| Author; No. of patients | Design; Duration; Intervention | Outcomes | Results |
| Conley et al. (1998) [39] n=60 | OL 7 weeks 60 TR-SCH patients, 23 with lifetime SUD OLZ (10-25 mg/d) | Psychopathology (BPRS, CGI, SANS) | No differences between patients with and without SUD in outcomes evaluated (BRPS, CGI, SANS), thus same efficacy of OLZ in patients with additional SUD |
| Berk et al. (1999) [31] n=30 | Pros, DB, RCT 4 weeks CIPD + CAA OLZ (10 mg/d) (n=15) or HAL (10 mg/d) (n=10) | Psychopathology (BPRS, CGI) Side effects (SAS, dose of BIP needed) | Comparable reduction of psychopathology, but more EPS with HAL |
| Noordsy and OŽKeefe (1999) [25] n=70 | Nat study 6 months 70 PSY patients, 58 with SCH or SAD + SUD OLZ (dosage N.S.) + Psychosocial RHB | Psychopathology Substance abuse | Reduction in alcohol and drug use and psychopathology |
| Littrell et al. (2001) [22] n=30 | Pros, OL 12 months SCH or SAD + AUD or SUD Alcohol + Cocaine 100%, Cannabis 60%, Hallucinogens 10%, Amphetamines 10% OLZ (10-25 mg/d) | Psychopathology (PANSS, HHI, service utilization) Substance abuse (SSAS, UTS, BAL) Safety (BAS, SAS, AIMS) | 70% of the patients achieved abstinence and 30% partial substance abuse remission. Improvement of psychopathology (p=0.048) and EPS (p<0.01) |
| Noordsy et al. (2001) [27] n=153 | Nat study, switch design 6 months PSY patients, 29% AA and 21% SA in the OLZ group, and 16% AA and 6% SA in the TAP group OLZ (dosage N.S.) | Psychopathology (MPRS, CGI) Psychosocial functioning (CMRS) Substance use (CMRS item 2) | Significant reduction in alcohol and substance use (p< 0.001) and improvement in psychopathology (p< 0.01) and psychosocial functioning (p=0.09) |
| Tsuang et al. (2002) [28] n=4 | Pros, DB, OL 24 weeks SCH + COA OLZ (5-20 mg/d) (n=2) or HAL (5-10 mg/d) (n=2) | Psychopathology Cocaine use and craving | Reduction of psychopathology and cocaine use and craving with OLZ |
| Sattar and Bhatia (2003) [26] n=1 | CR 6 months SAD + COD Switched to OLZ from depot HAL | Psychopathology Cocaine use and craving | Improvement in psychopathology and reduction in craving and substance use achieving abstinence |
| Green et al. (2004) [40] n=262 | MC, Pros, DB, RCT 12 weeks FE-PSY, 37% with lifetime SUD and 7.6% with current abuse Cannabis 28%, Alcohol 21%, Cocaine 6%, Hallucinogens 5%, Opioids 1% OLZ (5-20 mg/d, mean dosage 10.2 mg/d) or HAL (2-20 mg/d, mean dosage 4.8 mg/d) | Psychopathology (PANSS, MADRS, CGI) Psychosocial and vocational functioning Substance use | Among the SUD-Group 27% were responders (23% OLZvs. 31% HAL) as compared to 35% of non-SUD Group (38% OLZvs. 32% HAL) Patients with comorbid AUD showed poorer response to OLZ (27%) than to HAL (9%) (p< 0.02) Higher drop-out rate among SUD patients receiving HAL (49%) compared to OLZ (23%) (p< 0.04) |
| Leelahanj et al. (2005) [30] n=58 | Pros, DB, RCT 4 weeks AMP Psychosis OLZ (5-20 mg/d) (n=29) vs. HAL (5-20 mg/d) (n=29) | Clinical response Safety (SAS, BAS) | 93% of the OLZ patients and 79.3% of the HAL patients clinically improved at endpoint. These differences were not statistically significant (p=0.25). The differences of mean change in the SAS significantly favored OLZ (p< 0.01). The differences of mean change in the BAS favored OLZ (p=0.02) |
| Sayers et al. (2005) [32] n=24 | Pros, DB, RCT 6 months SCH + COA OLZ (5-20 mg/d) or HAL (5-20 mg/d) | Psychopathology (BPRS, SAPS, SANS, HRSD) Cocaine use (UTS) Cocaine craving (VAS) | No significant differences in regard to cocaine use (UTS), although there was a significant reduction with OLZ and a significant increase with HAL of cocaine use compared to the amount at baseline (p< 0.05). There was a significant increase of craving with OLZ (p< 0.05). No differences in psychopathology were observed |
| Smelson et al. (2006) [29] n=31 | Pros, DB, RCT 6 weeks SCH + SUD Cocaine 100% OLZ (5-20 mg/d) or HAL (5-20 mg/d) | Cocaine use (UTS) Cocaine craving (VCCQ) Psychopathology (PANSS) | Significant greater reduction of craving in the OLZ group (p=0.04). No significant differences in cocaine use and psychopathology |
| Stuyt et al. (2006) [38] n=55 | Ret, OL 2 years SCH (61%) or SAD (54%) + SUD or AUD Polyvalent SUD (34%), Alcohol (27%), Cocaine (16%), other SUD (21%) OLZ (2.5-30 mg/d, mean dosage 18.7 mg/d) (n=15) or RIS (n=16) (2-8 mg/d, mean dosage 3.9 mg/d) or ZIP (60-160 mg/d, mean dosage 132.8 mg/d) (n=10) or TAP depot (n=10) | Retention rate Success in completing a DD Programme | RIS and ZIP had higher rates of retention compared to OLZ(p=0.0002 and p=0.004, for RIS and ZIP respectively) and TAP (p=0.003 and p=0.03, for RIS and ZIP, respectively). There were no significant differences in the length of stay were found between RIS and ZIP. 88% of RIS patients and 64% of ZIP completed the DD program, whereas only 40% of patients taking TAP and 33% of patients in the OLZ successfully completed the program. This difference in successful completion was statistically significant for RIS vs. OLZ (p=0.02) and TAP (p=0.017) |
| Gerra et al. (2007) [23] n=61 | MC, Pros, OL 12 weeks Patients on MET or BUP treatment SSD + HD OLZ or HAL (N.S. dose) | Retention in treatment Psychopathology (SCL-90-R) Drug use (UTS) Craving reduction | Patients in the OLZ group remained significantly longer in treatment (p=0.001), had a significant superior decrease in the SCL-90 score(p=0.001) and more negative UTS (p=0.04) |
| Akelere and Levin (2007) [33] n=28 | P, DB, RCT 14 weeks SCH + SUD Cannabis (93%), Cocaine (78%), Alcohol (4%) OLZ (5-20 mg/d) or RIS (3-9 mg/d) | Psychopathology (PANSS, HDRS, CGI) Substance use and craving (MCR, CCR, QSUI, UTS) Side effects (AIMS, SAS) | Trend for a greater reduction of cocaine positive urines and significantly less self-reported days of use (for any drug) (p=0.02) in the OLZ group. There was a significant reduction in cannabis craving in the RIS group, with no modifications in the OLZ group (p=0.04). There were no significant differences between groups in cocaine craving |
| Swart et al. (2008) [41] n=1432 | Pros, RCT 18 months SCH, 643 with illicit SUD and 789 without illicit SUD Flexible doses of OLZ (mean dosage 20.1 mg/day) (n=330) or QUE (mean dosage 538.9 mg/day) (n=329) or RIS mean dosage 3.9 mg/day) (n=333) or ZIP (112.8 mg/day) (n=183) or TAP (n=257) | Discontinuation rate and time to discontinuation Psychopathology (PANSS, CGI, episodes of hospitalization) | Among non-users, OLZ was associated with significantly lower discontinuation rates and time to discontinuation compared to QUE (p< 0.001), RIS (p=0.01), TAP (p< 0.001), but not ZIP. Among illicit-drug users, no significant differences between treatment groups were found regarding discontinuation rates and time to discontinuation. OLZ group was associated with a greater psychopathological improvement as measured by the PANSS, CGI and number of hospitalizations, in both illicit-drug users and non-users, compared to the other treatment groups |
| Van Nimwegen et al. (2008) [34] n=128 | MC, Pros, DB, RCT 6 weeks RO-SCH, 41.3% of whom used cannabis OLZ (5-20 mg/d, mean dosage 11.1 mg/d) (n=63) or RIS (1-5 mg/d, mean dosage 3 mg/d) (n=65) | Subjective well-being (SWN) Cannabis craving (OCDUS, DDQ) | Similar improvements in subjective well-being were found in both groups. Similar decrease in craving for cannabis was found in both treatment conditions |
| Kim et al. (2010) [37] n=139 | Pros, RCT 8 weeks SCH + ND OLZ (n=32) or RIS (n=41) or ARI (n=31) or HAL (n=35) | Psychopathology (SANS, SAPS) EPS (AIMS) Severity of ND and cigarette craving (FTQ) | No significant differences in the degrees of change in psychiatric symptoms among the four groups. At 8 weeks, HAL was associated with higher EPS (p< 0.01). HAL was associated with less reduction in the severity of ND (p< 0.01) and cigarette craving (p< 0.01) compared to AAP. Among AAP, RIS increased cigarette craving (p=0.03), there were no significant changes in ND severity and cigarette craving associated with OLZ, and ARI showed a reduction in both severity of ND and cigarette craving (p< 0.01) |
| Sevy et al. (2011) [35] n=49 | Pros, RCT 16 weeks FE-SCH (SCH, SCHD, SAD) + CAUD OLZ (2,5-20 mg/d, mean dosage 15 mg/d) (n=28) or RIS (1-6 mg/d, mean dosage 4 mg/d) (n=21) | Psychopathology (SADS-C+PD, CGI, SANS) Substance Use (SUQ) | OLZ group did not differ significantly from RIS group in initial response rates of positive symptoms and rates of cannabis use or alcohol use. Negative symptoms (global asociality-anhedonia) improved over time but did not differ between groups |
| Machielsen et al. (2012) [36] n=123 | MC, Long, Nat study 6 years SCH, SCHD, SAD, DED or PDNOS + CAD CLO (mean dosage 350 mg/d) (n=23) or RIS (mean dosage 3.46 mg/d) (n=48) or OLZ (mean dosage 13.78 mg/d) (n=52) | Cannabis craving (OCDUS-CAN) | There were significant differences in craving reduction between RIS and CLO (p=0.001), and between RIS and OLZ (p=0.025), in favour of CLO and OLZ. No significant differences were found between CLO and OLZ |
| Sani et al. (2013) [42] n=80 | Pros, Obs, CC 8 weeks BD, 40 with SUD Add-on OLZ (5-20 mg/d, mean dose 17.31 mg/d) | Remission, response and relapse rates (YMRS, HDRS, BPRS) Days of substance abuse (TLFB) Craving (VAS) | Patients with SUD received significantly higher doses of OLZ compared to non-substance abusers. Remission, response and relapse rates were similar, with mood rating scores dropping significantly from baseline to end-point in both groups (p< 0.01). In the SUD group there was a significant reduction in days of substance abuse (p< 0.01) and craving (p< 0.03) |