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/)


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