Isotretinoin and adverse neuropsychiatric outcomes: retrospective cohort study using routine data

Background Severe neuropsychiatric outcomes have been reported in individuals exposed to isotretinoin, but the evidence is inconclusive and complicated by several methodological limitations. Objectives To establish and quantify the association between isotretinoin use for acne and 1-year incident neuropsychiatric adverse outcomes. Methods A propensity score-matched cohort study of electronic medical records between the years 2013 and 2019 with patients followed up for 1 year after their index dispensed prescription was conducted. The database included over 12 million patients aged 12-27 years. We analysed data for individuals with acne in this age range with a dispensed prescription for isotretinoin or a control prescription. Outcomes included diagnoses of any incident sleep or mental health disorder, or nonfatal self-harm within 1 year of the index prescription. Results We included 30 866 patients prescribed isotretinoin for their acne, 44 748 prescribed oral antibiotics, 108 367 prescribed topical anti-acne agents and 78 666 patients with acne but without an anti-acne prescription. After propensity score matching for baseline confounders, the odds ratio (OR) for any incident neuropsychiatric outcomes in patients with acne exposed to isotretinoin was 0 center dot 80 [95% confidence interval (CI) 0 center dot 74-0 center dot 87] compared with those on oral antibiotics; 0 center dot 94 (95% CI 0 center dot 87-1 center dot 02) compared with those using topical anti-acne medicines; and 1 center dot 06 (95% CI 0 center dot 97-1 center dot 16) compared with those without a prescription for anti-acne medicines. Patients exposed to isotretinoin experienced significantly more incident physical symptoms than patients in any of the three comparison cohorts. Conclusions Isotretinoin was not independently associated with excess adverse neuropsychiatric outcomes at the population level. When monitoring potential adverse outcomes during isotretinoin treatment, clinicians should also consider the high mental health burden associated with treatment-resistant acne and the potential contribution of physical side-effects of prescribed medication on mental health.