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A positron emission tomography study of the effects of treatment with valproate on brain 5-HT2A receptors in acute mania


Lakshmi N Yatham, MBBS, FRCPC, Mood Disorders Clinical Research Unit, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada V6T 2A1.
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Objective:  To examine the effects of treatment with valproate on brain 5-HT2A receptors in acute manic patients using positron emission tomography (PET) and [18F]-setoperone.

Methods:  Patients with DSM-IV bipolar I disorder–manic episode were recruited. Patients were drug free or drug naïve at the time of baseline PET scan. All patients were treated with valproate and one patient received lithium in addition to valproate for 3–5 weeks following which they had a post-treatment PET scan. The effect of treatment on brain 5-HT2A receptor binding was determined using statistical parametric mapping (SPM) and region of interest (ROI) analyses. Of the 12 manic patients recruited, seven patients had both baseline and post-treatment PET scans.

Results:  All seven patients improved with treatment and were in remission at the time of the second PET scan. Both SPM and ROI analyses showed that treatment with mood stabilizers had no significant effect on brain 5-HT2A receptor binding in manic patients.

Conclusion:  This study suggests that changes in brain 5-HT2A receptors are not involved in the antimanic effects of mood stabilizers however, we cannot exclude the possibility of 5-HT2A receptor involvement in down-stream signaling pathways.