Rational antipsychotic polypharmacy: AUGMENTATION OF CLOZAPINE WITH HALOPERIDOL(3)

Although haloperidol has been chosen as an example of a rational approach to antipsychotic augmentation of clozapine, it would be remiss to suggest that it is the only suitable agent. Although haloperidol certainly fits the desired pharmacodynamic and pharmacokinetic profile for combination with clozapine, it was selected over other possible candidates due to the relative abundance of reliable biochemical information. For example, trifluoperazine has a pharmacodynamic profile similar to that of haloperidol with the exceptions that trifluoperazine shows significant 5-HT2A affinity and much less alphaj-adrenergic affinity . Both of these differences are advantageous from a side effect perspective. Furthermore, because trifluoperazine is a less potent neuroleptic than haloperidol, a more precise low dose titration may be facilitated. Unfortunately, the literature pertaining to the pharmacokinetics of trifluoperazine is limited, especially in the field of metabolism, precluding a discussion of clozapine augmentation with trifluoperazine in the present report. buy asthma inhaler


The present report proposes the use of an additional antipsychotic agent at low dose for augmentation of antipsychotic monotherapy in patients who show partial but inadequate treatment response. This strategy is a departure from the usual practice of either increasing the antipsychotic dose or initiating a trial of a different agent and should be restricted to partial responders with a history of treatment refractoriness to monotherapy with one conventional agent and at least one novel agent. It is critical that any augmentation strategy be grounded in a rational pharmacodynamic and pharmacokinetic understanding of drug action until conclusive clinical trials have been performed in this field. Furthermore, these clinical trials should be designed to determine whether combination therapy is the cause of improvement or if the improvement is solely related to the addition of the latter agent. Finally, when applying a rational approach to antipsychotic polypharmacy, one must be cognizant of the limitations of using pharmacological theory to predict clinical outcomes in an etiologically complex disorder such as schizophrenia.

Category: Antipsychotic

Tags: Clozapine, Cytochrome P450, Haloperidol, Pharmacokinetics, Polypharmacy

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