Elsevier

Biological Psychiatry

Volume 68, Issue 2, 15 July 2010, Pages 156-162
Biological Psychiatry

Archival Report
Risperidone Long-Acting Injectable Monotherapy in the Maintenance Treatment of Bipolar I Disorder

https://doi.org/10.1016/j.biopsych.2010.01.015Get rights and content

Background

Treatment adherence is a significant problem in patients with bipolar disorder. This study was designed to determine the efficacy of risperidone long-acting injectable (LAI) in the maintenance treatment of bipolar I disorder.

Methods

Eligible patients with current or recent manic or mixed episodes (n = 559, aged 18–65 years) were treated with open-label oral risperidone for 3 weeks (period II) and open-label risperidone LAI for 26 weeks (n = 501; period III). Patients who maintained response (n = 303) were randomly allocated 1:1 to placebo injections (n = 149) or to continue risperidone LAI (n = 154) for up to 24 months (period IV).

Results

Most (77%) patients on risperidone LAI received a dose of 25 mg every 2 weeks during period IV. Time to recurrence for any mood episode (primary outcome variable) was significantly longer in the risperidone LAI group versus placebo (p < .001); the difference was significant for time to recurrence of elevated-mood episode (p < .001) but not time to recurrence of depressive episode (p = .805). Weight gains ≥7% (compared with the period's baseline) occurred in 15% of patients in period III; in 12% of patients on risperidone LAI and 3% of patients on placebo in period IV.

Conclusions

Risperidone LAI monotherapy significantly delayed the time to recurrence of mood episodes, versus placebo, in this controlled, randomized study in patients with bipolar I disorder. Risperidone LAI was tolerable and no new safety concerns emerged compared with previous studies of risperidone LAI.

Section snippets

Patients

Men and women, aged 18 to 65 years (inclusive), body mass index ≥17 and ≤33 kg/m2, with a diagnosis of bipolar I disorder (DSM-IV-TR criteria [15]) were enrolled. Patients were eligible if they experienced an acute manic or mixed episode (with a Young Mania Rating Scale [YMRS] score ≥20) (16) or were stable (Clinical Global Impressions-Severity [CGI-S] Scale ≤3) on risperidone (oral or LAI) or on other oral antipsychotics or mood stabilizers but requiring change due to safety or tolerability

Patient Demographics and Characteristics

Patient disposition is shown in Figure S1 in Supplement 1. The double-blind treatment groups were generally well-balanced (Table 1). Most (77%) patients in the risperidone LAI group received a dose of 25 mg every 2 weeks. Median duration of exposure was 280.5 days for patients on risperidone LAI and 151 days for patients on placebo. Lorazepam was the most commonly used concomitant medication (5% risperidone LAI; 10% placebo).

The preplanned interim analysis was performed after the 66th

Discussion

The 1997 Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines for management of bipolar disorder suggested that limited evidence existed to support use of first-generation antipsychotics in bipolar maintenance therapy and that individuals with mood disorders may be at particular risk for developing tardive dyskinesia (22). Further, in a small placebo-controlled trial, a first-generation depot neuroleptic did not have a prophylactic effect (23). In contrast, a credible database

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