Comparison 1. LOXAPINE versus PLACEBO.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Leaving the study early ‐ any reason	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	3	151	Risk Ratio (M‐H, Fixed, 95% CI)	0.74 [0.26, 2.17]
3 Global effect: 1. Not improved	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	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	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	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	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	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	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	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	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	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	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	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]