Combined Treatment With Sulpiride and Paroxetine for Accelerated Response in Patients With Major Depressive Disorder

Abstract

Although serotonin reuptake inhibitors are recommended as first-line agents for major depressive disorder, delayed onset of action is problematic, and faster effective treatment is needed. Sulpiride, a dopamine-mediated agent, has been reported to show faster antidepressant efficacy, and we examined the efficacy of adjunctive sulpiride in combination with paroxetine (PAX), compared with PAX alone, to clarify whether the combined treatment exerts faster effect. Forty-one major depressive disorder patients were enrolled in this 12-week open-label trial and were randomly assigned to a PAX (10-40 mg/d) or a PAX (10-40 mg/d) plus sulpiride (100 mg/d) group. Assessments included the Montgomery-Asberg Depression Rating Scale, the 17-item Hamilton Rating Scale for Depression, and the Zung Self-rating Depression Scale on an intent-to-treat basis, and safety was also monitored. Thirty-three patients completed the study. Both PAX + sulpiride and PAX treatments showed a mean reduction in the total Montgomery-Asberg Depression Rating Scale score of 34.4 to 5.6 and 32.2 to 10.4, respectively (P < 0.001). The combined treatment group had a significantly superior outcome in terms of the change in the total Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale for Depression, and Zung Self-rating Depression Scale scores between week 1 and the study end point (P < 0.05). Median times to response among responders alone for the combined treatment and monotherapy were 2 and 6 weeks, respectively. Both treatments were well tolerated, with no clinically significant differences in safety measures except for an elevation of prolactin in the combined treatment group. The combination treatment may be a safe and effective strategy for accelerating antidepressant response.

Activation of Dopamine D2 Receptor Is Critical for the Development of Form-Deprivation Myopia in the C57BL/6 Mouse

“…All of these D2R antagonists also appear to interact with other neurotransmitter receptors and at multiple sites in reducing depression and psychosis in humans. 28 These mixed results in relation to FDM likely reflect the complexity of D2R actions in the retina, depending on different basal DA levels and the partial specificity of many D2R drugs. Therefore, the exact role of D2R in the development of FDM remains to be critically evaluated.…”

Should adjunctive antipsychotic treatment be continued in remitted patients with depression?

“…The finding suggests that adjunctive sulpiride may be safely withdrawn in remitted depression. Taken together with the findings in the published reports, 1 although the adjunctive antipsychotic treatment may enhance antidepressant effects, discontinuation of an additional antipsychotic drug may need to be considered in remitted patients with major depressive disorder. These preliminary findings should be tested in larger samples.…”

“…WHILE ANTIPSYCHOTICS ARE suggested to be useful as an augmentation strategy for the treatment of depression, 1 they are also associated with metabolic disturbances such as prolactin elevation, which could result in amenorrhea and decreased bone density 2 . This notwithstanding, few studies have evaluated the effects of their discontinuation after achieving remission, which is the goal of treatment.…”

“…To minimize these side‐effects, we investigated if an adjunctive antipsychotic, sulpiride, could safely be discontinued following remission with sulpiride and paroxetine combination therapy. This study was an extension of the 12‐week clinical trial 1 and was approved by the institutional review board at participating sites. All participants provided their written informed consent.…”

Low-Dose Amisulpride and Elevation in Serum Prolactin

“…For example, other authors 8,10 have reported prolactin elevation with low-dose amisulpride. Prolactin elevation has also been reported with low doses of sulpiride 9,12 and levosulpiride. 7 Finally, dose-dependent prolactin elevation and greater prolactin elevation in women than in men has been described with other antipsychotic drugs, such as paliperidone, as well.…”