The relationship between blood perphenazine levels, early resolution of psychotic symptoms, and side effects

Serum perphenazine concentrations and early resolution of psychosis were examined to determine if blood level monitoring could be used to maximize drug efficacy while limiting extrapyramidal side effects (EPS). Sixty-six acutely psychotic inpatients were given perphenazine 0.5 mg/kg/day for 10 days, and their response was rated blind to blood level. Although 36 of 66 patients showed resolution of psychosis, neither perphenazine nor N-dealkylated perphenazine levels were related to global response or to Brief Psychiatric Rating Scale (BPRS) totals. Improvement in two individual BPRS items (hallucinations and conceptual disorganization) was related to serum perphenazine levels and suggestive of a lower therapeutic threshold of 0.8 ng/mL. Perphenazine level was not correlated with EPS; but benztropine, given only if required for serious EPS, was more likely to be used when perphenazine levels were elevated. The data suggest that higher perphenazine levels were no more effective than moderate levels but that higher levels may be associated with increased EPS; the data also suggest that individual symptoms rather than global response were associated with a lower therapeutic perphenazine threshold.