After achieving remission from a manic episode, can a patient taper down on one of their medications, such as an atypical antipsychotic, while maintaining valproate (valproic acid) at a therapeutic dose?

Tapering Atypical Antipsychotics After Mania Remission

After achieving remission from a manic episode, you can and should taper off the atypical antipsychotic at 24 weeks while maintaining valproate, as continuing the antipsychotic beyond this point provides no additional relapse prevention benefit and causes significant weight gain. 1

Evidence-Based Tapering Timeline

The optimal duration for continuing atypical antipsychotic adjunctive therapy after mania remission is 24 weeks. 1 A high-quality randomized controlled trial directly compared three durations of risperidone or olanzapine continuation (0 weeks, 24 weeks, and 52 weeks) in patients who achieved remission on combination therapy with lithium or valproate. 1

Key Findings on Duration

• Continuing the antipsychotic for 24 weeks significantly reduced relapse risk compared to immediate discontinuation (hazard ratio 0.53,95% CI: 0.33-0.86). 1
• Continuing beyond 24 weeks to 52 weeks provided no additional benefit - relapse rates were similar between the 24-week and 52-week groups (hazard ratio 1.18,95% CI: 0.71-1.99). 1
• For risperidone specifically, continuation beyond 24 weeks actually increased relapse risk (hazard ratio 1.85,95% CI: 1.00-3.41). 1
• The 52-week continuation group gained an average of 3.2 kg compared to weight loss in the shorter duration groups (-0.2 kg in 0-weeks, -0.1 kg in 24-weeks). 1

Clinical Algorithm for Tapering

At 24 Weeks Post-Remission:

1. Verify sustained remission - confirm patient has maintained mood stability for the full 24-week period on combination therapy. 1
2. Begin gradual taper of the atypical antipsychotic while maintaining therapeutic valproate levels (50-100 mcg/mL). 2
3. Continue valproate for at least 12-24 months total after the acute episode, as maintenance monotherapy. 3, 2

Monitoring During Taper:

• Schedule follow-up visits every 1-2 weeks initially during the taper period. 2
• Assess for early warning signs of relapse including mood destabilization, sleep disturbance, or increased irritability. 2
• Monitor valproate levels every 3-6 months to ensure therapeutic range is maintained. 2

Important Caveats and Pitfalls

Do not taper before 24 weeks. Immediate discontinuation at remission increases relapse risk substantially compared to 24-week continuation. 1 The American Academy of Child and Adolescent Psychiatry guidelines recommend continuing the regimen that successfully treated the acute episode for at least 12-24 months, but this high-quality trial demonstrates that the antipsychotic component specifically can be safely discontinued at 24 weeks while maintaining the mood stabilizer. 2, 1

Withdrawal of maintenance lithium or valproate therapy is associated with dramatically increased relapse risk - more than 90% of noncompliant patients relapsed versus 37.5% of compliant patients. 2 Therefore, while you can taper the antipsychotic, the mood stabilizer must continue.

The metabolic burden of continuing antipsychotics beyond 24 weeks is substantial - weight gain, metabolic syndrome, and diabetes risk accumulate with prolonged exposure, particularly with olanzapine. 2, 1 Since there is no relapse prevention benefit beyond 24 weeks for risperidone (and uncertain benefit for olanzapine), the risk-benefit ratio clearly favors discontinuation at this timepoint. 1

Special Consideration for Olanzapine vs Risperidone

The subgroup analysis showed discordant results between the two antipsychotics - olanzapine showed a trend toward benefit with longer continuation (HR 0.48, though not statistically significant), while risperidone showed harm with continuation beyond 24 weeks (HR 1.85). 1 However, even for olanzapine, any potential benefit must be weighed against the 3.2 kg average weight gain with 52-week continuation. 1