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Ziprasidone Combined With Mood Stabiliser Provides Effective Maintenance Therapy in Patients With Bipolar Mania: Presented at EPA

By Chris Berrie

LISBON, Portugal -- January 25, 2009 -- Ziprasidone is an effective, safe, and well-tolerated adjunctive treatment to a mood stabiliser for the long-term maintenance treatment of patients with bipolar I disorder, according to trial results presented here at the 17th European Congress of Psychiatry, organised by the European Psychiatric Association (EPA).

"Ziprasidone has an indication for acute mania, and this is why patients were initially treated openly with ziprasidone on top of lithium or valproate for acute mania," explained principal investigator Eduard Vieta, MD, PhD, Bipolar Disorder Programme, Clinical Institute of Neuroscience Hospital Clinic, University of Barcelona, Barcelona, Spain, speaking here at a presentation on January 25.

Dr. Vieta undertook a randomised, double-blind, placebo-controlled, phase 3 trial that included outpatients with bipolar I disorder who had a Mania Rating Scale (MRS) score of 14 or more (scores of 2 or greater on at least 4 items) and who were receiving therapeutic serum levels of lithium (0.6 to 1.2 mEq/L) or valproic acid (50 to 125 mcg/mL) for at least 2 weeks upon screening.

Patients on other mood stabilisers who had an MRS score of 18 or greater could enter the trial if they were willing to switch to lithium or valproic acid for 2 weeks prior to the addition of ziprasidone.

The initial open-label period included lithium or valproic acid with 2.5 to 4 months of ziprasidone at 80 to 160 mg/day. Patients with at least 8 consecutive weeks of symptom stability (n = 240) were randomised to continue the mood stabiliser without (n = 113; placebo) or with (n = 127) ziprasidone continuation for a further 6 months.

In this part of the study, with 19.7% of ziprasidone patients and 32.4% of placebo patients requiring mood intervention for a mood episode, the primary endpoint of time to intervention significantly favoured ziprasidone over placebo (P = .0104). Of those patients requiring intervention, the median time to intervention also favoured ziprasidone over placebo (43.0 vs 26.5 days, respectively).

Similarly, the secondary endpoint of time to discontinuation for any reason significantly favoured ziprasidone (P = .0047), with ziprasidone patients requiring less discontinuation compared with placebo patients (33.9% vs 51.4%, respectively).

The safety analysis demonstrated fewer patients on ziprasidone discontinuing due to adverse events (AEs) compared with placebo (12.6% vs 14.3%). Treatment-emergent AEs were also generally greater in the placebo group, except for tremor (3.6% placebo vs 6.3% ziprasidone).

In laboratory analyses, the majority of abnormal results were considered not to be clinically significant. Furthermore, ziprasidone was not associated with significant weight gain compared with placebo.

Dr. Vieta cautioned, however, that "if you are going to treat somebody with ziprasidone combined with lithium or valproate for acute manic episodes, it is better to keep the treatment going for at least 6 months, rather than to stop it after a few weeks or after remission."

The combination of a mood stabiliser with ziprasidone now represents an important treatment option for maintenance therapy in patients with bipolar mania, Dr. Vieta concluded.

First-line treatment of bipolar mania has generally been a mood stabiliser, although recent studies have indicated that adjunctive use of an atypical antipsychotic might provide improvement in efficacy and in depressive symptoms.

Funding for this study was provided by Pfizer Inc.

[Presentation title: A Six-Month, Randomised, Placebo-Controlled, Double-Blind Trial of Ziprasidone Plus a Mood Stabiliser in Subjects With Bipolar I Disorder. Abstract P1160]

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