FLUPHENAZINE PLASMA-LEVELS, DOSAGE, EFFICACY, AND SIDE-EFFECTS

Objective: The authors sought to determine whether fluphenazine dose o r plasma level predicts clinical improvement or side effects during ac ute treatment. Method: Oral fluphenazine was given in fixed, randomize d, double-blind doses (10, 20, or 30 mg/day) for 4 weeks to 72 inpatie nts with acute schizophrenic exacerbations. Outcome measures included percentage improvement in ratings of positive symptoms (hallucinations , delusions, and thought disorder), percentage improvement in negative symptoms, and maximum score for extrapyramidal symptoms. Response was defined as an improvement in positive symptoms of 40% or more. Result s: The 42 responders had a shorter duration of illness, less chronic c ourse, and lower rate of akathisia. Plasma level and dose did not diff erentiate responders and nonresponders, but they did predict percentag e improvement in positive symptoms within the responder subgroup. Akat hisia was more common and extrapyramidal symptoms were more severe at higher plasma levels. Conclusions: Responders showed the greatest impr ovement at fluphenazine plasma levels above 1.0 ng/ml and doses above 0.20-0.25 mg/kg per day. Since the literature suggests that optimal pl asma levels are similar during acute and maintenance treatment, monito ring of plasma levels may thus be useful. Conditions for applying the ''responder-only'' analytic strategy in future studies are discussed.