Maintenance therapy with mood stabilizers is the most critical phase of bipolar disorder treatment but the stage with the least available evidence about medication risks and benefits. The FDA’s recent approval of olanzapine for bipolar maintenance raises the question of whether atypical antipsychotics are really mood stabilizers. This article attempts to answer that question by:
- describing the “ideal” mood stabilizer
- discussing atypicals’ advantages over conventional antipsychotics in bipolar patients
- comparing efficacy data for the six available atypicals
- recommending strategies to prevent and treat atypicals’ potentially serious side effects during long-term therapy.
What is a ‘mood stabilizer’?
Successful mood stabilizer maintenance therapy decreases the time patients are sick and disabled. Although somewhat dated after only 2 years, the most recent American Psychiatric Association (APA) practice guidelines1 support using mood stabilizers for patients with bipolar I and bipolar II disorders.
Table 1
Bipolar maintenance treatment goals
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| Adapted from American Psychiatric Association practice guidelines for treating patients with bipolar disorder (reference 1) |
The goals of maintenance therapy are listed in Table 1. The ideal mood stabilizer would work in maintenance and all bipolar phases and treatment stages—from treating acute depression, mania, hypomania, and mixed states to preventing abnormal mood elevations and depressions. It would not precipitate depression or mania, rapid cycling, or cycle acceleration.
In other words, the best “mood stabilizer” would work in all four treatment roles of bipolar disorder: treating highs and lows, and preventing highs and lows. No such mood stabilizer exists, although lithium may come closest to the ideal.2
Most U.S. psychiatrists use combination therapies for bipolar disorder, particularly when treating acute manic states. The most common combination is a “known” mood stabilizer—such as lithium or divalproex—plus an antipsychotic to quickly control mania.
After mania remits, clinicians often try to eliminate the antipsychotic in hopes of maintaining mood stability and euthymia with the mood stabilizer alone. This was especially true before atypical antipsychotics were approved, given the risk for tardive dyskinesia (TD) associated with long-term use of conventional antipsychotics.
Unfortunately, patients frequently relapse with this strategy, so psychiatrists may leave their bipolar patients on atypical antipsychotics during long-term maintenance. But how good are atypicals as mood stabilizers? Perhaps more importantly, how safe is long-term use of atypicals in bipolar patients?
Antipsychotics as mood stabilizers
The 2002 APA practice guidelines discuss efficacy data for using lithium, divalproex or valproate, lamotrigine, carbamazepine, and electroconvulsive therapy for bipolar maintenance treatment. Two sentences on antipsychotic drug use note:
- one placebo-controlled study of a conventional antipsychotic showing no efficacy
- some data supporting clozapine as a prophylactic bipolar treatment.1
A 1998 review of five open trials3 touched on conventional depot antipsychotics’ value in reducing manic or affective illness. However, the authors warned:
- no controlled trials existed
- maintenance antipsychotic treatment may be associated with increased risk for tardive movement disorders
- conventional agents can exacerbate depressive symptoms in some patients.
Using conventional antipsychotics long-term in bipolar disorder is not advisable, with the possible exception of depot preparations in nonadhering patients with severe illness. Long-acting injectable atypicals—such as the recently approved IM risperidone—may displace any use of conventional antipsychotics in bipolar patients.
Atypical antipsychotics hold several advantages over conventional agents:
- significantly reduced risk for TD and extrapyramidal symptoms (EPS)
- lack of serum prolactin elevation (except with risperidone)
- improved cognition
- possible decreased suicidality, particularly with clozapine.4
Table 2
Tips for managing atypicals’ potentially serious side-effect risks
| Weight gain/obesity | ||
| Assessment | Prevention | Treatment |
| Evaluate comorbid conditions such as eating disorders or substance abuse Take nutritional and exercise history | Check weight and waist circumference at baseline and every visit Calculate body mass index at every visit Prescribe healthy diet and exercise | Patient education, careful monitoring, and prevention are most-effective treatments Drug therapy for persistent weight gain or early rapid gain (>7% in first 6 months). Agents of potential benefit include topiramate, sibutramine, metformin, zonisamide, and orlistat (see Table 3) |
| Glucose control/type 2 diabetes | ||
| Assessment | Prevention | Treatment |
| Take history of glucose intolerance or diabetes Ask about family history of diabetes, obesity, hypertension, heart disease | Check baseline weight and plasma glucose Obtain fasting plasma glucose every 3 months for first year, then annually Prescribe healthy diet and exercise | Primary prevention through careful monitoring is most effective Discontinue atypical antipsychotic; use other mood stabilizer unless atypical is only effective drug for that patient Oral hypoglycemics (metformin, others) |
| Hyperlipidemia | ||
| Assessment | Prevention | Treatment |
| Take history of hyperlipidemia or cardiovascular disease Ask about family history of hyperlipidemia | Check fasting lipid profile including triglycerides at baseline and every 3 months in first year Prescribe healthy diet and exercise | Monitor diet, exercise, weight, lipids regularly Change atypical antipsychotic or use other mood stabilizer (as described above) Oral antilipemics (simvastatin, others) |