Study Examines Relationship Between Methylphenidate and Risk of Depression


Investigators observed higher levels of depression in children and adolescents with ADHD during MPH treatment.

Andrii Zastrozhnov/Adobe Stock

Andrii Zastrozhnov/Adobe Stock

A study found a temporal relationship between methylphenidate (MPH) exposure and risk of depression in children and teenagers with attention-deficit/hyperactivity disorder (ADHD).

The study aimed to test the clinical concern that MPH exposure may increase risk of depression, especially in children. To explore this, the investigators pulled claims data from the Health Insurance Review and Assessment Service database, looking at ADHD medication prescription, depression diagnosis, and antidepressant medication prescription between January 2007 and December 2016. They identified 43,259 individuals between the ages of 6 and 19 who had been diagnosed with ADHD between July and December 2007. Of these, 2330 individuals were deemed eligible for participation in the study. The investigators then conducted a self-controlled case series study examining the occurrence of depression in the participants when they were exposed to MPH compared to when they we were not exposed to MPH.1

They found an elevated risk of major depressive disorder (MDD) in participants during the 90 days prior to MPH exposure, with an incidence rate ratio of 12.12 (95% confidence interval; 10.06 to 14.61, p < 0.0001). The incidence rate ratio during MPH treatment was 18.06 with a 95% confidence interval of 16.67 to 19.56 (p < 0.0001), although the rate returned to baseline level after 31 days following the discontinuation of MPH treatment. For participants between ages 6 and 9 years, the incidence rate ratio was 13.11 (95% confidence interval of 9.58 to 17.95) during the 90 days before exposure to MPH and 17.7 (95% confidence interval of 15.6 to 20.08) during MPH treatment; this also returned to baseline level after MPH treatment was discontinued.1

The investigators concluded that, although the absolute risk of depression is low, it is a risk that clinicians should consider, particularly during the period immediately after MPH treatment begins.1 “Our findings suggest that use of methylphenidate medication in young people with ADHD is temporally associated with the emergence of depression,” they wrote. “With the increased global use of ADHD drugs, the benefits of methylphenidate should be carefully evaluated against the potential risk of depression in children and adolescents.”


1. Oh Y, Joung Y, Kim J. Association between attention deficit hyperactivity disorder medication and depression: a 10-year follow-up self-controlled case study. Clin Psychopharmacol Neurosci. 2022;20(2):320-329.

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