Exploring Relationship Between Oral Isotretinoin Use and Psychiatric Symptoms

A stressed woman examining her skin in the mirror
Are patients with acne and are treated with isotretinoin or antibiotics more likely to have psychiatric disorders?

The relationship between oral isotretinoin and psychiatric disturbances in patients with acne was explored in study data published in the Journal of the American Academy of Dermatology. Compared with the general population, patients receiving oral isotretinoin were substantially less likely to engage in suicidal behavior. However, the diagnosis of psychiatric disorders appeared slightly more common in patients prescribed isotretinoin compared with patients prescribed antibiotics or control participants without acne, the study investigators noted.

To better inform the relationship between oral isotretinoin and psychiatric disturbances, investigators conducted a retrospective cohort study using insurance claims data from the IBM MarketScan Database for the years 2011 through 2017. The cohort study enrolled patients aged 12 to 35 years who received either oral isotretinoin or oral antibiotics for the treatment of acne. A control cohort of patients aged 12 to 35 years without acne was also assembled. Patients with acne were followed from 12 months before acne treatment initiation to 12 months after treatment. The primary outcomes were psychiatric disorders and/or suicidal behavior, identified through diagnostic codes and prescription records for psychiatric medications. Multivariable logistic regression was used to estimate the odds ratios (ORs) of psychiatric disturbances in the isotretinoin group compared with the oral antibiotics group and the control population. Models were adjusted for age, sex, and number of days enrolled in the study cohort.

The study cohort comprised 72,855 patients with acne, among whom 30,012 (41.2%) were in the isotretinoin group and 42,848 (58.8%) assigned to the antibiotics group. The control cohort comprised 8,123,436 individuals without acne. Overall, psychiatric disorders were present in 23.1% of the isotretinoin group, 24.1% of the antibiotics group, and 28.7% of the general population. Of the patients prescribed isotretinoin who had a psychiatric diagnosis, 57% were diagnosed before treatment and 43% were diagnosed after initiation of treatment. Suicidal behavior was less prevalent in the antibiotics group (0.67%) and the isotretinoin group (0.60%) compared with the general population (0.90%). In adjusted regression models, patients in the general population were at increased risk for suicidal behavior compared with the isotretinoin group (OR, 1.47; 95% CI, 1.27-1.70; P <.001). Risk for suicidality was not different in the antibiotics and isotretinoin groups (P =.973). However, compared with the isotretinoin group, the odds of diagnosis with any psychiatric disorder was slightly reduced in both the antibiotics-only group (OR, 0.88; 95% CI, 0.85-0.91) and the general population (OR, 0.87; 95% CI, 0.84-0.89) (both P <.001).

The pre-treatment prevalence rates of suicidality were 0.22% and 0.24% in the isotretinoin and antibiotic groups, respectively. During treatment, prevalence of suicidal behavior was nominally lower in the isotretinoin group compared to the antibiotics group (0.10% vs 0.26%; P =.0709). In the year after treatment initiation, however, the prevalence of suicidal behavior was greater in the isotretinoin group vs antibiotic group (0.34% vs 0.20%; P =.0006).

Per these data, isotretinoin was not associated with substantially increased risk for suicidal behavior compared to general population. Psychiatric symptoms, however, appeared slightly more likely in the isotretinoin group compared to the antibiotics group and control participants. The mechanisms which underpin these associations remain unclear, the researchers acknowledged. The known relationship between acne itself and psychiatric symptoms makes it difficult to parse out the true effects of isotretinoin.

Additional study limitations include the use of a private insurance database, which excludes patients with public insurance or no insurance.

“Compared to the general population, acne patients prescribed isotretinoin were less likely to engage in suicidal behavior,” investigators wrote. “Further exploration is warranted into the slight increase in suicidal behavior seen in isotretinoin patients one year after therapy.”

Disclosure: One study author declared affiliations with the pharmaceutical industry.

Please see the original reference for a full list of authors’ disclosures.


Ugonabo N, Love E, Wong PW, et al. Psychiatric disorders and suicidal behavior in patients with acne prescribed oral antibiotics versus isotretinoin: analysis of a large commercial insurance claims database. J Am Acad Dermatol Published online March 13, 2021. doi: 10.1016/j.jaad.2021.01.107.