Written by Keith A. Trujillo, Ph.D. and Andrea B. Chinn
Last Revised 10/2/96
Antimanics are a class of drugs used to treat bipolar disorder. Another term used for this class is mood stablizers, because they often work to decrease not only the manic phase but also the depressed phase of bipolar disorder. The only drug in this class for many years was lithium. More recently two antiseizure medications, carbamazepine and valproic acid have been found to be effective treatments for bipolar disorder. Although the mechanism of action of these drugs is still unknown, they are highly effective in stablizing the dramatic mood shifts seen in bipolar disorder.
Bipolar disorder, sometimes called manic depressive illness, is characterized by cyclical disturbances in mood, cognition and behavior. Individuals with this disorder experience periods of extreme stimulation, known as the manic phase, and periods of extreme lows, known as the depressed phase. The manic phase may include euphoria, impulsiveness and grandiosity, or agitation, irritibility and paranoia. During this phase individuals may experience flight of ideas and racing thoughts, excessive talkativeness, a decreased need for sleep, and often engage in reckless or dangerous activities. The depressed phase, which is indistinguishable from major depression, may include a loss of interest in normally pleasurable activities, extreme feelings of worthlessness and guilt, and thoughts of suicide and death. Although the different phases of the disorder may alternate with periods of relative normality, the extreme shifts in mood and behavior make this a particularly difficult disorder for patients, their families and friends. There is a high rate of suicide and accidental death associated with bipolar disorder. The goal of drug therapy is therefore to decrease both the highs and lows of this disorder.
Carbamazepine potently inhibits seizures, and is the drug of choice for the treatment of certain forms of epilepsy. Structurally, it is similar to the tricyclic antidepressant imipramine. Although several early reports indicated that this drug improved mood in patients treated for epilepsy, the first report of its effectiveness in bipolar disorder appeared in 1970. The use of carbamazepine was popularized by Post and collaborators, who demonstrated the effectiveness
Valproic acid...
Lithium decreases acute mania in 50% to 80% of patients with bipolar disorder. The antimanic effects occur gradually over a course of 10 to 14 days of treatment, and sometimes are delayed up to four weeks or more. Lithium is less effective in acutely reversing the depressive phase of bipolar disorder, with an effective response often delayed six to eight weeks.
The greatest therapeutic benefit of lithium is in attenuating subsequent cycles of bipolar disorder. Although it does not completely eliminate recurrences,when administered prophylactically, lithium decreases the severity of both manic and depressive episodes. Since lithium is not curative, patients typically receive lifetime treatment with this drug. Despite a remarkable ability to attenuate the dramatic mood shifts in bipolar disorder, lithium has few behavioral effects in normal individuals.
The anticonvulsant drugs carbamazepine and valproic acid have been found to be effective in the treatment of acute mania, with some studies showing a more rapid onset than lithium and others showing effects in patients refractory to lithium. Because of a lack of controlled studies, it is unclear how effective these drugs are in the long-term prevention of mood swings in bipolar patients.
| Drug Class | Generic Name | Trade Name |
|---|---|---|
| Lithium | Lithium carbonate | Eskalith Lithobid Lithonate |
| Anticonvulsants | Carbamazepine | Tegretol |
| Valproic acid | Depakote Sodium divalproex |
|
Although many neurobiological effects of lithium have been described, the mechanism of action of this drug as a mood-stabilizing agent remains unknown. One area receiving considerable attention is the effect of lithium on the phosphatidylinositol (PI) second messenger system. Certain receptors, when activated by a neurotransmitter or a drug, stimulate an intracellular cascade of events beginning with the cleavage of phosphatidylinositol, and ending with an impact on several cellular processes. At concentrations very similar to those used therapeutically, lithium has the ability to interfere with this cascade of events, thereby altering the ability of the neurotransmitter or drug to affect the cell. This dampening of receptor activation may be critical to the ability of lithium to dampen mood swings.
The mechanism of action of carbamazepine and valproic acid in the treatment of bipolar illness is presently unclear. Although specific neurochemical effects of these drugs have been identified, it is unknown which of these contribute to their mood stablizing effects.
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Keith A. Trujillo, Ph.D.
Andrea B. Chinn
Comments to author: keith@mailhost1.csusm.edu
All contents copyright (C) 1996, Keith A. Trujillo, Ph.D. All rights reserved.
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