A Metaanalysis of Clinical Trials Comparing Moclobemide with Selective Serotonin Reuptake Inhibitors for the Treatment of Major Depressive Disorder

Article excerpt

Objective: To compare response rates among patients with major depressive disorder (MDD) treated with either moclobemide, an antidepressant thought to simultaneously enhance both noradrenergic and serotonergic neurotransmission, or selective serotonin reuptake inhibitors (SSRIs).

Methods: Using a random-effects model, we combined 12 trials involving 1207 outpatients with MDD.

Results: Patients treated with moclobemide were as likely to experience clinical response as those treated with SSRIs (risk ratio 1.08; 95% confidence interval, 0.92 to 1.26; P = 0.314). Simply pooling response rates for the 2 agents resulted in a 62.1% response rate for moclobemide and a 57.5% response rate for the SSRIs. A metaregression did not reveal a statistically significant relation between the mean moclobemide dosage for each study and the risk ratio for response rates. Further, we found no difference between the 2 treatments in overall discontinuation rates, discontinuation rates due to adverse events, or discontinuation rates due to lack of efficacy. Also, rates of fatigue or somnolence and of insomnia were similar between the 2 treatment groups. However, SSRI treatment was associated with higher rates of nausea, headaches, and treatment-emergent anxiety than was treatment with moclobemide.

Conclusions: These results suggest that moclobemide and the SSRIs do differ with respect to their side effect profiles but not in their overall efficacy in the treatment of MDD.

(Can J Psychiatry 2006;51:783-790)

Information on funding and support and author affiliations appears at the end of the article.

Clinical Implications

* Decisions on whether to treat MDD with moclobemide or an SSRI cannot be based on overall differential efficacy.

* Decisions on whether to treat MDD with moclobemide or an SSRl cannot be based on overall differential tolerability.

* There appear to be differences in the side effect profiles of the 2 agents.

Limitations

* The absence of comparative studies involving citalopram and escitalopram precludes generalization to all SSRIs.

* The lack of placebo comparison groups means that no conclusion can be made about the assay sensitivity of these trials.

* There were no outcome data for the subset of patients with atypical depression.

Key Words: moclobemide, selective serotonin reuptake inhibitor, monoamine oxidase inhibitor, major depressive disorder

Abbreviations used in this article

CI confidence interval

HDRS Hamilton Depression Rating Scale

MADRS Montgomery-Asberg Depression Rating Scale

MDD major depressive disorder

RCT randomized clinical trial

RR risk ratio

SSRI selective serotonin reuptake inhibitor

The serendipitous discovery of the precursors of 2 of the major contemporary antidepressant families during the late 1950s-iproniazid for the monoamine oxidase inhibitors and imipramine for the tricyclic antidepressants-has led to the subsequent development of numerous antidepressant compounds (1). Unfortunately, many depression patients continue to remain symptomatic despite several treatments (2,3). Until recently, known differences among available antidepressants were generally limited to aspects of safety and tolerability (1). However, over the past few years, several studies have suggested that treatment with antidepressants simultaneously enhancing noradrenergic and serotonergic neurotransmission, including venlafaxine (4), duloxetine (5), and the tricyclic antidepressant clomipramine (6,7), may result in higher response or remission rates than treatment with antidepressants that selectively enhance serotonergic neurotransmission.

Similar to clomipramine, venlafaxine, and duloxetine, the antidepressant moclobemide also simultaneously enhances serotonergic and noradrenergic neurotransmission (1). Specifically, moclobemide is a selective and reversible inhibitor of the monoamine oxidase-A isoenzyme (1) and is approved for the treatment of depression in Europe, Canada, and Australia. …