Isotretinoin and neuropsychiatric side effects: Continued vigilance is needed

•Isotretinoin is higly effective for the treatment of acne.•Isotretinoin is in the family of compounds called retinoids that include the active form of Vitamin A.•Isotretinoin is an isomer of the active form of Vitamin A, retinoic acid, and both are highly teratogenic.•A number of cases of neuropsychiatric side effects including depression, suicidality, violence, aggression, anxiety and psychosis have been associated with isotretinoin use with evidence for a causal rol.•Isotretinoin use has declined in recent years but considerable caution is needed in its use. Isotretinoin (13-cis-retinoic acid, marketed under the names Accutane, Roaccutane, and others) is an effective treatment for acne that has been on the market for over 30 years, although reports of neuropsychiatric side effects continue to be reported. Isotretinoin is an isomer of the active form of Vitamin A, 13-trans-retinoic acid, which has known psychiatric side effects when given in excessive doses, and is part of the family of compounds called retinoids, which have multiple functions in the central nervous system. The literature was reviewed in pubmed and psychinfo for research related to isotretinoin and neuropsychiatric side effects including depression, suicidal thoughts, suicide, mania, anxiety, impulsivity, emotional lability, violence, aggression, and psychosis. Multiple case series have shown that successful treatment of acne with isotretinoin results in improvements in measures of quality of life and self esteem However, studies show individual cases of clinically significant depression and other neuropsychiatric events that, although not common, are persistent in the literature. Since the original cases of depression were reported to the United States Food and Drug Administration, numerous cases have been reported to regulatory agencies in the United Kingdom, France, Ireland, Denmark, Australia, Canada, and other countries, making isotretinoin one of the top five medications in the world associated with depression and other neuropsychiatric side effects. Clinicians are advised to warn patients of the risks of neuropsychiatric side effects with isotretinoin which may arise from the medication itself, and not just as a side effect of acne or youth.