Brain Changes in Patients Treated With Accutane

Bremner, J. Douglas, Fani, Negar, Ashraf, Ali, Votaw, John R., Brummer, Marijn E., Cummins, Thomas, Vaccarino, Viola, Goodman, Mark M., Reed, Lai, Siddiq, Sajid, Nemeroff, Charles B.

Functional Brain Imaging Alterations in Acne Patients Treated With Isotretinoin.

Am J Psychiatry 2005 162: 983-991

The purpose of this pilot study was to assess the possible effects of isotretinoin on brain functioning in acne patients. In order to establish a causal relationship between isotretinoin and the development of depression and suicide, it is necessary to establish a plausible biological pathway. The use of isotretinoin during pregnancy is known to result in central nervous system defects in newborns. This study sought to determine if the drug also had an effect on the functioning of the areas of the brain and the neurochemical systems that mediate depression. Previous studies, using positron emission tomography (PET) brain scans, have shown that people suffering from depression have decreased orbitofrontal cortical brain metabolism and that area of the brain is actually smaller in volume.

The study participants included twenty eight healthy men and women between the ages of 18 and 50 years with treatment-resistant acne. They had all undergone a three month course of antibiotic therapy without results and were seeking a second course of treatment. Eighty eight people were initially screened for the study and anyone with a serious medical, neurological or psychiatric illness, or current substance abuse problems was excluded. Forty four met the criteria, and were started on a course of antibiotic or isotretinoin. Sixteen of those later dropped out for a variety of reasons, six with a psychiatric diagnosis.

Thirteen of the participants were treated with 1 mg/kg/day of isotretinoin and the remaining fifteen with an antibiotic in a standard four month course of treatment for acne. There were no significant differences between the two treatment groups at baseline in terms of demographic, behavioral, and acne-related variables. Each participant received a PET brain scan at baseline and again after four month treatment period.

The brain scan data was analyzed to determine differences in the changes from pre- to post-treatment in regional brain metabolic rates between the isotretinoin and antibiotic treatment groups. Correlations between brain metabolism and behavioral variables were also examined by comparing the relationships between the changes, from before to after treatment, in scores on the Hamilton depression scale, clinician-administered acne questionnaire, Skindex, and acne severity self-report and the change in regional brain metabolism in both groups.

At the completion of the treatment period, those treated with isotretinoin had an average 21% decrease in orbitofrontal cortical metabolism as compared with a 2% decrease in participants treated with antibiotic. The largest decreases were observed in participants who developed symptoms of headache during the course of treatment with isotretinoin. Isotretinoin was not associated, however, with any changes in depressive symptom severity as measured with the Hamilton depression scale.

The findings of this study suggest that isotretinoin is associated with changes in brain functioning, providing a possible biological mechanism by which isotretinoin treatment could lead to depression in a minority of vulnerable acne patients.

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