1 Leaving the study early ‐ any reason Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 short term ‐ up to 6 weeks

2

82

Risk Ratio (M‐H, Fixed, 95% CI)

0.43 [0.16, 1.13]

1.2 medium term ‐ by 12 weeks

2

96

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.28, 0.98]

2 Removed from analysis Show forest plot

3

151

Risk Ratio (M‐H, Fixed, 95% CI)

0.74 [0.26, 2.17]

3 Global effect: 1. Not improved Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3.1 short term ‐ up to 4 weeks

2

78

Risk Ratio (M‐H, Fixed, 95% CI)

0.30 [0.14, 0.63]

3.2 medium term ‐ up to 12 weeks

2

71

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.36, 0.82]

4 Global effect: 2. Needing additional antipsychotic/sedative drugs Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 short term ‐ up to 6 weeks

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

1.39 [0.60, 3.20]

4.2 medium term‐ 7 ‐ 26 weeks

1

38

Risk Ratio (M‐H, Fixed, 95% CI)

0.64 [0.36, 1.13]

5 Mental state: Specific symptoms ‐ anxiety/tension Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 short term ‐ up to 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.14, 1.08]

6 Adverse effects: 1. Any adverse event Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 up to 6 weeks

2

67

Risk Ratio (M‐H, Fixed, 95% CI)

1.51 [1.04, 2.17]

6.2 by 12 weeks

1

38

Risk Ratio (M‐H, Fixed, 95% CI)

2.6 [1.12, 6.01]

7 Adverse effects: 2. Anticholinergic effects ‐ specific symptoms Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 blurred vision ‐ 12 weeks

1

38

Risk Ratio (M‐H, Fixed, 95% CI)

3.77 [0.21, 67.89]

7.2 constipation ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.09, 0.85]

7.3 constipation ‐ 12 weeks

1

36

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

7.4 dry mouth ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.14, 1.08]

8 Adverse effects: 3. Cardiovascular problems Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 ECG abnormalites ‐ 6 weeks

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

1.73 [0.54, 5.59]

8.2 ECG abnormalities ‐ 12 weeks

2

74

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.46, 2.32]

8.3 blood pressure ‐ hypertension ‐ 12 weeks

1

36

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 69.09]

8.4 blood pressure ‐ hypotension, 12 weeks

2

74

Risk Ratio (M‐H, Fixed, 95% CI)

3.77 [0.21, 67.89]

8.5 tachycardia ‐ 12 weeks

1

36

Risk Ratio (M‐H, Fixed, 95% CI)

9.0 [1.27, 63.89]

9 Adverse effects: 4. Gastrointestinal problems Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 abdominal pain ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.12, 0.89]

9.2 nausea or vomiting ‐ short term, up to 6 weeks

3

119

Risk Ratio (M‐H, Fixed, 95% CI)

0.41 [0.18, 0.97]

10 Adverse effects: 5. Movement disorders Show forest plot

6

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10.1 akathisia ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.31, 1.50]

10.2 akathisia ‐ 12 weeks

2

74

Risk Ratio (M‐H, Fixed, 95% CI)

4.65 [0.57, 38.23]

10.3 akinesia ‐ 12 weeks

1

38

Risk Ratio (M‐H, Fixed, 95% CI)

3.77 [0.21, 67.89]

10.4 bradykinesia ‐ 12 weeks

1

38

Risk Ratio (M‐H, Fixed, 95% CI)

4.85 [0.28, 83.66]

10.5 drooling ‐ 12 weeks

2

74

Risk Ratio (M‐H, Fixed, 95% CI)

3.43 [0.41, 29.03]

10.6 dyskinesia ‐ 4 weeks

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

3.47 [0.44, 27.24]

10.7 dyskinesia ‐ 12 weeks

1

38

Risk Ratio (M‐H, Fixed, 95% CI)

3.77 [0.21, 67.89]

10.8 dystonia ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.20, 1.22]

10.9 dystonia ‐ 12 weeks

1

38

Risk Ratio (M‐H, Fixed, 95% CI)

3.77 [0.21, 67.89]

10.10 extrapyramidal symptoms ‐ 4 weeks, unspecified

2

89

Risk Ratio (M‐H, Fixed, 95% CI)

9.68 [3.17, 29.55]

10.11 muscle cramp ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.14, 1.08]

10.12 needing additional anticholinergic medication ‐ 4 weeks

2

67

Risk Ratio (M‐H, Fixed, 95% CI)

4.11 [1.56, 10.83]

10.13 needing additional anticholinergic medication ‐ 12 weeks

1

38

Risk Ratio (M‐H, Fixed, 95% CI)

9.15 [0.57, 147.14]

10.14 oculogyric crisis ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.20, 1.22]

10.15 rigidity ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.53, 1.84]

10.16 rigidity ‐ 12 weeks

2

74

Risk Ratio (M‐H, Fixed, 95% CI)

9.78 [1.27, 75.55]

10.17 thick speech ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.25, 1.36]

10.18 tremor ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.25, 1.36]

10.19 tremor ‐ 12 weeks

1

36

Risk Ratio (M‐H, Fixed, 95% CI)

7.0 [0.39, 126.48]

11 Adverse effects: 6. Neurological Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

11.1 ataxia ‐ up to 6 weeks

2

93

Risk Ratio (M‐H, Fixed, 95% CI)

0.38 [0.14, 1.03]

11.2 dizziness ‐ up to 6 weeks

2

93

Risk Ratio (M‐H, Fixed, 95% CI)

0.46 [0.21, 1.00]

11.3 weakness ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.12, 0.89]

11.4 seizures ‐ 12 weeks

1

36

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.68]

12 Adverse effects: 7. Sleep problems Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

12.1 drowsiness ‐ 4 weeks

2

67

Risk Ratio (M‐H, Fixed, 95% CI)

2.46 [1.09, 5.56]

12.2 drowsiness ‐ 12 weeks

2

74

Risk Ratio (M‐H, Fixed, 95% CI)

6.75 [1.63, 27.89]

12.3 insomnia ‐ up to 6 weeks

2

82

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.25, 1.39]

13 Adverse effects: 8. Weight changes Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1 weight increase ‐ 4 weeks

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.11, 2.94]

13.2 weight increase ‐ 12 weeks

2

74

Risk Ratio (M‐H, Fixed, 95% CI)

6.65 [0.91, 48.77]

13.3 weight loss ‐ 4 weeks

1

28

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.11, 2.94]

13.4 weight loss ‐ 12 weeks

2

74

Risk Ratio (M‐H, Fixed, 95% CI)

0.24 [0.07, 0.87]

14 Adverse effects: 9.Others Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

14.1 abnormal blood results ‐ up to 6 weeks

2

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.32, 1.14]

14.2 abnormal blood results ‐ 12 weeks

2

74

Risk Ratio (M‐H, Fixed, 95% CI)

1.53 [0.76, 3.07]

14.3 eye pigments ‐ 12 weeks

1

36

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.07, 14.79]

14.4 headache ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.29 [0.11, 0.75]

14.5 lactation ‐ 12 weeks

1

36

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

14.6 libido ‐ decrease ‐ 4 weeks

1

39

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

14.7 ringing in ears ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.14, 1.08]

14.8 skin problems ‐ rash, up to 6 weeks

2

93

Risk Ratio (M‐H, Fixed, 95% CI)

0.27 [0.09, 0.85]

14.9 skin problems ‐ rash, 12 weeks

1

36

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

1 Leaving the study early ‐ any reason Show forest plot

16

1305

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.89, 1.38]

1.1 short term ‐ up to 6 weeks

7

380

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.84, 1.34]

1.2 medium term ‐ 7 ‐ 26 weeks

9

925

Risk Ratio (M‐H, Fixed, 95% CI)

1.22 [0.76, 1.97]

2 Removed from analysis Show forest plot

11

793

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.54, 1.79]

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

13

580

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.68, 1.09]

3.1 short term ‐ up to 6 weeks

6

294

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.58, 1.21]

3.2 medium term ‐ 7 ‐ 26 weeks

7

286

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.65, 1.19]

4 Global effect: 2. Not ready for discharge ‐ up to 4 weeks Show forest plot

2

73

Risk Ratio (M‐H, Fixed, 95% CI)

1.18 [0.87, 1.60]

5 Global effect: 3. Needing additional antipsychotic/sedative drugs ‐ up to 6 weeks Show forest plot

2

87

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.62, 2.12]

6 Global effect: 4. Participant rating of illness Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 did not feel better ‐ 4 weeks

2

104

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.69, 2.21]

6.2 much, or very much better ‐ 4 weeks

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.73, 1.37]

6.3 worse ‐ 4 weeks

2

104

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.04, 3.01]

6.4 would not prefer to stay on medication ‐ 4 weeks

2

104

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.78, 1.81]

6.5 prefer another medication ‐ 4 weeks

2

104

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.78, 1.81]

7 Mental state: 1a. General ‐ not improved, by 8 weeks (BPRS/PANSS) Show forest plot

6

915

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.76, 1.05]

8 Mental state: 1b. General ‐ average endpoint score, by 8 weeks (BPRS, high score=worse) Show forest plot

3

465

Mean Difference (IV, Fixed, 95% CI)

‐1.80 [‐2.92, ‐0.67]

9 Mental state: 1c. General ‐ average endpoint score, by 8 weeks (PANSS, high score=worse) Show forest plot

1

80

Mean Difference (IV, Fixed, 95% CI)

‐1.75 [‐8.60, 5.10]

10 Mental state: 1d. General ‐ average change score (BPRS, high score=worse) Show forest plot

3

465

Mean Difference (IV, Fixed, 95% CI)

‐1.38 [‐2.60, ‐0.16]

11 Mental state: 2. Specific Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

11.1 anxiety ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.44 [0.35, 5.81]

11.2 anxiety ‐ 7 ‐ 26 weeks

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.58]

11.3 behaviour changes (not specified), by 12 weeks

2

122

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.59, 1.50]

11.4 depression ‐ 4 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.5 [0.05, 5.19]

11.5 excitement ‐ 4 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

2.0 [0.19, 20.77]

11.6 restlessness ‐ 4 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.25 [0.38, 4.16]

11.7 restlessness ‐ 7 ‐ 26 weeks

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.58]

11.8 violence or aggression ‐ 4 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

2.0 [0.19, 20.77]

12 Adverse effects: 1. Average change score, by 8 weeks (TESS, high score=worse) Show forest plot

3

340

Mean Difference (IV, Fixed, 95% CI)

‐0.07 [‐0.11, ‐0.03]

13 Adverse effects: 2. Any adverse event Show forest plot

14

627

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.88, 1.06]

13.1 up to 6 weeks

7

318

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.91, 1.13]

13.2 7 ‐ 26 weeks

7

309

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.76, 1.05]

14 Adverse effects: 3. Anticholinergic effects ‐ specific symptoms Show forest plot

9

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

14.1 blurred vision ‐ up to 6 weeks

4

187

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.63, 1.39]

14.2 blurred vision ‐ 12 weeks

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

1.58 [0.52, 4.79]

14.3 constipation ‐ 4 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.92, 1.40]

14.4 constipation ‐ 7 ‐ 26 weeks

3

124

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.48, 2.96]

14.5 dry mouth ‐ up to 6 weeks

3

151

Risk Ratio (M‐H, Fixed, 95% CI)

1.35 [0.76, 2.39]

14.6 dry mouth ‐ 7 ‐ 26 weeks

3

147

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.60, 2.26]

14.7 nasal congestion ‐ 12 weeks

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

0.6 [0.11, 3.32]

15 Adverse effects: 4. Cardiovascular problems Show forest plot

12

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

15.1 hypertension ‐ 12 weeks

1

37

Risk Ratio (M‐H, Fixed, 95% CI)

0.53 [0.05, 5.33]

15.2 ECG abnormalites ‐ up to 4 weeks

2

76

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.37, 1.90]

15.3 ECG abnormalities ‐ up to 12 weeks

4

456

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.11, 1.47]

15.4 hypotension ‐ 7 ‐ 26 weeks

5

280

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.46, 1.52]

15.5 syncope ‐ 8 weeks

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

2.7 [0.30, 24.43]

15.6 tachycardia ‐ 7 to 26 weeks

6

365

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.78, 1.47]

15.7 unspecified ‐ 12 weeks

2

122

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.45, 1.54]

16 Adverse effects: 5. Gastrointestinal problems Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

16.1 abdominal pain ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.44 [0.35, 5.81]

16.2 appetite loss ‐ 4 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.49, 1.70]

16.3 constipation ‐ 8 weeks

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

5.0 [0.25, 99.95]

16.4 diarrhoea ‐ 4 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.5 [0.05, 5.19]

16.5 diarrhoea ‐ 12 weeks

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

0.18 [0.01, 3.60]

16.6 nausea or vomiting ‐ 4 weeks

2

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.15, 3.60]

16.7 nausea or vomiting ‐ 12 weeks

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

1.8 [0.17, 18.75]

16.8 stomach trouble ‐ 4 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.12, 3.68]

17 Adverse effects: 6. Movement disorders Show forest plot

19

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

17.1 agitation ‐ 8 weeks

1

132

Risk Ratio (M‐H, Fixed, 95% CI)

0.18 [0.01, 3.18]

17.2 akathisia ‐ up to 6 weeks

3

162

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.52, 2.19]

17.3 akathisia ‐ up to 12 weeks

3

157

Risk Ratio (M‐H, Fixed, 95% CI)

1.22 [0.80, 1.88]

17.4 akinesia ‐ 4 weeks

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

9.0 [0.51, 158.85]

17.5 dyskinesia ‐ 4 weeks

1

29

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.29, 3.03]

17.6 dystonia ‐ up to 6 weeks

4

205

Risk Ratio (M‐H, Fixed, 95% CI)

1.80 [0.91, 3.54]

17.7 dystonia ‐ up to 12 weeks

2

117

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.59, 2.42]

17.8 extrapyramidial ‐ up to 4 weeks

4

169

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.77, 1.23]

17.9 extrapyramidal ‐ up to 12 weeks

4

314

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.85, 1.38]

17.10 excess salivation ‐ 4 weeks

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

1.42 [0.87, 2.31]

17.11 excess salivation ‐ 7 ‐ 26 weeks

3

124

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.39, 2.19]

17.12 fixed stare ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.20, 3.27]

17.13 heavy muscles ‐ up to 6 weeks

2

108

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.21, 2.32]

17.14 muscle cramp ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.44 [0.35, 5.81]

17.15 muscle spasm ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.30, 3.87]

17.16 muscle spasm ‐ 26 weeks

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

2.0 [0.20, 19.78]

17.17 needing additional anticholinergic medication ‐ up to 6 weeks

7

302

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.81, 1.33]

17.18 needing additional anticholinergic medication ‐ up to 12 weeks

3

120

Risk Ratio (M‐H, Fixed, 95% CI)

1.10 [0.71, 1.72]

17.19 oculogyric crisis ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.35 [0.40, 4.48]

17.20 rigidity ‐ up to 6 weeks

4

212

Risk Ratio (M‐H, Fixed, 95% CI)

1.20 [0.96, 1.50]

17.21 rigidity ‐ 7 ‐ 26 weeks

3

124

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.51, 2.06]

17.22 thick speech ‐ up to 6 weeks

2

108

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.44, 3.39]

17.23 tremor ‐ up to 6 weeks

4

212

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.81, 1.51]

17.24 tremor ‐ 7 to 26 weeks

4

184

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.54, 1.32]

17.25 twisting movement ‐ 8 weeks

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

2.0 [0.19, 20.90]

18 Adverse effects: 7. Neurological problems Show forest plot

9

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

18.1 ataxia ‐ 4 weeks

1

41

Risk Ratio (M‐H, Fixed, 95% CI)

0.26 [0.03, 2.15]

18.2 clumsiness ‐ 26 weeks

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 68.26]

18.3 confusion/cloudiness ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.20, 3.27]

18.4 confusion/cloudiness ‐ 7 to 26 weeks

2

87

Risk Ratio (M‐H, Fixed, 95% CI)

2.85 [0.61, 13.24]

18.5 dizziness, fainting, weakness ‐ up to 6 weeks

2

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.37, 2.36]

18.6 dizziness/fainting, weakness ‐ 7 ‐ 26 weeks

3

137

Risk Ratio (M‐H, Fixed, 95% CI)

1.59 [0.67, 3.75]

18.7 giddiness ‐ 4 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.4 [0.08, 1.89]

18.8 seizures ‐ up to 12 weeks

3

302

Risk Ratio (M‐H, Fixed, 95% CI)

3.94 [0.45, 34.72]

18.9 unsteadiness ‐ 26 weeks

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.35, 25.68]

19 Adverse effects: 8. Sleep problems Show forest plot

12

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

19.1 drowsiness / sedation ‐ up to 6 weeks

6

279

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.79, 1.65]

19.2 drowsiness/ sedation ‐ up to 12 weeks

6

408

Risk Ratio (M‐H, Fixed, 95% CI)

1.38 [1.02, 1.86]

19.3 fatigue ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.17, 2.44]

19.4 insomnia ‐ up to 6 weeks

3

137

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.56, 1.81]

19.5 insomnia ‐ up to 12 weeks

2

189

Risk Ratio (M‐H, Fixed, 95% CI)

0.30 [0.13, 0.69]

19.6 lethargy ‐ up to 6 weeks

2

108

Risk Ratio (M‐H, Fixed, 95% CI)

1.69 [0.77, 3.75]

20 Adverse effects: 9. Weight changes Show forest plot

4

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

20.1 weight increase ‐ 6 weeks

1

29

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.10, 2.16]

20.2 weight increase 12 weeks

2

169

Risk Ratio (M‐H, Fixed, 95% CI)

0.57 [0.30, 1.10]

20.3 weight loss ‐ 6 weeks

1

29

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.12, 3.19]

20.4 weight loss ‐ 12 weeks

2

87

Risk Ratio (M‐H, Fixed, 95% CI)

1.38 [0.58, 3.31]

21 Adverse effects: 10. Others Show forest plot

16

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

21.1 abnormal blood results ‐ up to 6 weeks

5

235

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.60, 2.22]

21.2 abnormal blood results ‐ up to 12 weeks

5

506

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.76, 1.47]

21.3 anxiety ‐ 8 weeks

1

132

Risk Ratio (M‐H, Fixed, 95% CI)

0.29 [0.07, 1.20]

21.4 difficulty swallowing ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.20, 3.27]

21.5 headache ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.44 [0.35, 5.81]

21.6 headache ‐ 12 weeks

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

1.35 [0.24, 7.48]

21.7 libido ‐ decrease ‐ 4 weeks

1

41

Risk Ratio (M‐H, Fixed, 95% CI)

0.21 [0.01, 4.11]

21.9 opthalmic changes ‐ 12 weeks

2

86

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.15, 6.81]

21.10 ringing in ears ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.44 [0.35, 5.81]

21.11 skin problems ‐ rash ‐ 4 weeks

2

95

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.09, 1.33]

21.12 skin problems ‐ rash ‐ 7 ‐ 26 weeks

4

184

Risk Ratio (M‐H, Fixed, 95% CI)

0.20 [0.05, 0.77]

21.13 swelling of hands/face ‐ 4 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.28, 1.61]

21.14 swelling of hands/face ‐ 26 weeks

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

5.0 [0.26, 96.13]

21.15 tingling sensation ‐ 6 weeks

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.17, 2.44]

21.16 lactation ‐ 12 weeks

1

37

Risk Ratio (M‐H, Fixed, 95% CI)

0.35 [0.02, 8.09]

21.17 sweating ‐ 72 hours

1

47

Risk Ratio (M‐H, Fixed, 95% CI)

2.09 [0.20, 21.48]

21.18 sweating ‐ 12 weeks

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

0.30 [0.01, 7.09]

21.19 excitement ‐ 12 weeks

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

4.05 [0.96, 17.12]

21.20 depression ‐ 12 weeks

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

1.2 [0.48, 3.02]

21.21 lacrimation ‐12 weeks

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

2.71 [0.12, 63.84]

21.22 breathlessness ‐ 12 weeks

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

2.71 [0.12, 63.84]

21.23 bulimia ‐ 12 weeks

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

2.71 [0.12, 63.84]

21.24 hypersalivation ‐ 8 weeks

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

2.0 [0.55, 7.27]

1 Withdrawn from or leaving the study early ‐ by 72 hours Show forest plot

2

115

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.31, 1.08]

2 General effect: Not tranquilised Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 not sedated / still hostile ‐ at 1hour

3

145

Risk Ratio (M‐H, Fixed, 95% CI)

0.62 [0.47, 0.83]

2.2 not sedated / still hostile ‐ at 6‐24 hours

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.39 [0.04, 3.49]

2.3 requiring further sedation ‐ up to 6 days

2

115

Risk Ratio (M‐H, Fixed, 95% CI)

1.21 [0.62, 2.38]

3 Mental state: Average endpoint score ‐ at 72 hours (BPRS, high score=worse) Show forest plot

1

47

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐7.01, 7.01]

4 Adverse effects: 1. Any event ‐ 72 hours Show forest plot

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

0.8 [0.44, 1.45]

5 Adverse effects: 2. Movement ‐ specific symptoms Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 akathisia ‐ 72 hours

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.51, 2.64]

5.2 drooling ‐ 72 hours

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.14, 4.26]

5.3 dyskinesia ‐ 72 hours

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.06, 6.02]

5.4 dystonia ‐ 72 hours

2

84

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.42, 1.99]

5.5 oculogyric crisis ‐ 72 hours

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.16 [0.01, 3.04]

5.6 rigidity ‐ 72 hours

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.12, 2.90]

5.7 tremor ‐ 72 hours

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.16 [0.01, 3.04]

5.8 thick tongue ‐ 72 hours

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.06, 6.02]

6 Adverse effects: 3. Other Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 anticholinergic ‐ 72 hours

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

1.67 [0.48, 5.76]

6.2 blood test abnormalities ‐ 72 hours

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 68.26]

6.3 dizziness ‐ 72 hours

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

6.0 [0.82, 44.00]

6.4 drowsiness/fatigue ‐ 72 hours

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

1.33 [0.36, 4.97]

6.5 increased blood pressure ‐ 72 hours

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.18, 7.64]

6.6 increased pulse rate ‐ 72 hours

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.06, 6.02]

6.7 nervousness ‐ 72 hours

1

54

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.06, 6.02]

6.8 pain at injection site ‐ 72 hours

2

84

Risk Ratio (M‐H, Fixed, 95% CI)

1.5 [0.29, 7.73]

6.9 palpatations ‐ 72 hours

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 68.26]

1 Leaving the study early ‐ any reason ‐ 12 weeks Show forest plot

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.22 [0.01, 4.08]

2 Global effect: 1. Not improved ‐ 12 weeks Show forest plot

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.22, 1.34]

3 Global effect: 2. Needing additional antipsychotic/sedative drugs ‐ 12 weeks Show forest plot

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

1.3 [0.53, 3.17]

4 Adverse effects: 1. Any event ‐ 12 weeks Show forest plot

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

1.55 [0.88, 2.72]

5 Adverse effects: 2. Anticholinergic effects ‐ specific symptoms Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 blurred vision ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.15 [0.01, 2.70]

6 Adverse effects: 3. Cardiovascular problems Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 blood pressure ‐ hypotension ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.15 [0.01, 2.70]

6.2 ECG abnormalites ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

1.63 [0.60, 4.38]

7 Adverse effects: 4. Movement disorders Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 akathisia ‐ 12 weeks

1

29

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.29, 3.03]

7.2 akinesia ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.06, 5.24]

7.3 bradykinesia ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.36 [0.04, 3.02]

7.4 drooling ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.15 [0.01, 2.70]

7.5 dyskinesia ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.06, 5.24]

7.6 dystonia ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.06, 5.24]

7.7 needing additional anticholinergic medication ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.35, 3.40]

7.8 rigidity ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.33, 1.79]

7.9 tremor ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.37, 2.20]

8 Adverse effects: 5. Sleep problems Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 drowsiness ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

1.22 [0.71, 2.09]

9 Adverse effects: 6. Weight changes Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 weight increase ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.18, 6.53]

9.2 weight loss ‐ 12 weeks

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.54 [0.06, 5.24]

10 Adverse effects: 7. Others ‐ abnormal blood results ‐ 12 weeks Show forest plot

1

25

Risk Ratio (M‐H, Fixed, 95% CI)

0.36 [0.04, 3.02]

1 Leaving the study early‐any reason ‐ 8 weeks Show forest plot

3

218

Risk Ratio (M‐H, Fixed, 95% CI)

1.26 [0.32, 5.00]

2 Removed from analysis ‐ 8 weeks Show forest plot

1

68

Risk Ratio (M‐H, Fixed, 95% CI)

5.0 [0.25, 100.43]

3 Mental state: 1. Not Improved, up to 8 weeks (PANSS) Show forest plot

6

468

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.75, 1.53]

4 Mental state: 2a. Average endpoint score, by 8 weeks (BPRS, high score=worse) Show forest plot

1

60

Mean Difference (IV, Fixed, 95% CI)

1.38 [‐5.81, 8.57]

5 Mental state: 2b. Average endpoint score, by 8 weeks (PANSS, high score=worse) Show forest plot

5

408

Mean Difference (IV, Fixed, 95% CI)

‐1.13 [‐4.08, 1.81]

6 Adverse effects: 1. Average change score, by 8 weeks (TESS, high score=worse) Show forest plot

1

60

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.04, 0.14]

7 Adverse effects: 2. Movement disorders ‐ 8 weeks Show forest plot

5

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 agitation

1

87

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 1.96]

7.2 akathsia

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

6.79 [0.36, 126.24]

7.3 extraparyamidal

4

340

Risk Ratio (M‐H, Fixed, 95% CI)

2.18 [1.55, 3.06]

7.4 increased activity

1

68

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 1.99]

7.5 tremor

2

123

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.82, 1.42]

8 Adverse effects: 3. Cardiovascular ‐ 8 weeks Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 ECG abnormal

2

155

Risk Ratio (M‐H, Fixed, 95% CI)

1.80 [0.70, 4.63]

9 Adverse effects: 4. Sleep problems ‐ 8 weeks Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 insomnia

2

155

Risk Ratio (M‐H, Fixed, 95% CI)

0.18 [0.04, 0.78]

9.2 sleep disturbance

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

0.19 [0.05, 0.81]

10 Adverse effects: 5. Others ‐ 8 weeks Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10.1 amenhorrhea

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

0.32 [0.01, 7.65]

10.2 anxiety

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.27, 3.54]

10.3 dermatitis

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

0.32 [0.01, 7.65]

10.4 enuresis

1

63

Risk Ratio (M‐H, Fixed, 95% CI)

0.32 [0.01, 7.65]

10.5 haematological ‐ leucopenia

2

185

Risk Ratio (M‐H, Fixed, 95% CI)

0.12 [0.02, 0.95]