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Rapid antidepressant effect with the combined treatment by sulpiride and paroxetine
The delayed onset of action of antidepressants remains a problem for patients with major depressive disorder. It is all the more important to relieve depressive symptoms early since they tend to be more severe at the beginning of the treatment. Fast action should therefore lead to a better treatment compliance. Sulpiride, a dopamine D2 receptor antagonist, has been shown to have a faster antidepressant effect at low doses than classical compounds. A study examined the efficacy and rapidity of action of sulpiride associated to paroxetine in comparison with paroxetine alone.
In a 12-week open-label trial, 41 patients with major depressive disorder were randomly assigned to 10 - 40 mg/d of paroxetine or 10 - 40 mg/d of paroxetine plus 100 mg/d of sulpiride. Assessment of efficacy used the Montgomery-Asberg Depression Rating Scale (MADRS), the 17-item Hamilton Rating Scale for Depression (HRSD), the Zung self-rating Depression Scale (ZDS), and adverse events were monitored.
The completion rate was 82.5% (33/41 patients). Both treatments showed significant improvement for the MADRS, HRSD, and ZDS total scores. However, in the combined treatment group the change in the total scores of the three scales was significantly superior to the monotherapy group from week 1 through to the end of the study. Significantly shorter median times to response were observed in the responders of the combination treatment (2 weeks) than in those of the monotherapy (6 weeks) . There was no difference in the emergence of side effects in both groups.
This study has shown the utility of combining sulpiride with paroxetine for treating patients with major depressive disorder. Not only was the efficacy of the combined treatment superior at the study end point but the time to achieve response was significantly more rapid.
Uchida H, Takeuchi H, Suzuki T, Nomura K, Watanabe K, Kashima H. Combined treatment with sulpiride and paroxetine for accelerated response in patients with major depressive disorder. J Clin Psychopharmacol 2005, 25:545-551.

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