Table 2: Studies with risperidone

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)

AD: Alcohol Dependence, AIMS: Abnormal involuntary Movement Scale, AMP: Amphetamine, ARI: Aripiprazole, AUD: Alcohol Use Disorder, BPRS: Brief Psychiatric Rating Scale, CAA: Cannabis Abuse, CAD: Cannabis Dependence, CAUD: Cannabis Use Disorders, CCR: Cocaine Craving Report, CGI: Clinical Global Impression, CIPD: Cannabis Induced Psychotic Disorders, CLO: Clozapine, COD: Cocaine Dependence, CR: Case Report, CS: Case Series, DAS: Depression Anxiety Stress Scale, DB: Double Blinded, DED: Delusional Disorder, DD: Dual Diagnosis, DDQ: Drug Desire Questionnaire, DDSS-SV: Desire to Drink Scale, Spanish Version, EPS: Extrapyramidal Side Effects, FE-SCH: First Episode of Schizophrenia, FTQ: Fagerstrom Tolerance Questionnaire, HAL: Haloperidol, LAR: Long-acting RIS, MC: Multicenter, MCR: Marijuana Craving Report, ND: Nicotine Dependece, Nat: Naturalistic, N.S.: Not specified, OA: Opioid Abuse, HDRS: Hamilton Depression Rating Scale, OCDUS: Obsessive Compulsive Drug Use Scale, OCDUS-CAN: Obsessive Compulsive Drug Use Scale, Cannabis Version, OD: Opioid Dependence, OL: Open Label, OLZ: Olanzapine, PANSS: Positive and Negative Symptoms Rating Scale, PDNOS: Psychotic Disorder NOS, PICD: Psychotic Induced Cannabis Disorder, Pros: Prospective, PSY: Psychotic Disorder, QSUI: Quantitative Substance Use Inventory, RCT: Randomized Controlled Trial, Ret: Retrospective, RIS: Risperidone, RO-SCH: Recent Onset Schizophrenia, SA: Stimulant Abuse, 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, SD: Stimulant Dependence, SAD: Schizoaffective Disorder, SCH: Schizophrenia, SCHD: Schizophreniform Disorder, SU: Substance Abuse, SUD: Substance Use Disorder, SUQ: Substance Use Questionnaire, SWN: Subjective Well-Being Under Neuroleptics scale, TAP: Typical Antipsychotics, UKU: Udvalg für Undersogelser, UTS: Urine Toxicological Screenings, VCCQ: Voris Cocaine Craving Questionnaire, ZIP: Ziprasidone, ZUC: Zuclopenthixol.