Isotretinoin Therapy for Acne Not Linked to Neurologic Adverse Effects

Isotretinoin therapy among patients with acne is not associated with an increased risk for migraine, fibromyalgia, multiple sclerosis, or neuropathy, according to a research letter published in Journal of the American Academy of Dermatology.

Researchers conducted a retrospective cohort study using data from the Truven Health MarketScan Commercial Claims Database collected from January 1, 2017 to December 31, 2020. They compared the risk for migraine, fibromyalgia, multiple sclerosis, and neuropathy among patients with acne treated with isotretinoin vs tetracycline-class antibiotics such as doxycycline, minocycline, and sarecycline. The database included individuals from more than 160 large employers and health insurance plans in the United States.

Eligible participants had at least 1 diagnosis of acne, received at least 60 days of treatment with isotretinoin or tetracycline-class antibiotic, no previous encounters for the outcomes of interest, and no prior physician visits for depression or anxiety.

The 2 cohorts were matched 1:1 according to age, sex, and combined oral contraceptive use, which was a possible confounder for migraine outcomes. Codes from International Classification of Diseases, Tenth Revision, (ICD-10) were used to identify incident migraines, fibromyalgia, multiple sclerosis, and neuropathy, and Cox proportional hazards regression was performed. The participants were followed until they had an outcome of interest or were no longer included in the database.

A total of 26,380 participants who initiated isotretinoin were matched with 26,380 participants who received a tetracycline-class antibiotic. The participants were a mean age of 25.3 (SD 8.8) years, and 57.7% were women. The mean (SD) follow-up was 592.9 (397.2) days in the isotretinoin group and 604.8 (398.66) days in the tetracycline group.

Patients who were treated with isotretinoin were not at increased risk for migraine (hazard ratio [HR], 0.91; 95% CI, 0.83-1.01), fibromyalgia (HR, 1.00; 95% CI, 0.98-1.01), multiple sclerosis (HR, 0.92; 95% CI, 0.43-1.96), or neuropathy (HR, 0.93; 95% CI, 0.66-1.32), compared with those treated with tetracycline-class antibiotics.

Study limitations include the retrospective design and potential for unmeasured confounding.

“[I]sotretinoin is not associated with increased risk of migraine, fibromyalgia, multiple sclerosis, or neuropathy. While case series and registries such as the FDA Adverse Event Reporting System are an important source of risk signals in need of further study, these findings highlight the importance of cohort studies to assess whether there is additional evidence to support causality,” the letter author concludes.