No link between isotretinoin use, suicide risk, psych disorders

In a meta-analysis conducted by researchers from the National University of Singapore, isotretinoin use was not associated with increased risk of suicide or psychiatric conditions.

“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,” said the researchers.

“[Our study showed that] isotretinoin users do not have increased risk of suicide or psychiatric conditions … In fact, our findings suggest that isotretinoin may be associated with a lower risk of suicide attempt at 2–4 years following treatment,” they continued.

After adjusting for age, the likelihood of suicide attempts was lower among isotretinoin users compared with nonusers at 2 years (risk ratio [RR], 0.92), 3 years (RR, 0.86), and 4 years (RR, 0.85) following treatment. [JAMA Dermatol 2024;160:54-62]

Moreover, there was no association between isotretinoin use and suicide attempts during treatment (RR, 0.84), as well as at 6 months (RR, 1.14), 1 year (RR, 1.15), 5 years (RR, 0.85), and 10 years (RR, 1.04) following treatment.

Isotretinoin use was also not tied to a higher risk of all psychiatric disorders (RR, 1.08), depression (RR, 1.46), anxiety (RR, 0.97), psychotic disorders (RR, 0.80), and sleep disorders (RR, 1.61).

Of note however, isotretinoin users with a psychiatric history have a greater likelihood of developing incident psychiatric disorders (incidence rate ratio, 1.60) and were more likely to attempt suicide (odds ratio, 18.21).

Nonetheless, the 1-year pooled absolute risk of completed suicide, suicide attempt, suicide ideation, and self-harm were less than 0.5 percent each.

Relevant data were extracted from 24 studies that included a total of 1,625,891 participants. The average age of participants ranged between 16 and 38 years.

Black box warning

Isotretinoin is a common prescription medication for severe acne vulgaris that has been correlated with suicide and psychiatric disorders, including depression and anxiety. [Dermatoendocrinol 2009;1:162-169; J Affect Disord Rep 2021;6:100230] “[This] has resulted in a black box warning for suicide, depression, aggression, and psychosis issued by the US FDA in 2005,” the researchers noted.

“The potential link between isotretinoin and psychiatric disorders has been the subject of considerable debate, with conflicting findings in literature,” they continued. [J AmAcad Dermatol 1990;22:1112-1114; Pharmacopsychiatry 2007;40:128; Int J Epidemiol 2019;48:1623-1635; J Affect Disord 2022;296:277-282]

With the widespread use of isotretinoin and its potentially negative effect on mental health, it is thus imperative to clarify the link between its use and psychiatric disorders.

The results of the meta-analysis show that there is no epidemiological evidence to suggest an increased relative risk of suicide or psychiatric conditions among isotretinoin users at a population level.

“While these findings are reassuring, clinicians should continue to practice holistic psycho-dermatologic care and monitor patients for signs of mental distress during isotretinoin treatment,” the researchers concluded.

They called for further investigation to identify risk factors for psychiatric disorders among isotretinoin users, noting that “insights from future studies may guide clinicians in balancing the benefits and potential risks of prescribing isotretinoin treatment with improved patient outcomes.”