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Long-acting injectable antipsychotics outperform placebo, not active control

Meta-analysis results indicated that second-generation antipsychotic long-acting injections performed better than placebo for study-defined relapse rate and all-cause discontinuation, but not when compared with oral medication, in bipolar disorder.

“Evidence from studies in people with schizophrenia suggests that antipsychotic [long-acting injections] reduce relapses, medication discontinuation rates and admission to hospital compared to oral antipsychotics,” Asta R. Prajapati, BPharm, MSc, pharmacy department, Norfolk and Suffolk NHS Foundation Trust, Norwich, England, and colleagues wrote. “Clinical experience and evidence suggest that the use of [long-acting injections] for bipolar disorder is not infrequent.”

This systematic review and meta-analysis of randomized controlled trials reported the efficacy and safety outcomes — relapse rate and all-cause discontinuation— among patients with bipolar disorder using second-generation antipsychotic long-acting injections. Researchers searched online clinical databases for studies evaluating safety and efficacy of second-generation antipsychotic longacting injections for bipolar disorder that were 6 months or longer in duration.

The meta-analysis included seven trials that involved 1,192 participants. Prajapati and colleagues found that second-generation antipsychotic long-acting injections were superior to placebo in terms of study defined relapse rate (RR = 0.58; 95% CI, 0.490.68) and all-cause discontinuation (RR = 0.72; 95% CI, 0.640.82). However, they observed no significant difference between long-acting injectable antipsychotics and oral active control for relapse rate (RR = 0.92; P = .79) and all-cause discontinuation (RR = 1.2; P = .31).

In addition, second-generation antipsychotic long-acting injections outperformed placebo in relapse to mania/hypomania, Young Mania Rating Scales (YMRS), Clinical Global Impression Severity (CGIS) and Montgomery Asberg Depression Rating Scale (MADRS).

Although the results showed no significant difference between long-acting injectable antipsychotics and oral active control in relapse to mania/hypomania, YMRS, CGIS and weight gain, the active control outperformed the injectable antipsychotics in relapse to depression, MADRS, and prolactin-related adverse events.

“[Second-generation antipsychotic long-acting injections] may have a role in bipolar patients with known adherence problems with oral medication. However, this metaanalysis suggests that [second-generation antipsychotic long-acting injections] is better only compared to placebo and not active control,” the researchers wrote. “Considering the significant cost pressure and other issues which come with prescribing [second-generation antipsychotic long-acting injections] further high-quality active control studies are required to guide clinical practice.” – by Savannah Demko

Disclosure: Prajapati reports conference expenses from Janssen and research honoraria from Accession. Please see the study for all other authors’ relevant financial disclosures.