A Comparative Study on the Effectiveness of Valproate Versus Olanzapine as Add-On Therapy to Lithium in Manic or Hypomanic Relapse: A 24-Week Randomized Open-Label Study

Abstract

Background & Objectives:To compare the effectiveness, onset of action, and tolerability of adjunctive valproate versus olanzapine in patients with bipolar disorder experiencing manic or hypomanic relapse while maintained on lithium therapy.

Materials & Methods: In this 24-week, prospective, randomized, open-label study, patients with bipolar disorder receiving stable lithium therapy (800 mg/day) for at least one year and experiencing a manic or hypomanic relapse were randomly assigned to adjunctive therapy with either valproate (1000 mg/day) or olanzapine (10 mg/day).  The primary outcome measure was the change in the Young Mania Rating Scale (YMRS) total score from baseline to endpoint.  Secondary measures included early symptom reduction, response and remission rates, and adverse event profiles.

Results: Sixty-four patients were randomized to receive adjunctive valproate (n = 32) or olanzapine (n = 32).  Both groups demonstrated significant reductions in YMRS total scores from baseline to week 24 (within-group change: p < 0.001).  The mean reduction in YMRS scores at endpoint did not differ significantly between groups (mean difference = −1.2 points, 95% CI −3.8 to 1.4).  However, olanzapine add-on therapy resulted in a significantly greater reduction in YMRS scores during weeks 1–4 compared with valproate (week-2 difference = −3.5 points, 95% CI −6.1 to −0.9; p < 0.05; Cohen’s d ≈ 0.55).  Response and remission rates at endpoint were comparable.  The incidence and profile of adverse events were similar in both groups.

Conclusion: Both valproate and olanzapine can be used as adjuncts to lithium for managing manic or hypomanic episodes. In the long run, the efficacy of both appears to be similar, but olanzapine appears to be more rapid in reducing mania, which may be beneficial in clinical practice when rapid relief of symptoms is desired. The choice of treatment depends on the acuity of the situation, comorbid illnesses of the patient, and tolerability. Further studies are required to compare the efficacy and tolerability of both regimens.