Ziprasidone in the treatment of acute mania: a 12-week, placebo-controlled, haloperidol-referenced study

Abstract

This 12-week, double-blind, two-part study in 438 adults with bipolar-associated acute mania began with a 3-week period comparing ziprasidone (80-160 mg/day) and placebo with haloperidol (8-30 mg/day) as active reference. Changes from baseline Mania Rating Scale (MRS) scores for ziprasidone and haloperidol were superior to placebo from day 2 (P = 0.001) to week 3 (P < 0.001); change from baseline at week 3 was greater for haloperidol than ziprasidone (P <or= 0.001). At week 3, the response rate (>or=50% decrease from baseline MRS score) was 36.9, 54.7 and 20.5% for ziprasidone, haloperidol and placebo, respectively (P <or= 0.05, active treatments versus placebo and ziprasidone versus haloperidol). In the 9-week extension phase, ziprasidone replaced placebo to examine tolerability. Maintenance of improvement was evaluated for ziprasidone (40-160 mg/day) or haloperidol (4-30 mg/day). Responses were maintained through the last visit for 88.1% receiving ziprasidone and 96.3% receiving haloperidol. More patients receiving haloperidol than ziprasidone discontinued treatment during weeks 4-12 (21.1% versus 9.6%) and had significantly higher rates of movement disorders. Mean doses of ziprasidone and haloperidol for the first 3-week and 9-week extension were 116.2 mg/day and 121.4 mg/day and 16.0 mg/day and 16.1 mg/day, respectively. Ziprasidone was shown to be effective monotherapy for acute treatment of bipolar mania. Although haloperidol showed greater efficacy, ziprasidone showed a superior tolerability profile.

The World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Biological Treatment of Bipolar Disorders: Update 2009 on the Treatment of Acute Mania

“…Ziprasidone monotherapy was tested for antimanic efficacy in three double-blind placebocontrolled studies (Keck et al 2003c;Potkin et al 2005b;Vieta et al 2009b), one of them also had haloperidol as an internal comparator . All these studies confirmed the antimanic efficacy of ziprasidone.…”

Efficacy of pharmacotherapy in bipolar disorder: a report by the WPA section on pharmacopsychiatry

“…Several studies support the efficacy of haloperidol. The first one took place in 1975 [451], while more recent studies support the efficacy of up to 30 mg/day of haloperidol against acute mania, with a response rate of 47-56.1 % vs. a placebo 20-35 % at 3 weeks [341,463,537,565].…”

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013

“…During the nine-week extension phase, responses were maintained for the majority of patients receiving active treatments. Ziprasidone showed a superior tolerability profile and lower discontinuation rates during the extension phase (53).…”