Meta-Analysis: Suicide Risk Not Increased With Isotretinoin

Isotretinoin users have no increased risk of suicide or psychiatric conditions on a population level, a meta-analysis of 25 studies that included 1.6 million patients suggests.

Instead, those who are treated with the drug for severe acne may have a lower risk of suicide attempts 2-4 years after treatment, wrote the authors, led by Nicole Kye Wen Tan, MBBS, of Yong Loo Lin School of Medicine at the National University of Singapore. The results were published online in JAMA Dermatology.

The analysis showed that the 1-year absolute risk from between two and eight studies of suicide attempts, suicidal ideation, completed suicides, and self-harm were each less than 0.5%. For comparison, the absolute risk of depression was 3.83% (95% confidence interval [CI], 2.45-5.93; I² [measuring heterogeneity] = 77%) in 11 studies.

Less likely to attempt suicide

Isotretinoin users were less likely than were nonusers to attempt suicide at 2 years (relative risk [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.

Additionally, isotretinoin was not linked with the risk of "all psychiatric disorders" (RR, 1.08; 95% CI, 0.99-1.19; I² = 0%).

Among the study limitations, the authors noted that because of the widespread claims that isotretinoin can affect mental health, it is plausible that patients at high risk of psychiatric illness were less likely to be treated with isotretinoin in the first place, which could have resulted in underestimating psychiatric risks in the observational studies.

"Two things can be true"

John S. Barbieri, MD, MBA, assistant professor at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at the Brigham and Women's Hospital in Boston, who was not involved with this research, said the study helps confirm what he and many others have long thought.

The results of the meta-analysis show that "two things can be true, which often gets lost with isotretinoin," he said. At a population level, isotretinoin improves mental health but on the individual level, it may cause rare side effects that harm mental health, he added.

In making decisions on the use of isotretinoin, he continued, "we should feel reassured that the likely outcome is improved mental health compared to other alternatives that we have, but at the same time we should be vigilant about monitoring a patient's mental health while they are being treated with isotretinoin."

He said that this topic draws extreme views on social media, with people who want the drug off the market and those who discount concerns altogether.

"I think the real answer is a little more in the middle," he said. "We still have to be thoughtful when we use it."

Because outcomes such as suicide in patients on isotretinoin are not common, Dr. Barbieri said, smaller studies individually have lacked precision on effect. The size of this meta-analysis helps add confidence in the results, he said.

In addition, this study can help clinicians point to numbers when they talk with their patients about benefits and risks, he said.

What a meta-analysis might miss

In an accompanying editorial, Parker Magin, PhD, of the School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia, and Shaun Prentice, PhD, of the School of Psychology, Faculty of Health and Medical Sciences at the University of Adelaide, South Australia, wrote that though the work by Tan et al. is "broadly reassuring," they have concerns about the patients a meta-analysis might miss.

They wrote that other studies have shown evidence both of biological plausibility that isotretinoin may be linked with psychiatric effects and that it may cause these side effects. "One could conclude that it is plausible that isotretinoin has markedly adverse, idiosyncratic psychiatric effects in a small minority of individual patients," they wrote. "It is also plausible that these presumably rare occurrences are not detectable in studies where the majority of patients experience no adverse psychiatric outcomes or even positive outcomes."

Far from the "final word"

Dr. Magin and Dr. Prentice pointed out that while the study adds to the literature on his topic, the relationship between acne, psychiatric conditions, and isotretinoin is complex and thus these findings "are far from the final word."

Randomized, controlled trials have limited use in this area and observational studies are always susceptible to bias, they noted. "Clinicians, though, can take some degree of further reassurance from this extension of the literature around the psychiatric sequelae of isotretinoin," they wrote.

Senior author Hazel Oon, MD, of the National Skin Centre, Singapore, disclosed ties with AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, and Pfizer. No other author disclosures were reported. Dr. Barbieri is an associate editor at JAMA Dermatology and is cochair of the American Academy of Dermatology Acne Guidelines Work Group.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.