Remission with mirtazapine and selective serotonin reuptake inhibitors: a meta-analysis of individual patient data from 15 controlled trials of acute phase treatment of major depression.

Antidepressants that enhance both serotonergic and noradrenergic neurotransmission may be more effective than selective serotonin reuptake inhibitors (SSRIs) for acute-phase therapy of major depressive disorder. Mirtazapine in particular has been suggested to have a faster onset of action than reuptake inhibitors. The aim of this study is to compare the remission rates and time to remission in patients with major depression taking either mirtazapine or an SSRI in an all-inclusive set of studies. Data were obtained from all eligible randomized controlled studies contrasting mirtazapine and SSRIs. Meta-analyses of remission rates and time to remission, together with a supportive analysis of mean change from baseline Hamilton Depression Rating Scales-17 were performed, using individual patient data from 15 randomized controlled trials of mirtazapine (N = 1484) versus various SSRIs (N = 1487) across 6 weeks of double-blind therapy. Analyses were repeated for the eight studies that lasted at least 8 weeks. Remission rates for patients treated with mirtazapine were significantly higher when compared with those treated with an SSRI after 1 (3.4 vs. 1.6%, P = 0.0017), 2 (13.0 vs. 7.8%, P<0.0001), 4 (33.1 vs. 25.1%, P<0.0001), and 6 weeks (43.4 vs. 37.5%, P = 0.0006) of treatment. Mirtazapine-treated patients had a 74% higher likelihood of achieving remission during the first 2 weeks of therapy compared with patients treated with SSRIs. In conclusion, the findings indicate that mirtazapine may be a more rapidly effective antidepressant than SSRIs.

Longitudinal analysis of the suicidal behaviour risk in short-term placebo-controlled studies of mirtazapine in major depressive disorder.

OBJECTIVE: To examine suicidal behaviour risk in the short-term placebo-controlled studies of mirtazapine in Major Depressive Disorder (MDD). METHOD: Longitudinal Generalized Estimating Equations analyses were performed on pooled data from 15 placebo-controlled, randomized, double-blind, short-term trials of mirtazapine, using the suicide item scores from the Hamilton Depression Rating Scale (HAMD) as a proxy outcome measure for suicidality risk. RESULTS: The overall analysis using the convention that a patient is at risk if the HAMD suicide item score is > or =3, and excluding patients at risk at baseline, demonstrated a statistically significantly lower risk for mirtazapine- compared to placebo-treated patients on the HAMD (odds ratio mirtazapine versus placebo 0.38; 95% confidence interval 0.21-0.66; P= 0.0008). CONCLUSION: Our results based on pooled data from 15 placebo-controlled, short-term studies of mirtazapine in MDD using the suicide item scores from the HAMD as a proxy outcome measure for suicidality risk, demonstrate that mirtazapine was associated with statistically significantly lower suicidality risk compared to placebo.