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


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 trial1 and was approved by the institutional review board at participating sites. All participants provided their written informed consent.

Fifteen subjects with major depressive disorder (according to the Diagnostic and Statistical Manual of Mental Disorders) who achieved remission (i.e. a total score in the Montgomery–Asberg Depression Rating Scale [MADRS]3 of 8 or less) with the combined treatment of sulpiride and paroxetine in the parental study were approached; of these, eight subjects (mean ± SD age=38 ± 16 years, 4 men, mean ± SD dose of paroxetine = 32.5 ± 8.9 mg/day) participated in this 8-week open-label study. No clinical or demographic difference was found between these eight participants and the other seven with major depressive disorder. Sulpiride (50 mg twice daily) was abruptly discontinued while other medications, including paroxetine, were kept constant throughout the study period.

Seven out of eight subjects maintained remission at week 8 while one subject withdrew from the study because this subject wanted to receive sulpiride again. This subject did not provide clinical data at the time of dropout, and therefore the data from the remaining seven subjects were analyzed. No change in the MADRS or the Zung Self-Rating Depression Scale4 total scores was observed (mean ± SD, 3.0 ± 3.9 to 3.5 ± 5.2 and 35.1 ± 9.4 to 34.8 ± 8.7, respectively; both P > 0.05 by Wilcoxon signed ranks test). A mean ± SD serum prolactin level was decreased from 121.4 ± 104 ng/ml to 10.8 ± 9.5 ng/ml (P < 0.01 by Wilcoxon signed ranks test).

The finding suggests that adjunctive sulpiride may be safely withdrawn in remitted depression.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.

Received 8 July 2008; revised 2 August 2008; accepted 5 August 2008.