Fluphenazine (oral) versus placebo for schizophrenia

Hosam E Matar; Muhammad Qutayba Almerie; Stephanie J Sampson

doi:10.1002/14651858.CD006352.pub3

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Figure 1

Study flow diagram: 2006 search.

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Figure 2

Study flow diagram: 2012 update search (no additional studies).

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Figure 3

Study flow diagram: economic Cochrane Schizophrenia Group’s Health Economic Database (CSzGHED) search 23 July 2013.

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Figure 4

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 5

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 1: Global state: 1. Not improved or worsened

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Analysis 1.2

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 2: Global state: 2. Relapse

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Study	Intervention	Mean	SD	N
Global state: 3. Percentage of time in prodrome state (skewed data)
one‐year data
Marder 1994	Oral fluphenazine	10.5	15.90	17
Marder 1994	Placebo	19.4	22.30	19
two‐year data
Marder 1994	Oral fluphenazine	2.80	3.80	14
Marder 1994	Placebo	4.90	5.70	15

Analysis 1.3

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 3: Global state: 3. Percentage of time in prodrome state (skewed data)

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Study	Intervention	Mean	SD	N
Global state: 4. Percentage of time in exacerbated state (skewed data)
one‐year data
Marder 1994	Oral fluphenazine	11.8	15.00	17
Marder 1994	Placebo	7.20	10.70	19
two‐year data
Marder 1994	Oral fluphenazine	5.50	10.40	14
Marder 1994	Placebo	12.9	13.6	15

Analysis 1.4

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 4: Global state: 4. Percentage of time in exacerbated state (skewed data)

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Analysis 1.5

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 5: Global state: 5. average score: CGI ‐ severity of illness score (high = poor)

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Analysis 1.6

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 6: Leaving the study early: 1. Non‐specific reasons

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Analysis 1.7

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 7: Leaving the study early: 2. Specific reason ‐ short term

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Analysis 1.8

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 8: Leaving the study early: 3. Marked improvement/ hospital discharge

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Analysis 1.9

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 9: Adverse effects: 1. Anticholinergic effects ‐ short term

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Analysis 1.10

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 10: Adverse effects: 2. Cardivascular effects ‐ short term

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Analysis 1.11

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 11: Adverse effects: 3. CNS ‐ short term

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Analysis 1.12

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 12: Adverse effects: 4. Death ‐ long term

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Analysis 1.13

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 13: Adverse effects: 5. Endocrine ‐ short term

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Analysis 1.14

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 14: Adverse effects: 6a. Extrapyramidal effects ‐ short term

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Analysis 1.15

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 15: Adverse effects: 6b. Extrapyramidal effects ‐ medium term

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Analysis 1.16

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 16: Adverse effects: 7. Others ‐ short term

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Analysis 1.17

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 17: Sensitivity analysis: 1. CHRONIC versus ACUTE

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Analysis 1.18

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 18: Sensitivity analysis: 2. LOW DOSES (1‐5 mg/day) versus HIGH DOSES (5mg/day>)

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Analysis 1.19

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 19: Sensitivity analysis: 3. OPERATIONAL CRITERIA versus LOOSE DEFINITIONS

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Analysis 1.20

Comparison 1: ORAL FLUPHENAZINE versus PLACEBO, Outcome 20: Sensitivity analysis: 4. BEFORE 1990 versus AFTER 1990

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Summary of findings 1. ORAL FLUPHENAZINE versus PLACEBO for Schizophrenia

Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
ORAL FLUPHENAZINE versus PLACEBO for Schizophrenia
Patient or population: patients with Schizophrenia Settings: inpatient and outpatient (Australia and US) Intervention: ORAL FLUPHENAZINE versus PLACEBO
	Assumed risk	Corresponding risk
	Control	ORAL FLUPHENAZINE versus PLACEBO
Global state: Not improved or worsened ‐ medium term Dichotomised Montgomery‐Asberg Depression Rating Scale (MDRS) Follow‐up: 12 weeks	680 per 1000¹	762 per 1000 (537 to 1000)	RR 1.12 (0.79 to 1.58)	50 (1 study)	⊕⊝⊝⊝ very low^2,3
Global state: Relapse ‐ long term Clinical judgement Follow‐up: 52 weeks	Low		RR 0.39 (0.05 to 3.31)	86 (2 studies)	⊕⊝⊝⊝ very low^5,6	Note: high degree of heterogeneity between included studies.
	200 per 1000^1,4	78 per 1000 (10 to 662)
	Moderate
	600 per 1000^1,4	234 per 1000 (30 to 1000)
	High
	800 per 1000^1,4	312 per 1000 (40 to 1000)
Adverse effects: Death ‐ long term Occurrences of death Follow‐up: 52 weeks	Low⁷		RR 2.38 (0.1 to 55.72)	50 (1 study)	⊕⊕⊝⊝ low^3,5
	0 per 1000	0 per 1000 (0 to 0)
	Moderate⁷
	30 per 1000	71 per 1000 (3 to 1000)
	High⁷
	90 per 1000	214 per 1000 (9 to 1000)
Adverse effects: Extrapyramidal effects (akathisia) ‐ short term Instances of akathisia Follow‐up: mean 6 weeks	Low⁸		RR 3.43 (1.23 to 9.56)	227 (2 studies)	⊕⊕⊕⊝ moderate⁹
	0 per 1000	0 per 1000 (0 to 0)
	Moderate⁸
	100 per 1000	343 per 1000 (123 to 956)
	High⁸
	200 per 1000	686 per 1000 (246 to 1000)
Adverse effects: Extrapyramidal effects (rigidity) ‐ short term Instances of rigidity Follow‐up: mean 6 weeks	Low¹⁰		RR 3.54 (1.76 to 7.14)	227 (2 studies)	⊕⊕⊕⊝ moderate⁹
	50 per 1000	177 per 1000 (88 to 357)
	Moderate¹⁰
	250 per 1000	885 per 1000 (440 to 1000)
	High¹⁰
	500 per 1000	1000 per 1000 (880 to 1000)
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). CI: Confidence interval; RR: Risk ratio;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
¹ Mean baseline risk presented for single study. ² Risk of bias: rated 'very serious' (downgraded by 2 points) ‐ randomisation unclear, with no mention or description of methods. Raters of scales not stated to be independent of treatment. ³ Imprecision: rated 'serious' (downgraded by 1 point) ‐ 95% confidence intervals for best estimate of effect include both 'no effect' and appreciable benefit/harm. ⁴ Low risk: equates to intervention group (11%) in one study with a higher risk in the other included study (71%); high risk in the control group (74%). ⁵ Risk of bias: rated 'serious' (downgraded by 1 point) ‐ lack of information for participants leaving the study early. Not all adverse effects data reported, and data not reported for various rating scales by intervention group. ⁶ Imprecision: rated 'very serious' (downgraded by 2 points) ‐ only two small studies presented data on this outcome, with considerable heterogeneity present (P = 0.0003; I2 = 92%). ⁷ Low risk: equates to control group (0%), with a moderate risk in the intervention group (3.6%). ⁸ Low risk: equates to control group (3.4%), with a moderate risk in the intervention group (12.7%). ⁹ Risk of bias: rated 'serious' (downgraded by 1 point) ‐ one of the two included studies did not: provide details of randomisation; report SDs for continuous outcomes; account for participants lost to follow‐up. ¹⁰ Low risk: equates to control group (7.7%), with a moderate risk in the intervention group (27.3%). Key: High quality ‐ no downgrading of the evidence. Moderate quality ‐ evidence downgraded by 1 point ('serious'). Low quality ‐ evidence downgraded by 1 point twice ('serious') or 2 points ('very serious'). Very low quality ‐ evidence downgraded any further than listed above.

Summary of findings 1. ORAL FLUPHENAZINE versus PLACEBO for Schizophrenia

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Table 1. Economic summary

Study	Country	Participants	Perspective	Type of Economic Evaluation	Resource Use provided	Unit Costs Provided	ICER	QALY/DALY	Net Benefit Ratio	Grading

Table 1. Economic summary

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Table 2. Economic studies: excluded

Study ID

Status

Reasons for exclusion

Matar 2007

Excluded

Allocation: randomised (current systematic review).

Mardar 1984

Excluded

Allocation: randomised.

Particiapants: schizophrenia.

Interventions: fluphenazine IM.

Table 2. Economic studies: excluded

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Table 3. Economic outcomes: 1. Base case*

*Base Case*	Cost per day (£)	Cost of actual relapse (£)		Cost of relapse for study population (£)**
*Base Case*	Cost per day (£)	Fluphenazine	Placebo	Fluphenazine	Placebo
Median length¹ of stay and mean cost²	5,408	91,936	205,504	1,437	3,425
¹16 days. ²£338. Unlike the effectiveness data of this review, the included economic studies have not been weighted according to sample size; hence risk ratios (RR) of cost of relapse for the study population (if calculated) may not be equal to the RR as calculated by RevMan. Cost attributed to each individual participant within each arm of the trial, irrespective of whether they relapsed or not. **For ease of interpretation, lower number is preferred over higher.

Table 3. Economic outcomes: 1. Base case*

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Table 4. Economic outcomes: 2. Sensitivity analysis*

*Sensitivity analyses*	Cost per day (£)	Cost of actual relapse (£)		Cost of relapse for study population (£)**
*Sensitivity analyses*	Cost per day (£)	Fluphenazine	Placebo	Fluphenazine	Placebo
Mean length of stay¹ and mean cost³	18,049	306,833	685,862	4,794	11,431
Mean length of stay¹ and mean lower quartile cost⁴	15,966	271,422	606,708	4,241	10,112
Mean length of stay¹ and mean upper quartile cost⁵	20,078	341,326	762,964	5,333	12,716
Median length of stay² and mean lower quartile cost⁴	4,784	81,328	181,792	1,271	3,030
Median length of stay² and mean upper quartile cost⁵	6,016	102,272	228,608	1,598	3,810
¹53.4 days ²16 days ³£338 ⁴£299 ⁵£376 Unlike the effectiveness data of this review, the included economic studies have not been weighted according to sample size; hence risk ratios (RR) of cost of relapse for the study population (if calculated) may not be equal to the RR as calculated by RevMan. Cost attributed to each individual participant within each arm of the trial, irrespective of whether they relapsed or not. **For ease of interpretation, lower number is preferred over higher.

Table 4. Economic outcomes: 2. Sensitivity analysis*

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Comparison 1. ORAL FLUPHENAZINE versus PLACEBO

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Global state: 1. Not improved or worsened Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.1.1 short term (CGI/MDRS)	3	125	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.57, 1.12]
1.1.2 medium term (MDRS)	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.79, 1.58]
1.2 Global state: 2. Relapse Show forest plot	3	124	Risk Ratio (M‐H, Random, 95% CI)	0.35 [0.07, 1.68]

1.2.1 short term	1	38	Risk Ratio (M‐H, Random, 95% CI)	0.25 [0.06, 1.03]
1.2.2 long term	2	86	Risk Ratio (M‐H, Random, 95% CI)	0.39 [0.05, 3.31]
1.3 Global state: 3. Percentage of time in prodrome state (skewed data) Show forest plot	1		Other data	No numeric data

1.3.1 one‐year data	1		Other data	No numeric data
1.3.2 two‐year data	1		Other data	No numeric data
1.4 Global state: 4. Percentage of time in exacerbated state (skewed data) Show forest plot	1		Other data	No numeric data

1.4.1 one‐year data	1		Other data	No numeric data
1.4.2 two‐year data	1		Other data	No numeric data
1.5 Global state: 5. average score: CGI ‐ severity of illness score (high = poor) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.5.1 short term	1	36	Mean Difference (IV, Fixed, 95% CI)	‐0.77 [‐1.39, ‐0.15]
1.6 Leaving the study early: 1. Non‐specific reasons Show forest plot	5	363	Risk Ratio (M‐H, Fixed, 95% CI)	0.73 [0.49, 1.10]

1.6.1 short term	2	227	Risk Ratio (M‐H, Fixed, 95% CI)	0.68 [0.43, 1.07]
1.6.2 medium term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	5.00 [0.25, 99.16]
1.6.3 long term	2	86	Risk Ratio (M‐H, Fixed, 95% CI)	0.69 [0.24, 1.97]
1.7 Leaving the study early: 2. Specific reason ‐ short term Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.7.1 administrative/hospital transfer	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.07, 15.64]
1.7.2 AWOL	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.07, 15.64]
1.7.3 court cases, transfer, eloped	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	10.65 [1.39, 81.58]
1.7.4 incorrect diagnosis	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.07, 16.78]
1.7.5 marked early remission	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	2.13 [0.20, 23.10]
1.7.6 serious complication of treatment	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	11.71 [0.66, 208.85]
1.7.7 severe extrapyramidal effects	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	3.00 [0.13, 70.30]
1.7.8 treatment failure	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	0.11 [0.03, 0.35]
1.8 Leaving the study early: 3. Marked improvement/ hospital discharge Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.8.1 discharged due to marked improvement	1	36	Risk Ratio (M‐H, Fixed, 95% CI)	3.00 [0.13, 69.09]
1.9 Adverse effects: 1. Anticholinergic effects ‐ short term Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.9.1 blurred vision	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	5.26 [0.27, 102.66]
1.9.2 constipation	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	2.22 [1.19, 4.15]
1.9.3 drooling	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	3.16 [0.14, 72.84]
1.9.4 dryness mouth or throat	2	227	Risk Ratio (M‐H, Fixed, 95% CI)	3.62 [1.39, 9.42]
1.9.5 gastrointestinal distress and nausea	2	227	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.30, 2.72]
1.9.6 increased salivation	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	18.10 [1.06, 309.15]
1.9.7 nasal congestion	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	3.16 [0.14, 72.84]
1.9.8 urinary disturbance	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	3.20 [0.34, 30.17]
1.9.9 vomiting	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	5.32 [0.26, 109.41]
1.10 Adverse effects: 2. Cardivascular effects ‐ short term Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.10.1 dizziness, faintness, weakness	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	2.34 [0.85, 6.49]
1.10.2 hypotension	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	3.16 [0.14, 72.84]
1.10.3 syncope	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	3.16 [0.14, 72.84]
1.10.4 tachycardia	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	3.16 [0.14, 72.84]
1.11 Adverse effects: 3. CNS ‐ short term Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.11.1 anxiety, agitation, excitement and confusion	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.17, 6.72]
1.11.2 convulsion or seizures	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	0.35 [0.01, 8.60]
1.11.3 depression	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	0.35 [0.02, 8.09]
1.11.4 drowsiness	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	3.91 [1.98, 7.71]
1.11.5 headache	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	1.17 [0.52, 2.63]
1.11.6 sedation and lethargy	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	1.06 [0.31, 3.60]
1.12 Adverse effects: 4. Death ‐ long term Show forest plot	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	2.38 [0.10, 55.72]

1.13 Adverse effects: 5. Endocrine ‐ short term Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.13.1 amenorrhea	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.27, 4.14]
1.13.2 lactation	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	7.45 [0.39, 142.32]
1.13.3 swelling of breasts	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	5.32 [0.26, 109.41]
1.14 Adverse effects: 6a. Extrapyramidal effects ‐ short term Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.14.1 akinesia	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	3.16 [0.14, 72.84]
1.14.2 akathisia	2	227	Risk Ratio (M‐H, Fixed, 95% CI)	3.43 [1.23, 9.56]
1.14.3 associated movements	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	7.37 [0.41, 133.37]
1.14.4 dystonia	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	13.84 [0.79, 242.25]
1.14.5 facial rigidity	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	2.77 [1.03, 7.46]
1.14.6 loss of associated movements	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	6.39 [1.95, 20.98]
1.14.7 restlessness, insomnia	2	227	Risk Ratio (M‐H, Fixed, 95% CI)	0.99 [0.69, 1.40]
1.14.8 rigidity	2	227	Risk Ratio (M‐H, Fixed, 95% CI)	3.54 [1.76, 7.14]
1.14.9 tremor	2	227	Risk Ratio (M‐H, Fixed, 95% CI)	3.19 [1.25, 8.11]
1.15 Adverse effects: 6b. Extrapyramidal effects ‐ medium term Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.15.1 akathisia	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.20 [0.42, 3.43]
1.15.2 akinesia	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	11.00 [0.64, 188.95]
1.15.3 dystonia	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	1.09 [0.92, 1.29]
1.15.4 parkinsonism	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	5.50 [1.36, 22.32]
1.16 Adverse effects: 7. Others ‐ short term Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.16.1 convulsion or seizures	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	0.35 [0.01, 8.60]
1.16.2 diarrhoea	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	5.32 [0.26, 109.41]
1.16.3 intercurrent infection	1	190	Risk Ratio (M‐H, Fixed, 95% CI)	1.07 [0.22, 5.14]
1.16.4 rash	2	227	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.15, 3.78]
1.17 Sensitivity analysis: 1. CHRONIC versus ACUTE Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.17.1 Acute: Global state ‐ not improved ‐ short term	1	37	Risk Ratio (M‐H, Fixed, 95% CI)	0.59 [0.24, 1.42]
1.17.2 Chronic: global state ‐ not improved ‐ short term	1	50	Risk Ratio (M‐H, Fixed, 95% CI)	0.93 [0.56, 1.55]
1.18 Sensitivity analysis: 2. LOW DOSES (1‐5 mg/day) versus HIGH DOSES (5mg/day>) Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.18.1 High dose: Global state ‐ not improved ‐ short term	1	38	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.48, 1.31]
1.18.2 Flexible dose: Global state ‐ not improved ‐ short term	2	87	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.51, 1.25]
1.19 Sensitivity analysis: 3. OPERATIONAL CRITERIA versus LOOSE DEFINITIONS Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.19.1 DSM‐III‐R: Global state ‐ not improved ‐ short term	1	38	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.48, 1.31]
1.19.2 Loose definition: global state ‐ not improved ‐ short term	2	87	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.51, 1.25]
1.20 Sensitivity analysis: 4. BEFORE 1990 versus AFTER 1990 Show forest plot	3		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

1.20.1 Before 1990: Global state ‐ not improved ‐ short term	2	87	Risk Ratio (M‐H, Fixed, 95% CI)	0.80 [0.51, 1.25]
1.20.2 After 1990: Global state ‐ not improved ‐ short term	1	38	Risk Ratio (M‐H, Fixed, 95% CI)	0.79 [0.48, 1.31]

Comparison 1. ORAL FLUPHENAZINE versus PLACEBO

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