Meta-Analysis of Efficacy and Treatment-Emergent Suicidality in Adults by Psychiatric Indication and Age Subgroup Following Initiation of Paroxetine Therapy: A Complete Set of Randomized Placebo-Controlled Trials

Objective: This meta-analysis of placebo-controlled paroxetine trials examines suicidality incidence in adults, focusing on disorder and age as potential risk factors. The findings are put in context with an efficacy meta-analysis of the same trial datasets.

Data Sources: GlaxoSmithKline paroxetine clinical trial database(s).

Study Selection: All double-blind, randomized, placebo-controlled, parallel-group studies of paroxetine therapy in adults enrolling at least 30 patients total were included in the analysis. The dataset comprised 14,911 patients from 61 trials.

Data Extraction: Possible cases of suicidality were identified and blindly categorized by an expert panel, using methodology previously used by the US Food and Drug Administration. Incidences of suicidal behavior (preparatory act, suicide attempt, or completed suicide) and any suicidality (suicidal behavior or ideation) were compared between paroxetine and placebo. Efficacy assessments were based on standard depression rating scales (eg, Hamilton Depression Rating Scale or Montgomery-Asberg Depression Rating Scale) and Clinical Global Impressions Improvement scale (CGI-I) scores.

Results: In the primary dataset, ie, all disorders combined, there were no significant differences between paroxetine and placebo for overall suicidality (suicidal behavior or ideation: n/n = 83/8,958 [0.93%] vs n/n = 65/5,953 [1.09%], respectively; OR = 0.9 [95% CI, 0.7-1.3]; P = .649) or for suicidal behavior specifically (n/n = 50/8,958 [0.56%] vs n/n = 40/5,953 [0.67%], respectively; OR = 1.2 [95% CI, 0.8-1.9]; P = .483). However, in patients with major depressive disorder (MDD), a greater incidence of suicidal behavior occurred in paroxetine-treated patients than in placebo-treated patients (n/n = 11/3,455 [0.32%] vs n/n = 1/1,978 [0.05%], respectively; OR = 6.7 [95% CI, 1.1-149.4]; P = .058). Across all indications, a higher incidence of suicidal behavior occurred in paroxetine-treated versus placebo-treated adults aged 18 to 24 years (n/n = 17/776 [2.19%] vs n/n = 5/542 [0.92%], respectively; OR = 2.4 [95% CI, 0.9-7.3]). In older age groups, no increase in suicidality was observed. Efficacy was demonstrated in all disorders evaluated, including MDD.

Conclusions: Across all disorders, overall suicidality incidence was similar between paroxetine and placebo. However, a higher frequency of suicidal behavior occurred with paroxetine in MDD, which was largely explained by the higher incidence in young adults. These data support the efficacy of paroxetine therapy; however, they also highlight the need for careful monitoring of suicidality during antidepressant therapy, particularly in younger adults.

J Clin Psychiatry

Submitted: December 8, 2008; accepted May 26, 2010.

Online ahead of print: February 22, 2011 (doi:10.4088/JCP.08m04927blu).

Corresponding author: Regan Fong, PhD, Director, Discovery Medicine, GlaxoSmithKline, 2301 Renaissance Blvd, King of Prussia, PA 19406 ([email protected]).