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Although many drugs used in psychiatry can be assayed in body fluids, the measurement of agents such as the tricyclic antidepressants (TCAs) and the antipsychotic agents in the therapeutic setting remains controversial. This is due to both pharmacokinetic and pharmacodynamic factors. Pharmacokinetically, neither the TCAs nor the antipsychotics meet the criteria for therapeutic drug monitoring, because they undergo extensive first‐pass metabolism to active metabolites, their mechanism of action probably involves alteration in receptor responsiveness, and at least for the TCAs protein binding is not constant. The pharmacodynamic end points in assessing depression and schizophrenia have also proved difficult to define; thus the relationship between plasma levels and clinical response has proved elusive. Lithium, alone, is suitable for therapeutic drug monitoring because it has a narrow therapeutic range, is not protein bound, is not metabolized, and there is serum level variability for the same dose. Besides this agent, plasma level measurement is unlikely to add any benefit to the patient in the clinical setting.
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Carl Burgess (1986) studied this question.
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