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Plasma Haloperidol Levels and Clinical Effects in Schizophrenia and Schizoaffective Disorder

Jan Volavka, MD, PhD; Thomas B. Cooper, MA; Pal Czobor, PhD; Morris Meisner, PhD
Arch Gen Psychiatry. 1995;52(10):837-845. doi:10.1001/archpsyc.1995.03950220047010.
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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.

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