Psychostimulants in moderate to severe affective disorder: a systematic review of randomized controlled trials

Despite antidepressant therapy of appropriate trial duration and dose optimization, 50-60% of depressed patients have an adequate treatment response, whereas only 35-40% achieve remission. Psychostimulants have been suggested as potential candidates to promote acceleration of response and to alleviate residual symptoms of depression.

In this review results from randomized clinical trials (RCTs) exploring the efficacy of psychostimulants in the treatment of major depressive disorder (MDD) were analyzed to clarify the current empirically founded evidence for clinical approaches involving psychostimulants.

Literature research via PubMed retrieved 846 articles. 18 RCTs reporting on the use of psychostimulants in the treatment of adult patient populations, suffering from moderate-severe depression and having no other concomitant medical illnesses, were included in this review. 14 articles provided results for unipolar depression, two for bipolar depression, whereas two articles presented mixed samples of unipolar and bipolar patients.

Five different psychostimulants were evaluated: modafinil, methylphenidate, dexamphetamine, methylamphetamine and pemoline. Two studies examining modafinil demonstrated significant ameliorating characteristics pertaining to symptoms of depression. No clear evidence for the effectiveness of traditional psychostimulants in the therapeutic management of MDD was found. In general the quality of included trials was poor since the majority was of short-term duration, comprising relatively small sample sizes and some, especially older studies, were methodologically flawed.

Clearly larger well designed placebo-controlled studies with longer follow-up accompanied by evaluations of tolerance/dependence are warranted before psychostimulants can be recommended in routine clinical practice for the treatment of MDD.