levels, dietary intake and activities; the severity of diabetic complications or hypoglycemia may limit this form of therapy in some patients with type 1 diabetes. Patients can experience weight gain with intensive insulin therapy; regular exercise and monitoring dietary intake can prevent weight gain. (See "Patient information: Hypoglycemia (low blood glucose) in diabetes").
Type 2 diabetes — Blood glucose control in type 2 diabetes may be possible with lifestyle changes alone or in combination with oral medications. Insulin is necessary in some cases in early treatment; many patients who do not initially require insulin may do so over time as their ability to manufacture insulin decreases. Generally the insulin regimen for type 2 requires fewer injections and less intensive monitoring than for type 1, although intensive insulin therapy may be recommended for some patients (See "Patient information: Diabetes type 2: Insulin treatment").
EYE COMPLICATIONS — Regular eye examinations are essential for detecting eye complications (called retinopathy) at an early stage, when they can be monitored and treated to preserve vision. This examination should be performed by a doctor who specializes in the eyes (called an ophthalmologist or optometrist). An eye exam should include dilating the pupils (with medicated eye drops) in order to completely visualize the retina. Unless the pupils are medicated, they contract in response to light, making it impossible to view the entire retina.
In some patients with retinopathy, photographs of the retina will be taken to monitor and better visualize the changes. The risk of diabetic retinopathy varies with the type and duration of diabetes and with other life events. Thus, the screening guidelines differ from one person to another.
Type 1 diabetes — People with type 1 diabetes should have an eye examination by an ophthalmologist or optometrist beginning five years after they are diagnosed with diabetes, although screening is usually not necessary before puberty. Patients who have difficulty with their vision or who require glasses or contacts may need to be seen sooner. The frequency of subsequent examinations will depend upon the results of the initial exam. Doctors usually recommend eye exams every one to two years after the initial examination.
Type 2 diabetes — People with type 2 diabetes should have an eye examination by an ophthalmologist or optometrist when they are first diagnosed with diabetes. The frequency of subsequent exams will depend upon the results of the initial examination. Doctors usually recommend eye exams every one to two years after the initial examination.
FOOT CARE — Diabetes can decrease the blood supply to the foot and damage the nerves that carry sensation. These changes put the feet at risk for potentially serious complications such as foot ulcers. Foot complications are very common among people with diabetes, and may be unnoticed until the condition is severe. (See "Patient information: Foot care in diabetes").
Self exam — Patients with diabetes should examine their feet for changes every day. It is important to examine all parts of the feet, especially the area between the toes. Patients should look for broken skin, ulcers, blisters, areas of increased warmth or redness, or changes in callus formation; a healthcare provider should be notified if any of these changes are found.
Patients should include a self-examination in their daily bathing or dressing routine. It may be necessary to use a mirror to see the bottoms of the feet clearly. Patients who are unable to reach their feet or see them completely, even with the help of a mirror, should have someone else (such as a spouse or other family member) assist with the examination.
Clinical exam — During a routine medical visit, the clinician will check the blood flow and sensation in the feet. In people with type 1 diabetes, annual foot examinations should begin five years after diagnosis. In people with type 2 diabetes, annual foot exams should begin at the time of diagnosis.
During a foot examination, the clinician will look for changes such as ulcers, cold feet, thin skin, bluish skin color, and skin breaks associated with athlete's foot. The clinician will also test the sensation in the feet to determine if it is normal or diminished. Patients with decreased sensation are at risk for foot injuries that are unnoticed due to lack of pain.
KIDNEY COMPLICATIONS — Diabetes can alter the normal function of the kidneys. A urine test which measures the amount of protein (albumin) in the urine can alert a healthcare provider that diabetes is affecting the kidney's filtering action. Microscopic amounts of albumin in the urine (microalbuminuria) can be an early indicator of diabetes-related kidney complications (called nephropathy). The amount of albumin in the urine can also help the provider determine if nephropathy is worsening. (See "Patient information: Protein in the urine (proteinuria)").
Urine screening tests should begin in people with type 1 diabetes about five years after diagnosis, and in people with type 2 diabetes at the time of diagnosis. If the test shows that there is protein in the urine, tight blood glucose and lipid control are recommended; a medication may be recommended if albuminuria does not improve.
A blood pressure medication (an ACE inhibitor or angiotension receptor blocker [ARB]) is generally recommended for patients with albuminuria that does not improve, even if blood pressures are normal. Patients with elevated blood pressures and albuminuria are also treated with an ACE inhibitor or ARB. These medications decrease the amount of protein in the urine and can prevent or slow the progression of diabetes-related kidney disease.
HYPERTENSION AND RELATED COMPLICATIONS — Many people with diabetes have hypertension (high blood pressure). Although high blood pressure produces few symptoms, it has two negative effects: it stresses the cardiovascular system and increases the progression of diabetic complications of the kidney and eye. A healthcare provider can diagnose high blood pressure by measuring blood pressure on a regular basis. (See "Patient information: High blood pressure overview").
A blood pressure reading below 130/80 is an ideal goal for most people with diabetes who do not have kidney complications; a lower blood pressure goal (<120/75) may be recommended for people with diabetes who have kidney complications.
If a patient is diagnosed with prehypertension (>120/80), the healthcare provider may recommend weight loss, exercise, decreasing the amount of salt in the diet, quitting smoking, and decreasing alcohol intake. These measures can sometimes reduce blood pressure to normal. (See "Patient information: High blood pressure, diet and weight").
If these measures are not effective or the blood pressure must be lowered quickly, the provider will likely recommend one of several high blood pressure medications. The provider can discuss the pros and cons of each medication and the goals of treatment (See "Patient information: High blood pressure treatment").
HEART COMPLICATIONS — In addition to lowering blood glucose levels, a number of other measures are important to reduce the risk of cardiac disease. Quit smoking Manage high blood pressure with lifestyle modifications and/or medication(s) Patients should have a fasting lipid blood test to measure cholesterol and triglycerides, and modify their diets. some patients may need medication to lower their LDL ("bad cholesterol") or trigylcerides, if they are high.
If medication is needed, a statin drug should be included whenever possible. The statin drugs have been shown to decrease the future risk of heart attacks, strokes, and death in people with diabetes who are over age 40, even when cholesterol levels are normal. The American Diabetes Association recommends that patients with diabetes have a low density lipoprotein (LDL) cholesterol level less than 100 mg/dL. Some studies suggest lowering LDL to 70 to 80 mg/dL. (See "Patient information: High cholesterol and lipids (hyperlipidemia)"). Aspirin (81 to 162 mg per day) is recommended for all persons with diabetes over the age of 40 years. (See "Patient information: Aspirin and heart disease").
PREGNANCY AND DIABETES — Control of diabetes and its potential complications is especially important in women planning to become pregnant, as well as in those who already are pregnant. Controlling blood glucose levels before and during pregnancy decreases the risk of a number of complications in both the mother and the baby. A separate topic review is available on this subject. (See "Patient information: Care during pregnancy for women with type 1 or 2 diabetes").
Pregnancy can cause a worsening of diabetic retinopathy. Thus, women with type 1 or 2 diabetes who become pregnant should have an eye examination by an ophthalmologist or optometrist during the first trimester (three months) of their pregnancy. The frequency of subsequent eye exams during pregnancy will depend upon the results of the initial examination. In most cases, doctors recommend eye exams every three months until delivery.
These guidelines do not apply to women who have gestational diabetes -- a form of diabetes that develops during pregnancy and usually resolves after delivery. These women are not at risk for diabetic retinopathy.
THE IMPORTANCE OF REGULAR MEDICAL CARE — Regular medical care is critical to long-term health for people with diabetes, particularly when it comes to preventing, detecting, and slowing the progression of complications. A healthcare provider can recommend a regular schedule for visits, screening, and monitoring tests based upon a patient's type of diabetes (1 or 2), the duration of the disease, the presence of any complications, and the presence of other underlying medical problems.
In addition to diabetes care, patients also need to be sure they have regular screening for other health problems. For women, this may includes a cervical cancer screening, mammogram and clinical breast exam, and bone density testing. For men, prostate cancer screening is recommended after age 40. For both men and women, colon cancer screening is recommended after age 50. (See "Patient information: Screening for cervical cancer" and see "Patient information: Screening for breast cancer" and see "Patient information: Osteoporosis causes; diagnosis; and screening"). and see "Patient information: Prostate cancer screening" and see "Patient information: Screening for colon cancer").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Diabetes and Digestive and Kidney Diseases
(www.niddk.nih.gov/)
American Diabetes Association (ADA)
(800)-DIABETES (800-342-2383)
(www.diabetes.org)
The Hormone Foundation
(www.hormone.org/public/diabetes.cfm, available in English and Spanish)
[1-6]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329:977.
2. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995; 75:894.
3. Abraira, C, Colwell, JA, Nuttall, FQ, et al. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VACSDM): Results of a feasibility trial. Diabetes Care 1995; 18:1113.
4. Nathan, DM, Cleary, PA, Backlund, JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353:2643.
5. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA 2003; 290:2159.
6. Gray, A, Raikou, M, McGuire, A, et al. Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomised controlled trial (UKPDS 41). United Kingdom Prospective Diabetes Study Group. BMJ 2000; 320:1373.
Many of these complications produce no symptoms in the early stages, and most can be prevented or minimized with a combination of regular medical care and blood glucose monitoring.
CONTROLLING BLOOD SUGAR — The long-term complications of diabetes result from the effects of hyperglycemia (elevated blood glucose levels) on blood vessels. Two important studies, the Diabetes Control and Complications Trial (DCCT) in patients with type 1 diabetes and the United Kingdom Prospective Diabetes Study (UKPDS) in patients with type 2 diabetes, found that patients with lower blood glucose values had fewer complications than those with higher values.
Thus, keeping blood sugars close to normal can help prevent the long-term complications of diabetes mellitus. However, there are some risks associated with tight control, particularly an increased risk of hypoglycemia (low blood sugar).
Monitoring blood sugar levels — Monitoring blood sugars with finger sticks at home can indicate how well diabetes is controlled and serves as a guide to adjusting therapy. (See "Patient information: Self-blood glucose monitoring"). For most patients, a target for fasting blood glucose and for blood glucose levels before each meal is 80-120 mg/dl (4.4 to 6.6 mmol/L); however, these targets may need to be individualized for a patient by their doctor or health care team.
A blood test called A1C is also used to monitor blood sugar control; the result provides an average of blood glucose levels during the previous one to three months. An A1C of 7 percent or less is recommended; this corresponds to an average blood glucose of 150 mg/dL (8.3 mmol/L, show figure 1). The target may be somewhat higher in people who are older or who have other conditions that increase the risks associated with hypoglycemia. Patients who are unable to reach this goal can be reassured that even small decreases in A1C lowers the risk of diabetes-related complications to some degree.
The combination of A1C and fingerstick blood sugars provides information about the average blood sugar as well as daily fluctuations in blood sugar.
Type 1 diabetes — Blood sugar control in type 1 diabetes requires some form of insulin, which can be given with insulin injections, an insulin pump, or a combination of inhaled insulin and insulin injections. Most healthcare providers recommend intensive insulin therapy, which requires frequent injections, inhaled insulin, or use of an insulin pump and blood glucose monitoring. (See "Patient information: Diabetes type 1: Insulin treatment").
Intensive insulin therapy increases the risk of low blood glucose, is more expensive than traditional insulin therapy, and requires that patients monitor their blood glucose levels, dietary intake and activities; the severity of diabetic complications or hypoglycemia may limit this form of therapy in some patients with type 1 diabetes. Patients can experience weight gain with intensive insulin therapy; regular exercise and monitoring dietary intake can prevent weight gain. (See "Patient information: Hypoglycemia (low blood glucose) in diabetes").
Type 2 diabetes — Blood glucose control in type 2 diabetes may be possible with lifestyle changes alone or in combination with oral medications. Insulin is necessary in some cases in early treatment; many patients who do not initially require insulin may do so over time as their ability to manufacture insulin decreases. Generally the insulin regimen for type 2 requires fewer injections and less intensive monitoring than for type 1, although intensive insulin therapy may be recommended for some patients (See "Patient information: Diabetes type 2: Insulin treatment").
EYE COMPLICATIONS — Regular eye examinations are essential for detecting eye complications (called retinopathy) at an early stage, when they can be monitored and treated to preserve vision. This examination should be performed by a doctor who specializes in the eyes (called an ophthalmologist or optometrist). An eye exam should include dilating the pupils (with medicated eye drops) in order to completely visualize the retina. Unless the pupils are medicated, they contract in response to light, making it impossible to view the entire retina.
In some patients with retinopathy, photographs of the retina will be taken to monitor and better visualize the changes. The risk of diabetic retinopathy varies with the type and duration of diabetes and with other life events. Thus, the screening guidelines differ from one person to another.
Type 1 diabetes — People with type 1 diabetes should have an eye examination by an ophthalmologist or optometrist beginning five years after they are diagnosed with diabetes, although screening is usually not necessary before puberty. Patients who have difficulty with their vision or who require glasses or contacts may need to be seen sooner. The frequency of subsequent examinations will depend upon the results of the initial exam. Doctors usually recommend eye exams every one to two years after the initial examination.
Type 2 diabetes — People with type 2 diabetes should have an eye examination by an ophthalmologist or optometrist when they are first diagnosed with diabetes. The frequency of subsequent exams will depend upon the results of the initial examination. Doctors usually recommend eye exams every one to two years after the initial examination.
FOOT CARE — Diabetes can decrease the blood supply to the foot and damage the nerves that carry sensation. These changes put the feet at risk for potentially serious complications such as foot ulcers. Foot complications are very common among people with diabetes, and may be unnoticed until the condition is severe. (See "Patient information: Foot care in diabetes").
Self exam — Patients with diabetes should examine their feet for changes every day. It is important to examine all parts of the feet, especially the area between the toes. Patients should look for broken skin, ulcers, blisters, areas of increased warmth or redness, or changes in callus formation; a healthcare provider should be notified if any of these changes are found.
Patients should include a self-examination in their daily bathing or dressing routine. It may be necessary to use a mirror to see the bottoms of the feet clearly. Patients who are unable to reach their feet or see them completely, even with the help of a mirror, should have someone else (such as a spouse or other family member) assist with the examination.
Clinical exam — During a routine medical visit, the clinician will check the blood flow and sensation in the feet. In people with type 1 diabetes, annual foot examinations should begin five years after diagnosis. In people with type 2 diabetes, annual foot exams should begin at the time of diagnosis.
During a foot examination, the clinician will look for changes such as ulcers, cold feet, thin skin, bluish skin color, and skin breaks associated with athlete's foot. The clinician will also test the sensation in the feet to determine if it is normal or diminished. Patients with decreased sensation are at risk for foot injuries that are unnoticed due to lack of pain.
KIDNEY COMPLICATIONS — Diabetes can alter the normal function of the kidneys. A urine test which measures the amount of protein (albumin) in the urine can alert a healthcare provider that diabetes is affecting the kidney's filtering action. Microscopic amounts of albumin in the urine (microalbuminuria) can be an early indicator of diabetes-related kidney complications (called nephropathy). The amount of albumin in the urine can also help the provider determine if nephropathy is worsening. (See "Patient information: Protein in the urine (proteinuria)").
Urine screening tests should begin in people with type 1 diabetes about five years after diagnosis, and in people with type 2 diabetes at the time of diagnosis. If the test shows that there is protein in the urine, tight blood glucose and lipid control are recommended; a medication may be recommended if albuminuria does not improve.
A blood pressure medication (an ACE inhibitor or angiotension receptor blocker [ARB]) is generally recommended for patients with albuminuria that does not improve, even if blood pressures are normal. Patients with elevated blood pressures and albuminuria are also treated with an ACE inhibitor or ARB. These medications decrease the amount of protein in the urine and can prevent or slow the progression of diabetes-related kidney disease.
HYPERTENSION AND RELATED COMPLICATIONS — Many people with diabetes have hypertension (high blood pressure). Although high blood pressure produces few symptoms, it has two negative effects: it stresses the cardiovascular system and increases the progression of diabetic complications of the kidney and eye. A healthcare provider can diagnose high blood pressure by measuring blood pressure on a regular basis. (See "Patient information: High blood pressure overview").
A blood pressure reading below 130/80 is an ideal goal for most people with diabetes who do not have kidney complications; a lower blood pressure goal (<120/75) may be recommended for people with diabetes who have kidney complications.
If a patient is diagnosed with prehypertension (>120/80), the healthcare provider may recommend weight loss, exercise, decreasing the amount of salt in the diet, quitting smoking, and decreasing alcohol intake. These measures can sometimes reduce blood pressure to normal. (See "Patient information: High blood pressure, diet and weight").
If these measures are not effective or the blood pressure must be lowered quickly, the provider will likely recommend one of several high blood pressure medications. The provider can discuss the pros and cons of each medication and the goals of treatment (See "Patient information: High blood pressure treatment").
HEART COMPLICATIONS — In addition to lowering blood glucose levels, a number of other measures are important to reduce the risk of cardiac disease. Quit smoking Manage high blood pressure with lifestyle modifications and/or medication(s) Patients should have a fasting lipid blood test to measure cholesterol and triglycerides, and modify their diets. some patients may need medication to lower their LDL ("bad cholesterol") or trigylcerides, if they are high.
If medication is needed, a statin drug should be included whenever possible. The statin drugs have been shown to decrease the future risk of heart attacks, strokes, and death in people with diabetes who are over age 40, even when cholesterol levels are normal. The American Diabetes Association recommends that patients with diabetes have a low density lipoprotein (LDL) cholesterol level less than 100 mg/dL. Some studies suggest lowering LDL to 70 to 80 mg/dL. (See "Patient information: High cholesterol and lipids (hyperlipidemia)"). Aspirin (81 to 162 mg per day) is recommended for all persons with diabetes over the age of 40 years. (See "Patient information: Aspirin and heart disease").
PREGNANCY AND DIABETES — Control of diabetes and its potential complications is especially important in women planning to become pregnant, as well as in those who already are pregnant. Controlling blood glucose levels before and during pregnancy decreases the risk of a number of complications in both the mother and the baby. A separate topic review is available on this subject. (See "Patient information: Care during pregnancy for women with type 1 or 2 diabetes").
Pregnancy can cause a worsening of diabetic retinopathy. Thus, women with type 1 or 2 diabetes who become pregnant should have an eye examination by an ophthalmologist or optometrist during the first trimester (three months) of their pregnancy. The frequency of subsequent eye exams during pregnancy will depend upon the results of the initial examination. In most cases, doctors recommend eye exams every three months until delivery.
These guidelines do not apply to women who have gestational diabetes -- a form of diabetes that develops during pregnancy and usually resolves after delivery. These women are not at risk for diabetic retinopathy.
THE IMPORTANCE OF REGULAR MEDICAL CARE — Regular medical care is critical to long-term health for people with diabetes, particularly when it comes to preventing, detecting, and slowing the progression of complications. A healthcare provider can recommend a regular schedule for visits, screening, and monitoring tests based upon a patient's type of diabetes (1 or 2), the duration of the disease, the presence of any complications, and the presence of other underlying medical problems.
In addition to diabetes care, patients also need to be sure they have regular screening for other health problems. For women, this may includes a cervical cancer screening, mammogram and clinical breast exam, and bone density testing. For men, prostate cancer screening is recommended after age 40. For both men and women, colon cancer screening is recommended after age 50. (See "Patient information: Screening for cervical cancer" and see "Patient information: Screening for breast cancer" and see "Patient information: Osteoporosis causes; diagnosis; and screening"). and see "Patient information: Prostate cancer screening" and see "Patient information: Screening for colon cancer").
WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two patients are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.
This discussion will be updated as needed every four months on our web site (www.patients.uptodate.com). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.
A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable. National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)
National Institute of Diabetes and Digestive and Kidney Diseases
(www.niddk.nih.gov/)
American Diabetes Association (ADA)
(800)-DIABETES (800-342-2383)
(www.diabetes.org)
The Hormone Foundation
(www.hormone.org/public/diabetes.cfm, available in English and Spanish)
[1-6]
Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 1. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329:977.
2. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995; 75:894.
3. Abraira, C, Colwell, JA, Nuttall, FQ, et al. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes (VACSDM): Results of a feasibility trial. Diabetes Care 1995; 18:1113.
4. Nathan, DM, Cleary, PA, Backlund, JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353:2643.
5. Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA 2003; 290:2159.
6. Gray, A, Raikou, M, McGuire, A, et al. Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomised controlled trial (UKPDS 41). United Kingdom Prospective Diabetes Study Group. BMJ 2000; 320:1373.
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