Plasma haloperidol levels and clinical effects in schizophrenia and schizoaffective disorder

Plasma haloperidol levels between 5 and 11 ng/mL may be clinically optimal for acutely exacerbated schizophrenia, but the evidence for this therapeutic window has been inconsistent.

Haloperidol was administered in a double-blind manner during two consecutive 3-week experimental periods to 65 patients with acutely exacerbated schizophrenia or schizoaffective disorder. Two plasma levels were targeted: "low" (2 ng/mL) and "moderate" (10 ng/mL). The subjects were randomly assigned to four treatment sequences (low-low, low-moderate, moderate-moderate, or moderate-low).

In the first 3 weeks, the antipsychotic efficacy of haloperidol increased with plasma levels up to approximately 12 ng/mL. In the second 3 weeks, decrease of plasma levels reduced negative symptoms.

For most patients, plasma levels not exceeding 12 ng/mL yield the best results in the first 3 weeks of treatment. Subsequent lowering of the plasma levels may improve negative symptoms.