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Jan Volavka, MD, PhD; Thomas B. Cooper, MA; Pal Czobor, PhD; Morris Meisner, PhD

Arch Gen Psychiatry. 1995;52(10):837-845.

Abstract
Background
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.

Methods
Haloperidol was administered in a doubleblind 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).

Results
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.

Conclusion
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.

Author Affiliations
From the Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, and the Department of Psychiatry, New York (NY) University.

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