There is no epidemiological evidence indicating a greater relative risk of psychiatric disorders or suicidality among users of isotretinoin at a population level, according to new findings.¹

These findings resulted from a recent meta-analysis conducted to assess the absolute and relative risk, as well as the related factors, of suicidality and psychiatric issues among patients prescribed isotretinoin using existing research.

This new analysis was led by Nicole Kye Wen Tan, from the Yong Loo Lin School of Medicine at the National University of Singapore. Tan and colleagues noted that prior to their analysis, there had been mixed findings with regard to whether or not psychiatric struggles among patients could be linked to use of isotretinoin.^2,3

“This study aims to provide a comprehensive and up-to-date assessment of the absolute risk, relative risk, and risk factors for suicide and psychiatric disorders among isotretinoin users with the hope of providing valuable insight into the potential risks associated with isotretinoin use and guiding clinical practice in the management of acne vulgaris,” Tan and colleagues wrote.

Background and Findings

The investigators’ meta-analysis adhered to a pre-established systematic review protocol registered with PROSPERO. They conducted comprehensive searches over a total of 4 databases and implemented a specified search strategy to isolate the necessary literature on the link between isotretinoin and psychiatric outcomes.

In addition to the research team’s database searches, they also used manual screening of article bibliographies. Research deemed to be eligible, including randomized clinical trials as well as observational research, were independently screened by 2 authors.

The team’s extraction of their data covered various study details, with the risk of bias being assessed by using the Newcastle-Ottawa Scale (NOS). The Grading of Recommendations, Assessment, Development, and Evaluations system was also used by the investigators to look at the quality of their evidence at the outcome level.

Notably, the research team found that data regarding race and ethnicity were shown to be inconsistently available and thus they did not collect it for the meta-analysis.

The investigators sought to assess the subjects’ absolute risk, their relative risks (risk ratios [RR]), and their risk factors regarding suicide and psychiatric disorders. Overall, the team’s comprehensive review and analysis ended up covering 25 studies and 1,625,891 total participants, with ages ranging from 16 - 38 years.

The team found that the subjects’ 1-year pooled absolute risk for completed suicide, attempts at suicide, suicidal ideation, and reported self-harm was shown to each be less than 0.5%, though that of depression was noted as being 3.83% (95% CI, 2.45-5.93; I2 = 77%) among 11 total studies.

Subjects using Isotretinoin ended up having a notably lower likelihood of suicide attempts at 2, 3, and 4 years following their reported treatments. The investigators also found that isotretinoin did not show a link with risk of all psychiatric disorders (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%).

The research team’s meta-regression indicated that research involving older subjects showed lower 1-year absolute risk of reported depression, though they found that those with a higher percentage of male subjects had a higher 1-year absolute risk of completed suicide.

The investigators did note, however, that a potential confounder could be that patients determined to be in the higher risk category of psychiatric illness may have also been less likely to be treated with isotretinoin given the treatment’s reputation. They acknowledged the necessity of future research.

“At present, few studies have explored the risk factors associated with suicide and psychiatric disorders among isotretinoin users, indicating a need for more research,” they wrote. “The insights from future studies may guide clinicians in balancing the benefits and potential risks of prescribing isotretinoin treatment with improved patient outcomes.”

References

1. ^{Tan NKW, Tang A, MacAlevey NCYL, Tan BKJ, Oon HH. Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users: A Meta-Analysis. JAMA Dermatol. Published online November 29, 2023. doi:10.1001/jamadermatol.2023.4579.}
2. ^{Scheinman PL, Peck GL, Rubinow DR, DiGiovanna JJ, Abangan DL, Ravin PD. Acute depression from isotretinoin. J Am Acad Dermatol. 1990;22(6 Pt 1):1112-1114. doi:10.1016/S0190-9622(08)81018-3.}
3. ^{Droitcourt C, Nowak E, Rault C, et al. Risk of suicide attempt associated with isotretinoin: a nationwide cohort and nested case-time-control study. Int J Epidemiol. 2019;48(5):1623-1635. doi:10.1093/ije/dyz093.}