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In the cortex of animals, serotonin (5-HT) levels increase after several weeks of treatment with selective serotonin reuptake inhibitors (SSRIs). Studies using an intrasubject design to examine the effects of SSRI treatment on 5-HT_2A receptors in the cortex of drug-free depressed patients are needed. In theory, agonist stimulation of 5-HT_2A receptors could be relevant to SSRI treatment by promoting neuronal growth and survival as well as direct elevation of mood. The objective of this study was to evaluate the effect of 6 weeks of paroxetine treatment on 5-HT_2A receptors in depressed patients. After a medication-free period of at least 3 months, 19 depressed patients were treated for 6 weeks with paroxetine, 20 mg/day. The authors used [¹⁸F]setoperone and positron emission tomography to assess 5-HT_2A receptor binding potential in the patients before and after treatment and in 19 age …