Isotretinoin may not increase adverse mental health outcomes
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Patients who take isotretinoin for severe acne did not show signs of adverse neuropsychiatric impacts compared with those who took antibiotics for acne, according to a study.
“There has been a concern that isotretinoin could have a negative impact on mental health,” Seena Fazel, MD, FRCPsych, professor of psychiatry at the University of Oxford, and Tapio Paljarvi, PhD, of the department of forensic psychiatry at the University of Eastern Finland, told Healio in an email correspondence. “This study, however, showed that isotretinoin medication was unlikely to be causing poor mental health. Accumulating evidence is now supporting this conclusion.”
Researchers completed a propensity score-matched cohort study of electronic medical records that included 30,866 patients who were prescribed isotretinoin, 44,748 patients prescribed oral antibiotics, 108,367 patients with acne prescribed topical anti-acne medications and 78,666 patients with acne without anti-acne medication.
Patients were propensity matched for baseline cofounders and the OR for neuropsychiatric diagnoses, including psychotic disorders, mood disorders, anxiety, dissociative, stress-related somatoform and other nonpsychotic mental disorders.
Acne diagnosis was associated with increased odds of incident adverse neuropsychiatric outcomes (OR = 1.46; 95% CI, 1.43-1.5) before controlling for severity or treatment type.
Patients exposed to isotretinoin had an odds ratio of 0.8 (95% CI, 0.74-0.87) compared with those on oral antibiotics, and an odds ratio of 0.94 (95% CI, 0.87-1.02) compared with those on topical anti-acne medications. In addition, the odds ratio of those on isotretinoin was 1.06 (95% CI, 0.97-1.16) compared with those without any acne prescriptions.
“We observed a consistent association between increasing acne severity as indicated by anti-acne treatment options and incidence of adverse neuropsychiatric outcomes, but the findings showed that isotretinoin exposure did not add to the risk of neuropsychiatric adverse outcomes over and above what was associated with oral antibiotics,” the authors wrote in the study.
Increased odds for nonfatal self-harm and a higher incidence of adverse neuropsychiatric outcomes were found in patients with prescriptions for oral antibiotics, but not isotretinoin.
“This study found that people who took isotretinoin medication had slightly better mental health than people who took oral antibiotics for acne,” Fazal and Paljarvi said in the email. “The current practice for additional mental health assessments before people are started on isotretinoin, which are recommended in some countries, can be reviewed in the light of this and related evidence. In monitoring potential adverse outcomes during isotretinoin treatment, clinicians should also consider the high mental health burden associated with treatment-resistant acne and the potential contribution of physical side effects of the prescribed medication on mental health.”
Perspective
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Although isotretinoin is a highly effective treatment for acne, there have been concerns that isotretinoin may be associated with increased risk of neuropsychiatric adverse events such as depression and suicide. However, it is important to consider that acne itself is also associated with an increased risk of mental health comorbidities. This study by Paljarvi and colleagues adds to a growing body of literature supporting that isotretinoin is not associated with an increased risk of neuropsychiatric adverse events, and in fact may be protective for those with moderate to severe acne. This intuitively makes sense as treating acne would be expected to improve neuropsychiatric symptoms associated with acne.
Unfortunately, patients with acne who are also suffering from depression or anxiety are often told that they are not candidates for isotretinoin due to these mental health comorbidities. The work by Paljarvi and colleagues as well as others in this area are helpful resources to educate our patients that depression related to acne may be a relative indication for treatment with isotretinoin, rather than a contraindication.
Nevertheless, this study is not without limitations. While we can be reassured that at a population level isotretinoin is not associated with increased risk of neuropsychiatric adverse events, it is still possible that individual patients may experience idiosyncratic side effects. In fact, small case series documenting positive dechallenge and rechallenge responses support that this may be the case. While we can reassure our patients that isotretinoin is expected to cause improved mood for most, it is prudent to educate the patient about this potential rare side effect and to monitor all patients with acne for potential neuropsychiatric comorbidities that are common in this population.
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