OBJECTIVE: The authors sought to determine whether fluphenazine dose or
plasma level predicts clinical improvement or side effects during acute
treatment. METHOD: Oral fluphenazine was given in fixed, randomized,
double-blind doses (10, 20, or 30 mg/day) for 4 weeks to 72 inpatients 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. RESULTS: The 42 responders had a
shorter duration of illness, less chronic course, and lower rate of
akathisia. Plasma level and dose did not differentiate responders and
nonresponders, but they did predict percentage improvement in positive
symptoms within the responder subgroup. Akathisia was more common and
extrapyramidal symptoms were more severe at higher plasma levels.
CONCLUSIONS: Responders showed the greatest improvement 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 plasma levels are similar during
acute and maintenance treatment, monitoring of plasma levels may thus be
useful. Conditions for applying the "responder-only" analytic strategy in
future studies are discussed.