Table 2.
Study characteristics.
| Study (Sample Size) | Study Design and Setting | Percentage of Male Participants | Mean Age (SD) of the Participants | Number (%) of Cases with a Psychotic Disorder | Number (%) of Cases with Other Psychiatric Disorders | Abstinence before the Start of the Study | Intervention Group(s) | Other Interventions | Treatment Duration | Assessment Time Points | Drinking Measures | Drinking Outcomes | Other Outcomes | Completion Rate | Results | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Self-Report | Bio-markers | ||||||||||||||||
| Disulfiram | |||||||||||||||||
| Mueser et al., 2003 [19](N = 33) | RCROutpatients | 64% | 37 years (± 7.1) | N = 25 (76%)(S: n = 15; SAD: n = 8;UP: n = 1; SPD: n = 1) | N = 8 (24%)(BD: n = 5;MDD: n = 3) | Not reported | Disulfiram 125-500 mg/day | AP + OPTNFS | < 1 month (n = 4);1-3 months (n = 7); 3-6 months (n = 3); 6-12 months (n = 3); 1-2 years (n = 8); 2-3 years (n = 3): > 3 years (n = 8) | 1-, 2-, and 3-years following initiation of disulfiram treatment | AUS | None | AUS, remission from AUD | DUS, number of days spent in hospital (per year), number of weeks worked (per year), side effects. | 100%(52 weeks) | Reduced AUS scores were observed at 1-, 2-, and 3-years follow-up compared to baseline.Remission from AUD was seen in 21 patients (64%) for at least one year during the follow-up period, in 10 patients (30%) for two years, and in 3 patients (10%) for the full three years of follow-up.Reduced DUS scores were observed at 1-, 2-, and 3-years follow-up compared to baseline.A reduction in the number of days spent in the hospital was observed at the 3-year follow-up compared to baseline.Mild to moderate side effects were reported by 7 patients. Alcohol-disulfiram reactions were experienced by 7 patients. | |
| Disulfiram vs. Naltrexone | |||||||||||||||||
| Petrakis et al., 2005, 2006 [42, 53](N = 254) | DB/OL RCT (DB naltrexone/OL disulfiram)Outpatients | 97% | 47 years (± 8.2) | N = 18 (7%)(S/SAD: n = 18) | MDD: n = 178 (70%)PTSD: n = 109 (43%)GAD: n = 57 (20%)CUD: n = 50 (22%)BD: n = 49 (19%) | min. 3 days; max. 29 days | Naltrexone50 mg/day (n = 59) vs.Disulfiram 250 mg/day (n = 66) vs.Naltrexone 50 mg/day+ disulfiram 250 mg/day (n = 65) vs.Placebo (n = 64) | AP + OPTNFS | 12 weeks | Week 12 | TLFB | GGTSGOTSGPT | CDA, DA, DDW, HDD, TA, GGT, SGOT, SGPT | OCDS, BSI, side effects (HCSL) | 89% | Overall, patients treated with either disulfiram or naltrexone had more CDA and fewer DDW post-treatment compared to the placebo group. Disulfiram-treated patients had reduced levels of GGT at post-treatment compared to naltrexone-treated patients. Patients with PD (S, SAD, BD) had fewer CDA and more HDD than those without PD. Also, patients treated with either disulfiram or naltrexone had more DA and fewer HDD compared with a placebo.Overall, disulfiram-treated patients had lower OCDS and BSI scores at post-treatment compared to naltrexone-treated participants.Patients treated with either disulfiram or naltrexone had lower OCDS and BSI scores post-treatment compared to the placebo group.Overall, there was no advantage of combining disulfiram and naltrexone with respect to any of the outcomes. This was also the case among patients with PD.Mild to severe side effects. Symptoms potentially related to side effects were reported by 96.9% of the participants. Patients with PD were more likely to report mild to moderate side effects compared to those without PD.Fourteen adverse events were recorded, 3 in the combined disulfiram and naltrexone group, 6 in the disulfiram group, 1 in the naltrexone group, and 4 in the placebo group. 43% (n = 6) of the adverse events were reported by patients with PD. | |
| Vasile et al., 2013 [43]*(N = 20) | OL RCTSetting not reported | 45% | 40 years (SD not reported)/ | N = 20 (100%)(S: n = 20) | None | Not reported | Naltrexone 50 mg/day (n = 8) vs.Disulfiram 250 mg/day (n = 12) | AP | 24 weeks | Week 24 | None | None | None | CGI-S, GAF, IDTS-A, PANSS, side effects | Max. 75% | Both the disulfiram and naltrexone groups exhibited improvements from baseline to post-treatment on all outcomes, with no differences observed between the two groups.Mild to moderate side effects were observed in both the disulfiram (6 patients) and naltrexone (4 patients) groups. | |
| Naltrexone | |||||||||||||||||
| Maxwell and Shinder-mann 2000 [51](N = 72) | RCROutpatients | 71% | Not reported | N = 24 (33%)S: n = 17(23.3%)SAD: n = 7(5.5%) | MDD: n = 37(50.7%)BD: n = 11(15.1%)GID: n = 4(4.1%) | Not required | Naltrexone unknown dose | OPTNFS2 | 8 weeks | week 8 | Not reported | None | Reduced drinking | Side effects | 82% | Reduced drinking was observed at post-treatment compared to baseline. Completers reduced their drinking by at least 75%, and only 17% of the patients relapsed after 8 weeks.Mild side effects. | |
| Batki et al., 2007 [49](N = 19) | Single-arm, OL trialOutpatients | 79% | 43 years (±12) | N = 19 (100%)(S: n = 11; SAD: n = 7; UP: n = 1) | None | Not required | Naltrexone 350 mg/ week | AP + OPTNFS | 8 weeks | week 4week 8 | TLFB | CDTGGT | DDW, DWDDD, DDI% CDT% GGT | ASIVAS (craving and VAS QoH), PANSS, side effects | 74% | A reduction in DW, DDD, and DDI, as well as in scores on the ASI, VAS, and PANSS, was observed at post-treatment compared to baseline.No associations were found between self-reported drinking outcomes and alcohol biomarkers.Mild to moderate side effects. | |
| Batki et al., 2010 [48]*(N = 25) | Single-arm, OL trialOutpatients | 52% | 44 years (SD not reported) | N = 17 (68%)(S :n = 6; SAD: n = 11) | N = 8(BD: n = 8) | Not reported | Extended-release naltrexone 380 mg/ q4wk | AP + PI (motivational counselling- weekly sessions) | 12 weeks | week 12 | TLFB (outcome not reported) | None | DW, DD, HDD, DDD | Side effects | 84% | Significant improvements were observed from baseline to post-treatment with respect to all outcomes.Mild to moderate side effects. One serious adverse event was recorded. | |
| Vasiliu et al., 2020 [52]*(N = 12) | RCRInpatients | 33% | 29 years (SD not reported) | N = 12 (100%)(SAD-bipolar type: n = 2; SAD-depressive type: n = 10) | None | min. 10 days | Naltrexone 50mg/day | AP | Not reported | At discharge from hospital 4 weeks after hospital discharge | AUDIT | None | AUDIT score | CGI-S, CDSS, GAF, PANSS, side effects | Not reported | AUDIT and PANSS scores improved from baseline to (1) the time of discharge from the hospital and (2) four weeks after hospital discharge. CGI-S and GAF scores improved from baseline to time of discharge from hospital. CDSS scores improved significantly from baseline to four weeks after hospital discharge.Mild to moderate side effects. | |
| Petrakis et al., 2004 [44](N = 31) | DB RCTOutpatients | 100% | 46 years (± 5.7) | N = 31 (100%)(S: n = 18; SAD: n = 13) | None | Not required | Naltrexone 50 mg/day (n = 16) vs.Placebo (n = 15) | AP + PI (cognitive behavioral relapse prevention strategies – weekly sessions) | 12 weeks | week 12 | TLFB (used to validate UTS but outcome is not reported) | UTS | DD, HDD, TDSP | TCQ, PANSS, side effects (HSCL) | 81% | A reduction in DD and HDD at post-treatment was observed in the naltrexone group compared to the placebo group. There was no drug-by-time interaction effect with respect to either DD or HDD. A reduction in TCQ scores at post-treatment was observed in the naltrexone group compared to the placebo group.Mild side effects. A total of 4 adverse events were recorded, 3 in the naltrexone group and 1 in the placebo group. | |
| Batki et al., 2009 [45]* (N = 90) | DB RCTOutpatients | 71% | 42.5 years (SD not reported) | N = 90 (100%)(S: n = 45; SAD: n = 45) | None | Not reported | Naltrexone 350 mg/week (n = 45) vs.Placebo (n = 45) | PI (motivational counselling- weekly sessions) | 12 weeks | week 12 | TLBF (outcome not reported) | None | DW, DD, HDD | VAS (craving and QoH) | Not reported | At post-intervention, a reduction in HDD was observed in the naltrexone group compared to the placebo group.Side effects were not examined. | |
| Naltrexone vs. Acamprosate | |||||||||||||||||
| Bratu and Sopterean 2014 [46]* (N = 36) | OL RCTSetting not reported | 67% | Mean age not reportedAge range: 18-65 years. | N = 36 (100%)(S: n = 36) | None | min. 7 days | Naltrexone 50 mg/day (n = 12) vs.Acamprosate 999 mg/day (n = 12) vs.Counselling (n = 12) | AP | 24 weeks | Week 24 | Not reported | TL | DA, HDD, change in TL | GAF, IDTS-A, PANSS, side effects | Not reported | At post-treatment, an increase in DA and a reduction in HDD were observed in both medication groups compared to the counselling group. An increase in DA was observed in the acamprosate group compared to the naltrexone group, but the naltrexone group had fewer HDD than the acamprosate group. Both medication groups also exhibited improved TL scores compared to the counselling group.Both naltrexone and acamprosate treatment were well tolerated, with no severe adverse effects. | |
| Acamposate | |||||||||||||||||
| Ralevski et al., 2011 [47] (N = 23) | DB RCTOutpatients | 83% | 51 years (±7.3) | N = 23 (100%)(S: n = 9, SAD: n = 10; UP: n = 4) | None | min. 5 days; max. 21 days | Acamprosate 1998 mg/day (n = 12)Placebo (n = 11) | AP + PI (skills training in relapse prevention) | 12 weeks | Week 12 | TLFB | None | ASP, CDA, DD, DDD, HDD | OCDS, PANSS,side effects | 65% | At post-intervention, the acamprosate group did not differ significantly from the placebo group with respect to any of the outcomes (including side effects).No differences in side effects were observed between the two groups.A total of 16 adverse events were recorded, 7 in the placebo group (2 events reported by the same participant), 2 in the acamprosate group, and 7 events were deemed unrelated to study participation. | |
| Nalmefene | |||||||||||||||||
| Vasile et al., 2014 [50]*(N = 22) | Single-arm, OL trialInpatients | 45% | 44 years (SD not reported) | N = 22 (100%)(S: n = 22) | None | Not required | Nalmefene 18 mg pro necessitate | AP | 24 weeks | Week 24 | None | GGT | Change in GGT | CGI-S, GAF, IDTS-A, PANSS, side effects | 82% | A reduction in GGT levels, along with improved scores on the CGI-S, GAF, IDTS-A, and PANSS, were observed at post-treatment compared to baseline.Mild to moderate side effects (12 patients). | |
Abbreviations: AP: antipsychotics; ASI: addiction severity index; ASP: abstinence in study period; AUD: alcohol use disorder; AUDIT: alcohol use disorder identification test; AUS: alcohol use scale; BP: bipolar disorder; BSI: brief symptom inventory; CDA: consecutive days abstinent; CDT: carbohydrate-deficient transferrin; CDSS: Calgary Scale for Depression in Schizophrenia; CGI-S: clinical global impressions - severity; CUD: cocaine use disorder; DA: days abstinent; DB: double-blind; DD: drinking days; DH: days hospitalized; DDD: drinks per drinking day; DDI: days of drinking to intoxication; DDW: drinking days per week; DUS: drug use scale; DW: drinks per week; GAD: generalized anxiety disorder; GAF: global assessment of functioning; GGT: gamma-glutamyltransferase; GID: gender identity disorder; HDD: heavy drinking days; HSCL: Hopkins Symptom Checklist; IDTS-A: inventory of drug taking situations – alcohol focused version; MDD: major depressive disorder; OCDS: obsessive compulsive drinking scale; OL: open-label (unblinded); OPTNFS: outpatient psychiatric treatment not further specified; PANSS: positive and negative syndrome scale; PI: psychological intervention; PTSD: post traumatic stress disorder; QoH: quality of alcohol high; RCR: retrospective chart review; RCT: randomized controlled trial; RD: reduced drinking; S: schizophrenia; SAD: schizoaffective disorder; SGOT, serum glutamic-oxaloacetic transaminase; SGPT: serum glutamic pyruvic transaminase; SPD: schizoid personality disorder; TA: total abstinence ; TCQ: Tiffany Craving questionnaire; TDSP: total drinks in study period; TL: transaminase level; TLFB: Timeline Followback; UP: unspecified psychosis; UTS: urine toxicology screen; VAS: visual analog scale.
*conference abstract.