Haloperidol versus placebo for schizophrenia
Information
- DOI:
- https://doi.org/10.1002/14651858.CD003082.pub3Copy DOI
- Database:
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- Cochrane Database of Systematic Reviews
- Version published:
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- 15 November 2013see what's new
- Type:
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- Intervention
- Stage:
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- Review
- Cochrane Editorial Group:
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Cochrane Schizophrenia Group
- Copyright:
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- Copyright © 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Cited by:
Authors
Contributions of authors
Claire Irving (nee Joy) ‐ selection of trials, data extraction, writing original review.
Clive Adams ‐ 10% check of trials, writing review and help with update.
Steve Laurie ‐ selection of trials, 10% data extraction check, writing original review.
Hanna Bergman ‐ updated the review to the current version, including applying new methods and adding 'Summary of findings' table.
Sources of support
Internal sources
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Cochrane Schizophrenia Group General Fund, UK.
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University of Oxford Department of Psychiatry, UK.
External sources
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NHS Executive Anglia and Oxford R&D Directorate, UK.
Declarations of interest
Claire Irving (nee Joy) ‐ None.
Clive Adams (CEA) ‐ has attended and presented at functions sponsored by Janssen‐Cilag and Eli Lilly. These companies have provided travel, accommodation and speaker expenses but no funds have been paid directly to CEA. Payments related to participation in meetings have been paid to an account to support schizophrenia research. The Cochrane Schizophrenia Group has multiple, and hopefully, balancing, competing interests. Potential conflicts of interest of the Group and individuals are described on http://cebmh.warne.ox.ac.uk/csg/ and sources and quantities of all funding, listed.
Steve Lawrie ‐ has been paid for speaking about critical appraisal by employees of the manufacturers of olanzapine, quetiapine, risperidone, and ziprasidone, and has been paid to speak about the management of schizophrenia by employees of the manufacturers of amisulpiride, olanzapine, risperidone, and clozapine. AM and ZN declare that they have no competing interests.
Hanna Bergman ‐ works for Enhance Reviews. Enhance Reviews Ltd is a private company that performs systematic reviews of the literature.
Acknowledgements
The review authors would like to thank the funders (NHS R&D, UK) who had the vision to support this important review. Dr Jo Wood, then of Janssen‐Cilag Limited, UK, was also generous of her time and supplied a stream of rare reports of trials. We would also like to thank those who have provided editorial input to this review.
Enhance Reviews provided support for the 2012 update of this review in the screening, data extraction, analysis and write‐up of results.
Version history
| Published | Title | Stage | Authors | Version |
| 2013 Nov 15 | Haloperidol versus placebo for schizophrenia | Review | Clive E Adams, Hanna Bergman, Claire B Irving, Stephen Lawrie | |
| 2006 Oct 18 | Haloperidol versus placebo for schizophrenia | Review | Claire B Irving, Clive E Adams, Stephen Lawrie | |
| 2001 Apr 23 | Haloperidol versus placebo for schizophrenia | Review | Claire Bronwen Joy, Clive E Adams, Stephen Lawrie | |
Differences between protocol and review
We have updated the methods section to reflect new Cochrane methodology since the last publication of this review, for example addition of a 'Summary of findings' table.
Keywords
MeSH
Medical Subject Headings (MeSH) Keywords
- Akathisia, Drug‐Induced [etiology];
- Antipsychotic Agents [adverse effects, *therapeutic use];
- Dystonia [chemically induced];
- Haloperidol [adverse effects, *therapeutic use];
- Parkinsonian Disorders [chemically induced];
- Placebo Effect;
- Randomized Controlled Trials as Topic;
- Schizophrenia [*drug therapy];
- Treatment Outcome;
Medical Subject Headings Check Words
Humans;
PICOs
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 1 Global state: 1a. Overall improvement: No marked global improvement.
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 2 Global state: 1b. Overall improvement: Average change in CGI‐S score (up to 6 weeks; high = poor).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 3 Global state: 2. Hospital discharge: Not discharged from hospital (> 6‐24 weeks).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 4 Global state: 3. Relapse (< 52 weeks).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 5 Global state: 4. Leaving the study early.
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 6 Mental state: 1. No clinical improvement (< 20% reduction in BPRS score; up to 6 weeks).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 7 Mental state: 2a. General symptoms: Average BPRS total score (up to 6 weeks; high = poor).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 8 Mental state: 2b. General symptoms: Average change in PANSS total score (up to 6 weeks; high = poor).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 9 Mental state: 3. Positive symptoms: Average change in PANSS positive score (up to 6 weeks; high = poor).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 10 Mental state: 4. Negative symptoms: Average change in PANSS negative score (up to 6 weeks; high = poor).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 11 Mental state: 5. Mood: Average change in CDS score (up to 6 weeks; high = poor).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 12 Adverse effects: 1a. Movement disorders: Extrapyramidal symptoms.
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 13 Adverse effects: 1b. Movement disorders: Tardive dyskinesia.
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 14 Adverse effects: 1c. Movement disorders: Average changes scores (various scales; up to 6 weeks).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 15 Adverse effects: 2. Other CNS.
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 16 Adverse effects: 3. Cardiovascular effects.
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 17 Adverse effects: 4. Other adverse effects.
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 18 SUBGROUP ANALYSIS: 1. MEN vs WOMEN: Global state: Overall improvement: No marked global improvement, > 6‐24 weeks (clinician rated).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 19 SUBGROUP ANALYSIS: 2. 18‐65 YEARS vs < 18 YEARS: Global state: Overall improvement: No marked global improvement, > 6‐24 weeks (clinician rated).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 20 SUBGROUP ANALYSIS: 3. ACUTE vs CHRONIC: Global state: Overall improvement: No marked global improvement, > 6‐24 weeks (clinician rated).
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 21 SUBGROUP ANALYSIS: 4. LOW DOSE vs MEDIUM TO HIGH DOSE.
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 22 SUBGROUP ANALYSIS: 5. DIAGNOSTIC CRITERIA vs NO DIAGNOSTIC CRITERIA.
Comparison 1 HALOPERIDOL versus PLACEBO, Outcome 23 SENSITIVITY ANALYSIS: 1. ASSUMPTIONS FOR MISSING DATA vs NO ASSUMPTIONS FOR MISSING DATA: Global state: Overall improvement: No marked global improvement, up to 6 weeks (clinician rated).
| HALOPERIDOL versus PLACEBO for schizophrenia | ||||||
| Patient or population: patients with schizophrenia | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | HALOPERIDOL versus PLACEBO | |||||
| Death ‐ suicide and natural causes | See comment | See comment | Not estimable | 0 | See comment | No studies reported on this outcome. |
| Overall improvement: No marked global improvement | 841 per 1000 | 564 per 1000 | RR 0.67 | 307 | ⊕⊕⊕⊝ | Another four trials reported on this outcome at up to six weeks follow‐up, and one trial at > 6‐24 weeks follow‐up using a nurse‐rated scale, both sub‐analyses showed significant results in favour of haloperidol. |
| Not discharged from hospital | 625 per 1000 | 531 per 1000 | RR 0.85 | 33 | ⊕⊝⊝⊝ | |
| Relapse | 1000 per 1000 | 690 per 1000 | RR 0.69 | 70 | ⊕⊝⊝⊝ | |
| Leaving the study early | 134 per 1000 | 72 per 1000 | RR 0.54 | 304 | ⊕⊕⊕⊝ | Another 16 trials reported on this outcome at up to six weeks follow‐up showing a significant result in favour of haloperidol. One trial at < 52 weeks follow‐up showed no difference between haloperidol and placebo. |
| Satisfaction with treatment | See comment | See comment | Not estimable | 0 | See comment | No studies reported on this outcome. |
| Adverse effects: Movement disorders ‐ parkinsonism | 28 per 1000 | 154 per 1000 | RR 5.48 | 485 | ⊕⊕⊕⊝ | Several studies also reported on other, specific movement disorders: there was a significant result favouring placebo for akathisia, dystonia, needing anti‐Parkinson medication, rigidity and tremor; there was no difference between haloperidol and placebo for tardive dyskinesia, oculogyric crises, teeth grinding and 'thick' speech. |
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1 Seven out of the eight included studies had an unclear risk of bias for random sequence generation and for allocation concealment. Blinding of participants and personnel was unclear in four studies and blinding of assessors was unclear in six. Two studies had an unclear risk of bias for incomplete outcome data. One study had a high risk of other bias as they were funded by industry and three an unclear risk of bias as the drugs were provided by a pharmaceutical company. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Global state: 1a. Overall improvement: No marked global improvement Show forest plot | 11 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 1.1 up to 6 weeks (clinician rated) | 4 | 472 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.56, 0.80] |
| 1.2 > 6‐24 weeks (clinician rated) | 8 | 307 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.58, 0.78] |
| 1.3 > 6‐24 weeks (nurse rated) | 1 | 28 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.59 [0.37, 0.92] |
| 2 Global state: 1b. Overall improvement: Average change in CGI‐S score (up to 6 weeks; high = poor) Show forest plot | 2 | 353 | Mean Difference (IV, Fixed, 95% CI) | ‐0.49 [‐0.73, ‐0.25] |
| 3 Global state: 2. Hospital discharge: Not discharged from hospital (> 6‐24 weeks) Show forest plot | 1 | 33 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.85 [0.47, 1.52] |
| 4 Global state: 3. Relapse (< 52 weeks) Show forest plot | 2 | 70 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.55, 0.86] |
| 5 Global state: 4. Leaving the study early Show forest plot | 24 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 5.1 up to 6 weeks | 16 | 1812 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.87 [0.80, 0.95] |
| 5.2 > 6‐24 weeks | 8 | 304 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.54 [0.29, 1.00] |
| 5.3 < 52 weeks | 1 | 50 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.58 [0.14, 46.83] |
| 6 Mental state: 1. No clinical improvement (< 20% reduction in BPRS score; up to 6 weeks) Show forest plot | 1 | 24 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.76 [0.54, 1.08] |
| 7 Mental state: 2a. General symptoms: Average BPRS total score (up to 6 weeks; high = poor) Show forest plot | 3 | 108 | Mean Difference (IV, Fixed, 95% CI) | ‐9.76 [‐14.60, ‐4.93] |
| 8 Mental state: 2b. General symptoms: Average change in PANSS total score (up to 6 weeks; high = poor) Show forest plot | 1 | 119 | Mean Difference (IV, Fixed, 95% CI) | ‐15.58 [‐23.92, ‐7.24] |
| 9 Mental state: 3. Positive symptoms: Average change in PANSS positive score (up to 6 weeks; high = poor) Show forest plot | 2 | 353 | Mean Difference (IV, Fixed, 95% CI) | ‐3.29 [‐4.70, ‐1.89] |
| 10 Mental state: 4. Negative symptoms: Average change in PANSS negative score (up to 6 weeks; high = poor) Show forest plot | 2 | 353 | Mean Difference (IV, Fixed, 95% CI) | ‐1.18 [‐2.32, ‐0.04] |
| 11 Mental state: 5. Mood: Average change in CDS score (up to 6 weeks; high = poor) Show forest plot | 1 | 234 | Mean Difference (IV, Fixed, 95% CI) | ‐0.30 [‐1.20, 0.60] |
| 12 Adverse effects: 1a. Movement disorders: Extrapyramidal symptoms Show forest plot | 11 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 12.1 akathisia | 6 | 695 | Risk Ratio (M‐H, Fixed, 95% CI) | 3.66 [2.24, 5.97] |
| 12.2 dystonia | 5 | 471 | Risk Ratio (M‐H, Fixed, 95% CI) | 11.49 [3.23, 40.85] |
| 12.3 needing antiparkinson medication | 4 | 480 | Risk Ratio (M‐H, Fixed, 95% CI) | 3.23 [2.20, 4.72] |
| 12.4 oculogyric crises | 2 | 83 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.97 [0.14, 6.57] |
| 12.5 parkinsonism (including EPS) | 5 | 485 | Risk Ratio (M‐H, Fixed, 95% CI) | 5.48 [2.68, 11.22] |
| 12.6 rigidity | 5 | 461 | Risk Ratio (M‐H, Fixed, 95% CI) | 4.98 [2.74, 9.05] |
| 12.7 teeth grinding | 1 | 33 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.53 [0.11, 57.83] |
| 12.8 'thick' speech | 1 | 33 | Risk Ratio (M‐H, Fixed, 95% CI) | 5.89 [0.33, 105.81] |
| 12.9 tremor | 5 | 447 | Risk Ratio (M‐H, Fixed, 95% CI) | 3.93 [1.96, 7.91] |
| 13 Adverse effects: 1b. Movement disorders: Tardive dyskinesia Show forest plot | 2 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 13.1 dyskinesia and tardive dyskinesia | 2 | 157 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.00 [0.14, 7.13] |
| 14 Adverse effects: 1c. Movement disorders: Average changes scores (various scales; up to 6 weeks) Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 14.1 AIMS (high = poor) | 1 | 231 | Mean Difference (IV, Fixed, 95% CI) | ‐0.29 [‐0.71, 0.13] |
| 14.2 BAS (high = poor) | 1 | 231 | Mean Difference (IV, Fixed, 95% CI) | 0.31 [0.10, 0.52] |
| 14.3 SAS (high = poor) | 1 | 231 | Mean Difference (IV, Fixed, 95% CI) | 1.48 [0.76, 2.20] |
| 15 Adverse effects: 2. Other CNS Show forest plot | 3 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 15.1 blurred vision | 2 | 240 | Risk Ratio (M‐H, Fixed, 95% CI) | 3.96 [1.21, 12.93] |
| 15.2 confusion | 1 | 33 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.53 [0.11, 57.83] |
| 15.3 dry mouth | 1 | 33 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.67 [0.62, 4.46] |
| 15.4 sedation | 1 | 238 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.86 [0.24, 3.11] |
| 16 Adverse effects: 3. Cardiovascular effects Show forest plot | 5 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 16.1 blood pressure ‐ dizziness/low BP | 3 | 245 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.01 [0.36, 2.79] |
| 16.2 blood pressure ‐ high BP | 1 | 16 | Risk Ratio (M‐H, Fixed, 95% CI) | 3.0 [0.14, 64.26] |
| 16.3 bradycardia | 1 | 124 | Risk Ratio (M‐H, Fixed, 95% CI) | 4.27 [0.49, 37.10] |
| 17 Adverse effects: 4. Other adverse effects Show forest plot | 9 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 17.1 agitation | 2 | 362 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.07 [0.54, 2.12] |
| 17.2 anxiety | 2 | 362 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.84 [0.33, 2.16] |
| 17.3 drooling | 3 | 207 | Risk Ratio (M‐H, Fixed, 95% CI) | 4.00 [0.88, 18.21] |
| 17.4 facial oedema | 1 | 33 | Risk Ratio (M‐H, Fixed, 95% CI) | 2.83 [0.12, 64.89] |
| 17.5 headache | 4 | 593 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.93 [0.62, 1.39] |
| 17.6 infection | 1 | 24 | Risk Ratio (M‐H, Fixed, 95% CI) | 7.0 [0.40, 122.44] |
| 17.7 insomnia | 4 | 629 | Risk Ratio (M‐H, Fixed, 95% CI) | 1.11 [0.76, 1.63] |
| 17.8 nausea/vomiting | 2 | 231 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.90 [0.49, 1.65] |
| 17.9 oral hypoaesthesia | 1 | 238 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.15 [0.01, 2.92] |
| 17.10 perspiration | 2 | 93 | Risk Ratio (M‐H, Fixed, 95% CI) | 4.74 [0.58, 38.81] |
| 17.11 sleepiness | 7 | 686 | Risk Ratio (M‐H, Fixed, 95% CI) | 3.09 [1.51, 6.31] |
| 17.12 weight gain | 2 | 441 | Risk Ratio (M‐H, Fixed, 95% CI) | 4.89 [1.41, 16.95] |
| 17.13 weight loss | 3 | 385 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.77 [0.36, 1.64] |
| 18 SUBGROUP ANALYSIS: 1. MEN vs WOMEN: Global state: Overall improvement: No marked global improvement, > 6‐24 weeks (clinician rated) Show forest plot | 3 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 18.1 only men | 1 | 24 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.47 [0.27, 0.82] |
| 18.2 only women | 2 | 88 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.69 [0.55, 0.87] |
| 19 SUBGROUP ANALYSIS: 2. 18‐65 YEARS vs < 18 YEARS: Global state: Overall improvement: No marked global improvement, > 6‐24 weeks (clinician rated) Show forest plot | 8 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 19.1 18‐65 years | 7 | 284 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.70 [0.61, 0.80] |
| 19.2 < 18 years | 1 | 24 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.27 [0.10, 0.74] |
| 20 SUBGROUP ANALYSIS: 3. ACUTE vs CHRONIC: Global state: Overall improvement: No marked global improvement, > 6‐24 weeks (clinician rated) Show forest plot | 8 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 20.1 acute phase of illness | 1 | 58 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.56 [0.30, 1.06] |
| 20.2 chronic phase of illness | 7 | 250 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.68 [0.59, 0.78] |
| 21 SUBGROUP ANALYSIS: 4. LOW DOSE vs MEDIUM TO HIGH DOSE Show forest plot | 11 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 21.1 low dose (≤ 5 mg/day) ‐ Global state: Overall improvement: No marked global improvement, up to 6 weeks (clinician rated) | 1 | 234 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.85 [0.69, 1.04] |
| 21.2 medium to high dose (> 5 mg/day) ‐ Global state: Overall improvement: No marked global improvement, up to 6 weeks (clinician rated) | 3 | 238 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.48 [0.35, 0.66] |
| 21.3 low dose (≤ 5 mg/day) ‐ Global state: Overall improvement: No marked global improvement, > 6‐24 weeks (clinician rated) | 4 | 149 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.55, 0.81] |
| 21.4 medium to high dose (> 5 mg/day) ‐ Global state: Overall improvement: No marked global improvement, > 6‐24 weeks (clinician rated) | 5 | 165 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.54, 0.83] |
| 22 SUBGROUP ANALYSIS: 5. DIAGNOSTIC CRITERIA vs NO DIAGNOSTIC CRITERIA Show forest plot | 13 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 22.1 operational criteria used for diagnosis ‐ Global state: Overall improvement: No marked global improvement, up to 6 weeks (clinician rated) | 3 | 414 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.67 [0.56, 0.81] |
| 22.2 no operational criteria used for diagnosis ‐ Global state: Overall improvement: No marked global improvement, up to 6 weeks (clinician rated) | 1 | 58 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.64 [0.33, 1.24] |
| 22.3 operational criteria used for diagnosis ‐ Global state: Overall improvement: No marked global improvement, > 6‐24 weeks (clinician rated) | 1 | 24 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.27 [0.10, 0.74] |
| 22.4 no operational criteria used for diagnosis ‐ Global state: Overall improvement: No marked global improvement, > 6‐24 weeks (clinician rated) | 7 | 284 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.70 [0.61, 0.80] |
| 22.5 operational criteria used for diagnosis ‐ Global state: Relapse (< 52 weeks) | 1 | 50 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.57, 0.91] |
| 22.6 no operational criteria used for diagnosis ‐ Global state: Relapse (< 52 weeks) | 1 | 20 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.62 [0.37, 1.03] |
| 23 SENSITIVITY ANALYSIS: 1. ASSUMPTIONS FOR MISSING DATA vs NO ASSUMPTIONS FOR MISSING DATA: Global state: Overall improvement: No marked global improvement, up to 6 weeks (clinician rated) Show forest plot | 3 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
| 23.1 no assumptions for missing data | 3 | 353 | Risk Ratio (M‐H, Fixed, 95% CI) | 0.72 [0.60, 0.87] |
