Rational antipsychotic polypharmacy: AUGMENTATION OF CLOZAPINE WITH HALOPERIDOL(1)

Haloperidol fulfills the desired pharmacodynamic criteria for clozapine augmentation. Its affinity for the D2 receptor is approximately 83 times greater than that of clozapine, while its affinity for the 5-HT2A receptor is less than 5% of that of clozapine and its affinity for the muscarinic and histaminic receptors is less than 1% of that of clozapine . These circumstances are extremely beneficial; low doses of haloperidol may be added to therapeutic doses of clozapine to bolster D2 blockade without exacerbating side effects resulting from his-taminic and cholinergic receptor blockade. At the same time, the benefit of clozapine’s affinity for the 5-HT2a and cholinergic receptors on minimizing the incidence of EPS associated with high D2 blockade is conceivably maintained. Haloperi-dol’s affinity for the alpha1-adrenergic receptor is less than that of clozapine; thus, augmentation with low dose haloperi-dol should not further enhance the alpha1-adrenergic blockade resulting from clozapine. buy flovent inhaler

As a result of its binding profile, it is expected that low dose haloperidol augmentation of clozapine is viable for the following reasons.

Haloperidol shows the desired increased D2 receptor affinity.

Possible EPS associated with haloperidol should be minimized by the relatively high 5-HT2A receptor blockade associated with therapeutic doses of clozapine.

Haloperidol has low affinity for muscarinic and histaminic receptors and, therefore, is unlikely to exacerbate side effects associated with their blockade.

Category: Antipsychotic

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

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