Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users: A Meta-Analysis

Abstract

Importance: Isotretinoin is hypothesized to contribute to the development of psychiatric disorders, but the epidemiological association and risk factors associated with psychiatric disorders among isotretinoin users remain unclear.

Objective: To clarify the absolute and relative risk and risk factors associated with suicide and psychiatric disorders among isotretinoin users.

Data sources: PubMed, Embase, Web of Science, and Scopus were searched from inception until January 24, 2023.

Study selection: Randomized trials and observational studies were selected if they reported the absolute risk, relative risk, and risk factors for suicide and psychiatric disorders among isotretinoin users.

Data extraction and synthesis: Relevant data were extracted and risk of bias was evaluated at the study level using the Newcastle-Ottawa Scale. Data were pooled using inverse variance-weighted meta-analyses. Heterogeneity was measured using the I2 statistic, and meta-regression analyses were performed.

Main outcomes and measures: Absolute risk (percentage), relative risks (risk ratios [RR]), and risk factors (RR) of suicide and psychiatric disorders among isotretinoin users.

Results: A total of 25 studies including 1 625 891 participants were included in the review and 24 in the meta-analysis. Among the included studies, participants' average age ranged from 16 to 38 years, and distribution by sex ranged from 0% to 100% male. The 1-year pooled absolute risk from between 2 and 8 studies of completed suicide, suicide attempt, suicide ideation, and self-harm were each less than 0.5%, while that of depression was 3.83% (95% CI, 2.45-5.93; I2 = 77%) in 11 studies. Isotretinoin users were less likely than nonusers to attempt suicide at 2 years (RR, 0.92; 95% CI, 0.84-1.00; I2 = 0%), 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%), and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment. Isotretinoin was not associated with the risk of all psychiatric disorders (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%). Study-level meta-regression found that studies with participants of older age reported lower 1-year absolute risk of depression, while those with a higher percentage of male participants reported a higher 1-year absolute risk of completed suicide.

Conclusions and relevance: The findings suggest that at a population level, isotretinoin users do not have increased risk of suicide or psychiatric conditions but may instead have a lower risk of suicide attempts at 2 to 4 years following treatment. While these findings are reassuring, clinicians should continue to practice holistic psychodermatologic care and monitor patients for signs of mental distress during isotretinoin treatment.

Figure 1.. PRISMA Flow Diagram of Study Selection

Figure 2.. Random-Effects Meta-Analyses of the 1-Year Absolute Risk of Completed Suicide, Suicide Attempt, Suicide Ideation, and Self-Harm

Diamonds represent the estimated pooled absolute risk for each meta-analysis; gray box sizes, the relative weight apportioned to studies in each meta-analysis.

Figure 3.. Random-Effects Meta-Analyses of the 1-Year Absolute Risk of Depression, Mood Disorder, and Bipolar Disorder

Diamonds represent the estimated pooled absolute risk for each meta-analysis; gray box sizes, the relative weight apportioned to studies in each meta-analysis.

Figure 4.. Random-Effects Meta-Analyses of the Association Between Isotretinoin Use and Relative Risk of Suicide Attempt During Treatment and at 6 Months and 1, 2, 3, 4, 5, and 10 Years Following Treatment

Diamonds represent the estimated pooled relative risk ratio (RR) for each meta-analysis; gray box sizes, the relative weight apportioned to studies in each meta-analysis.