Alpha1-adrenergic receptor blockade resulting from low dose haloperidol is low relative to that of clozapine.

Haloperidol is also an appropriate choice for clozapine augmentation from a pharmacokinetic standpoint. The predominant cytochrome P450 isoform involved in the metabolism of haloperidol to 1,2,3,6-tetrahydropyridine is cytochrome P450 3A4. 1,2,3,6-tetrahydropyridine is further metabolized to haloperidol pyridium by both cytochrome P450 3A4 and cytochrome P450 2D6 . Neither of these haloperidol metabolites shows more potent pharmacodynamic effects at any receptor site than haloperidol. Furthermore, haloperidol influences cytochrome P450 2D6 in a complex fashion that involves both stimulatory and inhibitory effects . However, because clozapine is not metabolized by cytochrome P450 2D6, its metabolism should be unaffected by the presence of haloperidol. It has been suggested that clozapine noncompetitively inhibits cytochrome P450 3A and that clozapine elevates cytochrome P450 3A . Neither claim seems to have corroborating evidence in the literature. Although the effect of clozapine on haloperidol metabolism is uncertain, low dose haloperidol titration should limit potential problems. buy asthma inhalers

Recommendations for specific doses of clozapine and ha-loperidol in combination are difficult to make due to the wide therapeutic dosage range associated with clozapine. However, before deciding to add haloperidol to a clozapine regimen, the clinician should make sure that the clozapine dose has been optimized with a minimum trial period of three months . It is unlikely that a patient would receive any added benefit from doses of haloperidol that exceed 2 to 3 mg/day because total D2 receptor occupancy in the mesolimbic pathway would be expected to reach between 70% to 80% at this dose of haloperidol in combination with clozapine. Further increases in the dose of haloperidol would likely contribute to side effects without providing any additional therapeutic benefit.