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Since the efficacy of the various antidepressants is similar, their side effects, cost and overdose toxicity are preferentially considered when deciding which drug to use. Recently, selective serotonin reuptake inhibitors (SSRIs) have been more frequently prescribed than tricyclic antidepressants, because of their less frequent side effects. Also, the use of noradrenergic and specific serotonergic antidepressants (NaSSAs) is increasing. These new antidepressants have characteristic side effect profiles consisting mainly of gastrointestinal side effects, weight gain and sexual dysfunction, which serve as a direct cause of noncompliance. In the present study, we compared the drug side effects of patients with major depressive disorder who had taken either mirtazapine or SSRIs. Patients with DSM-IV major depressive disorder who were treated with either mirtazapine or SSRI (fluoxetine, paroxetine) monotherapy as an antidepressant were enrolled in this study. Subjects with physical illnesses or poor drug compliance were excluded. A self-rating questionnaire was used to assess the drug side effects. A total of 86 patients (mirtazapine; 24, SSRIs; 62 [fluoxetine 18, paroxetine 44]) participated in this study. There was no difference in the mean age, sex ratio or mean duration of administration between the two groups. Those patients taking mirtazapine experienced significantly less side effects than those taking SSRIs in terms of decreased appetite, yawning, decreased libido and anorgasmia. Those patients taking SSRIs had significantly less side effects in terms of peripheral edema than those taking mirtazapine. There were differences in some of the side effects between mirtazapine and the SSRIs. Mirtazapine showed more favorable side effect profiles than the SSRIs in terms of the gastrointestinal and sexual side effects. This data should help to establish useful guidelines for the selection of antidepressants.

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