Onset of improvement and response to mirtazapine in depression: a multicenter naturalistic study of 4771 patients.

The purpose of this open multicenter study of 4771 patients with a DSM-IV diagnosis of Major Depressive Episode was to analyse the response to mirtazapine in general practice and primary care. Patients with a baseline score of at least 20 on the Montgomery-Asberg Depression Rating Scale (MADRS) were treated with mirtazapine for 6 weeks (30 mg/day) and clinically assessed by their psychiatrists at weekly intervals through the MADRS and Clinical Global Improvement (CGI) rating scales. The data analysis was carried out on an "intent-to-treat" basis to collect outcome information on all patients. Our results suggested that the efficacy of the antidepressant effect relates to a nonspecific process. Nearly all patients (95%) showed at least slight improvement at the end of the observation period, while the response to treatment was independent of the clinical forms of depression. In particular, all measures of efficacy displayed the maximum change within the first 2 weeks of treatment, with further improvement occurring at much slower rates. Significant improvement within the first 2 weeks of treatment was highly predictive of the final response, and can serve as a guideline for clinicians when deciding about increased dosage, augmentation, or change of medication in unresponsive patients. Detailed analyses of individual MADRS items showed that mirtazapine's pharmacological profile, unlike selective serotonin reuptake inhibitors, led relatively quickly to a significant reduction of suicidal thoughts, a fact of particular clinical relevance.