Key Psychiatric Adverse Events Associated With Isotretinoin Use Are Identified

Patients treated with isotretinoin, particularly patients treated for acne, may experience psychiatric adverse events (AEs) that require focused monitoring during treatment, including psychosis, mood disturbances, suicide, and self-injury, according to study findings published in the Journal of the American Academy of Dermatology.

Conflicting reports suggest isotretinoin use may increase or decrease depression and suicide risk. Isotretinoin prescriptions are increasing, as the treatment is recommended for non-acne dermatologic conditions in addition to being a first-line therapy for severe acne. Beyond the possibilities of depression and suicide, it remains uncertain which AEs should be prioritized for monitoring during isotretinoin use. Therefore, investigators identified psychiatric AEs associated with higher reporting frequencies (positive signals) for isotretinoin and assessed the positive signals to identify which psychiatric AEs need priority monitoring.

The investigators conducted a retrospective cross-sectional study analyzing psychiatric AEs reported in the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to June 2024. Among the total medications included in FAERS with reports of psychiatric AEs, isotretinoin was ranked 31 by number of reporters. Common co-medications include antidepressants, antipsychotics, and contraceptives. The AEs were categorized based on clinical significance as weak, moderate, or strong, with moderate or higher clinical priority levels typically indicating important AEs warranting focused monitoring.

Among thousands of isotretinoin-related psychiatric AEs (N=19,412) reported by 12,312 patients, a total of 96 positive signals for psychiatric AEs were identified. The most frequently reported psychiatric AEs among the total events were depression (47.5%), suicidal ideation (17.7%), anxiety (15.0%), and altered mood (11.7%). The frequency of psychiatric AEs reported by patients who used isotretinoin was higher than those who did not use isotretinoin across the database (reporting odds ratio [ROR], 3.30; 95% CI, 3.25-3.35).

The investigators identified 50 positive signals that each included more than 20 cases. Important signals (n=25) were identified by moderate clinical priority and were grouped into affective disorder, anxiety disorder, bipolar disorder, depressive disorder, mood change, psychosis, and suicide and self-injury. Suicide ideation (ROR, 11.16), completed suicide (ROR, 1.39), and major depression (ROR, 5.07) had the top priority scores.

Patients with acne vs patients without acne presented more important signals and had a higher relative frequency of psychiatric AEs. The median time-to-onset (TTO) was 80 days (interquartile range, 31-265) for moderate priority signals, displaying an early failure-type pattern (β, 0.55; 95% CI, 0.54-0.56) in the Weibull shape parameter analysis.

Study limitations include the cross-sectional design precluding establishment of causality, the inability to calculate actual incidence rates vs reported rates, and unaccounted-for confounding effects of acne severity.

“Our study broadens the scope of psychiatric adverse events requiring focused monitoring during isotretinoin use, especially among acne patients, highlighting mood disturbances, suicide and self-injury, and psychosis,” the investigators concluded. They added, “Dermatologists should prioritize monitoring these psychiatric adverse events throughout early isotretinoin treatment, conduct regular follow-ups, and educate patients on recognizing and reporting symptoms.”

This article originally appeared on Dermatology Advisor