More New Treatments for Bipolar Disorder
abstract & commentary
Synopsis: Olanzapine (Zyprexa), although currently marketed as an antipsychotic medication, may have a much broader spectrum of efficacy. The current controlled study demonstrates the efficacy of olanzapine in the treatment of acute mania with and without psychotic symptoms.
Source: Tohen M, et al. Olanzapine versus placebo in the treatment of acute mania. Am J Psychiatry 1999;156: 702-709.
The prevalence of bipolar disorder (manic depression) in primary care practice is 0.42%, and the lifetime prevalence in the general population of the United States ranges from 1.0-1.6%. Bipolar disorder is also associated with significant mortality risk, with approximately 25% of patients attempting suicide at some time during their lives and 11% of patients dying by suicide. All patients who present with depression should be asked if they have a history of manic episodes (i.e., bipolar disorder). Of depressed patients without a history of mania, approximately 12.5% have subsequent manic or hypomanic episodes when followed for 2-11 years.1 Many primary care physicians encounter bipolar patients in their practice and are unsure how to manage them. For acute mania, these patients require a mood stabilizer (e.g., lithium, valproate, carbamazepine), short-term use of a benzodiazepine for agitation and insomnia, and short-term use of an antipsychotic medication for psychosis. For bipolar depression, patients need a mood stabilizer and use of an antidepressant for 3-6 months. Once in remission, patients need a mood stabilizer long-term for prophylaxis.
In the current study, Tohen and colleagues compare the efficacy of olanzapine, an atypical antipsychotic, vs. placebo for acute bipolar mania. The introduction emphasizes that new medications are needed for bipolar mania for several reasons: 1) a substantial proportion of patients fail to respond to conventional mood stabilizers; 2) conventional mood stabilizers have common side effects that affect adherence; 3) conventional mood stabilizers have rare but potentially serious side effects that require monitoring (e.g., renal toxicity with lithium); and 4) typical antipsychotics (e.g., haloperidol [Haldol]) are also efficacious for bipolar mania, but have potentially serious side effects (e.g., tardive dyskinesia). The premise for trying olanzapine is the success of atypical antipsychotic medications (e.g., clozapine, olanzapine, risperidone) in open trials for the treatment of mania. Patients between the ages of 18 and 65 years were enrolled after being diagnosed with bipolar mania via a structured psychiatric interview; those with medical or substance etiologies for mania were excluded. After a 2 to 4 day medication washout period, patients were randomized to olanzapine 10 mg per day or placebo with dose adjustment as necessary; prn medication included a benzodiazepine for agitation or insomnia and benztropine for extrapyramidal side effects. Mania, quality of life, and side effects were assessed in an ongoing manner. A 50% decrease in manic symptoms was the a priori criterion for a positive response to medication. The sample size was 139 patients. Statistical analyses were done on an intent-to-treat basis; that is, data on all randomly assigned patients were included in the analysis (not just those who finished the study). At three weeks, olanzapine was superior to placebo in reducing mania, with 48.6% and 24.2% of patients meeting criteria for a positive response; olanzapine was equally effective in nonpsychotic and psychotic mania. The average olanzapine dose was about 15 mg/d. The olanzapine-treated patients also had improved physical functioning compared to the placebo-treated patients. More somnolence, dry mouth, dizziness, and weight gain occurred in the olanzapine group than the placebo group. No clinically significant extrapyramidal side effects or laboratory changes were noted. The dropout rates were 65.2% for placebo and 38.6% for olanzapine.
Comment by Donald M. Hilty, MD
This study suggests that atypical antipsychotic medications may be effective as mood stabilizers for the treatment of bipolar mania. An identical study is in progress to attempt to replicate the findings. In addition, studies comparing risperidone (another atypical antipsychotic medication) to placebo are in progress. While olanzapine is effective for the treatment of mania, nothing is known about how it directly compares to conventional mood stabilizers, its ability to prophylaxe against mania, or what factors predict a positive response to olanzapine relative to other mood stabilizers.
It is not yet clear how these findings will affect selection of medication by primary care physicians and psychiatrists. Lithium is perhaps the mood stabilizer most familiar to primary care physicians. Valproate is currently the most commonly prescribed mood stabilizer, surpassing lithium in recent years after gaining FDA approval for bipolar disorder in 1995. Finally, new anticonvulsants (e.g., lamotrigine and gabapentin) are being studied for the treatment of bipolar disorder and another recent study abstracted in this issue suggests a possible role for omega-3 fatty acids. A recent review article discusses the epidemiology, assessment, and management of bipolar disorder by psychiatrists in mental health settings,2 and it is currently being adapted to a review article for primary care practice.
References
1. Akiskal HS, et al. Switching from "unipolar" to bipolar II. Arch Gen Psychiatry 1995;52:114-123.
2. Hilty DM, et al. Bipolar disorder in adults: A review of recent literature. Psychiatric Services 1999;50:201-213.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content