Elsevier

The Lancet

Volume 359, Issue 9302, 19 January 2002, Pages 241-247
The Lancet

Seminar
Bipolar disorder

https://doi.org/10.1016/S0140-6736(02)07450-0Get rights and content

Summary

Bipolar, or manic-depressive, disorder is a frequent, severe, mostly recurrent mood disorder associated with great morbidity. The lifetime prevalence of bipolar disorder is 1·3 to 1·6%. The mortality rate of the disease is two to three times higher than that of the general population. About 10–20% of individuals with bipolar disorder take their own life, and nearly one third of patients admit to at least one suicide attempt. The clinical manifestations of the disease are exceptionally diverse. They range from mild hypomania or mild depression to severe forms of mania or depression accompanied by profound psychosis. Bipolar disorder is equally prevalent across sexes, with the exception of rapid cycling, a severe and difficult to treat variant of the disorder, which arises mostly in women. Because of the high risk of recurrence and suicide, long-term prophylactic pharmacological treatment is indicated. Lithium salts are the first choice long-term preventive treatment for bipolar disorder. They also possess well documented antisuicidal effects. Second choice prophylactic treatments are carbamazepine and valproate, although evidence of their effectiveness is weaker.

Section snippets

Diagnostic features

There are two main types of mood disorder, each with different sex and genetic characteristics: major depressive (unipolar) and manic-depressive (bipolar). Bipolar disorder can be further subdivided into bipolar I disorder, a recurrent mood disorder, featuring either one or more manic or mixed episodes, or both manic and mixed episodes and at least one major depressive episode, or bipolar II disorder, characterised by one or more episodes of major depression and at least one hypomanic episode (

Course of illness

The peak age of onset falls between age 15 and 24 years, although there is often a 5–10-year interval before treatment is obtained.1 If the onset of symptoms occurs after age 60 years, the condition is probably secondary to other medical causes—eg, neurological (trauma, neoplasm, multiple sclerosis, epilepsy), endocrine (hyperthyroidism, Cushing's disease), infectious (AIDS), inflammatory (systemic lupus erythematosus) disorders. Bipolar disorder has a high rate of recurrence; more than 90% of

Pathophysiology

In-vivo biochemical studies, neuropathological studies, and studies with new neuroimaging techniques are being done to try to understand the cause of bipolar disease.7, 8, 9

One traditional line of research focuses on potential changes to the function of neurotransmitters such as norepinephrine, dopamine, and serotonin. In the 1970s, many thought that bipolar disorder was caused by an imbalance between cholinergic and catecholaminergic neuronal activity, since centrally active cholinergic

Genetic factors

Results of family-studies and twin-studies suggest a genetic basis for bipolar disorder.22 The lifetime risk of bipolar disorder in first-degree relatives of a bipolar patient is 40–70% for a monozygotic twin and 5–10% for all other first-degree relatives. However, the mode of inheritance seems complex, indicating a non-Mendelian inheritance and a contribution by several genes. Genomic imprinting and mitochondrial inheritance are also thought to contribute to the inheritance pattern. Because of

Management

In view of the devastating course of bipolar disorder, prevention strategies that are effective, evidence-based, and safe need to be developed. In the meantime, the choice of treatments for bipolar disorder is constantly being revised, as new drugs become available and anticonvulsants take on an increasingly important role. New treatment regimens to counteract resistance to primary treatment or prophylaxis have also been developed. Here, we review and comment on evidence available for treatment

Search strategy

A computer-aided search of MEDLINE database for 1966 to November, 2000, was done with the subject headings “bipolar disorder” and various subjects pertinent for this review. A review of identified report bibliographies and an intensive search by hand with standard textbooks on bipolar disorder was also done. Because of the large number of articles identified and the limitations for quoting references in this article, authors made selections according to the valid criteria of what is judged

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