Achieving and sustaining remission in bipolar I disorder with ziprasidone : a post hoc analysis of a 24-week, double-blind, placebo-controlled study.

BACKGROUND AND

OBJECTIVE

A number of operational definitions have been proposed to describe outcomes in bipolar disorders; the criteria used to define terms such as recurrence, relapse, response, remission and recovery have varied both in observational studies and in clinical trials. We carried out a post hoc analysis of rates of symptomatic point remission and sustained remission using four different remission criteria that had been evaluated in a previously published 24-week, double-blind, placebo-controlled study.

METHODS

After stabilization for 8 consecutive weeks on open-label ziprasidone plus lithium or valproate, stabilized subjects were randomized to two groups, ziprasidone with lithium or valproate (ziprasidone group), or placebo with lithium or valproate (placebo group) for 16 weeks. Four remission criteria included (i) Mania Rating Scale (MRS) score ≤7, (ii) MRS ≤7 + Montgomery-Åsberg Depression Rating Scale (MADRS) score ≤10, (iii) MRS ≤7 + Clinical Global Impression-Improvement (CGI-I) = 1, (iv) MRS score ≤7 + MADRS score ≤10 + CGI-I score = 1. We examined the percentages of subjects in each treatment group achieving symptomatic point (i.e. at each visit) and sustained (i.e. for ≥8 weeks) remission during the double-blind phase.

RESULTS

At week 24, symptomatic point remission based on the above two more stringent criteria was achieved by 48.0 and 24.4% of the ziprasidone group versus 36.9 and 18.0% of placebo recipients, respectively (p = 0.04 and 0.14). Sustained remission rates at 24 weeks were 42.5 and 18.1% for ziprasidone, respectively (vs 33.3 and 14.4% for placebo, p = 0.04 and 0.21, respectively).

CONCLUSION

This analysis indicates that ziprasidone plus lithium or valproate treatment showed modest to moderate remission rates at week 24 based on four different remission criteria in terms of symptomatic and sustained remission, despite the stringent criteria. Our findings indicate that ziprasidone may be effective in achieving sustained remission in bipolar I disorder and propose that a better understanding regarding the definition of remission in bipolar disorders should be required in clinical practice since our results showed different remission rates with different remission criteria.