Decrease in brain serotonin 2 receptor binding in patients with major depression following desipramine treatment - A positron emission tomography study with fluorine-18-labeled setoperone

Background: The neuroreceptor changes involved in therapeutic efficacy of v arious antidepressants remain unclear. Preclinical studies have shown that long-term administration of various antidepressants causes down-regulation of brain serotonin 2 (5-HT2) receptors in rodents, but it is unknown if sim ilar changes occur following antidepressant treatment in depressed patients . Our purpose, therefore, was to assess the effects of treatment with desip ramine hydrochloride on brain 5-HT2 receptors in depressed patients using p ositron emission tomography (PET) and fluorine-18 (F-18)-labeled setoperone . Methods: Eleven patients who met DSM-IV criteria for major depression as de termined by a structured clinical interview for DSM-III-R diagnosis and sui table for treatment with desipramine were recruited. Ten patients underwent a PET scan before and another after 3 to 4 weeks of treatment with desipra mine. Results: Eight of the 10 patients responded to desipramine treatment as ind icated by more than 50% decrease in Hamilton Depression Rating Scale scores . Depressed patients showed a significant decrease in 5-HT2 receptor bindin g as measured by setoperone binding in frontal, temporal, parietal, and occ ipital cortical regions following desipramine treatment. The decrease in 5- HT2 receptor binding was observed bilaterally and was particularly prominen t in frontal cortex. Conclusions: Depressed patients showed a significant reduction in available 5-HT2 receptors in the brain following desipramine treatment, but it is un known if this change in S-HT2 receptors is due to clinical improvement or a n effect of desipramine that is unrelated to clinical status.