Psychiatric Adverse Events in Patients Taking Isotretinoin as Reported in a Food and Drug Administration Database From 1997 to 2017

IMPORTANCE Isotretinoin is a highly effective medication for severe acne. Although no causal link between isotretinoin and psychiatric adverse effects has been established, widespread media reporting of depression and suicidality with use of isotretinoin have raised concerns in both patients and clinicians and generated numerous cases of costly litigation. OBJECTIVE To evaluate reports of psychiatric adverse events associated with isotretinoin use submitted to the US Food and Drug Administration from January 1, 1997, through December 31, 2017. DESIGN, SETTING, AND PARTICIPANTS This retrospective study evaluated reports of psychiatric adverse events with isotretinoin as the primary suspect drug in the US Food and Drug Administration's Adverse Event Reporting System from 1997 through 2017. Publicly available data on number of patients enrolled in the iPLEDGE program were used to calculate rates of completed suicide per 100000 patients enrolled in iPLEDGE in 2009 and 2010. All data were analyzed between July 1, 2018, and January 31, 2019. MAIN OUTCOMES AND MEASURES The main outcomes were frequency and type of psychiatric adverse events in patients taking isotretinoin. Secondary analyses were stratification by age and sex and evaluation of completed suicide rates. RESULTS Between 1997 and 2017, 17829 psychiatric adverse events with isotretinoin use were reported to the US Food and Drug Administration, with depressive disorders, emotional lability, and anxiety disorders reported most frequently. Of these events, 8936 (50.1%) were reported among men and 8362 (46.9%) among women; the sex of the individual was not reported for 531 events (3.0%). Of the 13553 reports that included patient age, the mean (SD) age was 22.1 (8.6) years. More than half (52.5%) of all events occurred in 10- to 19-year-old individuals. Whereas depression and anxiety were reported equally between sexes, eating disorders were more common in females (58 of 85 [68.2%]), while attention-deficit/hyperactivity disorder (55 of 83 events [66.3%]) and completed suicides (290 of 368 [78.8%]) were more common in males. The rates of completed suicide were 8.4 and 5.6 suicides per 100000 patients enrolled in iPLEDGE in 2009 and 2010, respectively. CONCLUSIONS AND RELEVANCE Although depressive disorders and suicidality were frequently reported with isotretinoin use, these reports must be considered in the context of elevated rates of depression and suicide among patients with acne at large. These data suggest that the rate of completed suicide in patients taking isotretinoin may be lower than that of the general US population. Many psychiatric adverse events unrelated to depression and suicidality were also reported, but it is unclear if they were a result of isotretinoin therapy. Although no causal link between isotretinoin and psychiatric risk has been established, patients taking the drug appear vulnerable to psychiatric concerns. Mandated monthly iPLEDGE visits may provide an opportunity to screen patients for psychiatric conditions and improve outcomes.