Comparison 5. COMPARISON 5. ARIPIPRAZOLE versus OLANZAPINE.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global state: 1.No clinically significant response (as defined by the original studies)	11	1739	Risk Ratio (M‐H, Random, 95% CI)	1.06 [0.96, 1.17]
1.1 up to 12 weeks‐ short term	10	1422	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.86, 1.21]
1.2 from 12 to 26 weeks (medium‐term)	1	317	Risk Ratio (M‐H, Random, 95% CI)	1.08 [0.95, 1.22]
2 Global state: 2. Not responded (decline in PANSS of 30% or more)	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
2.1 by up to 12 weeks (short‐term)	1	566	Risk Ratio (M‐H, Random, 95% CI)	1.16 [1.01, 1.34]
2.2 more than 26 weeks (long‐term)	1	566	Risk Ratio (M‐H, Random, 95% CI)	1.13 [1.00, 1.27]
3 Global state: 3. Remission not achieved (as defined in the study)	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
3.1 by up to 12 weeks (short‐term)	1	566	Risk Ratio (M‐H, Random, 95% CI)	1.01 [0.91, 1.13]
3.2 more than 26 weeks (long‐term)	1	566	Risk Ratio (M‐H, Random, 95% CI)	1.38 [1.23, 1.56]
4 Global state: 4. Average endpoint EI score (CGI, high=poor)	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
4.1 up to 12 weeks ‐ short term	2	180	Mean Difference (IV, Random, 95% CI)	0.0 [‐0.16, 0.16]
5 Global state: 5. Average endpoint CGI score decreased rate (short term, low=poor)	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
6 Global state: 6. Average change score (CGI‐S, decline=best)	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
6.1 more than 26 weeks (long‐term)	1	566	Mean Difference (IV, Random, 95% CI)	0.10 [‐0.12, 0.32]
7 Global state: 7. Improvement (CGI‐I, high=poor)	1	566	Mean Difference (IV, Random, 95% CI)	0.10 [‐0.12, 0.32]
8 Mental state: 1. Average endpoint scale score (PANSS, high=poor)	13		Mean Difference (IV, Random, 95% CI)	Subtotals only
8.1 up to 12 weeks ‐ short term	11	1500	Mean Difference (IV, Random, 95% CI)	0.61 [‐0.23, 1.46]
8.2 12‐ 26 weeks ‐ medium term	2	139	Mean Difference (IV, Random, 95% CI)	0.80 [‐5.26, 6.87]
8.3 more than 26 weeks (long‐term)	1	566	Mean Difference (IV, Random, 95% CI)	4.20 [0.10, 8.30]
9 Mental state: 2. Average endpoint scale score (SANS, high=poor)	2	137	Mean Difference (IV, Random, 95% CI)	‐0.04 [‐2.04, 1.97]
9.1 up to 12 weeks ‐ short term	1	89	Mean Difference (IV, Random, 95% CI)	‐0.04 [‐2.52, 2.44]
9.2 more than 26 weeks ‐ long term	1	48	Mean Difference (IV, Random, 95% CI)	‐0.03 [‐3.45, 3.39]
10 Mental state: 3. average endpoint score (PANSS, high=poor, data skewed)			Other data	No numeric data
10.1 PANSS total			Other data	No numeric data
10.2 PANSS negative symptom subscale score			Other data	No numeric data
10.3 PANSS positive symptom subscale score			Other data	No numeric data
11 Mental state: 4. Specific ‐ average endpoint positive score (PANSS, high=poor)	7	1043	Mean Difference (IV, Random, 95% CI)	0.71 [0.17, 1.26]
11.1 by up to 12 weeks ‐ short term	5	429	Mean Difference (IV, Random, 95% CI)	0.77 [‐0.16, 1.70]
11.2 12‐ 26 weeks ‐ medium term	1	48	Mean Difference (IV, Random, 95% CI)	0.66 [‐1.54, 2.86]
11.3 more than 26 weeks	1	566	Mean Difference (IV, Random, 95% CI)	0.80 [‐0.03, 1.63]
12 Mental state: 5. Specific ‐ average endpoint negative subscale score (PANSS, high=poor)	6	967	Mean Difference (IV, Random, 95% CI)	0.42 [‐0.25, 1.09]
12.1 up to 12 weeks ‐ short term	5	401	Mean Difference (IV, Random, 95% CI)	0.16 [‐0.59, 0.92]
12.2 more than 26 weeks	1	566	Mean Difference (IV, Random, 95% CI)	1.40 [‐0.07, 2.87]
13 Mental state: 6. Specific ‐ average endpoint general pathological score (PANSS, high=poor )	8	642	Mean Difference (IV, Random, 95% CI)	‐0.80 [‐2.24, 0.64]
13.1 up to 12 weeks ‐ short term	7	594	Mean Difference (IV, Random, 95% CI)	‐0.94 [‐2.49, 0.60]
13.2 12‐ 26 weeks ‐ medium term	1	48	Mean Difference (IV, Random, 95% CI)	0.80 [‐3.08, 4.68]
14 Mental state: 7. Specific ‐ binary outcomes	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
14.1 anxiety ‐ labelled as"adverse effect"	2	778	Risk Ratio (M‐H, Random, 95% CI)	1.23 [0.79, 1.90]
14.2 depression ‐ labelled as"adverse effect"	1	566	Risk Ratio (M‐H, Random, 95% CI)	0.27 [0.08, 0.95]
14.3 exacerbation of schizophrenia ‐ labelled as"adverse effect"	2	778	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.50, 1.56]
15 Mental state: 8. Various scale scores decreased rate (low=poor, data skewed)			Other data	No numeric data
15.1 PANSS positive symptom subscale			Other data	No numeric data
15.2 PANSS negative symptom subscale			Other data	No numeric data
15.3 PANSS general pathology subscale			Other data	No numeric data
15.4 BPRS total			Other data	No numeric data
15.5 PANSS total			Other data	No numeric data
16 Adverse effects: 1. At least one adverse effect	9		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
16.1 non‐specific	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.69, 1.30]
16.2 endocrine dyscrasia	1	80	Risk Ratio (M‐H, Random, 95% CI)	0.08 [0.01, 0.61]
16.3 high prolactin level	1	317	Risk Ratio (M‐H, Random, 95% CI)	0.27 [0.12, 0.60]
16.4 liver function abnormal	5	348	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.20, 1.07]
16.5 skin adverse reaction	1	89	Risk Ratio (M‐H, Random, 95% CI)	1.63 [0.41, 6.41]
16.6 sweating‐ increase	2	138	Risk Ratio (M‐H, Random, 95% CI)	3.0 [0.32, 28.16]
16.7 flu syndrome	1	212	Risk Ratio (M‐H, Random, 95% CI)	0.49 [0.16, 1.54]
16.8 respiratory infection	1	212	Risk Ratio (M‐H, Random, 95% CI)	1.54 [0.50, 4.69]
17 Adverse effects: 2. Cardiac effects	8		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
17.1 abnormal ECG	2	121	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.15, 6.29]
17.2 blood pressure‐ decrease	1	89	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.01, 7.80]
17.3 QTc prolongation	3	618	Risk Ratio (M‐H, Random, 95% CI)	0.40 [0.11, 1.38]
17.4 tachycardia	5	339	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.39, 2.08]
18 Adverse effects: 3a. Cardiac ‐ QTc change from baseline (in ms)	1	317	Mean Difference (IV, Random, 95% CI)	‐3.70 [‐9.51, 2.11]
19 Adverse effects: 3b. Central / peripheral nervous system	9		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
19.1 dizziness	6	1057	Risk Ratio (M‐H, Random, 95% CI)	0.98 [0.62, 1.53]
19.2 blurred vision	1	75	Risk Ratio (M‐H, Random, 95% CI)	0.13 [0.01, 2.35]
19.3 headache	5	991	Risk Ratio (M‐H, Random, 95% CI)	2.03 [0.82, 5.07]
19.4 fatigue	3	721	Risk Ratio (M‐H, Random, 95% CI)	0.58 [0.21, 1.62]
19.5 insomnia	7	1141	Risk Ratio (M‐H, Random, 95% CI)	1.81 [0.95, 3.45]
19.6 somnolence	5	1003	Risk Ratio (M‐H, Random, 95% CI)	0.65 [0.42, 1.01]
19.7 headache/dizziness	1	89	Risk Ratio (M‐H, Random, 95% CI)	0.29 [0.09, 1.00]
19.8 sedation	2	883	Risk Ratio (M‐H, Random, 95% CI)	0.37 [0.23, 0.60]
19.9 nervousness	1	212	Risk Ratio (M‐H, Random, 95% CI)	1.32 [0.42, 4.19]
19.10 CNS stimulation	1	212	Risk Ratio (M‐H, Random, 95% CI)	0.73 [0.21, 2.52]
20 Adverse effects: 4. Endocrine ‐ Prolactin ‐ average increase	1	566	Mean Difference (IV, Random, 95% CI)	‐8.89 [‐12.96, ‐4.82]
21 Adverse effects: 5. Extrapyramidal ‐ various	8		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
21.1 Akathisia	6	1320	Risk Ratio (M‐H, Random, 95% CI)	1.56 [0.67, 3.60]
21.2 Tremor	1	61	Risk Ratio (M‐H, Random, 95% CI)	7.23 [0.95, 55.31]
21.3 Extrapyramidal symptoms	4	667	Risk Ratio (M‐H, Random, 95% CI)	0.99 [0.62, 1.59]
21.4 Parkinsonism	3	618	Risk Ratio (M‐H, Random, 95% CI)	0.80 [0.46, 1.38]
22 Adverse effects: 6. Gastrointestinal	7		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
22.1 nausea / vomiting	6	948	Risk Ratio (M‐H, Random, 95% CI)	1.34 [0.80, 2.26]
22.2 constipation	6	443	Risk Ratio (M‐H, Random, 95% CI)	0.46 [0.21, 1.04]
22.3 dry mouth	5	854	Risk Ratio (M‐H, Random, 95% CI)	0.67 [0.38, 1.19]
22.4 abdominal pain ‐ upper	1	566	Risk Ratio (M‐H, Random, 95% CI)	2.96 [1.09, 8.03]
23 Adverse effects: 7. Hormonal	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
23.1 menstrual changes	3	198	Risk Ratio (M‐H, Random, 95% CI)	0.20 [0.04, 1.13]
24 Adverse effects: 8a. Metabolic ‐ binary measures	10		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
24.1 appetite‐ increase	2	655	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.06, 2.00]
24.2  blood glucose ‐ increase	3	227	Risk Ratio (M‐H, Random, 95% CI)	0.12 [0.03, 0.44]
24.3 cholesterol ‐ abnormally high cholesterol value	1	223	Risk Ratio (M‐H, Random, 95% CI)	0.32 [0.19, 0.54]
24.4 lactation	1	60	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.01, 7.87]
24.5 PRL‐ increase	1	89	Risk Ratio (M‐H, Random, 95% CI)	0.09 [0.01, 1.56]
24.6 weight gain	9	1538	Risk Ratio (M‐H, Random, 95% CI)	0.25 [0.15, 0.43]
25 Adverse effects: 8b. Metabolic ‐ continuous measures (high=poor)	5		Mean Difference (IV, Random, 95% CI)	Subtotals only
25.1 weight ‐ average endpoint level (in kg)	3	242	Mean Difference (IV, Random, 95% CI)	‐7.43 [‐9.21, ‐5.65]
25.2 weight gain ‐ change from baseline (in kg)	2	656	Mean Difference (IV, Random, 95% CI)	‐3.03 [‐7.35, 1.29]
25.3 cholesterol ‐ change from baseline (in mg/dl)	2	789	Mean Difference (IV, Random, 95% CI)	‐15.37 [‐21.62, ‐9.11]
25.4 cholesterol ‐ TC average endpoint level (in mmol/L)	2	182	Mean Difference (IV, Random, 95% CI)	‐1.00 [‐1.44, ‐0.56]
25.5 cholesterol ‐ TG average endpoint level (in mmol/L)	1	102	Mean Difference (IV, Random, 95% CI)	‐1.0 [‐1.31, ‐0.69]
25.6 blood glucose ‐ PBG average endpoint level (in mg/dl)	1	60	Mean Difference (IV, Random, 95% CI)	‐0.95 [‐1.27, ‐0.63]
25.7 glucose ‐ change from baseline (in mg/dl)	2	883	Mean Difference (IV, Random, 95% CI)	‐3.39 [‐7.98, 1.19]
26 Adverse effects: 9. Average endpoint scale score (TESS, high=poor, data skewed)			Other data	No numeric data
27 Leaving the study early	9		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
27.1 Any reason	9	2331	Risk Ratio (M‐H, Random, 95% CI)	1.15 [1.05, 1.25]
27.2 Economic issues	1	80	Risk Ratio (M‐H, Random, 95% CI)	3.0 [0.13, 71.51]
27.3 Early discharge	1	60	Risk Ratio (M‐H, Random, 95% CI)	3.0 [0.13, 70.83]
27.4 Refusing therapy	1	60	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.01, 7.87]
27.5 adverse events	4	1352	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.92, 1.59]
27.6 inefficacy	4	1352	Risk Ratio (M‐H, Random, 95% CI)	1.81 [1.23, 2.67]
27.7 lost to follow‐up	2	821	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.46, 1.17]
27.8 medication noncompliance	1	255	Risk Ratio (M‐H, Random, 95% CI)	2.23 [0.71, 7.06]
27.9 others	2	780	Risk Ratio (M‐H, Random, 95% CI)	2.21 [0.77, 6.34]
27.10 patient decision	3	1035	Risk Ratio (M‐H, Random, 95% CI)	1.04 [0.60, 1.81]
27.11 protocol entry or interim criteria not met	1	566	Risk Ratio (M‐H, Random, 95% CI)	0.20 [0.02, 1.68]
27.12 protocol violation	2	821	Risk Ratio (M‐H, Random, 95% CI)	0.80 [0.42, 1.53]
27.13 sponsor decision	1	566	Risk Ratio (M‐H, Random, 95% CI)	0.33 [0.01, 8.03]
27.14 death	1	214	Risk Ratio (M‐H, Random, 95% CI)	0.35 [0.01, 8.55]
28 Quality of life: 1. Average endpoint general quality of life score (GQOLI‐74, low=poor)	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
28.1 Total score	1	68	Mean Difference (IV, Random, 95% CI)	‐1.26 [‐6.37, 3.85]
28.2 Physical health	1	68	Mean Difference (IV, Random, 95% CI)	‐0.19 [‐4.72, 4.34]
28.3 Mental health	1	68	Mean Difference (IV, Random, 95% CI)	‐2.46 [‐8.20, 3.28]
28.4 Social function	1	68	Mean Difference (IV, Random, 95% CI)	1.21 [‐3.41, 5.83]
28.5 Material life	1	68	Mean Difference (IV, Random, 95% CI)	‐0.77 [‐4.62, 3.08]