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Accutane Brain?

Patients taking isotretinoin have visible functional changes on brain scans.

Isotretinoin is a highly effective acne treatment, but case reports of associated depression have suggested that isotretinoin might have central effects. Vitamin A toxicity has been associated with a wide variety of psychiatric symptoms, such as personality changes, but no convincing data have shown that isotretinoin causes depression. Reasoning that for isotretinoin to cause depression it must have an effect on the brain, these authors used brain imaging to look for changes before and after isotretinoin treatment. In an open-label study, 28 acne patients underwent positron emission tomography (PET) and MRI scanning before and after 4 months of treatment with an antibiotic (15 patients; 14 receiving tetracyclines) or isotretinoin (1 mg/kg daily; 13 patients).

There were no quantifiable differences in depression between groups. PET scans showed a decrease in brain metabolism in the orbitofrontal cortex after 4 weeks of isotretinoin therapy, a finding that is also seen in depression. Antibiotic therapy was not associated with such changes. Five patients taking isotretinoin reported headaches and irritability or mood changes; all five had decreased brain metabolism, the greatest decreases in those who developed headaches.

Comment: Isotretinoin decreased metabolism in a key frontal brain area, more so in patients with headaches, but the significance of this finding is unknown. This important story is far from over, but the results show the potential value of structural and functional studies of the brain in subjects on retinoids, especially isotretinoin. The generalizability of these finding in subjects with psychiatric histories is also unknown. The finding that headache was associated with the most dramatic decreases in metabolism and with aggressive behavior may be a useful clinical observation. More studies are urgently needed.

— Neil H. Shear, MD, FRCPC

Published in Journal Watch Dermatology May 24, 2005

Citation(s):

Bremner JD et al. Functional brain imaging alterations in acne patients treated with isotretinoin. Am J Psychiatry 2005 May; 162:983-91.

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