Efficacy and Safety of Mirtazapine in Major Depressive Disorder Patients After SSRI Treatment Failure: An Open-Label Trial

Objective: To evaluate the efficacy and safetyof mirtazapine in depressed outpatients who have shownnonresponse or intolerance to selective serotonin reuptakeinhibitor (SSRI) therapy.

Method: In this open-label, 8-week study, theefficacy and safety of mirtazapine among 103 outpatients withDSM-IV major depressive disorder who had failed previous therapywith an SSRI (fluoxetine, paroxetine, or sertraline) wereevaluated. The primary efficacy measure was the 17-item HamiltonRating Scale for Depression (HAM-D-17), and safety assessmentsincluded reported adverse events, routine laboratory assessments,physical examinations, and assessments of vital signs. A 4-daywashout period followed by mirtazapine treatment was comparedwith an immediate switch from the SSRI to mirtazapine.

Results: Based on mean HAM-D-17 scores atendpoint and response rates of 48% based on the criterion of>= 50% reduction in HAM-D-17 score, mirtazapine was found tobe an effective treatment for a substantial proportion ofpatients for whom an SSRI was ineffective and/or poorlytolerated. Mirtazapine was well tolerated, with sedation andappetite increase/weight gain the most commonly reported adverseevents. In addition, no difference in efficacy, safety, ortolerability was observed for patients undergoing an immediateswitch from an SSRI (after having been tapered to the minimaleffective dose) to mirtazapine, compared with those undergoingthe imposition of a 4-day drug-free washout. 

Conclusion: In this clinical trial with depressed, hypogonadal men, antidepressant effects of testosterone replacement could not be differentiated from those of placebo.