1 Adverse effects: 1. Autonomic ‐ specific ‐ orthostatic Show forest plot

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.29 [0.01, 6.60]

2 Adverse effects: 2. Extrapyramidal effects Show forest plot

2

64

Risk Ratio (M‐H, Fixed, 95% CI)

5.73 [1.12, 29.34]

2.1 general ‐ extrapyramidal effects ‐ UKU side effect rating scale

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

6.07 [0.86, 43.04]

2.2 specific ‐ tremor

1

36

Risk Ratio (M‐H, Fixed, 95% CI)

5.0 [0.26, 97.37]

3 Adverse effects: 3. 'Psychic' side effects ‐ related to level of arousal Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 specific ‐ excitation

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

2.63 [0.12, 59.40]

3.2 specific ‐ sleepiness / sedation

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

2.89 [1.01, 8.30]

4 Adverse effects: 5. Weight ‐ change (kg) Show forest plot

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.43 [0.17, 1.11]

4.1 loss or gain of weight of 10 pounds (high change=poor)

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.43 [0.17, 1.11]

5 Leaving the study early Show forest plot

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.29 [0.01, 6.60]

5.1 due to adverse effects

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.29 [0.01, 6.60]

1 Global state: 1. Not improved (CGI) Show forest plot

7

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 not 'mildly ill or normal'

2

114

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.55, 1.66]

1.2 unchanged or worse

7

357

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.53, 0.98]

2 Global state: 2. Average score (CGI, high score = poor) Show forest plot

1

40

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐1.30, 0.90]

3 Mental state: 1. Average scores (BPRS, high score=poor) Show forest plot

1

41

Mean Difference (IV, Fixed, 95% CI)

‐2.66 [‐9.09, 3.77]

4 Mental state: 2. Average scores (data skewed, high score=poor) Show forest plot

Other data

No numeric data

4.1 BPRS

Other data

No numeric data

4.2 CPRS

Other data

No numeric data

5 Adverse effects: 1. General non‐specific Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 rated on TESS ‐ unspecified

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

1.5 [0.99, 2.27]

5.2 needing treatment with drugs not used for psychiatric disorders

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.47, 2.10]

5.3 needing treatment with hypnotics/sedative drugs

3

162

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.76, 1.56]

5.4 needing treatment with additional neuroleptic drugs

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.63 [0.35, 1.12]

5.5 adverse effects interfering with patient's functioning

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.64, 1.29]

6 Adverse effects: 2. Autonomic side effects Show forest plot

2

92

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.35, 2.24]

6.1 general ‐ autonomic side effects(UKU side effect rating scale)

1

49

Risk Ratio (M‐H, Fixed, 95% CI)

2.36 [0.71, 7.85]

6.2 specific ‐ orthostatic side effects

1

43

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 1.73]

7 Adverse effects: 3. Extrapyramidal effects Show forest plot

8

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 general ‐ needing antiparkinsonian medication

6

280

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.86, 1.33]

7.2 general ‐ extrapyramidal effects ‐ UKU side effect rating scale

2

92

Risk Ratio (M‐H, Fixed, 95% CI)

0.78 [0.56, 1.09]

7.3 specific ‐ akathisia

1

49

Risk Ratio (M‐H, Fixed, 95% CI)

2.06 [0.60, 7.07]

7.4 specific ‐ hypokinesia / akinesia

1

49

Risk Ratio (M‐H, Fixed, 95% CI)

0.76 [0.30, 1.93]

7.5 specific ‐ dystonia

1

49

Risk Ratio (M‐H, Fixed, 95% CI)

0.30 [0.01, 6.94]

7.6 specific ‐ tremor

2

85

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.29, 1.73]

8 Adverse effects: 4. 'Psychic' side effects ‐ related to level of arousal Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 general ‐ 'psychic' side effects(UKU side effect rating scale)

1

49

Risk Ratio (M‐H, Fixed, 95% CI)

1.77 [0.79, 3.95]

8.2 specific ‐ asthenia

1

49

Risk Ratio (M‐H, Fixed, 95% CI)

1.77 [0.50, 6.28]

8.3 specific ‐ excitation

1

43

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.07, 5.47]

8.4 specific ‐ sleepiness / sedation

2

92

Risk Ratio (M‐H, Fixed, 95% CI)

1.57 [0.93, 2.65]

9 Adverse effects: 5a. Weight ‐ change (kg) Show forest plot

1

43

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.20, 1.23]

9.1 loss or gain of weight of 10 pounds (high change=poor)

1

43

Risk Ratio (M‐H, Fixed, 95% CI)

0.50 [0.20, 1.23]

10 Adverse effects: 5b. Weight ‐ total weight increase (kg) Show forest plot

1

83

Mean Difference (IV, Fixed, 95% CI)

‐1.89 [‐7.89, 4.11]

11 Leaving the study early Show forest plot

10

488

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.52, 0.97]

11.1 any reason

8

424

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.51, 0.95]

11.2 due to adverse effects

2

64

Risk Ratio (M‐H, Fixed, 95% CI)

1.28 [0.18, 8.82]

1 Global state: Unchanged or worse(CGI) Show forest plot

1

98

Risk Ratio (M‐H, Fixed, 95% CI)

1.30 [0.80, 2.11]

2 Mental state: 1. No clinical response Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 not achieving clinical response (at least 20% reduction in the total PANSS score)

1

98

Risk Ratio (M‐H, Fixed, 95% CI)

1.39 [0.92, 2.10]

2.2 not achieving clinical response for the total PANSS ‐ derived BPRS score

1

98

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.82, 1.86]

3 Mental state: 2. Average scores(BPRS, data skewed, high score=poor) Show forest plot

Other data

No numeric data

4 Adverse effects: 1. General ‐ reporting adverse effects (UKU‐side effect rating scale) Show forest plot

1

98

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.87, 1.11]

5 Adverse effects: 2. Autonomic side effects Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 specific ‐ gastrointestinal side effects

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

0.15 [0.01, 2.82]

5.2 specific ‐ anticholinergic side effects

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.29, 2.63]

5.3 specific ‐ orthostatic reaction

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

0.35 [0.01, 8.36]

5.4 specific ‐ headache

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.07, 16.25]

5.5 specific ‐ hypersalivation

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.07, 16.25]

5.6 specific ‐ dizziness

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.16, 7.10]

6 Adverse effects: 3. Extrapyramidal effects Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 general ‐ extrapyramidal side effects(ESRS)

1

98

Risk Ratio (M‐H, Fixed, 95% CI)

1.5 [0.92, 2.44]

6.2 general ‐ needing antiparkinsonian medication

1

98

Risk Ratio (M‐H, Fixed, 95% CI)

1.92 [1.12, 3.28]

6.3 specific ‐ hypokinesia

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.07, 16.25]

6.4 specific ‐ hyperkinesia

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

3.16 [0.13, 75.20]

6.5 specific ‐ rigor

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

2.11 [0.20, 22.29]

6.6 specific ‐ tremor

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

2.11 [0.20, 22.29]

6.7 specific ‐ akathisia

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.07, 16.25]

7 Adverse effects: 4. 'Psychic' side effects ‐ related to level of arousal Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 specific ‐ drowsiness

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.29, 3.91]

7.2 specific ‐ stimulation

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.24, 1.83]

7.3 specific ‐ confusion

1

74

Risk Ratio (M‐H, Fixed, 95% CI)

0.35 [0.01, 8.36]

8 Adverse effects: 5. Weight ‐ change (kg) Show forest plot

1

40

Mean Difference (IV, Fixed, 95% CI)

‐1.60 [‐10.06, 6.86]

9 Leaving the study early Show forest plot

2

159

Risk Ratio (M‐H, Fixed, 95% CI)

1.48 [0.98, 2.22]

1 Global state: Unchanged or worse (CGI) Show forest plot

3

131

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.76, 1.52]

2 Adverse effects: 1. General non‐specific ‐ interfering with functioning/outweighing therapeutic effect Show forest plot

3

131

Risk Ratio (M‐H, Fixed, 95% CI)

0.74 [0.46, 1.21]

3 Adverse effects: 1. Extrapyramidal effects ‐ treatment with antiparkinsonian drug Show forest plot

1

20

Risk Ratio (M‐H, Fixed, 95% CI)

1.4 [0.67, 2.94]

4 Adverse effects: 3. 'Psychic' ‐ sedation Show forest plot

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

0.19 [0.02, 1.55]

5 Leaving the study early ‐ by 1 week Show forest plot

2

29

Risk Ratio (M‐H, Fixed, 95% CI)

5.0 [0.27, 92.62]