Antipsychotic medication for early episode schizophrenia

John R Bola; Dennis Kao; Haluk Soydan; Clive E Adams

doi:10.1002/14651858.CD006374.pub2

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Figure 1

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 2

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 CHLORPROMAZINE vs PLACEBO, Outcome 1 Leaving the study early.

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Analysis 1.2

Comparison 1 CHLORPROMAZINE vs PLACEBO, Outcome 2 Global state: not improved after 8 years (Psychiatric rating scale, not improved=1,2; improved=4,5).

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Analysis 1.3

Comparison 1 CHLORPROMAZINE vs PLACEBO, Outcome 3 Rehospitalisation within 3 years ‐ completer.

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Analysis 1.4

Comparison 1 CHLORPROMAZINE vs PLACEBO, Outcome 4 Rehospitalisation within 3 years ‐ intent to treat.

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Analysis 1.5

Comparison 1 CHLORPROMAZINE vs PLACEBO, Outcome 5 Adverse effects: various outcomes.

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Analysis 2.1

Comparison 2 FLUPHENAZINE vs PLACEBO, Outcome 1 Leaving the study early.

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Analysis 2.2

Comparison 2 FLUPHENAZINE vs PLACEBO, Outcome 2 Adverse effects: various outcomes.

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Analysis 3.1

Comparison 3 THIORIDAZINE vs PLACEBO, Outcome 1 Leaving the study early.

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Analysis 3.2

Comparison 3 THIORIDAZINE vs PLACEBO, Outcome 2 Adverse effects: various outcomes.

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Analysis 4.1

Comparison 4 TRIFLUOPERAZINE vs PSYCHOTHERAPY, Outcome 1 Leaving the study early.

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Analysis 4.2

Comparison 4 TRIFLUOPERAZINE vs PSYCHOTHERAPY, Outcome 2 Global state: Overall Health Score ‐ Meninger Health Sickness Scale (higher score=better) 2‐years post‐discharge.

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Analysis 4.3

Comparison 4 TRIFLUOPERAZINE vs PSYCHOTHERAPY, Outcome 3 Adverse effects: number of adverse events.

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Analysis 5.1

Comparison 5 TYPICAL ANTIPSYCHOTIC vs PSYCHOSOCIAL TREATMENT, Outcome 1 Global state: 1.Global Psychopathology Scale.

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Analysis 5.2

Comparison 5 TYPICAL ANTIPSYCHOTIC vs PSYCHOSOCIAL TREATMENT, Outcome 2 Global state: 2. Global Improvement Scale.

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Comparison 1. CHLORPROMAZINE vs PLACEBO

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Leaving the study early Show forest plot	3	353	Risk Ratio (M‐H, Fixed, 95% CI)	0.40 [0.29, 0.54]

2 Global state: not improved after 8 years (Psychiatric rating scale, not improved=1,2; improved=4,5) Show forest plot	1	40	Risk Ratio (M‐H, Fixed, 95% CI)	0.76 [0.53, 1.11]

3 Rehospitalisation within 3 years ‐ completer Show forest plot	1	80	Risk Ratio (M‐H, Fixed, 95% CI)	2.29 [1.31, 4.03]

4 Rehospitalisation within 3 years ‐ intent to treat Show forest plot	1	127	Risk Ratio (M‐H, Fixed, 95% CI)	2.30 [1.50, 3.54]

5 Adverse effects: various outcomes Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

5.1 drowsiness	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	5.65 [2.72, 11.73]
5.2 restlessness	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	1.19 [0.83, 1.71]
5.3 constipation	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	2.71 [1.37, 5.35]
5.4 nausea or upper gastrointestinal distress	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	6.17 [1.92, 19.79]
5.5 dryness of mouth or throat	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	4.63 [1.67, 12.82]
5.6 dizziness, faintness or weakness	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	4.41 [1.59, 12.29]
5.7 muscle rigidity	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	1.54 [0.60, 3.97]
5.8 nasal congestion	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	2.10 [0.69, 6.43]
5.9 facial rigidity	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	2.31 [0.77, 6.96]
5.10 tremor of hands, arms or face	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	1.05 [0.29, 3.77]
5.11 headache	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	0.84 [0.33, 2.13]
5.12 loss of associated movements	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [0.22, 7.35]
5.13 akathesis‐restlessness of feet	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	1.40 [0.35, 5.67]

Comparison 1. CHLORPROMAZINE vs PLACEBO

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Comparison 2. FLUPHENAZINE vs PLACEBO

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Leaving the study early Show forest plot	1	240	Risk Ratio (M‐H, Fixed, 95% CI)	0.51 [0.34, 0.77]

2 Adverse effects: various outcomes Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 drowsiness	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	4.07 [1.92, 8.62]
2.2 restlessness	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.60, 1.34]
2.3 constipation	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	2.26 [1.12, 4.54]
2.4 nausea or upper gastrointestinal distress	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	1.36 [0.33, 5.49]
2.5 dryness of mouth or throat	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	3.46 [1.22, 9.83]
2.6 dizziness, faintness, weakness	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	2.24 [0.74, 6.73]
2.7 muscle rigidity	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	2.98 [1.28, 6.97]
2.8 nasal congestion	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	2.24 [0.74, 6.73]
2.9 facial rigidity	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	2.64 [0.90, 7.77]
2.10 tremor of hands, arms, face	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	2.24 [0.74, 6.73]
2.11 headache	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	1.12 [0.47, 2.64]
2.12 loss of associated movements	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	7.32 [1.75, 30.53]
2.13 akathesis‐restlessness of feet	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	3.52 [1.04, 11.90]

Comparison 2. FLUPHENAZINE vs PLACEBO

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Comparison 3. THIORIDAZINE vs PLACEBO

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Leaving the study early Show forest plot	1	236	Risk Ratio (M‐H, Fixed, 95% CI)	0.44 [0.28, 0.69]

2 Adverse effects: various outcomes Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only

2.1 drowsiness	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	5.46 [2.62, 11.36]
2.2 restlessness	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	1.01 [0.69, 1.48]
2.3 constipation	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	1.72 [0.83, 3.57]
2.4 nausea or upper gastrointestinal distress	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	8.13 [2.58, 25.59]
2.5 dryness of mouth or throat	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	5.69 [2.09, 15.50]
2.6 dizziness, faintness, weakness	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	4.47 [1.61, 12.41]
2.7 muscle rigidity	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	0.54 [0.16, 1.85]
2.8 nasal congestion	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	3.25 [1.14, 9.31]
2.9 facial rigidity	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	1.63 [0.51, 5.19]
2.10 tremor of hands, arms, face	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	2.44 [0.82, 7.25]
2.11 headache	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	0.81 [0.32, 2.06]
2.12 loss of associated movements	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	0.16 [0.01, 3.34]
2.13 akathesis‐restlessness of feet	1	165	Risk Ratio (M‐H, Fixed, 95% CI)	1.36 [0.33, 5.49]

Comparison 3. THIORIDAZINE vs PLACEBO

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Comparison 4. TRIFLUOPERAZINE vs PSYCHOTHERAPY

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Leaving the study early Show forest plot	1	94	Risk Ratio (M‐H, Fixed, 95% CI)	0.96 [0.25, 3.61]

2 Global state: Overall Health Score ‐ Meninger Health Sickness Scale (higher score=better) 2‐years post‐discharge Show forest plot	1	92	Mean Difference (IV, Fixed, 95% CI)	5.80 [1.61, 9.99]

3 Adverse effects: number of adverse events Show forest plot	1	162	Risk Ratio (M‐H, Fixed, 95% CI)	5.65 [2.72, 11.73]

Comparison 4. TRIFLUOPERAZINE vs PSYCHOTHERAPY

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Comparison 5. TYPICAL ANTIPSYCHOTIC vs PSYCHOSOCIAL TREATMENT

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global state: 1.Global Psychopathology Scale Show forest plot	1	89	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.55, 0.57]

2 Global state: 2. Global Improvement Scale Show forest plot	1	89	Mean Difference (IV, Fixed, 95% CI)	‐0.03 [‐0.49, 0.43]

Comparison 5. TYPICAL ANTIPSYCHOTIC vs PSYCHOSOCIAL TREATMENT

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