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There are data in support of an important role for serotonin (5-HT) in the pathophysiology of schizophrenia.¹ Atypical antipsychotic drugs exhibit an increased ratio of 5-HT2A to dopamine D2 receptor–binding affinities as compared with typical agents, which may explain the improved efficacy and adverse effect profiles of the of the former.¹ Previous investigations of 5-HT systems via acute tryptophan depletion (ATD) in psychotically ill individuals have involved subjects taking typical antipsychotics.^2-3 Here, we describe the effects of ATD in clozapine-maintained individuals using a previously described, randomized, double-blind, placebo-controlled, counter-balanced ATD paradigm.⁴

Seven clozapine-responsive subjects with schizophrenia entered, and 5 (4 with schizophrenia; 1 with a schizoaffective disorder) subjects completed both active and sham ATD challenges.⁴ The mean ± SD age of subjects completing treatment was 44.0 ± 3.5 years; mean ± SD clozapine dose was 510.0 ± 135.6 mg per day; duration of clozapine treatment was 12.1 ± 8.2 months. . . . [Full Text of this Article]