Methylphenidate hydrochloride as an antidepressant: controversy, case studies, and review

The use of psychostimulants as antidepressants remains controversial in the field of psychiatry. While methylphenidate hydrochloride (MPH) and dextroamphetamine (DA) are often considered to be equivalent drugs, differences in their neurobiologic mechanism of action may account for different clinical response patterns. Hence, clinical trials and literature reviews that examine the antidepressant efficacy of psychostimulants without distinguishing between MPH and DA may reach inaccurate conclusions. This paper is a critical review of controlled and uncontrolled studies examining the use of MPH as an antidepressant. We discuss the methodologic limitations of existing placebo-controlled trials that have reached mixed conclusions about the efficacy of MPH as an antidepressant. These studies are offset by uncontrolled open trials and clinical case reports that endorse the drug's effectiveness in alleviating depressive symptoms. The series of patients we treated with MPH demonstrates the safety and efficacy of this drug in alleviating depressive symptoms in the medically ill elderly with a variety of mood disorders. Reviewing these six cases and balancing the positive and negative reports in the literature, we provide practical guidelines for identifying patients who are potential candidates for treatment with MPH.