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) |