Table 1: Studies with olanzapine

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)

AA: Alcohol Abuse, AIMS: Abnormal Involuntary Movement Scale, AMP: Amphetamine, ARI: Aripiprazole, AUD: Alcohol Use Disorders, BAL: Blood Alcohol Levels, BAS: Barnes Akathisia Scale, BD: Bipolar Disorder, BIP: Biperiden, BPRS: Brief Psychiatric Rating Scale, BUP: Buprenorphine, CAA: Cannabis abuse, CAD: Cannabis Dependence, CAUD:Cannabis Use Disorders, CC: Case-Control, CCR: Cocaine Craving Report, CGI: Clinical Global Impression, CIPD: Cannabis Induced Psychotic Disorder, CLO: Clozapine, CMRS: Case Manager Rating Scale, COA: Cocaine Abuse, COD: Cocaine Dependence, DB: Double-blinded, DED: Delusional Disorder, DDQ: Drug Desire Questionnaire, EPS: Extrapyramidal symptoms, FE-PSY: First Episode of Psychosis, FTQ: Fagerstrom Tolerance Questionnaire, HAL: Haloperidol, HDRS: Hamilton Depression Rating Scale, HD: Heroin Dependence, MADRS: Montgomery-Asberg Depression Rating Scale, MC: Multicenter, MET: Methadone, MPRS: Mini Psychiatric Rating Scale, HHI: Herth Hope Index, MCR: Marijuana Craving Report, ND: Nicotine Dependence, NAT: Naturalistic, N.S: Not specified, Obs: Observational, OCDUS: Obsessive Compulsive Drug Use Scale, OCDUS-CAN: Obsessive Compulsive Drug Use Scale, cannabis version, OL: Open label, OLZ: Olanzapine, PANSS: Positive and Negative Syndrome Scale, PDNOS: Psychotic Disorder NOS, Pros: Prospective, PSY: Psychotic Disorder, QSUIL: Quantitative Substance Use Inventory, RCT: Randomized controlled trial, RHB: Rehabilitation, RIS: Risperidone, RO-SCH: Recent Onset Schizophrenia, SA: Substance Abuse, SAD: Schizoaffective Disorder, SADS-C+PD: Schedule for Affective Disorders and Schizophrenia- Change Version with psychosis and disorganization items, SANS: Scale for the Assessment of Negative Symptoms, SAPS: Scale for the Assessment of Positive Symptoms, SAS: Simpson Angus Scale, SCH: Schizophrenia, SCHD: Schizophreniform Disorder, SCL-90-R: Symptoms Checklist 90, SSAS: Schizophrenia/Substance Abuse Schedule, SSD: Schizophrenic Spectrum Disorders, SUD: Substance Use Disorder; SUQ: Substance Use Questionnaire, SWN: Subjective Well Being Under Neuroleptics Scale, TAP: Typical Antipsychotics, TLFB: Timeline Follow-Back, TR-SCH: Treatment Resistant Schizophrenia, UTS: Urine Toxicological Screens, VAS: Visual Analogue Scale, VCCQ: Voris Cocaine Craving Questionnaire, YMRS: Young Mania Rating Scale.