Citalopram causes no significant alterations in plasma neuroleptic levels in schizophrenic patients

• Steady-state plasma concentrations of commonly used neuroleptic drugs were measured in 90 schizophrenic patients before and after adding placebo or citalopram (40 mg/day) to their treatment regimen. Plasma concentrations of citalopram and its main metabolite, desmethylcitalopram, were also measured. In addition, patients with exceptionally high neuroleptic levels or an increase in adverse effects during the 12-week study period were evaluated for their debrisoquine/sparteine hydroxylase (CYP2D6) genotype, an enzyme responsible for oxidative metabolism of several neuroleptics and selective serotonin re-uptake inhibitors. There were no significant changes in plasma concentrations of haloperidol, chlorpromazine, zuclopenthixol, levomepromazine, thioridazine or perphenazine during the study. Plasma concentrations of citalopram and desmethylcitalopram were well within the levels reported previously with monotherapy, and remained stable throughout the study. None of the 15 patients analysed for the CYP2D6 genotype was a poor metabolizer. It is concluded that clinically important pharmacokinetic drug interactions do not play a crucial role when citalopram is used as an augmentation therapy in neuroleptic-treated schizophrenic patients.

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