Antidepressant and Antimanic Medications: Antipsychotic Drugs
Antipsychotic drugs were some of the first drugs used to treat acute mania, and numerous studies have shown their effectiveness. Although the onset of action of antipsychotic drugs is often more rapid than that of lithium, carbamazepine, and valproic acid, there are serious potential side effects that limit their use.
The most serious side effect is the potential for development of tardive dyskinesia. Tardive dyskinesia may occur more frequently in patients with mood disorders than in those with schizophrenia, and in patients with intermittent exposure than in those with continuous exposure, placing patients with bipolar disorder at higher risk. Because of this higher risk and the availability of safer and better-tolerated drugs, antipsychotic medications should only be used in manic patients for the management of acute agitation, excitement, or psychosis or in those few patients who clearly relapse on gradual discontinuation of antipsychotics.
Studies suggest that the atypical antipsychotic drug clozapine may be effective in the treatment of dysphoric mania. In one study of 14 bipolar patients with psychotic features, 12 (86%) showed significant improvement, and 7 of these patients were observed for an additional 3-5 years with no further hospitalizations. Because of the risk of potentially fatal agranulocytosis, clozapine should not be used unless other first-line agents or traditional antipsychotic drugs have failed.
Newer antipsychotics that share some of the pharmacological properties of clozapine but without the risk of agranulocytosis have now begun to become clinically available. These “atypical” antipsychotics are being intensively studied for the treatment of bipolar and unipolar mood disorders because they may have a lower risk of tardive dyskinesia and are associated with a lower overall side-effect profile compared with older antipsychotics. Olanzapine, risperidone, and quetiapine are all being studied both as monotherapy and as an adjunctive therapy for treatment of acute mania. Of the three, olanzapine is the best studied, with double-blind comparator trials as well as double-blind placebo-controlled trials in acute mania. All of these drugs are being widely used for the treatment of agitation and psychosis in manic or psychotically depressed patients, despite the absence of controlled data. Interestingly, olanzapine and risperidone have both been reported to cause mania in some patients with schizophrenia or with schizoaffective or bipolar disorder. At this point, none of these drugs should be used for long-term monotherapy of bipolar disorder in patients who have been tried on other available agents, since no long-term studies have been completed.
Antidepressant and Antimanic Medications
Combined Medication and Psychotherapy
Treatment-Resistant Mood Disorders
Treatment of Mood Disorders in the Medically Ill Patient
Strategies and Tactics in the Treatment of Depression
Revision date: July 7, 2011
Last revised: by Jorge P. Ribeiro, MD