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

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.

Haloperidol. Plasma levels and prolactin response as predictors of clinical improvement in schizophrenia: chemical v radioreceptor plasma level assays.

The relationship between clinical response of schizophrenic patients to haloperidol and (1) blood levels of the medication, determined by both gas-liquid chromatography (GLC) and radioreceptor (RR) assays, or (2) prolactin response to the medication, was examined in an inpatient study using several fixed doses of haloperidol. Regression analysis disclosed a substantial curvilinear relationship between steady-state GLC-determined plasma haloperidol levels and decrease in Brief Psychiatric Rating Scale (BPRS) Psychosis factor scores; however, no substantial relationship was found between clinical response and RR plasma haloperidol levels or serum prolactin response to haloperidol. Our results suggest that steady-state plasma levels of haloperidol determined by the GLC chemical assay are a better predictor of decreases in BPRS Psychosis factor scores than RR assayed plasma haloperidol levels or prolactin response to haloperidol.

Blood levels of haloperidol and thioridazine during maintenance neuroleptic treatment of schizophrenic outpatients.

Plasma and red blood cell levels of haloperidol, thioridazine, and thioridazine's main metabolite mesoridazine were measured in schizophrenic outpatients during treatment with fixed doses of haloperidol or thioridazine for several months. These drug levels were compared to those in schizophrenic inpatients treated with fixed doses of the same neuroleptics. There were large interpatient variations in plasma and red blood cell levels at a given dose for schizophrenic outpatients as well as for inpatients. The intrapatient day-to-day fluctuation was much greater in the outpatients. The mean coefficient of variation of thioridazine or mesoridazine levels was about two-fold higher in schizophrenic outpatients than in inpatients. Differences in blood sampling time or compliance in medication ingestion do not fully explain the issue. The factors accounting for the increased intrapatient variability of plasma levels of thioridazine, mesoridazine, and haloperidol in schizophrenic outpatients remain unclear.

Plasma and red cell levels of thioridazine and clinical response in schizophrenia.

The relationship of plasma and red blood cell (RBC) levels of thioridazine to clinical response in schizophrenia was evaluated in a fixed-dose study. Steady-state plasma and RBC levels of thioridazine, mesoridazine, and sum of thioridazine and mesoridazine, determined by gas-liquid chromatography, were not significantly correlated with clinical response as measured by improvement on the Brief Psychiatric Rating Scale. RBC thioridazine levels were not substantially more strongly correlated with clinical response than plasma levels.

Nuclear magnetic resonance in schizophrenia: a preliminary study.

Nuclear magnetic resonance (NMR) scans were performed in nine patients with schizophrenia and five control subjects. NMR scans allowed multiple-plane views of the brains of schizophrenic patients and demonstrated much greater detail of morphological structure than computed tomographic (CT) scans. This small sample of subjects, however, showed no significant differences in several quantitative measurements between schizophrenic patients and control subjects. Problems in the interpretation of image intensity measures of NMR scans are discussed.

Red blood cell and plasma levels of thioridazine and mesoridazine in schizophrenic patients.

Thioridazine and mesoridazine levels and levels of thioridazine plus metabolites were determined in plasma and red blood cells (RBC) by gas-liquid chromatography (GLC) and spectrofluorometry (SP), respectively, in schizophrenic patients treated with fixed doses of thioridazine. There was wide interpatient variability in RBC:plasma ratios for thioridazine and mesoridazine, a higher ratio of thioridazine to mesoridazine in RBC than plasma, and a higher ratio of GLC total (thioridazine plus mesoridazine), to SP-determined total drug constituents in RBC than in plasma. RBC showed a monotonic increase in drug levels with dose, whereas levels of drug in the plasma began to level off above the 250 mg/day dose. Drug levels 24 h after the acute dose did not predict steady-state blood levels in plasma or RBC.

Prolactin response to single and multiple doses of haloperidol in schizophrenic patients.

Serum prolactin and blood levels of haloperidol were assessed in schizophrenic patients after single acute oral doses of haloperidol and during fixed dose treatment with this medication. Although significant intrapatient correlations between prolactin responses to different doses of haloperidol were found, no statistically significant interpatient relationship between haloperidol dose and prolactin response emerged. There were statistically significant relationships between steady-state plasma and red cell haloperidol levels (measured by radioreceptor or gas liquid chromatographic techniques) and serum prolactin response, but not between blood levels after the acute haloperidol dose and prolactin response.

Blood levels of haloperidol in schizophrenic patients.

Plasma and red blood cell levels of haloperidol were measured in psychotic patients after an acute dose of haloperidol and during treatment with fixed doses for several weeks. There was wide variability of haloperidol plasma and red blood cell levels at a given dose and a nonlinear relationship between haloperidol dose and blood levels. The red blood cell/plasma ratio (0.40) had a narrow range among different patients. Haloperidol blood levels were not correlated with the age of the patient. Concomitant administration of benztropine mesylate did not decrease plasma haloperidol levels. Steady state plasma or red cell haloperidol levels could not be predicted from levels 24 hours after the acute dose.

RBC and plasma levels of haloperidol and clinical response in schizophrenia.

The authors conducted a fixed-dose study of haloperidol blood levels and clinical response in schizophrenic in patients and found that those with steady-state RBC haloperidol levels in the range of 2.4--5.4 ng/ml showed greater improvement than those with lower or higher levels. They found a similar , although nonsignificant, curvilinear relationship between plasma haloperidol levels and clinical response. These findings suggest that the relationship between haloperidol blood levels and clinical response fits a therapeutic window for the treatment of schizophrenia.