Isotretinoin’s Relationship to Psychiatric Disorders

An elevated risk for suicidal ideation and a comparable risk for suicidal attempts is seen in patients with acne who are managed with isotretinoin vs patients with acne managed with oral antibiotics, according to study findings published in the Journal of the American Academy of Dermatology. Isotretinoin was also associated with a decreased risk for PTSD, anxiety, bipolar disorder, schizophrenia, adjustment disorder, and all-cause mortality.

Investigators sought to assess risk for psychiatric outcomes among patients with acne treated with isotretinoin vs oral antibiotics. The secondary endpoint was to assess the influence of these treatments on all-cause mortality.

This global population-based retrospective cohort study included patients with acne managed with isotretinoin (n=75,708) and patients with acne managed with oral antibiotics (n=75,708), all deidentified (48.3% women; mean age 21.75 years). Electronic medical records were accessed through TriNetX Analytics network platform with access to 117.5 million patients from 86 healthcare organizations worldwide.

Investigators screened all 117.5 million records for diagnostic codes indicating acne, creating 1 cohort of patients treated with isotretinoin and a second cohort of patients treated with oral antibiotics (tetracycline, doxycycline, roxithromycin, minocycline, and azithromycin) but without a prior isotretinoin prescription. Cohorts were well matched for comorbidities (ischemic heart disease, chronic kidney disease, obesity, smoking, diabetes mellitus, hypertension, and hyperlipidemia), demographic variables (sex, race, age, ethnicity), and socioeconomic determinants of health (ICD-10 codes of “problems related to employment and unemployment,” “occupational exposure to risk factors,” and “problems related to education and literacy.”)

Risk for outcomes (depression, anxiety, major depressive disorder [MDD], suicidal ideation, suicidal attempt, bipolar disorder, posttraumatic stress disorder, schizophrenia, and adjustment disorder) were evaluated over time. Isotretinoin is a third-line therapy for acne, following treatment with topical antibiotics, topical retinoids, and oral antibiotics, meaning most patients prescribed isotretinoin had also been treated with oral antibiotics.

Patients prescribed isotretinoin experienced comparable risk for major depressive disorder (hazard ratio [HR], 0.97; 95% CI, 0.92-1.03; P =.318), a comparable risk for suicide attempts (HR, 0.97; 95% CI, 0.85-1.11; P =.663), and a significantly elevated risk for suicidal ideation (HR, 1.41; 95% CI, 1.32-1.50; P <.001) vs patients treated with oral antibiotics.

Patients prescribed isotretinoin experienced lower risk for posttraumatic stress disorder (HR, 0.75; 95% CI, 0.68-0.82), bipolar disorder (HR, 0.65; 95% CI, 0.59-0.72), risk of depression (HR, 0.90; 95% CI, 0.87-0.93), anxiety (HR, 0.84; 95% CI, 0.82-0.87), schizophrenia (HR, 0.60; 95% CI, 0.48-0.76), and adjustment disorder (HR, 0.82; 95% CI, 0.77-0.87) vs patients treated with oral antibiotics (all P <.001).

Patients in the isotretinoin cohort (117 deaths) had a significantly lower risk for all-cause mortality vs patients in the oral antibiotic cohort (337 deaths) (HR, 0.56; 95% CI, 0.45-0.69; P <.001).

Study limitations include the retrospective design, reliance on incomplete or inaccurate electronic healthcare data that fails to include all possible confounding factors, under-representation of patients with low access to healthcare facilities, unaccounted for isotretinoin or antibiotic dosage, lacking details on clinical characteristics of acne and psychiatric disorders, unaccounted for preexisting psychiatric conditions, and indication bias.

Investigators concluded they found “a decreased risk of depression, and comparable risk of MDD and suicidal attempts in acne patients prescribed isotretinoin as compared to those prescribed oral antibiotics.” They added, “Isotretinoin was additionally associated with a declined risk of PTSD, anxiety, bipolar disorder, schizophrenia, adjustment disorder, and all-cause mortality.”