Serum Haloperidol Concentrations and Clinical Response in Acute Psychosis

Dd, Miller; La, Hershey; Jp, Duffy; Dr, Abernethy; Dj, Greenblatt

doi:10.1097/00004714-198412000-00002

Cited by 33 publications

(8 citation statements)

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“…Additionally, for the majority of our patients (in both groups) haloperidol plasma concentrations were within the proposed therapeutic ranges of 3-40 ng/ml (Miller et al 1984). Hollister and Kim (1982) have suggested that patients with haloperidol concentrations above 50 ng/ml are likely to be nonresponders to haloperidol therapy.…”

Section: Discussionsupporting

confidence: 64%

Effects of smoking on haloperidol and reduced haloperidol plasma concentrations and haloperidol clearance

et al. 1986

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Plasma concentrations of haloperidol and its reduced metabolite (reduced haloperidol) were investigated in cigarette smokers (N = 23) and nonsmokers (N = 27). Steady-state plasma concentrations were obtained 12 h post bedtime dose. Haloperidol and reduced haloperidol concentrations were determined by RIA. Reduced haloperidol was separated by selective succinylation and liquid chromatography. Patients were clinically assessed with the Clinical Global Impression Scale (CGIS). Smokers had significantly lower haloperidol and reduced haloperidol plasma concentrations than nonsmokers (P less than 0.01, P less than 0.05). Clearance of haloperidol was significantly greater in smokers compared to nonsmokers (P = 0.0052). CGIS assessments did not show significant differences between smokers and nonsmokers. Plasma concentrations should be carefully monitored when patients either start or stop smoking.

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Section: Discussionsupporting

confidence: 64%

Effects of smoking on haloperidol and reduced haloperidol plasma concentrations and haloperidol clearance

et al. 1986

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“…Extein et al (1982) reported a 'therapeutic window' between 5 and 15 fotg/L after 4 weeks' haloperidol treatment in 14 schizophrenic and 4 schizoaffective patients. In a prospective study involving 21 acutely psychotic patients Miller et al (1983) reported an apparent 'curvilinear' (i.e. bellshaped, inverted U) relationship between serum haloperidol concentrations and clinical response with a 'therapeutic window' of 10 to 40 J!g/L.…”

Section: Haloperidolmentioning

confidence: 99%

Plasma Level Monitoring of Antipsychotic Drugs Clinical Utility

Dahl

1986

Clinical Pharmacokinetics

145

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The steady-state plasma concentrations of antipsychotic drugs show large interpatient variations but remain relatively stable from day to day in each individual patient. Monitoring of antipsychotic drug concentrations in plasma might be of value provided the patients are treated with only 1 antipsychotic drug. Some studies have reported a relationship between therapeutic response and serum antipsychotic drug 'concentrations' as measured using the radioreceptor assay (RRA) method, which measures dopamine receptor-blocking activity in plasma. Most studies, however, have failed to demonstrate such a relationship, and the RRA does not seem to provide the generally useful tool for plasma concentration monitoring of antipsychotic drugs that was hoped for initially. A lack of correlation between dopamine receptor-blocking activity in plasma and therapeutic response may be due to differences in the blood-brain distribution of both antipsychotic drugs and their active metabolites. Chemical assay methods (e.g. GLC and HPLC) have been used in studies which examined the relationships between therapeutic response and antipsychotic drug concentrations in red blood cells and in plasma. It seems that for these drugs, measuring red blood cell concentrations does not offer any significant advantage over measuring plasma concentrations. Reasonably controlled studies of plasma concentration-response relationships using randomly allocated, fixed dosages of chlorpromazine, fluphenazine, haloperidol, perphenazine, sulpiride, thioridazine and thiothixene have been published but often involve relatively few patients. A correlation between therapeutic response and plasma concentrations of thioridazine and its metabolites has not been demonstrated, and plasma level monitoring of thioridazine and its metabolites therefore appears to have no clinical value. Clinical behavioural deterioration concomitant with high plasma concentrations of chlorpromazine and haloperidol have been reported. A dosage reduction might be considered after 2 to 4 weeks' treatment in non-responders who have plasma chlorpromazine concentrations above 100 to 150 micrograms/L or plasma haloperidol concentrations above 20 to 30 micrograms/L. Non-responders and good responders to chlorpromazine treatment, however, have plasma drug concentrations in the same range, and a therapeutic range of plasma chlorpromazine levels has not been defined. Therapeutic plasma haloperidol concentrations (i.e. 'window') in the range of 5 to 20 micrograms/L have been reported by some investigators, but others have found no such relationship.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…A detailed discussion of this is found in a previous publication (4). Except for one study (6) all the studies retained in this paper had a quality score of >0.60 (good or excellent). When study (6) was deleted, the results did not change.…”

Section: Quality Scoringmentioning

confidence: 99%

“…(8) Santos ef al. (22,23) Besides the above windows, we tested the following concentration ranges: [6][7][8][9][10][11][12][13][14][15][16][17][18] Median' 9-19 5-20 Perry ef al. (24) meta-analysis Pharmacodynamic study by Wolkin et al (25) 0 After confirmation of any of the concentration ranges above, perform the following analysis.…”

Section: 5-165mentioning

confidence: 99%

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Haloperidol blood levels and clinical outcome: a meta-analysis of studies relevant to testing the therapeutic window hypothesis

Oliveira¹,

Sena²,

Pereira

et al. 1996

Journal of Clinical Pharmacy and Therapeutics

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SUMMARY Haloperidol, the most studied antipsychotic drug, is the only one about which reliable statements on the relationship between blood levels and clinical outcome can be made. A systematic overview was undertaken to determine whether there was an optimum blood concentration range for clinical efficacy. Eighteen published studies which provided individual patient data in tables or graphs were reviewed. Clinical benefits tended to decline when the haloperidol blood concentration was increased above 26 ng/ml. Our data support the existence of a therapeutic window between 4 and 26 ng/ml for haloperidol in the treatment of schizophrenic, schizoaffective and schizophreniform disorders.

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Serum Haloperidol Concentrations and Clinical Response in Acute Psychosis

Cited by 33 publications

References 0 publications

Effects of smoking on haloperidol and reduced haloperidol plasma concentrations and haloperidol clearance

Effects of smoking on haloperidol and reduced haloperidol plasma concentrations and haloperidol clearance

Plasma Level Monitoring of Antipsychotic Drugs Clinical Utility

Haloperidol blood levels and clinical outcome: a meta-analysis of studies relevant to testing the therapeutic window hypothesis

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