Measurement of 5‐HT1A receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [11C]WAY‐100635

Objective: To assess effects of chronic antidepressant drug treatment on serotonin type‐1A receptor (5‐HT1AR) binding potential (BP) in major depressive disorder. Methods: Depressed subjects (n = 27) were imaged using PET and [11C]WAY‐100635 at baseline and following a median of 9.4 weeks of treatment with selective serotonin reuptake inhibitor or dual reuptake inhibitor antidepressant agents. Fifteen subjects had complete pre‐ and post‐treatment scan data. The 5‐HT1AR BP was derived from the tissue time‐radioactivity concentrations from regions‐of‐interest defined a priori, using a simplified reference tissue model (SRTM), and in a subset of subjects, compartmental modeling (CMOD). Results: Chronic treatment had no effect on pre‐ or post‐synaptic 5‐HT1AR BP, as confirmed by both the SRTM and CMOD analyses. These results were unaffected by treatment response status and were consistent across brain regions. Among the 22 subjects for whom the clinical response‐to‐treatment was established, the treatment nonresponders (n = 7) had higher baseline BP values in the left (P = 0.01) and right orbital cortex (P = 0.02) than the responders (n = 15). Conclusions: Chronic antidepressant drug treatment did not significantly change cerebral 5‐HT1AR binding, consistent with preclinical evidence that the alterations in serotonergic function associated with antidepressant drug administration are not accompanied by changes in 5‐HT1AR density. Higher baseline 5‐HT1AR binding was associated with poorer response to treatment. Synapse 61:523–530, 2007. © 2007 Wiley‐Liss, Inc.

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