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Going to Extremes: Manic-Depressive Illness

There is a tendency to romanticize manic-depressive illness. Many artists, musicians and writers have suffered from its mood swings. But in truth, many lives are ruined by this disease and, without effective treatment, the illness leads to suicide in nearly 20 percent of cases. Manic-depressive illness, also known as bipolar disorder, a serious brain disease that causes extreme shifts in mood, energy, and functioning, affects approximately 2.3 million adult Americans – about one percent of the population. Men and women are equally likely to develop this disabling illness. Different from normal mood states of happiness and sadness, symptoms of manic-depressive illness can be severe and life threatening. Manic-depressive illness typically emerges in adolescence or early adulthood and continues to flare up across the life course, disrupting or destroying work, school, family, and social life. Manic-depressive illness is characterized by symptoms that fall into several major categories:

Depression: Symptoms include a persistent sad mood; loss of interest or pleasure in activities that were once enjoyed; significant change in appetite or body weight; difficulty sleeping or oversleeping; physical slowing or agitation; loss of energy; feelings of worthlessness or inappropriate guilt; difficulty thinking or concentrating; and recurrent thoughts of death or suicide.

Mania: Abnormally and persistently elevated (high) mood or irritability accompanied by at least three of the following symptoms: overly-inflated self-esteem; decreased need for sleep; increased talkativeness; racing thoughts; distractibility; increased goal-directed activity such as shopping; physical agitation; and excessive involvement in risky behaviors or activities.

Psychosis: Severe depression or mania may be accompanied by periods of psychosis. Psychotic symptoms include: hallucinations (hearing, seeing, or otherwise sensing the presence of stimuli that are not there) and delusions (false personal beliefs that are not subject to reason or contradictory evidence and are not explained by a person's cultural concepts). Psychotic symptoms associated with manic-depressive illness typically reflect the extreme mood state at the time.

"Mixed" state: Symptoms of mania and depression are present at the same time. The symptom picture frequently includes agitation, trouble sleeping, significant change in appetite, psychosis, and suicidal thinking. Depressed mood accompanies manic activation.

Symptoms of mania, depression, or mixed state appear in episodes, or distinct periods of time, which typically recur and become more frequent across the life span. These episodes, especially early in the course of illness, are separated by periods of wellness during which a person suffers few to no symptoms. When four or more episodes of illness occur within a 12-month period, the person is said to have manic-depressive illness with rapid cycling. Manic-depressive illness is often complicated by co-occurring alcohol or substance abuse.


A variety of medications are used to treat manic-depressive illness. But even with optimal medication treatment, many people with manic-depressive illness do not achieve full remission of symptoms. Psychotherapy, in combination with medication, often can provide additional benefit.

Lithium has long been used as a first-line treatment for manic-depressive illness. Approved for the treatment of acute mania in 1970 by the U.S. Food and Drug Ad-ministration (FDA), lithium has been an effective mood-stabilizing drug for many people with manic-depressive illness.

Anticonvulsant medications, particularly valproate and carbamazepine, have been used as alternatives to lithium in many cases. Valproate was FDA approved for the treatment of acute mania in 1995. Newer anticonvulsant medications, including lamotrigine and gabapentin, are being studied to determine their efficacy as mood stabilizers in manic-depressive illness. Some research suggests that different combinations of lithium and anticonvulsants may be helpful.

During a depressive episode, people with manic-depressive illness commonly require treatment with antidepressant medication. The relative efficacy of various antidepressant medications in this disorder has not yet been determined by adequate scientific study. Typically, lithium or anticonvulsant mood stabilizers are given along with an antidepressant to protect against a switch into mania or rapid cycling, which can be provoked in some people with manic-depressive illness by antidepressant medications.

In some cases, the newer, atypical anti-psychotic drugs such as clozapine or olanzapine may help relieve severe or refractory symptoms of manic-depressive illness and prevent recurrences of mania. Further research is necessary, however, to establish the safety and efficacy of atypical antipsychotics as long-term treatments for manic-depressive illness.

Recent Research Findings

More than two-thirds of people with manic-depressive illness have at least one close relative with the disorder or with unipolar major depression, indicating that the disease has a heritable component. Studies seeking to identify the genetic basis of manic-depressive illness indicate that susceptibility stems from multiple genes. Despite tremendous research efforts, however, the specific genes involved have not yet been conclusively identified. Scientists are continuing their search for these genes using advanced genetic analytic methods and large samples of families affected by the illness. The researchers are hopeful that identification of susceptibility genes for manic-depressive illness, and the brain proteins they code for, will make it possible to develop better treatments and preventive interventions targeted at the underlying illness process.

Genetics researchers believe that a person's risk for developing manic-depressive illness most likely increases with each susceptibility gene carried, and that inheriting just one of the genes is probably not sufficient for the disorder to appear. The particular mix of genes may determine various features of the illness, such as age of onset, type of symptoms, severity, and course. In addition, environmental factors are known to play an important role in determining whether and how the genes are expressed.

New Clinical Trial

The National Institute of Mental Health has initiated a large-scale study at 20 sites across the U.S. to determine the most effective treatment strategies for people with manic-depressive illness. The study will follow patients and document their treatment outcome for 5 - 8 years. More information about the study can be found through the Clinical Trials page of the NIMH website.

All material in this fact sheet is in the public domain and may be copied or reproduced without permission from the Institute. Citation of the source is appreciated.

NIH Publication No. 01-4595

Updated: January 01, 2001