Comparison 1. Antipsychotic dose increase versus antipsychotic dose maintenance.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Global state: 1a. Clinically relevant response as defined by trials	9	533	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.86, 1.40]
2 Global state: 1b. Any change (improvement in Global Assesment scale)	1	23	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.32, 1.80]
3 Global state: 2a. Average endpoint score (CGI‐Severity , high = poor)	3	196	Mean Difference (IV, Random, 95% CI)	‐0.11 [‐0.40, 0.19]
4 Global state: 2b. Average change score ( CGI‐Severity, high = poor)	1	95	Mean Difference (IV, Random, 95% CI)	‐0.4 [‐0.80, ‐0.00]
5 Global state: 2c. Average endpoint score (CGI‐Improvement, high = poor)	1	103	Mean Difference (IV, Random, 95% CI)	0.0 [‐0.35, 0.35]
6 Leaving the study early: 1. Tolerability ‐ due to adverse events	7	496	Risk Ratio (M‐H, Random, 95% CI)	1.63 [0.52, 5.07]
7 Leaving the study early: 2. Acceptability of treatment ‐ due to any reason	5	353	Risk Ratio (M‐H, Random, 95% CI)	1.30 [0.89, 1.90]
8 Leaving the study early: 3. Efficacy ‐ due to inefficacy	4	336	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.30, 2.28]
9 Mental state: 1a. General ‐ average endpoint score (PANSS total, high = poor)	2	191	Mean Difference (IV, Random, 95% CI)	‐1.81 [‐7.31, 3.69]
10 Mental state: 1b. General ‐ average change score (PANSS total, high = poor)	3	258	Mean Difference (IV, Random, 95% CI)	‐1.44 [‐6.85, 3.97]
11 Mental state: 1c. General ‐ average endpoint and/or change score (PANSS total, high = poor)	4	389	Mean Difference (IV, Random, 95% CI)	‐2.13 [‐6.16, 1.90]
12 Mental state: 1d. General ‐ average endpoint score (BPRS total, high = poor)	3	99	Mean Difference (IV, Random, 95% CI)	‐1.25 [‐4.60, 2.11]
13 Mental state: 1e. General ‐ average change score (BPRS total, high = poor)	1	42	Mean Difference (IV, Random, 95% CI)	‐2.38 [‐6.15, 1.39]
14 Mental state: 1f. General ‐ average endpoint and/or change score (BPRS total, high = poor)	4	141	Mean Difference (IV, Random, 95% CI)	‐1.75 [‐4.25, 0.76]
15 Mental state: 1g. General ‐ average change score (NOSIE total, high = poor)	1	42	Mean Difference (IV, Random, 95% CI)	3.70 [‐5.38, 12.78]
16 Mental state: 2a. Positive symptoms ‐ Clinically important change	1	17	Risk Ratio (M‐H, Random, 95% CI)	1.33 [0.58, 3.07]
17 Mental state: 2b. Positive symptoms ‐ average endpoint subscore (PANSS positive, high = poor)	2	191	Mean Difference (IV, Random, 95% CI)	‐0.94 [‐2.79, 0.90]
18 Mental state: 2c. Positive symptoms ‐ average change subscore (PANSS positive, high = poor)	3	238	Mean Difference (IV, Random, 95% CI)	0.04 [‐1.31, 1.40]
19 Mental state: 2d. Positive symptoms ‐ average endpoint subscore (BPRS positive,high = poor)	1	17	Mean Difference (IV, Random, 95% CI)	0.40 [‐2.94, 3.74]
20 Mental state: 3a. Negative symptoms ‐ average endpoint subscore (PANSS negative, high = poor)	2	191	Mean Difference (IV, Random, 95% CI)	0.32 [‐1.48, 2.11]
21 Mental state: 3b. Negative symptoms ‐ average change subscore (PANSS negative, high = poor)	2	163	Mean Difference (IV, Random, 95% CI)	‐0.15 [‐0.96, 0.67]
22 Mental state: 3c. Negative symptoms ‐ average endpoint subscore (BPRS negative, high = poor)	1	17	Mean Difference (IV, Random, 95% CI)	‐0.40 [‐1.97, 1.17]
23 Mental state: 3d. Negative symptoms ‐ average endpoint score (SANS, high = poor)	1	34	Mean Difference (IV, Random, 95% CI)	1.5 [‐14.33, 17.33]
24 Adverse effects ‐ At least one adverse effect	2	191	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.55, 1.50]
25 Adverse effects ‐ Cardiac: QTc prolongation	2	206	Risk Ratio (M‐H, Random, 95% CI)	2.47 [0.12, 50.39]
26 Adverse effects ‐ Cardiac: Orthostatic hypotension	2	102	Risk Ratio (M‐H, Random, 95% CI)	1.09 [0.25, 4.82]
27 Adverse effects ‐ Cardiac: Palpitations	1	42	Risk Ratio (M‐H, Random, 95% CI)	3.0 [0.13, 69.70]
28 Adverse effects ‐ Cardiac: Premature Ventricular Contractions	1	42	Risk Ratio (M‐H, Random, 95% CI)	3.0 [0.13, 69.70]
29 Adverse effects ‐ Constipation	2	102	Risk Ratio (M‐H, Random, 95% CI)	1.53 [0.44, 5.38]
30 Adverse effects ‐ Dizziness	2	173	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.41, 1.44]
31 Adverse effects ‐ Drooling	1	42	Risk Ratio (M‐H, Random, 95% CI)	2.0 [0.20, 20.41]
32 Adverse effects ‐ Death (suicide or naturalistic cause)	1	131	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
33 Adverse effects ‐ Extrapyramidal: Categorical deterioration (AIMS, high = poor)	1	131	Risk Ratio (M‐H, Random, 95% CI)	1.38 [0.59, 3.26]
34 Adverse effects ‐ Extrapyramidal: average endpoint score (AIMS, high = poor)	1	60	Mean Difference (IV, Random, 95% CI)	0.7 [‐0.87, 2.27]
35 Adverse effects ‐ Extrapyramidal: average change score (AIMS, high = poor)	2	163	Mean Difference (IV, Random, 95% CI)	0.41 [‐1.15, 1.96]
36 Adverse effects ‐ Extrapyramidal: akathisia	2	65	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.04, 14.02]
37 Adverse effects ‐ Extrapyramidal: categorical deterioration (BAS, high = poor)	1	131	Risk Ratio (M‐H, Random, 95% CI)	1.47 [0.42, 5.14]
38 Adverse effects ‐ Extrapyramidal: average endpoint score (BAS, high = poor)	1	60	Mean Difference (IV, Random, 95% CI)	‐0.2 [‐0.74, 0.34]
39 Adverse effects ‐ Extrapyramidal: average change score (BAS, high = poor)	2	163	Mean Difference (IV, Random, 95% CI)	‐0.11 [‐0.59, 0.37]
40 Adverse effects ‐ Extrapyramidal: dystonia and/or dyskinesia	3	196	Risk Ratio (M‐H, Random, 95% CI)	0.48 [0.09, 2.73]
41 Adverse effects ‐ Extrapyramidal: categorical deterioration in SAS	1	131	Risk Ratio (M‐H, Random, 95% CI)	1.22 [0.51, 2.93]
42 Adverse effects ‐ Extrapyramidal: average endpoint score (SAS, high = poor)	2	191	Mean Difference (IV, Random, 95% CI)	0.93 [‐1.04, 2.91]
43 Adverse effects ‐ Extrapyramidal: average change score (SA, high = poor)	2	163	Mean Difference (IV, Random, 95% CI)	0.21 [‐0.83, 1.26]
44 Adverse effects ‐ Extrapyramidal: tremor	2	173	Risk Ratio (M‐H, Random, 95% CI)	1.59 [0.59, 4.26]
45 Adverse effects ‐ Headache	2	173	Risk Ratio (M‐H, Random, 95% CI)	1.46 [0.52, 4.08]
46 Adverse effects ‐ Somnolence and/or drowsiness	4	256	Risk Ratio (M‐H, Random, 95% CI)	1.76 [0.81, 3.81]
47 Adverse effects ‐ Weight at endpoint (high = poor)	2	165	Mean Difference (IV, Random, 95% CI)	‐1.85 [‐7.09, 3.39]
48 Behaviour: average endpoint score (BARS, high = good)	1	60	Mean Difference (IV, Random, 95% CI)	‐0.10 [‐0.50, 0.30]
49 Functioning ‐ Global Assessment of Functioning: average change score (GAF, high = good)	1	103	Mean Difference (IV, Random, 95% CI)	‐0.60 [‐1.00, 1.80]
50 Functioning ‐ Social ‐ Adaptive Functioning Evaluation: average endpoint score (SAFE, high = poor)	1	60	Mean Difference (IV, Random, 95% CI)	0.16 [‐0.47, 0.79]
51 Functioning ‐ Social and Occupational Functioning Assessment: average endpoint score (SOFAS, high = good)	1	131	Mean Difference (IV, Random, 95% CI)	0.5 [‐3.80, 4.80]
52 Quality of life: Clinically important change (at least 50% improvement HQLS, high = good)	1	17	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
53 Quality of life: Average endpoint score (HQLS, high = good)	1	17	Mean Difference (IV, Random, 95% CI)	5.5 [‐13.66, 24.66]