How Long Should Antipsychotics Be Used After a Manic Episode? Insights from a Key Study

February 17, 2025

Written by Joao L. de Quevedo, MD, PhD

For individuals with bipolar I disorder, preventing relapse after a manic episode is a crucial part of long-term treatment. Atypical antipsychotics like risperidone and olanzapine are often prescribed alongside mood stabilizers such as lithium or valproate. However, the optimal duration for continuing these medications after remission has remained debated.

A 2016 CANMAT randomized, double-blind trial published in Molecular Psychiatry explored this question, offering valuable guidance for clinicians and patients alike (Yatham et al., 2016).

Researchers followed 159 patients who had recently achieved remission from a manic episode while on risperidone or olanzapine in combination with a mood stabilizer. These patients were divided into three groups:

  1. 0-week group – Discontinued the antipsychotic immediately and switched to a placebo.
  2. 24-week group – Continued taking the antipsychotic for 24 weeks before switching to a placebo.
  3. 52-week group – Continued taking the antipsychotic for the entire study duration (one year).

The key outcome measure was time to relapse—how long patients remained stable before experiencing another manic or depressive episode.

Key findings:

  • Stopping antipsychotics immediately led to a higher risk of relapse.
  • Continuing antipsychotic treatment for 24 weeks significantly reduced relapse risk compared to immediate discontinuation.
  • Extending treatment to 52 weeks did not provide a clear additional benefit over stopping at 24 weeks.
  • Weight gain was a significant concern, especially for those who continued olanzapine for the full 52 weeks.

This study remains an essential reference for clinicians managing bipolar I disorder. The findings suggest that continuing antipsychotic treatment for 24 weeks after a manic episode is beneficial, but extending it beyond that period may not offer additional protection—at least for risperidone.

For olanzapine, the study hinted at a possible benefit beyond 24 weeks, but the increased risk of weight gain raises concerns about long-term use. These findings emphasize the importance of balancing relapse prevention with the side effects of prolonged antipsychotic therapy.

Though this study was conducted years ago, it remains relevant today in guiding personalized treatment plans for bipolar disorder.

Reference

Yatham, L. N., Beaulieu, S., Schaffer, A., Kauer-Sant’Anna, M., Kapczinski, F., Lafer, B., Sharma, V., Parikh, S. V., Daigneault, A., Qian, H., Bond, D. J., Silverstone, P. H., Walji, N., Milev, R., Baruch, P., da Cunha, A., Quevedo, J., Dias, R., Kunz, M., Young, L. T., Lam, R. W., & Wong, H. (2016). Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized, double-blind trial. Molecular Psychiatry, 21, 1050–1056. https://doi.org/10.1038/mp.2015.158

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