| Author; No. of patients | Design; Duration, Intervention | Outcomes | Results |
| Huang (1996) [43] n=7 | Nat study 3 months 7 SCH + AD RIS (dose N.S.) | Alcohol use | Reduction in alcohol use |
| Berk et al. (2000) [54] n=30 | Pros, DB, RCT 4 weeks CIPD + CAA RIS (6 mg/d) (n=15) or HAL (10 mg/d) (n=15) | Psychopathology (BPRS) Side effects (EPS) | No differences in the reduction of psychopathology, no differences in EPS |
| Grupta and Basu (2001) [47] n=1 | CR 10 months SCH + OD RIS (4 mg/day) | Psychopathology Substance use Craving | Reduction of psychopathology, substance use and craving |
| Albanese (2001) [44] n=14 | Nat study, CS 9 weeks 7 SCH and SAD + SUD Alcohol (57%), Cocaine (36%), Opiate (7%), polyvalent (21%) Add-on RIS (2-8 mg/d, average 3.6 mg/d) | Clinical response Tolerability | 11 of 14 patients showed clinical improvement. RIS was well tolerated |
| Casas et al. (2001) [48] n=180 | OL 6 months PSY + OA or OD RIS (0.5-12 mg/d, average 2.4 mg/d) | Psychopathology (BPRS, CGI, DDS-SV) Opiate use Side effects (UKU) | Improvement in psychopathology and reduction in opiate use from 39% to 18% Reduction in neurological side effects (p< 0.0001) |
| Bobes et al. (2001) [49] n=146 | Pros, MC, OL 6 months PSY + SA or SD RIS (N. S. dose) | Psychopathology (BPRS, CGI, DAS) Side effects (UKU) Cocaine and cannabis use | Rates of patients using cocaine decreased from 89.7% to 17.7% and rates of patients using cannabis decreased from 52.1% to 27.1%, being these differences statistically significant (p< 0.0001) |
| Gutierrez et al. (2001) [50] n=146 | Alcohol use | Rates of patients using alcohol was reduced from 68.5% to 33.3% , being these differences statistically significant (p< 0.0001) | |
| Smelson et al. (2002) [51] n=18 | Pros, OL 6 weeks SCH + SUD Cocaine (100%) RIS (6 mg/d) (n=8) or TAP (n=10) | Psychopathology (PANSS) Substance use Substance craving (VCCQ) | Reduction in psychopathology (trend towards significance in the PANSS negative ant total subscale), of substance use and craving |
| Tsuang et al. (2002) [28] n=2 | CR 2 months SCH + COD RIS (8 mg/d) | Psychopathology Cocaine use and craving | After switching from TAP to RIS there were no changes of craving and cocaine use, as well as of psychopathology |
| Green et al. (2003) [55] n=41 | Ret, OL 12 months SCH or SAD + SUD or AUD Alcohol (78%), Cannabis (51%) RIS (average 3.9 mg/d) (n=8) or CLO (average 440 mg/d) (n=33) | Substance use | Significantly more patients stopped SU with CLO (54%) than with RIS (12.5%) |
| Rubio et al. (2006) [52] n=115 | MC, OL, RCT 24 weeks SCH + SUD LAR (47 mg/2 weeks) + RIS (3.4 mg/d) (n=57) or depot ZUC (200 mg/3 weeks) + Oral ZUC (15 mg/d) (n=58) | Substance use (UTS) Psychopathology (PANSS) Side effects Compliance | Significantly less drug use (fewer positive UTS), greater improvement in psychopathology (PANSS), less EPS and better compliance with LAR |
| 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). No significant differences in 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) |
| Albanese and Suh (2006) [45] n=16 | Nat study N.S. duration DD (N.S.) + COD RIS (mean dose 2.3 mg/d) | Overall functioning (CGI) Craving Safety (AIMS) Compliance | 81% of the patients improved in the CGI scale, 100% of the patients reported mild o no craving, 88% completed the programme |
| 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 |
| Kim et al. (2008) [56] n=61 | Pros, Nat, Obs 2 years SCH + AUD CLO (mean dosage 423.6 mg/d) (n=25) or RIS (mean dosage 7.6 mg/d) (n=36) | Hospitalization rates Time to hospitalization | CLO treated patients were readmitted to hospital significantly later than the RIS treated patients (p=0.045). At the end of the study, 75% of the RIS treated patients had been admitted to the hospital, compared to 48% of patients of the CLO treated patients |
| 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 |
| Farnia et al. (2014) [53] n=45 | Pros, DB, RCT 1 year follow-up AMP induced psychosis RIS (4 mg/d) or ARI (15 mg/d) | Psychopathology (SANS, SAPS) | SANS and SAPS scores decreased significantly in both groups. Mean SAPS score reduction was greater in the RIS group (p< 0.001). Mean SANS score reduction was greater in the ARI group (p=0.08) |