Salloum 2005.
| Methods | Randomised placebo‐controlled double‐blind study | |
| Participants | 59 participants; mean age 38 years; 71% male; 15% married; 58% employed; 58% met criteria for mixed bipolar subtype, 21% were manic and 21% were depressed; half of participants had other substance use disorders (cannabis abuse or dependence and cocaine abuse were the most frequent diagnoses); 16 years on average duration of heavy drinking (up to intoxication); 96 on average the number of drinks per week; 20.8 average score at 25‐item HDRS; 14 years on average duration of bipolar disorder Inclusion criteria: men and non‐pregnant, non‐nursing women aged 18 to 65 years; meeting four of the seven DSM‐IV alcohol dependence criteria; actively drinking alcohol in the past month; having a concurrent acute episode of bipolar I disorder (manic, mixed or depressed) evaluated with the SCID for DSM‐IV (First 1994) Exclusion criteria: schizophrenia, schizoaffective disorder, any non‐bipolar psychotic disorder, mental retardation or signs of impaired cognitive functioning; current DSM‐IV diagnosis of opioid or cocaine dependence or current use of intravenous drugs; epilepsy, history of brain injury or any organic brain syndrome; severe cardiac, liver, kidney, endocrine, haematological or other unstable medical condition; persistent elevation of liver function enzyme levels greater than three‐fold above reference range of AST, ALT, GGT and alkaline phosphatase; inability or unwillingness to use contraception; inability to read or understand study forms and to agree to informed consent. Participants were not excluded for other DSM‐IV substance use disorders such as cannabis abuse or dependence, nicotine dependence or other substance abuse disorders |
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| Interventions | (1) Valproate plus lithium, 29 participants; (2) placebo plus lithium, 30 participants Drug dose: valproate serum concentration 50 to 100 μg/mL; lithium serum concentration 0.7 to 1.2 mEq/L Psychosocial associated intervention: dual diagnosis recovery counselling, consisting of weekly individual sessions that integrate psychoeducational and cognitive‐behavioural principles (Daley 1994) Setting: outpatient Duration: 24 weeks. Country of origin: USA |
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| Outcomes | Primary outcome: proportion of heavy drinking days (defined as four drinks per day for women and five drinks per day for men) and number of drinks per heavy drinking day
Secondary outcomes: proportion of any drinking days, number of drinks per any drinking day, time to relapse to sustained heavy drinking (defined as three consecutive heavy drinking days) Alcohol use was measured with the TLFB (Sobell 1992) and breath alcohol concentration; use of other drugs was measured with the urine drug screen Mood outcomes: remission of mania (defined as a score of seven on the Bech‐Rafaelsen Mania Scale) (Bech 1979) and remission of depression (defined as a score of seven on the HRSD‐25 (Thase 1983)). For psychiatric evaluation, Charting of Bipolar Episodes (Post 1986), BRMS, HRSD‐25 and the Global Assessment Scale (Endicott 1976) were used Adverse effects were measured with the Somatic Symptoms Checklist and the Medication Adherence Form |
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| Notes | All participants were recruited for the study after acute withdrawal symptoms cleared | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Balanced coin randomisation method used to stratify groups (Efron 1971) |
| Allocation concealment (selection bias) | Unclear risk | Insufficient information to permit judgement |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Statistical analyses completed on a
modified intent‐to‐treat study group, as defined by completion of at least one assessment while participant was receiving double‐blind therapy Mixed model with restricted maximum likelihood estimation method and unrestricted covariance matrix allowed to handle missing data |
| Blinding of participants and personnel (performance bias) all outcomes | Low risk | Valproate and placebo identical‐appearing. Procedures adopted to ensure double‐blindness of participants and personnel |
| Blinding of outcome assessment (detection bias) subjective | Low risk | Evaluators blind to group intervention assignment |
| Blinding of outcome assessment (detection bias) objective | Low risk | Evaluators blind to group intervention assignment |