Bipolar maintenance: Are atypical antipsychotics really ‘mood stabilizers’?
Atypical antipsychotics are being used more frequently for bipolar maintenance. Do we know enough about their long-term efficacy and safety?
All atypicals can cause weight gain, although olanzapine and clozapine are associated with the greatest mean weight gains. In three long-term trials (47 weeks to 18 months), bipolar patients who received olanzapine gained significantly more weight (mean 2 to 3 kg) than those receiving lithium or divalproex.19
Cases with much greater weight gain—even leading to clinical obesity—have been observed, particularly with olanzapine. Although evidence from registration trials and clinical experience show lesser weight gains with risperidone, quetiapine, ziprasidone, and aripiprazole, some of our patients do gain weight while taking these agents—either alone or in combination with lithium or divalproex.
Weight management. Because patients with bipolar disorder may be at increased risk for weight gain and obesity, weight management techniques may improve their health by:
- decreasing morbidity and mortality tied to weight-related physical illnesses
- enhancing psychological well-being.1
In addition to diet and exercise counseling, some bipolar patients taking long-term atypical antipsychotics may benefit from adjunctive weight-loss medications (Table 3). We generally use such medications for bipolar patients who:
- persistently gain weight despite best dietary practices
- gain substantial weight early in treatment with an atypical antipsychotic that is providing effective symptomatic relief.
Early weight gain—particularly gains of >7% within the first 6 weeks—might predict large weight gain over time.
Diabetes. In September 2003, the FDA requested a class-wide labeling change to warn about a possible link between atypical antipsychotics and diabetes. The FDA recommended blood sugar monitoring of patients taking atypicals, especially those with obesity risk factors or family history of diabetes.
Type 2 diabetes develops in some patients taking atypicals, whether or not they gain substantial weight.22 This suggests that weight gain associated with bipolar disorder and the use of atypical antipsychotics may be independent risk factors for diabetes—a clear concern when treating bipolar patients.
Evidence provides no clear answer as to which atypicals may increase diabetes risk. Cautious use and vigilant monitoring of blood glucose are therefore recommended for every patient taking an atypical for long-term therapy. Also watch for increases in triglycerides and cholesterol17 in patients taking atypicals as bipolar maintenance therapy.
Conclusion
Atypical antipsychotics are valuable therapies in preventing bipolar relapses, although olanzapine is the only atypical with this indication so far. Collective data and clinical experience suggest that atypicals are indeed mood stabilizers, although—like other mood stabilizers such as lithium or divalproex—they have limitations. None achieve ideal efficacy in all four bipolar treatment roles: treating the highs and lows, and preventing the highs and lows. Atypicals seem more effective in treating and preventing the highs than the lows, reminding us that effective depression treatment is the greatest unmet need in bipolar disorder.
More double-blind, randomized, controlled trials are needed to fully understand whether all atypicals are mood stabilizers and to determine their safety and side effects in long-term therapy for patients with bipolar disorder.
Related resources
- Depression and Bipolar Support Alliance. www.dbsalliance.org
- Muzina DJ, Calabrese JR. Guidelines for treatment of bipolar disorder.In: Stein DJ, Kupfer DJ, Schatzberg AF (eds). Textbook of mood disorders Washington, DC: American Psychiatric Publishing, 2004 (in press).
Drug brand names
- Aripiprazole • Abilify
- Carbamazepine • Tegretol
- Clozapine • Clozaril
- Divalproex/valproate • Depakote, Depakene
- Lamotrigine • Lamictal
- Lithium • Eskalith, Lithobid, et al
- Metformin • Glucophage
- Olanzapine • Zyprexa
- Orlistat • Xenical
- Quetiapine • Seroquel
- Risperidone • Risperdal, Risperdal Consta
- Sibutramine • Meridia
- Simvastatin • Zocor
- Topiramate • Topamax
- Ziprasidone • Geodon
- Zonisamide • Zonegran
Disclosure
Dr. Muzina receives research grants from AstraZeneca Pharmaceuticals, Eli Lilly and Co., and Abbott Laboratories, is a consultant to AstraZeneca Pharmaceuticals and Pfizer, Inc., and a speaker for AstraZeneca Pharmaceuticals, Pfizer Inc., Eli Lilly and Co., and GlaxoSmithKline.
