Table 1.
Description of included studies in meta-analysis
| Study | Country | Total no. of patients | Study design | Duration in weeks | Mean age (SD) | % male | Duration of illness in years (SD) | Previous violence or hostility | Outcome measure | No. of pts per arm | Dose (fixed, range or mean) | Chlorpromazine equivalent | Sponsored | Results |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| [40] | US | 39 | RAN, DB | 10 | CLO 34 (6) HAL 35 (8) |
CLO 68.42 HAL 75 |
CLO 14 (6) HAL 14 (6) |
No | BPRS hostility item | CLO 19 HAL 20 |
Mean (SD) CLO 410.5 (45.8) HAL 24.8 (5.5) | CLO 616 HAL 1488 |
No | CLO superior to HAL |
| [18] | US | 217a | RAN, DB, PLA | 6 | QUE 37.4 (9.4) HAL 37.3 (10.9) | QUE 73.1 HAL 78.6 | UN | No | BAS | QUE 175 HAL 42 | Fixed: QUE 150, 300, 600 or 750 HAL 12 | QUE 120, 240, 480 or 600 HAL 720 |
Yes | QUE therapeutic effects on hostility and behavioral agitation |
| [41] | US | 157 | RAN, DB | 14 | 40.8 (9.2) | 85 | 19.5 (8.4) | No | PANSS hostility item | OLA 39 CLO 40 RIS 41 HAL 37 |
Mean (SD) CLO 526.6 (140.3) OLA 30.4 (6.6) RIS 11.6 (3.2) HAL 25.7 (5.7) |
CLO 789.9 OLA 912 RIS 1160 HAL 1542 |
Yes | CLO advantage to HAL and RIS but not to OLA |
| [26] | 20 countries | 567 | RAN, SB | 6 | ZIP 34 (10.5) HAL 34.6 (10.5) | ZIP 66.7 HAL 65.9 |
UN | No | BPRS hostility item | ZIP 429 HAL 138 |
Mean (SD) ZIP 116 (30.4) HAL11.5 (3.6) |
ZIP 435 HAL 690 |
Yes | ZIP superior to HAL |
| [42] | US | 107 | RAN, DB | 8 | 30 (median) | 60.92 | UN | No | BPRS hostile suspiciousness cluster | CLO 52 CHL 55 |
Mean: CLO 390 CHL 698 | CLO 585 CHL 698 |
No | CLO superior to CHL |
| [43] | US | 109a | RAN, DB, PLA | 9 | UN | UN | UN | PANSS hostility ≥3 | PANSS hostility item | RIS 85 HAL 24 | Fixed: RIS 6, 10, or 16 HAL 20 | RIS 600, 1000, or 1600 HAL 1200 | Yes | RIS greater selective effect on hostility than HAL |
| [44] | GER | 37 | RAN, DB | 6 | AMI 43.3 (9.1) HAL 40.1 (10.2) | AMI 81 HAL 80 | AMI 17.3 HAL 14.3 | No | BPRS hostility item | AMI 20 HAL 17 | Range: AMI 490–1000 HAL 5-40 | AMI 421–860 HAL 300–2400 |
No | Positive but not significant trend in favor of AMI |
| [45] | GER | 151 | RAN, DB | 52 | RIS 30.9 (9.6) HAL 32.3 (10.5) | RIS 68.8 HAL 47.3 |
UN | No | PANSS hostility/ excitement | RIS 77 HAL 74 |
Mean (SD) RIS 3.9 (2.0) HAL 3.6 (1.8) |
RIS 390 HAL 216 |
Yes | HAL superior to RIS |
| [46] | US | 268 | RAN, DB | 6 | UN | UN | UN | No | BPRS hostility | CLO 126 CHL 142 |
Mean: CLO 450 CHL 900 |
CLO 675 CHL 900 |
Yes | CLO superior to CHL |
| [47] | US | 71 | RAN, DB | 29 | CLO 41 (10) HAL 40 (8) | CLO 70 HAL 71 | UN | No | BPRS hostile suspiciousness cluster | CLO 37 HAL 34 | Mean (SD) CLO 523 (171) HAL 18.9 (7.0) |
CLO 784.5 HAL 1134 | Yes | CLO superior to HAL |
| [48] | US and EUR | 1996 | RAN, DB | 6 | OLA 38.7 (11.6) HAL 38.3 (11.1) |
OLA 65 HAL 64.7 |
OLA 14.5 (10.5) HAL 14.9 (10.1) |
No | BPRS hostility | OLA 1336 HAL 660 |
Mean (SD) OLA 10.47 (3.54) HAL 9.38 (3.48) |
OLA 314 HAL 562.8 |
Yes | OLA greater improvement than HAL |
| [49] | US CAN | 397 | RAN, DB | 8 | 37 (10.3) | 83 | UN | No | PANSS hostility/excitement | RIS2 87 Ris 6–16 225 HAL 85 |
Fixed: RIS 2 or 6–16 HAL 20 | RIS 200 or 600–1600 HAL 1200 |
Yes | RIS superior to HAL |
| [50] | US | 63 | RAN, DB | 104 | RIS 43.7 (9.2) HAL 43.3 (8.4) |
RIS 87.9 HAL 96.7 |
UN | No | BPRS hostile suspiciousness cluster | RIS 33 HAL 30 |
Mean (SD) RIS 5.7 (2.5) HAL 4.5 (2.4) | RIS 570 HAL 270 | Yes | No significant difference |
| [24] | KOR | 35 | RAN, DB | 8 | 34.1 | 48.7 | UN | No | BPRS hostility item | RIS 16 HAL 19 |
Mean: RIS 7.5 HAL 8.95 |
RIS 750 HAL 537 |
Yes | No significant difference |
| [51] | 5 countries | 307 | RAN, DB | 4 | 36 (11.3) | 62 | UN | No | BPRS hostile suspiciousness cluster | AMI 100 58 AMI 400 62 AMI 800 63 AMI1200 64 HAL 60 |
Fixed: AMI100, 400, 800, or 1200 HAL 16 | AMI 86, 344, 688 or 1032 HAL 960 | Yes | AMI superior to HAL |
| [25] | 15 countries | 1362 | RAN, DB | 8 | RIS 1 38.4 RIS 4 38.1 RIS 8 37.6 RIS12 37.9 RIS 16 38.5 HAL 38.1 |
RIS 1 72.48 RIS4 66.96 RIS 8 62.61 RIS 12 62.83 RIS 16 62.50 HAL 66.3 |
UN | No | BPRS hostility cluster scores | RIS 1 229 RIS 4 227 RIS 8 230 RIS 12 226 RIS 16 224 HAL 226 |
Fixed: RIS 1, 4, 8, 12 or 16 HAL 10 | RIS 100, 400, 800, 1200 or 1600 HAL 600 | Yes | |
| [27] (Eufest) | 14 countries | 302 | RAN, OL | 52 | AMI 25.4 (5.1) OLA 26.3 (6.1) QUE 26.3 (5.7) ZIP 26.3 (5.5) HAL 24.5 (5.4) |
AMI 58 OLA 57 QUE 64 ZIP 46 HAL 61 |
UN | PANSS hostility ≥1 | PANSS hostility item | AMI 62 OLA 67 QUE 67 ZIP 52 HAL 54 |
Mean (SD): AMI 448.4 (221.2) OLA 11.5 (6.0) QUE 509.7 (310.7) ZIP 96.0 (52.1) HAL 3.3 (2.3) |
AMI 385.96 OLA 345 QUE 407.76 ZIP 360 HAL 198 |
Yes | OLA superior to HAL, QUE and Ami in the first 3 months but not significant in the last 6 months |
| [52] (Catie) | US | 614 | RAN, DB | 78 | OLA 40.3 (10.4) QUE 40.4 (11.6) RIS 39.9 (11.8) ZIP 39.8 (11.1) PER 38.7 (11.1) |
OLA 70 QUE 72 RIS 75 ZIP 66 PER 71 |
UN | PANSS hostility ≥ 2 | PANSS hostility item | OLA 136 QUE 147 RIS 144 ZIP 74 PER 113 |
Range: OLA 7.5–30 QUE 200–800 RIS 1.5–6.0 ZIP 40–160 PER 8–32 |
OLA 225–900 QUE 160–640 RIS 150–600 ZIP 150–600 PER 160–640 |
No | OLA superior to other |
HAL haloperidol, AMI amisulpride, RIS risperidon, OLA olanzapine, CLO clozapine, QUE quetiapine, ZIP ziprasidone, PER perphenazine, CHL chlorpromazine, RAN randomized, DB double blind, PLA placebo controlled, UN unknown, BPRS Brief Psychiatric Rating Scale, PANSS Positive and Negative Symptom Scale, BAS Behavioral Agitation Score (from BPRS agitation item, combined anxiety, tension, hostility, uncooperativeness and excitement)
aThe placebo arms are not included in this meta-analysis and the total number of patients is reduced by the number of patients in the placebo arm