Users of the acne drug isotretinoin do not experience an increased risk of suicide, according to a recent meta-analysis, but may actually have a lower risk of suicide attempts two to four years after treatment.
Of the 25 studies included in the analysis, which encompassed 1 625 891 participants, the one-year absolute risk of completed suicide, suicide attempt, suicide ideation and self-harm among isotretinoin users was less than 0.5% each, while depression risk was 3.83%.
Also known by the brand names Roaccutane and Reticutan, the drug is an effective treatment for severe acne or when there is a risk of permanent scarring – and was not, said the researchers, associated with a relative risk for all psychiatric disorders.
The study (published in JAMA Dermatology) was led by researchers from Yong Loo Lin School of Medicine at the National University of Singapore and the National Skin Centre and Skin Research Institute, also in Singapore.
A potential link between isotretinoin and psychiatric disorders – including suicide – has been the subject of considerable debate, with conflicting findings in the literature. While some studies have suggested its use may be linked to suicide and psychiatric disorders, others have found no such association.
Still, reports Medpage Today, the perceived risk resulted in a “black box” warning for suicide, depression, aggression and psychosis from the FDA in 2005.
Given the ongoing debate – and the continued widespread use of isotretinoin –the meta-analysis sought to provide a comprehensive assessment of the absolute risk, relative risk, and risk factors for suicide and psychiatric disorders among users.
The goal was to provide fresh insight into potential risks associated with the medication and, in turn, to help guide clinical practice in the management of acne vulgaris.
Key findings
The results suggested a low absolute risk and no increased relative risk of suicide and psychiatric disorders among patients, however, a psychiatric history was associated with an increased risk of suicide attempt and psychiatric disorders among isotretinoin users, while a higher cumulative dose of isotretinoin was associated with a lower risk of suicide attempt.
Further, the meta-analysis showed that 4.57% of isotretinoin users developed a psychiatric disorder over a one-year period. The one-year absolute risk of self-harm, suicide ideation, suicide attempt, and completed suicide were each less than 0.5%.
The pooled one-year absolute risk of suicide attempt was 0.14%, which is lower than the one-year absolute risk of suicide attempts in adolescents reported in separate studies.
Underlying potential explanations
The relationship among acne, isotretinoin and psychiatric disorders is complex. Prior studies have provided strong evidence for a direct causal relationship between the drug and mood changes in rare individuals, due to certain biological effects on the central nervous system.
However, isotretinoin may also improve mood in many users as a result of improved acne and self-image. This is consistent with the findings of the current meta-analysis.
While the findings are reassuring, clinicians should remain vigilant and provide counselling for rare idiosyncratic mood changes that could increase the risk of suicide.
Although isotretinoin appears to be safe at the population level, a holistic psychodermatologic approach to care is recommended, as is monitoring patients for signs of mental distress during treatment.
Study details
Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users
Nicole Kye Wen Tan, Adelina Tang, Neil Chen Yi Lun MacAlevey et al.
Published in JAMA Dermatology on 29 November 2023
Abstract
Importance
Isotretinoin is hypothesised to contribute to the development of psychiatric disorders, but the epidemiological association and risk factors associated with psychiatric disorders among 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
Randomised 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 two to four years after 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.
JAMA Dermatology article – Risk of Suicide and Psychiatric Disorders Among Isotretinoin Users (Open access)
Medpage Today article – Isotretinoin and Suicide Risk: The Latest Findings (Open access)
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