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Meta-Analysis
. 2015 Jan 16;1(1):CD009831.
doi: 10.1002/14651858.CD009831.pub2.

Haloperidol versus first-generation antipsychotics for the treatment of schizophrenia and other psychotic disorders

Markus Dold  1 , Myrto T Samara, Chunbo Li, Magdolna Tardy, Stefan Leucht
Affiliations
Meta-Analysis

Haloperidol versus first-generation antipsychotics for the treatment of schizophrenia and other psychotic disorders

Markus Dold et al. Cochrane Database Syst Rev. .

Abstract

Background: Haloperidol is worldwide one of the most frequently used antipsychotic drugs with a very high market share. Previous narrative, unsystematic reviews found no differences in terms of efficacy between the various first-generation ("conventional", "typical") antipsychotic agents. This established the unproven psychopharmacological assumption of a comparable efficacy between the first-generation antipsychotic compounds codified in textbooks and treatment guidelines. Because this assumption contrasts with the clinical impression, a high-quality systematic review appeared highly necessary.

Objectives: To compare the efficacy, acceptability, and tolerability of haloperidol with other first-generation antipsychotics in schizophrenia and schizophrenia-like psychosis.

Search methods: In October 2011 and July 2012, we searched the Cochrane Schizophrenia Group's Trials Register, which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. To identify further relevant publications, we screened the references of all included studies and contacted the manufacturers of haloperidol for further relevant trials and missing information on identified studies. Furthermore, we contacted the corresponding authors of all included trials for missing data.

Selection criteria: We included all randomised controlled trials (RCTs) that compared oral haloperidol with another oral first-generation antipsychotic drug (with the exception of the low-potency antipsychotics chlorpromazine, chlorprothixene, levopromazine, mesoridazine, perazine, prochlorpromazine, and thioridazine) in schizophrenia and schizophrenia-like psychosis. Clinically important response to treatment was defined as the primary outcome. Secondary outcomes were global state, mental state, behaviour, overall acceptability (measured by the number of participants leaving the study early due to any reason), overall efficacy (attrition due to inefficacy of treatment), overall tolerability (attrition due to adverse events), and specific adverse effects.

Data collection and analysis: At least two review authors independently extracted data from the included trials. The methodological quality of the included studies was assessed using The Cochrane Collaboration`s 'Risk of bias' tool.We analysed dichotomous outcomes with risk ratios (RR) and continuous outcomes with mean differences (MD), both with the associated 95% confidence intervals (CI). All analyses were based on a random-effects model and we preferably used data on an intention-to-treat basis where possible.

Main results: The systematic review currently includes 63 randomised trials with 3675 participants. Bromperidol (n = 9), loxapine (n = 7), and trifluoperazine (n = 6) were the most frequently administered antipsychotics comparator to haloperidol. The included studies were published between 1962 and 1993, were characterised by small sample sizes (mean: 58 participants, range from 18 to 206) and the predefined outcomes were often incompletely reported. All results for the main outcomes were based on very low or low quality data. In many trials the mechanism of randomisation, allocation, and blinding was frequently not reported. In short-term studies (up to 12 weeks), there was no clear evidence of a difference between haloperidol and the pooled group of the other first-generation antipsychotic agents in terms of the primary outcome "clinically important response to treatment" (40 RCTs, n = 2132, RR 0.93 CI 0.87 to 1.00). In the medium-term trials, haloperidol may be less effective than the other first-generation antipsychotic group but this evidence is based on only one trial (1 RCT, n = 80, RR 0.51 CI 0.37 to 0.69).Based on limited evidence, haloperidol alleviated more positive symptoms of schizophrenia than the other antipsychotic drugs. There were no statistically significant between-group differences in global state, other mental state outcomes, behaviour, leaving the study early due to any reason, due to inefficacy, as well as due to adverse effects. The only statistically significant difference in specific side effects was that haloperidol produced less akathisia in the medium term.

Authors' conclusions: The findings of the meta-analytic calculations support the statements of previous narrative, unsystematic reviews suggesting comparable efficacy of first-generation antipsychotics. In efficacy-related outcomes, there was no clear evidence of a difference between the prototypal drug haloperidol and other, mainly high-potency first-generation antipsychotics. Additionally, we demonstrated that haloperidol is characterised by a similar risk profile compared to the other first-generation antipsychotic compounds. The only statistically significant difference in specific side effects was that haloperidol produced less akathisia in the medium term. The results were limited by the low methodological quality in many of the included original studies. Data for the main results were low or very low quality. Therefore, future clinical trials with high methodological quality are required.

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Conflict of interest statement

Markus Dold: has received a travel grant from Janssen‐Cilag. Myrto Samara: none to declare. Chunbo Li: none to declare. Magdolna Tardy: none to declare. Stefan Leucht has received honoraria for lectures from Lilly, Lundbeck, Pfizer, Janssen, BMS, Janssen, Johnson and Johnson, Lundbeck, Roche, SanofiAventis, ICON, Abbvie; for consulting from Roche, Janssen, Lundbeck and Lilly; and for the preparation of Educational Material and publications from the Lundbeck Institute and Roche. EliLilly has provided medication for a clinical trial led by SL as principal investigator.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
3
3
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Funnel plot of comparison: 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, outcome: 1.1 Global state: 1. Clinically important response.
1.1
1.1. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 1 Global state: 1. Clinically important response.
1.2
1.2. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 2 Global state: 2. Average score (CGI, endpoint, short term, high = poor).
1.3
1.3. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 3 Mental state: 1. General ‐ a. Average score (BPRS total, endpoint, high = poor).
1.4
1.4. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 4 Mental state: 1. General ‐ b. Average score ‐ short term (various scales, endpoint, high = poor).
1.5
1.5. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 5 Mental state: 2. Specific ‐ a. Depersonalisation average score ‐ short term (AMDP, high = poor).
1.6
1.6. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 6 Mental state: 2. Specific ‐ b. Depressive symptoms average score (HAM‐D, high = poor).
1.7
1.7. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 7 Mental state: 2. Specific ‐ c. Negative symptoms average score ‐ short term (SANS, endpoint, high = poor).
1.8
1.8. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 8 Mental state: 2. Specific ‐ d.i. Positive symptom average score ‐ short term.
1.10
1.10. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 10 Behaviour: 1a. Average score ‐ short term (NOSIE, endpoint, high = poor).
1.11
1.11. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 11 Behaviour: 1b. Average score ‐ short term (Wing’s Ward Behaviour Scale, endpoint, high = poor).
1.12
1.12. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 12 Leaving the study early: 1. Due to any reason ‐ as a measure of overall acceptability.
1.13
1.13. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 13 Leaving the study early: 2. Due to inefficacy of treatment ‐ as a measure of overall efficacy (short term).
1.14
1.14. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 14 Leaving the study early: 3. Due to adverse events ‐ as a measure of overall tolerability.
1.15
1.15. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 15 Adverse effects: 1. General ‐ at least one adverse effect.
1.16
1.16. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 16 Adverse effects: 2. Specific ‐ a. Movement disorders.
1.17
1.17. Analysis
Comparison 1 HALOPERIDOL versus FIRST‐GENERATION ANTIPSYCHOTIC DRUGS, Outcome 17 Adverse effects: 2. Specific ‐ b. Various.
2.1
2.1. Analysis
Comparison 2 Sensitivity analyses, Outcome 1 Sensitivity analysis ‐ Implication of randomisation, Outcome: overall symptoms of schizophrenia (short term).
2.2
2.2. Analysis
Comparison 2 Sensitivity analyses, Outcome 2 Sensitivity analysis ‐ Exclusion of cross‐over‐trials, Outcome: overall symptoms of schizophrenia (short term).
2.3
2.3. Analysis
Comparison 2 Sensitivity analyses, Outcome 3 Sensitivity analysis ‐ Exclusion of non double‐blind trials, Outcome: overall symptoms of schizophrenia (short term).
2.4
2.4. Analysis
Comparison 2 Sensitivity analyses, Outcome 4 Sensitivity analysis ‐ Fixed versus random‐effects models, Outcome: overall symptoms of schizophrenia (short term).
3.1
3.1. Analysis
Comparison 3 Subgroup analyses, Outcome 1 Subgroup analysis ‐ different antipsychotic drugs (short term).
3.2
3.2. Analysis
Comparison 3 Subgroup analyses, Outcome 2 Subgroup analysis ‐ different antipsychotic drugs (medium term).
3.3
3.3. Analysis
Comparison 3 Subgroup analyses, Outcome 3 Subgroup analysis ‐ treatment‐resistant participants (short term).
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Update of

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    1. Serafetinides EA. Consistency and similarity of drug EEG responses in chronic schizophrenic patients. International Pharmacopsychiatry 1973;8:214‐6. - PubMed
    1. Serafetinides EA. Voltage laterality in the EEG of psychiatric patients. Diseases of the Nervous System 1973;34:190‐1. - PubMed
    1. Serafetinides EA, Clark ML. Psychological effects of single dose antipsychotic medication. Biological Psychiatry 1973;7:263‐7. - PubMed
    1. Serafetinides EA, Collins S, Clark ML. Haloperidol, clopenthixol, and chlorpromazine in chronic schizophrenia. Chemically unrelated antipsychotics as therapeutic alternatives. Journal of Nervous and Mental Disease 1972;154:31‐42. - PubMed
    1. Serafetinides EA, Willis D. A method of quantifying EEG for psychopharmacological research. International Pharmacopsychiatry 1973;8:245‐7. - PubMed
Shalev 1993 {published data only}
    1. Shalev A, Hermesh H, Rothberg J, Munitz H. Poor neuroleptic response in acutely exacerbated schizophrenic patients. Acta Psychiatrica Scandinavica 1993;87:86‐91. - PubMed
Silverstone 1984 {published data only}
    1. Silverstone T, Cookson J, Ball R, Chin CN, Jacobs D, Lader S, et al. The relationship of dopamine receptor blockade to clinical response in schizophrenic patients treated with pimozide or haloperidol. Journal of Psychiatric Research 1984;18:255‐68. - PubMed
Spina 1992 {published data only}
    1. Spina E, Domenico P, Bonanzinga M, D'Agostino MA, Gitto C, Rosa AE, et al. A double‐blind comparative study of bromperidol versus haloperidol in schizophrenic patients. New Trends in Experimental and Clinical Psychiatry 1992;7:67‐71.
Stewart 1969 {published data only}
    1. Stewart A, Lafave HG, Segovia G. Haloperidol ‐ new addition to the drug treatment of schizophrenia. Behavioral Neuropsychiatry 1969;1:23‐8. - PubMed
Teja 1975 {published data only}
    1. Teja JS, Grey WH, Clum JM, Warren C. Tranquilizers or anti‐depressants for chronic schizophrenics: a long term study. Australian and New Zealand Journal of Psychiatry 1975;9:241‐7. - PubMed
Tobin 1980 {published data only}
    1. Tobin JM, Robinson GM. Double blind comparison of haloperidol and thiothixene with after care treatment evaluation in psychiatric outpatients with schizophrenia. Psychiatric Journal of the University of Ottowa 1980;5:168‐74.
Tuason 1986 {published data only}
    1. Tuason VB. A comparison of parenteral loxapine and haloperidol in hostile and aggressive acutely schizophrenic patients. Journal of Clinical Psychiatry 1986;47:126‐9. - PubMed
Ulmar 1990 {published data only}
    1. Ulmar G, Edler R, Hagen M. Trifluperidol vs haloperidol – a double‐blind trial. Proceedings of the 17th Collegium Internationale Neuro‐Psychopharmacologicum Congress; 1990 Sep 10‐14; Kyoto, Japan. 1990:296.
Versiani 1978 {published data only}
    1. Versiani M, Silva JA, Frota LH, Mundim FD. Double‐blind comparison between loxapine and haloperidol in the treatment of adolescent schizophrenic patients. Current Therapeutic Research 1978;24:559‐66.
White 1981 {published data only}
    1. Eaton EM, Busk J, Maloney MP, Sloane RB, Whipple K, White K. Hemispheric dysfunction in schizophrenia: assessment by visual perception tasks. Psychiatry Research 1979;1:325‐32. - PubMed
    1. White K, Busk J, Eaton E, Gomez G, Razani J, Sloane RB. Dysphoric response to neuroleptics as a predictor of treatment outcome with schizophrenics. A comparative study of haloperidol versus mesoridazine. International Pharmacopsychiatry 1981;16:34‐8. - PubMed

References to studies excluded from this review

Al Haddad 1996 {published data only}
    1. Al Haddad MK, Kamel C, Sequeria RP, Mawgood MA. Zuclopenthixol versus haloperidol in the initial treatment of schizophrenic psychoses, affective psychoses and paranoid states: a controlled clinical trial. Arab Journal of Psychiatry 1996;7:44‐54.
Alpert 1995 {published data only}
    1. Alpert M, Pouget ER, Sison C, Yahia M, Allan E. Clinical and acoustic measures of the negative syndrome. Psychopharmacology Bulletin 1995;31:321‐6. - PubMed
Azima 1960 {published data only}
    1. Azima H, Durost H, Arthurs D. The effect of R‐1625 (haloperidol) in mental syndromes: a multiblind study. American Journal of Psychiatry 1960;117:546‐7. - PubMed
Barch 2005 {published data only}
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Baro 1972 {published data only}
    1. Baro F, Lommel R, Dom R, Mesmaecker L. Pimozide treatment of chronic schizophrenics as compared with haloperidol and penfluridol maintenance treatment. A multidisciplinary approach. Acta Psychiatrica Belgica 1972;72:199‐214. - PubMed
Bechelli 1986 {published data only}
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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 des neuroleptiques: substances, doses, instruments de mesure utilises]. Psychiatrie and Psychobiologie 1987;2:296‐305.
Brook 1998 {published data only}
    1. Brook S, Berk M, Selemani S, Kolloori J, Nzo I. A randomised controlled double blind study of zuclopenthixol acetate compared to haloperidol in acute psychosis. Proceedings of the 10th European College of Neuropsychopharmacology Congress; 1997 Sep 13‐17; Vienna, Austria. 1997.
    1. Brook S, Berk M, Selemani S, Kolloori J, Nzo I. A randomized controlled double blind study of zuclopenthixol acetate compared to haloperidol in acute psychosis. Human Psychopharmacology 1998;13:17‐20.
Chin 1998 {published data only}
    1. Chin CN, Hamid AR, Philip G, Ramlee T, Mahmud M, Zulkifli G, et al. A double‐blind comparison of zuclopenthixol acetate with haloperidol in the management of acutely disturbed schizophrenics. Medical Journal of Malaysia 1998;53:365‐71. - PubMed
Classen 1988 {published data only}
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Cole 1970 {published data only}
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Costa 2007 {published data only}
    1. Costa AMN, Lima MS, Faria M, Filho SR, Oliveira IR, Jesus Mari J. A naturalistic, 9‐month follow‐up, comparing olanzapine and conventional antipsychotics on sexual function and hormonal profile for males with schizophrenia. Journal of Psychopharmacology 2007;21:165‐70. - PubMed
Crow 1986 {published data only}
    1. Crow TJ, MacMillan JF, Johnson AL, Johnstone EC. A randomised controlled trial of prophylactic neuroleptic treatment. British Journal of Psychiatry 1986;148:120‐7. - PubMed
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Davies 2007 {published data only}
    1. Davies LM, Lewis S, Jones PB, Barnes TRE, Gaughran F, Hayhurst K, et al. Cost‐effectiveness of first‐ v second‐generation antipsychotic drugs: results from a randomised controlled trial in schizophrenia responding poorly to previous therapy. British Journal of Psychiatry 2007;191:14‐22. - PubMed
de Jesus Mari 2004 {published data only}
    1. Jesus Mari J, Lima MS, Costa AN, Alexandrino N, Rodrigues‐Filho S, Oliveira IR, et al. The prevalence of tardive dyskinesia after a nine month naturalistic randomised trial comparing olanzapine with conventional treatment for schizophrenia and related disorders. European Archives of Psychiatry and Clinical Neuroscience 2004;254:356‐61. - PubMed
Digo 1967 {published data only}
    1. Digo R, Karavokyros D, Mlynarski JC. Use of a new butyrophenone in psychiatric service. Outline of a differential study [Utilisation d'une nouvelle butyrophenone dans un service psychiatrique. Esquisse d'une etude differentielle]. L'Encephale 1967;56:75‐91. - PubMed
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;46:475‐8. - PubMed
Durost 1964 {published data only}
    1. Durost H, Lee H, Arthurs D. An early evaluation of haloperidol. In: Lehmann HE, Ban TA editor(s). The Butyrophenones in Psychiatry. Quebec Psychopharmacological Research Association, 1964:70‐3.
Ehmann 1987 {published data only}
    1. Ehmann TS, Delva NJ, Beninger RJ. Flupenthixol in chronic schizophrenic inpatients: a controlled comparison with haloperidol. Journal of Clinical Psychopharmacology 1987;7:173‐5. - PubMed
Eitan 1992 {published data only}
    1. Eitan N, Levin Y, Ben Artzi E, Levy A, Neumann M. Effects of antipsychotic drugs on memory functions of schizophrenic patients. Acta Psychiatrica Scandinavica 1992;85:74‐6. - PubMed
Engelhardt 1973 {published data only}
    1. Engelhardt DM, Polizos P, Waizer J, Hoffman SP. A double‐blind comparison of fluphenazine and haloperidol in outpatient schizophrenic children. Journal of Autism and Childhood Schizophrenia 1973;3:128‐37. - PubMed
Fitzgerald 1969 {published data only}
    1. Fitzgerald CH. A double‐blind comparison of haloperidol with perphenazine. Current Therapeutic Research 1969;11:515‐9. - PubMed
Galderisi 1994 {published data only}
    1. Galderisi S, Maj M, Mucci A, Bucci P, Kemali D. QEEG alpha1 changes after a single dose of high‐potency neuroleptics as a predictor of short‐term response to treatment in schizophrenic patients. Biological Psychiatry 1994;35:367‐74. - PubMed
Gerlach 1978 {published data only}
    1. Gerlach J, Simmelsgaard H. Tardive dyskinesia during and following treatment with haloperidol, haloperidol + biperiden, thioridazine, and clozapine. Psychopharmacology 1978;59:105‐12. - PubMed
Gillis 1977 {published data only}
    1. Gillis JS. The effects of selected antipsychotic drugs of human judgment. Current Therapeutic Research, Clinical and Experimental 1977;21:224‐32. - PubMed
Harris 1992 {published data only}
    1. Harris MJ, Panton D, Caligiuri MP, Krull AJ, Tran Johnson TK, Jeste DV. High incidence of tardive dyskinesia in older outpatients on low doses of neuroleptics. Psychopharmacology Bulletin 1992;28:87‐92. - PubMed
Holden 1970 {published data only}
    1. Holden JM, Itil TM, Keskiner A. Assessment and significance of changes in laboratory values with haloperidol and fluphenazine hydrochloride therapy. Biological Psychiatry 1970;2:173‐82. - PubMed
Huang 2005 {published data only}
    1. Huang TL, Chen JF. Serum lipid profiles and schizophrenia: effects of conventional or atypical antipsychotic drugs in Taiwan. Schizophrenia Research 2005;80:55‐9. - PubMed
Hyugano 1986 {published data only}
    1. Hyugano H. The clinical psychopharmacological efficacy of bromperidol for schizophrenia comparison with haloperidol by the single‐blind cross‐over method. Shinryo to Shinyaku 1986;21:1296‐306.
Itil 1975 {published data only}
    1. Itil TM, Marasa J, Saletu B, Davis S, Mucciardi AN. Computerized EEG: predictor of outcome in schizophrenia. Journal of Nervous and Mental Disease 1975;160:188‐203. - PubMed
Jones 2006 {published data only}
    1. Jones PB, Barnes TRE, Davies L, Dunn G, Lloyd H, Hayhurst KP, et al. Randomized controlled trial of the effect on quality of life of second‐ vs first‐generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS 1). Archives of General Psychiatry 2006;63:1079‐87. - PubMed
Karsten 1981 {published data only}
    1. Karsten D, Kivimaki T, Linna SL, Pollari L, Turunen S. Neuroleptic treatment of oligophrenic patients. A double‐blind clinical multicentre trial of cis(z)‐clopenthixol and haloperidol. Acta Psychiatrica Scandinavica Supplementum 1981;294:39‐45. - PubMed
Kazamatsuri 1972 {published data only}
    1. Kazamatsuri H, Chien C, Cole JO. Treatment of tardive dyskinesia. II. Short‐term efficacy of dopamine‐blocking agents haloperidol and thiopropazate. Archives of General Psychiatry 1972;27:100‐3. - PubMed
Kelwala 1984 {published data only}
    1. Kelwala S, Ban TA, Berney SA, Wilson WH. Rapid tranquilization ‐ a comparative study of thiothixene and haloperidol. Progress in Neuropsychopharmacology and Biological Psychiatry 1984;8:77‐83. - PubMed
Kurt 2007 {published data only}
    1. Kurt E, Akman B, Alata G, Dadelen S, Oral T. Comparison of cardiac influences of antipsychotic drugs in patients with schizophrenia [Sizofreni tanili hastalarda antipsikotik laclarin kardiyak etkilerinin karilatirilmasi]. Klinik Psikofarmakoloji Bülteni 2007;17:155‐61.
Lamure 2003 {published data only}
    1. Lamure M, Toumi M, Chabannes JP, Dansette GY, Benyaya J, Hansen K. Zuclopenthixol versus haloperidol: an observational randomised pharmacoeconomic evaluation of patients with chronic schizophrenia exhibiting acute psychosis. International Journal of Psychiatry in Clinical Practice 2003;7:177‐85.
Lehmann 1967 {published data only}
    1. Lehmann HE, Ban TA, Lee H. The effectiveness of combined phenothiazine and butyrophenone treatment in chronic schizophrenic patients. Current Therapeutic Research, Clinical and Experimental 1967;9:36‐7. - PubMed
Levenson 1976 {published data only}
    1. Levenson AJ, Burnett GB, Nottingham JD, Sermas CE, Thornby JI. Speed and rate of remission in acute schizophrenia: a comparison of intramuscularly administered fluphenazine HC1 with thiothixene and haloperidol. Current Therapeutic Research, Clinical and Experimental 1976;20:695‐700. - PubMed
Liu 1996 {published data only}
    1. Liu K, Lung FW. Difference in prolactin response of schizophrenic patients to equivalent doses of haloperidol, remoxipride and sulpiride. Kao Hsiung I Hsueh Ko Hsueh Tsa Chih Kaohsiung (Journal of Medical Sciences) 1996;12:685‐90. - PubMed
Lovett 1987 {published data only}
    1. Lovett WC, Stokes DK, Taylor LB, Young ML, Free SM, Phelan DG. Management of behavioral symptoms in disturbed elderly patients: comparison of trifluoperazine and haloperidol. Journal of Clinical Psychiatry 1987;48:234‐36. - PubMed
Lublin 1991 {published data only}
    1. Lublin H, Gerlach J, Hagert U, Meidahl B, Molbjerg C, Pedersen V, et al. Zuclopenthixol, a combined dopamine D1/D2 antagonist, versus haloperidol, a dopamine D2 antagonist, in tardive dyskinesia. European Neuropsychopharmacology 1991;1:541‐8. - PubMed
Malt 1995 {published data only}
    1. Malt UF, Nystad R, Bache T, Noren O, Sjaastad M, Solberg KO, et al. Effectiveness of zuclopenthixol compared with haloperidol in the treatment of behavioural disturbances in learning disabled patients. British Journal of Psychiatry 1995;166:374‐7. - PubMed
Mosolov 2000 {published data only}
    1. Mosolov SN, Molodetskikh AV, Eryomin AV, Graikov GM, Nourislamov SV. Effect and tolerability of clopixol and haloperidol in patients with acute symptoms of schizophrenia: comparative randomised investigation. Sotsial'naia I Klinicheskaia Psikhiatria 2000;10:47‐52.
Nahunek 1982 {published data only}
    1. Nahunek K, Svestka J, Ceskova E, Rysanek R. Blind comparison of oxyprothepin and haloperidol in six‐week treatment periods in schizophrenia. Activitas Nervosa Superior 1982;24:219‐20.
Nordic 1986 {published data only}
    1. Gerlach J. Tardive dyskinesia: pathophysiological mechanisms and clinical trials. L'Encephale 1988;14:227‐32. - PubMed
    1. Nordic Dyskinesia Study Group. Effect of different neuroleptics in tardive dyskinesia and parkinsonism. A video‐controlled multicenter study with chlorprothixene, perphenazine, haloperidol and haloperidol + biperiden. Psychopharmacology 1986;90:423‐9. - PubMed
    1. Povlsen UJ, Noring U, Meidahl B, Korsgaard S, Waehrens J, Gerlach J. The effects of neuroleptics on tardive dyskinesias. A video‐controlled, randomized study of chlorprothixene, perphenazine, haloperidol and haloperidol + biperiden [En videokontrolleret, randomiseret undersogelse med klorprotixen, perfenazin, haloperidol og haloperidol + biperiden]. Ugeskrift for Laeger 1987;25:1682‐5. - PubMed
Onodera 1984 {published data only}
    1. Onodera I, Ito K, Ito K. The double‐blind comparative study of bromperidol and haloperidol in the treatment of schizophrenic inpatients. Kiso to Rinsho 1984;18:3349‐71.
Paprocki 1977 {published data only}
    1. Paprocki J, Versiani M. A double‐blind comparison between loxapine and haloperidol by parenteral route in acute schizophrenia. Current Therapeutic Research, Clinical and Experimental 1977;21:80‐100. - PubMed
Pedros Rosello 2004 {published data only}
    1. Pedros Rosello A, Tenias JM. Neuroleptics election and clinical outcomes in acute psychosis: a comparative study of risperidone versus other neuroleptics [Eleccion de neuroleptico y respuesta clinica en psicosis aguda: un estudio comparativo de risperidona frente a otros neurolepticos]. Anales de Psiquiatria 2004;20:167‐71.
Reimold 2007 {published data only}
    1. Reimold M, Solbach C, Noda S, Schaefer JE, Bartels M, Beneke M, et al. Occupancy of dopamine D(1), D (2) and serotonin (2A) receptors in schizophrenic patients treated with flupentixol in comparison with risperidone and haloperidol. Psychopharmacology 2007;190:241‐9. - PubMed
Reznik 2000 {published data only}
    1. Reznik I, Sirota P, Psych M. Obsessive and compulsive symptoms in schizophrenia: a randomized controlled trial with fluvoxamine and neuroleptics. Journal of Clinical Psychopharmacology 2000;20:410‐6. - PubMed
Saletu 1986 {published data only}
    1. Saletu B, Kufferle B, Grunberger J, Anderer P. Quantitative EEG, SPEM, and psychometric studies in schizophrenics before and during differential neuroleptic therapy. Pharmacopsychiatry 19;1986:434‐7. - PubMed
Samuels 1961 {published data only}
    1. Samuels AS. A controlled study of haloperidol: the effects of small dosages. American Journal of Psychiatry 1961;11:253‐4. - PubMed
Serban 1984 {published data only}
    1. Serban G, Siegel S. Response of borderline and schizotypal patients to small doses of thiothixene and haloperidol. American Journal of Psychiatry 1984;141:1455‐8. - PubMed
Simpson 1967 {published data only}
    1. Simpson GM, Angus JW, Edwards JG. A controlled study of haloperidol in chronic schizophrenia. Current Therapeutic Research, Clinical and Experimental 1967;9:407‐12. - PubMed
    1. Simpson GM, Cooper TB, Braun GA. Further studies on the effect of butyrophenones on cholesterol synthesis in humans. Current Therapeutic Research, Clinical and Experimental 1967;9:413‐8. - PubMed
Singh 1976 {published data only}
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Smith 1984 {published data only}
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Stotsky 1977 {published data only}
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Su 2002 {published data only}
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Taymeeyapradit 2002 {published data only}
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Terminska 1989 {published data only}
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van Lommel 1974 {published data only}
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van Putten 1984 {published data only}
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van Putten 1986 {published data only}
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Zuoning 1999 {published data only}
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