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Meta-Analysis
. 2013 Aug 28;2013(8):CD001951.
doi: 10.1002/14651858.CD001951.pub2.

Haloperidol dose for the acute phase of schizophrenia

Lorna Donnelly  1 , John Rathbone, Clive E Adams
Affiliations
Meta-Analysis

Haloperidol dose for the acute phase of schizophrenia

Lorna Donnelly et al. Cochrane Database Syst Rev. .

Abstract

Background: Haloperidol is a benchmark, accessible antipsychotic drug against which the effects of newer treatments are gauged.

Objectives: To determine the best range of doses for haloperidol for the treatment of people acutely ill with schizophrenia.

Search methods: We searched the Cochrane Schizophrenia Group Trials Register (February 2010), which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO.

Selection criteria: We selected studies if they involved people being treated for acute schizophrenia, randomised to two or more dose ranges of non-depot haloperidol, and if they reported clinically meaningful outcomes.

Data collection and analysis: For this update, we inspected all citations and independently re-inspected a sample of citations in order to ensure reliable selection. We resolved any disagreement by discussion, and where doubt remained, we acquired the full-text article for further inspection. We then ordered papers, and reliably re-inspected and quality assessed the full reports, and extracted data. For homogeneous dichotomous data, we calculated the risk ratio (RR) with 95% confidence intervals (CI) on an intention-to-treat (ITT) basis. We assumed that people who left the study early or were lost to follow-up had a negative outcome. We calculated mean differences (MD) for continuous outcomes that reported ITT, last observation carried forward (LOCF) data. We excluded data if loss to follow-up was greater than 50%.

Main results: We included 19 trials with 19 different randomised dose comparisons. No studies reported data on relapse rates or quality of life and only one compared low dose (> 1.5 to 3 mg/day) haloperidol to higher dose ranges. Using standard lower dose (> 3 to 7.5 mg/day) did not result in loss of efficacy (no clinically important improvement in global state, versus standard higher dose (> 7.5 to 15 mg/day, n = 48, 1 RCT, RR 1.09, 95% CI 0.7 to 1.8, very-low-quality evidence); versus high dose (> 15 to 35 mg/day, n = 81, 2 RCTs, RR 0.95, 95% CI 0.8 to 1.2, very-low-quality evidence). Doses of haloperidol in the range of > 3 to 7.5 mg/day had a lower rate of development of clinically significant extrapyramidal adverse effects than higher doses (clinically significant extrapyramidal adverse effects, versus standard higher dose, n = 64, 2 RCTs, RR 0.12, 95% CI 0.01 to 2.1, very-low-quality evidence); versus high dose, n = 144, 3 RCTs, RR 0.59, 95% CI 0.5 to 0.8, very-low-quality evidence; versus very high dose (> 35 mg/day, n = 86, 2 RCTs, RR 0.70, 95% CI 0.5 to 1.1, very-low-quality evidence). None of the other comparisons between dose ranges yielded statistically significant differences, but several, particularly with lower dose ranges, were underpowered to detect clinically meaningful differences.

Authors' conclusions: Noresults were conclusive and all were based on small, short studies of limited quality. However, it would be understandable if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia, and if people with schizophrenia were equally reticent to take greater doses. Further research is needed regarding the efficacy and tolerability of the lower dose ranges, especially > 1.5 to 3 mg/day.

PubMed Disclaimer

Conflict of interest statement

None known.

Figures

1
1
Study flow diagram (from results of 2010 search only).
2
2
Study flow diagram (2002 review).
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
4
4
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1 DOSES: 1. ULTRA LOW DOSE (> 0.25 to 1.5 mg/day) versus OTHER DOSES, Outcome 1 Leaving the study early (2‐10 weeks).
1.2
1.2. Analysis
Comparison 1 DOSES: 1. ULTRA LOW DOSE (> 0.25 to 1.5 mg/day) versus OTHER DOSES, Outcome 2 Global state: no clinically significant response in global state (2‐10 weeks).
1.3
1.3. Analysis
Comparison 1 DOSES: 1. ULTRA LOW DOSE (> 0.25 to 1.5 mg/day) versus OTHER DOSES, Outcome 3 Global state: use of adjunctive medication for sedation (2‐10 weeks).
1.4
1.4. Analysis
Comparison 1 DOSES: 1. ULTRA LOW DOSE (> 0.25 to 1.5 mg/day) versus OTHER DOSES, Outcome 4 Mental state/behaviour: clinically significant agitation (2‐10 weeks).
1.5
1.5. Analysis
Comparison 1 DOSES: 1. ULTRA LOW DOSE (> 0.25 to 1.5 mg/day) versus OTHER DOSES, Outcome 5 Adverse effects: clinically significant EPSE (2‐10 weeks).
1.6
1.6. Analysis
Comparison 1 DOSES: 1. ULTRA LOW DOSE (> 0.25 to 1.5 mg/day) versus OTHER DOSES, Outcome 6 Adverse effects: use of antiparkinsonism drugs (2‐10 weeks).
2.1
2.1. Analysis
Comparison 2 DOSES: 1. LOW DOSE (> 1.5 to 3 mg) versus OTHER DOSES, Outcome 1 Leaving the study early (2‐10 weeks).
2.2
2.2. Analysis
Comparison 2 DOSES: 1. LOW DOSE (> 1.5 to 3 mg) versus OTHER DOSES, Outcome 2 Global state: 1. No clinically significant response in global state (2‐10 weeks).
2.3
2.3. Analysis
Comparison 2 DOSES: 1. LOW DOSE (> 1.5 to 3 mg) versus OTHER DOSES, Outcome 3 Global state: 2. Use of adjunctive medication for sedation (2‐10 weeks).
2.6
2.6. Analysis
Comparison 2 DOSES: 1. LOW DOSE (> 1.5 to 3 mg) versus OTHER DOSES, Outcome 6 Mental state/behaviour: 1. Clinically significant agitation (2‐10 weeks).
2.8
2.8. Analysis
Comparison 2 DOSES: 1. LOW DOSE (> 1.5 to 3 mg) versus OTHER DOSES, Outcome 8 Mental state/behaviour: 3. PANSS positive endpoint score.
2.11
2.11. Analysis
Comparison 2 DOSES: 1. LOW DOSE (> 1.5 to 3 mg) versus OTHER DOSES, Outcome 11 Adverse effects: 1. Clinically significant extrapyramidal side effects (2‐10 weeks).
2.12
2.12. Analysis
Comparison 2 DOSES: 1. LOW DOSE (> 1.5 to 3 mg) versus OTHER DOSES, Outcome 12 Adverse effects: 2a. Use of any antiparkinsonism drugs (2‐10 weeks).
2.14
2.14. Analysis
Comparison 2 DOSES: 1. LOW DOSE (> 1.5 to 3 mg) versus OTHER DOSES, Outcome 14 Adverse effects: 3. Dystonic reaction (duration unclear).
2.15
2.15. Analysis
Comparison 2 DOSES: 1. LOW DOSE (> 1.5 to 3 mg) versus OTHER DOSES, Outcome 15 Adverse effects: 4. Dyskinesia (duration unclear).
2.16
2.16. Analysis
Comparison 2 DOSES: 1. LOW DOSE (> 1.5 to 3 mg) versus OTHER DOSES, Outcome 16 Adverse effects: 5. Akathisia (duration unclear).
3.1
3.1. Analysis
Comparison 3 DOSES: 2. STANDARD LOWER DOSE (> 3 to 7.5 mg) versus OTHER DOSES, Outcome 1 Leaving the study early (2‐10 weeks).
3.2
3.2. Analysis
Comparison 3 DOSES: 2. STANDARD LOWER DOSE (> 3 to 7.5 mg) versus OTHER DOSES, Outcome 2 Global state: 1. No clinically significant response in global state (2‐10 weeks).
3.3
3.3. Analysis
Comparison 3 DOSES: 2. STANDARD LOWER DOSE (> 3 to 7.5 mg) versus OTHER DOSES, Outcome 3 Global state: 2. Use of adjunctive medication for sedation.
3.4
3.4. Analysis
Comparison 3 DOSES: 2. STANDARD LOWER DOSE (> 3 to 7.5 mg) versus OTHER DOSES, Outcome 4 Mental state/behaviour: clinically significant agitation (2‐10 weeks).
3.5
3.5. Analysis
Comparison 3 DOSES: 2. STANDARD LOWER DOSE (> 3 to 7.5 mg) versus OTHER DOSES, Outcome 5 Mental state/behaviour: no psychotic symptoms (2‐10 weeks).
3.6
3.6. Analysis
Comparison 3 DOSES: 2. STANDARD LOWER DOSE (> 3 to 7.5 mg) versus OTHER DOSES, Outcome 6 Adverse effects: 1. Clinically significant extrapyramidal side effects (2‐10 weeks).
3.7
3.7. Analysis
Comparison 3 DOSES: 2. STANDARD LOWER DOSE (> 3 to 7.5 mg) versus OTHER DOSES, Outcome 7 Adverse effects: 2. Use of any antiparkinsonism drugs (2‐10 weeks).
3.8
3.8. Analysis
Comparison 3 DOSES: 2. STANDARD LOWER DOSE (> 3 to 7.5 mg) versus OTHER DOSES, Outcome 8 Adverse effects: 3. Specific adverse effects‐blurred vision (< 2 weeks).
4.1
4.1. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 1 Mortality (3 days‐2 weeks).
4.2
4.2. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 2 Leaving the study early (day 1‐2).
4.3
4.3. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 3 Leaving the study early: 1. By between 3 and 14 days.
4.4
4.4. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 4 Leaving the study early: 2. By between 2 and 10 weeks.
4.5
4.5. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 5 Global state: 1. No clinically significant response (3 days‐2 weeks).
4.6
4.6. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 6 Global state: 2. No clinically significant response in global state (2‐10 weeks).
4.7
4.7. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 7 Global state: 3. Mean change CGI.
4.8
4.8. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 8 Global state: 4. Use of adjunctive medication for sedation.
4.11
4.11. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 11 Mental state/behaviour: 1. No clinically significant response in psychotic symptoms (3 days‐2 weeks).
4.12
4.12. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 12 Mental state/behaviour: 2. Clinically significant agitation (2‐10 weeks).
4.14
4.14. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 14 Mental state/behaviour: 3. PANSS positive endpoint score.
4.17
4.17. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 17 Adverse effects: 1. Acute dystonia (3 days‐2 weeks).
4.18
4.18. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 18 Adverse effects: dystonic reaction (duration unclear).
4.19
4.19. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 19 Adverse effects: dyskinesia (duration unclear).
4.20
4.20. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 20 Adverse effects: akathisia (duration unclear).
4.21
4.21. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 21 Adverse effects: 2a. Clinically significant extrapyramidal side effects (2‐10 weeks).
4.23
4.23. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 23 Adverse effects: 3. Mean score/change in EPS.
4.24
4.24. Analysis
Comparison 4 DOSES: 3. STANDARD HIGHER DOSE (7.5 to 15 mg) versus OTHER DOSES, Outcome 24 Adverse effects: 4. Postural hypotension (3 days‐2 weeks).
5.1
5.1. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 1 Leaving the study early (2‐10 weeks).
5.2
5.2. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 2 Global state: 1. No clinically significant response in global state (2‐10 weeks).
5.3
5.3. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 3 Global state: 2. Mean change CGI.
5.4
5.4. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 4 Global state: 3a. Use of adjunctive medication for sedation.
5.5
5.5. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 5 Global state: 3b. Use of adjunctive medication for sedation (< 2 weeks)..
5.6
5.6. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 6 Global state: 3c. Use of adjunctive medication for sedation (2‐10 weeks)..
5.7
5.7. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 7 Mental state/behaviour 1: No psychotic symptoms (2‐10 weeks).
5.8
5.8. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 8 Mental state/behaviour: 2. No clinically important change in psychotic symptoms.
5.9
5.9. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 9 Mental state/behaviour: 3. Clinically significant agitation (2‐10 weeks).
5.10
5.10. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 10 Mental state/behaviour: 4. Mean score ‐ SADS mean score.
5.11
5.11. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 11 Adverse effects: 1. Clinically significant extrapyramidal side effects (2‐10 weeks).
5.12
5.12. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 12 Adverse effects: 2. Mean score/change in EPS on Simpson Angus scale.
5.13
5.13. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 13 Adverse effects: 3. Use of any antiparkinsonism drugs (2‐10 weeks).
5.14
5.14. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 14 Adverse effects: 4. Akathisia.
5.15
5.15. Analysis
Comparison 5 DOSES: 4. HIGH DOSE (> 15 to 35 mg/day) versus OTHER DOSES, Outcome 15 Adverse effects: 3. Specific adverse effects‐blurred vision (< 2 weeks).
6.1
6.1. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 1 Death (3 days‐2 weeks).
6.2
6.2. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 2 Leaving the study early: 1. By between 3 and 14 days.
6.3
6.3. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 3 Leaving the study early: 2. By between 2 and 10 weeks.
6.4
6.4. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 4 Global state: 1. No clinically significant response (3 days‐2 weeks).
6.5
6.5. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 5 Global state: 2. No clinically significant response (2‐10 weeks).
6.6
6.6. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 6 Global state: 3. Mean change CGI.
6.7
6.7. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 7 Global state: 4. Use of adjunctive medication for sedation.
6.8
6.8. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 8 Mental state/behaviour: 1. No clinically significant response in psychotic symptoms (3 days‐2 weeks).
6.9
6.9. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 9 Mental state/behaviour: 2. No clinically important change in psychotic symptoms.
6.10
6.10. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 10 Mental state/behaviour: 3. Mean score SADS mean score.
6.11
6.11. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 11 Mental state/behaviour: 4. Clinically significant agitation (2‐10 weeks).
6.12
6.12. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 12 Adverse effects: 1. Acute dystonia (3 days‐2 weeks).
6.13
6.13. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 13 Adverse effects: 2. Clinically significant extrapyramidal side effects (2‐10 weeks).
6.14
6.14. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 14 Adverse effects: 3. Mean score/change in EPS Simpson Angus Scale.
6.15
6.15. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 15 Adverse effects: 4. Use of any antiparkinsonism drugs (2‐10 weeks).
6.16
6.16. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 16 Adverse effects: 5. Akathisia.
6.17
6.17. Analysis
Comparison 6 DOSES: 5. VERY HIGH DOSE (> 35 mg/day) versus OTHER DOSES, Outcome 17 Adverse effects: 6. Postural hypotension (3 days‐2 weeks).
7.1
7.1. Analysis
Comparison 7 DOSES: 6. HIGH AND VERY HIGH DOSES (> 15 mg/day) versus OTHER DOSES, Outcome 1 versus standard higher dose (> 7.5‐15 mg/day).
8.1
8.1. Analysis
Comparison 8 PLASMA LEVELS: 1. VERY LOW LEVELS (> 1.4 to 3.5 ng/mL) versus OTHER PLASMA LEVELS, Outcome 1 Leaving the study early (2‐10 weeks).
8.2
8.2. Analysis
Comparison 8 PLASMA LEVELS: 1. VERY LOW LEVELS (> 1.4 to 3.5 ng/mL) versus OTHER PLASMA LEVELS, Outcome 2 Global state: clinically significant response in global state (2‐10 weeks).
8.3
8.3. Analysis
Comparison 8 PLASMA LEVELS: 1. VERY LOW LEVELS (> 1.4 to 3.5 ng/mL) versus OTHER PLASMA LEVELS, Outcome 3 Mental state: clinically significant response in mental state, positive symptoms (unclear duration).
8.4
8.4. Analysis
Comparison 8 PLASMA LEVELS: 1. VERY LOW LEVELS (> 1.4 to 3.5 ng/mL) versus OTHER PLASMA LEVELS, Outcome 4 Adverse effects: clinically significant extrapyramidal side effects (2‐10 weeks).
9.1
9.1. Analysis
Comparison 9 PLASMA LEVELS: 2. MEDIUM LEVELS (> 7.0 to 16.5 ng/mL) versus OTHER PLASMA LEVELS, Outcome 1 Leaving the study early (2‐10 weeks).
9.2
9.2. Analysis
Comparison 9 PLASMA LEVELS: 2. MEDIUM LEVELS (> 7.0 to 16.5 ng/mL) versus OTHER PLASMA LEVELS, Outcome 2 Global state: no clinically significant response in global state (2‐10 weeks).
9.3
9.3. Analysis
Comparison 9 PLASMA LEVELS: 2. MEDIUM LEVELS (> 7.0 to 16.5 ng/mL) versus OTHER PLASMA LEVELS, Outcome 3 Mental state: clinically significant response in mental state, positive symptoms (duration unclear).
9.4
9.4. Analysis
Comparison 9 PLASMA LEVELS: 2. MEDIUM LEVELS (> 7.0 to 16.5 ng/mL) versus OTHER PLASMA LEVELS, Outcome 4 Adverse effects: clinically significant extrapyramidal side effects (2‐10 weeks).
10.1
10.1. Analysis
Comparison 10 PLASMA LEVELS: 3. HIGH LEVELS (> 16.5 ng/mL) versus OTHER PLASMA LEVELS, Outcome 1 Leaving the study early (2‐10 weeks).
10.2
10.2. Analysis
Comparison 10 PLASMA LEVELS: 3. HIGH LEVELS (> 16.5 ng/mL) versus OTHER PLASMA LEVELS, Outcome 2 Global state: no clinically significant response in global state (2‐10 weeks).
10.3
10.3. Analysis
Comparison 10 PLASMA LEVELS: 3. HIGH LEVELS (> 16.5 ng/mL) versus OTHER PLASMA LEVELS, Outcome 3 Adverse effects: clinically significant extrapyramidal side effects (2‐10 weeks).
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    1. Garver DL, Steinberg JL, McDermott BE, Yao JK, Ramberg JE, Lewis S, et al. Etiologic heterogeneity of the psychoses: is there a dopamine psychosis?. Neuropsychopharmacology 1997;16(3):191‐201. - PubMed
    1. Stone CK, Garver DL, Griffith J, Hirschowitz J, Bennett J. Further evidence of a dose‐response threshold for haloperidol in psychosis. American Journal of Psychiatry 1995;152(8):1210‐12. - PubMed
Volavka 1992 {published data only}
    1. Bitter I, Volavka J, Cooper J, Scheurer, Camus L, Bakall R. Haloperidol blood levels and clinical effects in schizophrenia. Proceedings of the 8th World Congress of Psychiatry; 1989 Oct 13‐19; Athens, Greece. 1989.
    1. Chou JC, Douyon R, Czobor P, Volavka J, Cooper TB. Change in plasma prolactin and clinical response to haloperidol in schizophrenia and schizoaffective disorder. Psychiatry Research 1998;81(1):51‐5. - PubMed
    1. Convit A, Volavka J, Czobor P, Asis J, Evangelista C. Effect of subtle neurological dysfunction on response to haloperidol treatment in schizophrenia. American Journal of Psychiatry 1994;151(1):49‐56. - PubMed
    1. Cooper TB, Volavka J, Czobor P. Plasma drug level and clinical response. Journal of Clinical Psychopharmacology 1992;12(2):134‐6. - PubMed
    1. Czobor P, Volavka J. Dimensions of the brief psychiatric rating scale: an examination of stability during haloperidol treatment. Comprehensive Psychiatry 1996;37(3):205‐15. - PubMed
Volavka 1995 {published data only}
    1. Chou JC, Douyon R, Czobor P, Volavka J, Cooper TB. Change in plasma prolactin and clinical response to haloperidol in schizophrenia and schizoaffective disorder. Psychiatry Research 1998;81(1):51‐5. - PubMed
    1. Czobor P, Volavka J. Dimensions of the Brief Psychiatric Rating Scale: an examination of stability during haloperidol treatment. Comprehensive Psychiatry 1996;37(3):205‐15. - PubMed
    1. Czobor P, Volavka J. Positive and negative symptoms: is their change related?. Schizophrenia Bulletin 1996;22(4):577‐90. - PubMed
    1. Volavka J, Cooper TB, Czobor P, Meisner M. Effect of varying haloperidol plasma levels on negative symptoms in schizophrenia and schizoaffective disorder. Psychopharmacology Bulletin 1996;32(1):75‐9. - PubMed
    1. Volavka J, Cooper TB, Czobor P, Meisner M. Haloperidol plasma levels and clinical effects. Psychopharmacology Bulletin 1995;31:536. - PubMed
Winter 1984 {published data only}
    1. Lehmann E, Lienert GA. Differential improvements from haloperidol in two types of schizophrenics. Psychopharmacology 1984;84(1):96‐7. - PubMed
    1. Winter M, Lehmann E, Scholz OB. Effects of high and low dosage of haloperidol on the brain in relation to schizophrenic thought disorder. Neuropsychobiology 1984;2‐3:115‐21. - PubMed

References to studies excluded from this review

Bjorndal 1980 {published data only}
    1. Bjorndal N, Bjerre M, Gerlach J, Kristjansen P, Magelund G, Oestrich IH, et al. High dosage haloperidol therapy in chronic schizophrenic patients: a double‐blind study of clinical response, side effects, serum haloperidol, and serum prolactin. Psychopharmacology 1980;67(1):17‐23. - PubMed
Boyer 1987 {published data only}
    1. Boyer P, Puech AJ. Determinants for clinical activity of neuroleptic drugs: chemical substances, doses, assessment tools [Modalities d'action clinique ses neuroleptiques: substances, doses, instruments de mesure utilises]. Psychiatrie and Psychobiologie 1987;2(4):296‐305.
Coryell 1990 {published data only}
    1. Coryell W, Kelly M, Perry PJ, Miller DD. Haloperidol plasma levels and acute clinical change in schizophrenia. Journal of Clinical Psychopharmacology 1990;10(6):397‐402. - PubMed
    1. Kelly MW, Perry PJ, Coryell WH, Miller DD, Arndt SV. Reduced haloperidol plasma‐concentration and clinical‐response in acute exacerbations of schizophrenia. Psychopharmacology 1990;102(4):514‐20. - PubMed
Coryell 1998 {published data only}
    1. Coryell W, Miller DD, Perry PJ. Haloperidol plasma levels and dose optimization. American Journal of Psychiatry 1998;155(1):48‐53. - PubMed
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Davis 1985 {published data only}
    1. Davis JM, Ericksen SE, Hurt S, Chang SS, Javaid JI, Dekirmenjian H, et al. Blood levels of haloperidol and clinical response. Psychopharmacology Bulletin 1985;21(1):48‐51. - PubMed
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Dubin 1985 {published data only}
    1. Dubin WR, Waxman HM, Weiss KJ, Ramchandani D, Tavani‐Petrone C. Rapid tranquilization: the efficacy of oral concentrate. Journal of Clinical Psychiatry 1985;46(11):475‐8. - PubMed
Dutoit 1995 {published and unpublished data}
    1. Dutoit D, Thomas P, Leroux JM, Vaiga G, Pommery J, Cottencin O, et al. Erythrocyte ketone reductase activity, total plasma haloperidol and acute psychoses [Activite cetone reductase erythrocytaire, taux plasmatiques d'haloperidol et psychoses aigues]. Encephale 1995;21(6):417‐24. - PubMed
Garver 1984 {published data only}
    1. Garver DL, Kelly K, Fried KA, Magnusson M, Hirschowitz J. Drug response patterns as a basis of nosology for the mood‐incongruent psychoses (the schizophrenias). Psychological Medicine 1988;18:873‐85. - PubMed
    1. Mavroidis ML, Garver DL, Kanter DR, Hirschowitz J. Plasma haloperidol levels and clinical response: confounding variables. Psychopharmacology Bulletin 1985;21(1):62‐5. [MEDLINE: ] - PubMed
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Garver 1985 {published data only}
    1. Garver DL, Hirschowitz J, Glicksteen GA, Kanter DR, Mavroidis ML. Haloperidol plasma and red blood cell levels and clinical antipsychotic response. Journal of Clinical Psychopharmacology 1984;4(3):133‐7. - PubMed
Gerlach 1985a {published data only}
    1. Gerlach J, Behnke K, Heltberg J, Munk‐Andersen, Nielsen H. Dogmatil and haloperidol for the treatment of schizophrenia. Double blind cross‐over study of therapeutic effectiveness, side effects and plasma concentrations [Le dogmatil et l'haloperidol dans le traitement de la schizophrenie. Etude croisee en double aveugle de l'action therapeutique, des effets secondaires et des concentrations plasmatiques]. Semaine des Hopitaux 1985;61(19):1309‐16.
Hirschowitz 1997 {published data only}
    1. Hirschowitz J, Hitzemann R, Piscani K, Burr G, Frecska E, Culliton D, et al. The Dose Reduction in Schizophrenia (DORIS) Study: a final report. Schizophrenia Research 1997;23(1):31‐43. - PubMed
Levin 1996 {published data only}
    1. Levin ED, Wilson W, Rose JE, McEvoy J. Nicotine‐haloperidol interactions and cognitive performance in schizophrenics. Neuropsychopharmacology 1996;15(5):429‐36. - PubMed
Ortega‐Soto 1993 {published data only}
    1. Ortega‐Soto HA, Fernandez AE, Pinedo H, Torre P, Brunner E, Apiquian R. Clinical trial of haloperidol threshold doses. Proceedings of the 146th Annual Meeting of the American Psychiatric Association; 1993 May 22‐27; San Francisco. 1993.
Ortega‐Soto 1994 {published data only}
    1. Ortega‐Soto HA, Brunner E, Apiquian R, Torre P. Therapeutic minimum dose of haloperidol in schizophrenia. Neuropsychopharmocology 1994;10(3S Pt 2):140S.
    1. Ortega‐Soto HA, Fernandez AE, Pinedo H, Torre P, Brunner E, Apiquian R. Clinical trial of haloperidol threshold doses. Patient Care for the 21st Century: Asserting Professional Values with Economic Restraints. Proceedings of the 146th Annual Meeting of the American Psychiatric Association; 1993, May 22‐27; San Francisco. 1993.
Reschke 1974 {published data only}
    1. Reschke RW. Parenteral haloperidol for rapid control of severe, disruptive symptoms of acute schizophrenia. Diseases of the Nervous System 1974;35(3):112‐5. [MEDLINE: ] - PubMed
Santos 1989 {published data only}
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    1. Santos JL, Cabranes JA, Vazquez C, Fuentenebro F, Almoguera I, Ramos JA. Clinical response and plasma haloperidol levels in chronic and subchronic schizophrenia. Biological Psychiatry 1989;26(4):381‐8. - PubMed
    1. Santos JL, Ramos JA, Prieto P, Almoguera I, Vazquez C, Rubio ME, et al. Determination of plasma haloperidol concentrations by radioreceptor assay in schizophrenia‐clinical utility. Progress in Neuro‐Psychopharmacology & Biological Psychiatry 1989;13(6):917‐25. - PubMed
Sim 1989 {published data only}
    1. Sim CB, Lee YC, Hwang JP. Haloperidol for schizophrenic inpatients with three doseage regimens. Psychiatry Today: Accomplishments and Promises; Proceedings of the 8th World Congress of Psychiatry; 1989, Oct 12‐19; Athens, Greece. London: Excerpta Medica International Congress Series 899, 1989:817.
Smith 1984 {published data only}
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    1. Smith RC. The interpretation of plasma haloperidol concentrations‐reply. Archives of General Psychiatry 1985;42(8):839‐40. - PubMed
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    1. Smith RC, Baumgartner R, Misra CH, Mauldin M, Shvartsburd A, Ho BT, et al. Haloperidol. Plasma levels and prolactin response as predictors of clinical improvement in schizophrenia: chemical v radioreceptor plasma level assays. Archives of General Psychiatry 1984;41(11):1044‐9. - PubMed
    1. Smith RC, Burd A, Baumgartner R, Ravichandran GK, Mauldin M. Haloperidol and thioridazine drug levels and clinical‐response in schizophrenia‐comparison of gas‐liquid‐chromatography and radioreceptor drug level assays. Psychopharmacology Bulletin 1985;21(1):52‐8. - PubMed
Smith 1987 {published data only}
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Van Putten 1990 {published data only}
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Volavka 2000 {published data only}
    1. Volavka J, Cooper TB, Czobor P, Lindenmayer J P, Citrome LL, Mohr P, et al. High dose treatment with haloperidol: the effect of dose reduction. Journal of Clinical Psychopharmacology 2000;20(2):252‐6. [MEDLINE: ] - PubMed
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Zimbroff 1997 {published data only}
    1. Baker R, Mack R, Morris D, Sebree T, Kashkin KB. The efficacy and safety of three doses of sertindole versus three doses of haloperidol in schizophrenic patients. Proceedings of the 9th European College of Neuropsychopharmacology Congress; 1996 Sep 21‐25; Amsterdam, Netherlands. 1996.
    1. Bark N, Mack R, Zborowski J, Morris D, Sebree T, Shook S, et al. Efficacy and safety of three doses of sertindole and haloperidol in schizophrenic patients. Biological Psychiatry 1996;39:597.
    1. Larson GL, Mack RJ, Zborowski J, Morris DD, Sebree TB, Wallin BA. Three doses each of sertindole and haloperidol in schizophrenics. Proceedings of the 10th World Congress of Psychiatry; 1996 Aug 23‐28; Madrid, Spain. 1996.
    1. Tamminga C, Mack R, Zborowski J, Morris D, Sebree T, Wallin B. Efficacy and safety of three doses of sertindole and haldol in schizophrenic patients. Proceedings of the 20th Collegium Internationale Neuro‐Psychopharmacologicum Congress; 1996 Jun 23‐27; Melbourne, Australia. 1996.
    1. Zimbroff DL, Kane JM, Tamminga C, Daniel DG, Mack RJ, Wozniak PJ, et al. Controlled, dose‐response study of sertindole and haloperidol in the treatment of schizophrenia. Sertindole study group. American Journal of Psychiatry 1997;154(6):782‐91. - PubMed

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