Comparative efficacy of red cell and plasma haloperidol as predictors of clinical response in schizophrenia

Abstract

The relative utility of steady-state (SS), plasma (Pl), and red blood cell (RBC) haloperidol levels for predicting clinical response was evaluated in a fixed-dose study in schizophrenic inpatients. There were significant curvilinear relationships between the decrease in BPRS Psychosis Factor Scores by day 24 of haloperidol treatment and both Pl (R2 = 0.34) and RBC (R2 = 0.38) haloperidol levels. Although SS RBC haloperidol levels consistently showed a slightly stronger relationship to clinical response than Pl levels in several comparisons, the differences in R2s between Pl and RBC haloperidol were not statistically significant. Ninety percent confidence intervals for the blood level ranges associated with optimal clinical response in our sample of patients were: 6.5-16.5 ng/ml Pl haloperidol and 2.2-6.8 ng/ml RBC haloperidol.

A Pharmacodynamic Model to Predict the Time Dependent Adaptation of Dopaminergic Activity During Constant Concentrations of Haloperidol

“…Higher concentrations, however, resulted in a decrease of HVA accumulation and a bell-shaped (inverted U-shaped) concentration-response curve was obtained (Fig. 2) similar to that observed in humans for the antipsychotic effects (Mavroides et al 1983; Smith et al 1985). It was interesting that the therapeutic window observed in plasma of patients corresponds to the steady state blood concentrations needed for the maximal accumulation of HVA in the rat.…”

“…Haloperidol is one of the most widely used neuroleptic drugs in the treatment of schizophrenia. Although there are large individual variations in pharmacokinetics and pharmacodynamics, there seems to be a clear indication of a therapeutic range of plasma concentrations below and above which the effects are not beneficial (Forsman & ohman 1977;Magliozzi et al 1981;Extein et al 1982;Mavroidis et al 1983;Smith et al 1985).…”

Haloperidol Plasma Level after a Test Dose as Predictor for the Clinical Response to Treatment in Acute Schizophrenic Patients

“…BPRS Score day zero -BPRS Score day X• BPRS Score day zero CI(%) = The HL steady-state plasma level (using the mean ofthree to four individual values sampled between days 8 and 42, according to Smith et al, 1985;Shvartsburd et al, 1983) was also calculated, in order to study its relationship with the c1inical improvement ofthe patients on days 8 and 29. The extrapyramidal effeets of HL were rated with the scales by Simpsonand Angus (1970) and Webster(l968).…”

“…Haloperidol (HL), which has a well-studied pharmacokinetic profile, has only one active metabolite and appears to be an ideal drug to elucidate these questions (Forsman and Öhman, 1977;SettleandAyd, 1983;Dahl,1986). Some studies that have tried to relate HL plasma level with cIinical response have shown a significant relationship (Maggliozzi, et al, 1981;Mi/ler et al, 1984;Smith et al, 1984;Smith et al, 1985) while others found no association between these two variables (Linkowskiet al, 1984;Ger/ach et al, 1985;Bigelowet al, 1985). The increase in plasma prolactin (PRL) induced by neurolepties was sometimes used in association with plasma levels of antipsychoties in order to try to find a possible association between these and the cIinical response to the treatment.…”

Serum haloperidol levels and clinical response in chronic, treatment-resistant schizophrenic patients

“…High dose HPL treatment does not appear to offer advantages to the majority of acutely ill schizophrenic patients (Ericksen, Hurt and Chang, 1978;Donlon et al, 1980;Modestin et al, 1983) and may cause i unacceptably high levels of unwanted side-effects (Bollini et al, 1984). A curvilinear relationship has been suggested by several authors and a range of 'therapeutic windows' proposed: [8][9][10][11][12][13][14][15][16][17][18] ng/ml (Magliozzi et al, 1981) 5-15 ng/ml (Smith et al, 1982;Extein, Pottash and Gold, 1983) 4.2-11.0 n /ml (Mavroidis et al, 1983) 11-126 ng ml (Kucharski et al, 1984) 4-26 ng/ml (Potkin et al, 1985) 6.5-16.5 ng/ml (Smith et al, 1985) Hollister and Kim (1982) proposed a therapeutic range at a higher level (20-50 ng/ml) for 'treatment-resistant' cases.…”