Acitretin Increases Risk for Psychiatric Disorders in Patients With Psoriasis

The risk for developing psychiatric disorders among patients with psoriasis is greater in those receiving acitretin compared with those receiving disease-modifying antirheumatic drugs (DMARDs), according to study findings published in Dermatology.

Researchers conducted a nationwide matched cohort study using Taiwan’s National Health Insurance Research Database of adult patients who received a primary diagnosis of psoriasis between 1997 and 2013. A total of 1152 patients with psoriasis who were prescribed acitretin for at least an average of 30 days per year were included in the study.

Participants were well-matched by sex, age, and interval after psoriasis diagnosis to start of systemic anti-psoriatic medications in a 1:2 ratio with 2304 participants with psoriasis who were prescribed DMARDs for an average of at least 30 days per year. Excluded from the final analysis were those who were prescribed the corresponding cohort medication for more than 7 days during the observation period and patients with preexisting comorbidities possibly treated with DMARDs or retinoids.

The participants in the acitretin cohort (25.7% women; mean age, 53.1±15.2 years) had acitretin prescriptions that covered a mean of 376 days and comorbidities of hypertension (32%), diabetes (19%), and chronic obstructive pulmonary disease (14%). These patients were well-matched with patients in the DMARDs cohort except for comorbidities of hyperlipidemia (absolute difference, 4.3%) and psoriatic arthritis (absolute difference, 33.2%).

The 4-year cumulative incidence of overall psychiatric disorders was significantly higher in those in the acitretin cohort (19.62%; 95% CI, 17.08%-22.16%) vs those in the DMARDs cohort (12.06%; 95% CI, 10.48%-13.64%). The 4-year cumulative incidence of mood disorders was significantly higher among participants in the acitretin cohort (12.81%; 95% CI, 10.68%-14.95%) vs participants in the DMARDs cohort (7.67%; 95% CI, 6.38%-8.96%), and the same for the incidence of psychosis in the acitretin cohort (7.21%; 95% CI, 5.58%-8.83%) vs the DMARDs cohort (4.63%; 95% CI, 3.62%-5.64%; all P <.001).

Using multivariate analysis, acitretin was independently associated with psychiatric disorders (hazard ratio [HR], 1.51; 95% CI, 1.23-1.85) and included other independent risk factors of increasing age (HR, 1.02; 95% CI, 1.02-1.02), female sex (HR, 1.43; 95% CI, 1.13-1.80), acute coronary syndrome (HR, 1.48; 95% CI, 1.06-2.06), and insomnia (HR, 1.95; 95% CI, 1.35-2.81).

In all stratified analysis, acitretin associated with greater risk in comorbid subgroups of psoriatic arthritis (HR, 3.23; 95% CI, 1.75-5.97), chronic liver disease (HR, 2.60; 95% CI, 1.56-4.33), patients less than 56 years of age (HR, 1.83; 95% CI, 1.32-2.54), patients starting acitretin more than 1 year following psoriasis diagnosis (HR, 1.72; 95% CI, 1.27-5.97), and men (HR, 1.47; 95% CI, 1.13-1.90).

Study limitations include the observational study design, lack of data on subtypes of psoriasis, disease severity, family status, and relationships resulting in possible confounding by indication.

“Compared with disease-modifying antirheumatic drugs, acitretin was associated with higher hazards of psychiatric disorders among [patients with psoriasis],” the study authors conclude. “The influence of acitretin on mental health is independent of gender, age, or comorbidities and exists in subgroups of [patients with psoriasis].”