Effects of Isotretinoin: A Brain Imaging Study

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Effects of Isotretinoin: A Brain Imaging Study

Isotretinoin recipients without psychiatric disorders showed changes in the orbitofrontal cortex, but not in depression levels.

A consideration in prescribing lithium to adolescents is the potential development or worsening of cystic acne. In these situations, clinicians may hesitate to prescribe isotretinoin, due to case reports of depression and suicide. In a study funded in part by litigators against the manufacturer, researchers performed brain imaging among 28 individuals (mean age, 29) to investigate whether isotretinoin is associated with the imaging changes reported with depression. For obvious ethical reasons, participants with current psychiatric disorders were excluded.

In this open-label, nonrandomized pilot study, researchers recruited isotretinoin-naïve patients whose doctors were planning to switch their therapy for treatment-resistant acne. Fifteen participants were switched to isotretinoin, and 13 were switched to one of four antibiotics. Two antibiotic recipients and no isotretinoin recipients had past psychiatric disorders.

At baseline and at 4 months, researchers used standardized scales to measure depression and acne severity and performed PET scans and MRIs (for co-registration with the PET scans). Multiple brain regions were examined, including the orbitofrontal cortex, which has been found to be significantly affected in depression.

At 4 months, glucose metabolism in the orbitofrontal cortex decreased significantly more in isotretinoin recipients than in antibiotic-treated patients (mean decreases, 21% vs. 2%). Isotretinoin recipients who developed headaches experienced the greatest decreases. Depression scale scores did not differ between or within groups at baseline or follow-up. Imaging findings were not related to depression or acne-severity scores.

Comment: This novel and important study supports anecdotal evidence that by activating depression-specific areas of the brain, isotretinoin might be problematic for adolescents with mood disorders. But, in another study involving adolescents with acne but without mood disorders (and unknown family histories of mood disorders), scores on an epidemiologic depression scale did not differ significantly between those who received isotretinoin and those who did not (Arch Dermatol 2005; 141:557). Overall, these clinical trial and imaging results leave unresolved the clinical conundrum of whether it is safe to give isotretinoin to teenagers with mood disorders or with family diatheses for mood disorders.

— Barbara Geller, MD

Published in Journal Watch Psychiatry June 22, 2005