Johnson 2007.
| Methods | Randomised placebo‐controlled double‐blind study | |
| Participants | 371 participants; mean age 47.3 years; 73% male; 33.4 years on average age of alcoholism onset; 19.4% heavy drinking days in previous 28 days; 4.5 drinks/drinking days; 1.4 CIWA‐Ar score on average (Sullivan 1989) Inclusion criteria: between 18 and 65 years old; fulfilling DSM‐IV (APA 1994) diagnostic criteria for alcohol dependence using SCID (First 1997); drinking 35 or more (men) and 28 or more (women) standard drinks per week as measured by TLFB (Sobell 1992); scoring eight or higher on Alcohol Use Disorders Identification Test (Bohn 1995 a); having a body mass index higher than 18; having a negative urine toxicological screening result for opioids, cocaine, amphetamines, antidepressants, propoxyphene, barbiturate, tetrahydrocannabinol and benzodiazepines; expressing a desire to stop or reduce consumption of alcohol, with the possible long‐term goal of abstinence Exclusion criteria: having a current Axis I psychiatric diagnosis on DSM‐IV other than alcohol, nicotine or caffeine dependence; having a history of substance abuse or dependence excluding dependence on alcohol, nicotine or caffeine; having clinically significant alcohol withdrawal symptoms (CIWA‐Ar score > 10; Sullivan 1989); having made more than four unsuccessful formal inpatient treatment attempts to curb alcohol dependence; having received formal psychotherapy for a psychiatric disorder other than alcohol dependence; taking antipsychotics, antiepileptics, mood stabilisers, carbonic anhydrase inhibitors, opioid analgesics or systemic steroids; having clinically significant depression; having suicidal ideation or having attempted suicide; receiving treatment for alcohol dependence other than Alcoholics Anonymous; having clinically significant medical condition (i.e. on physical examination, electrocardiogram recording, haematological assessment, biochemistry including bilirubin concentration and urinalysis); having a history of or current renal impairment (i.e. creatinine clearance 60 mL/min), renal stones, seizures or unstable hypertension; having progressive neurodegenerative disorders or clinically significant neurological disorders including seizures; being pregnant or lactating; taking medications that could affect alcohol consumption or a carbonic anhydrase inhibitor; having been compelled to receive treatment for alcohol dependence to avoid imprisonment, parole, probation or loss of employment; being from the same household as another study participant |
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| Interventions | (1) Topiramate, 183 participants; (2) placebo, 188 participants Drug dose: topiramate up to 300 mg/d Participants involved in weekly BBCET (Johnson 2003b) Setting: outpatient Duration: 14 weeks. Country of origin: USA |
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| Outcomes | Primary outcome: percentage of heavy drinking days (number of days on which men consumed five standard drinks per day and women consumed four standard drinks per day divided by the number of study days) Secondary outcome: percentage of days abstinent; drinks per drinking day; laboratory measure of alcohol consumption (plasma GGT) Safety outcome: vital signs; haematological and biochemical tests (including liver function tests, bicarbonate and pH level); depressed mood (Montgomery‐Asberg Depression Rating Scale) (Montgomery 1979); withdrawal symptoms (CIWA‐Ar) (Sullivan 1989); concomitant medications; adherence with taking medication; dose‐serum topiramate level concordance; retention; breath alcohol concentration; adverse events |
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| Notes | To be enrolled, participants had to express a desire to stop or reduce their consumption of alcohol, with the possible long‐term goal of abstinence | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: randomly assigned "in a 1:1 ratio to topiramate or placebo according to a computer‐generated code. Randomization was balanced using permuted blocks" |
| Allocation concealment (selection bias) | Low risk | Participants and investigators blinded to treatment assignment. To maintain the blind, sealed envelopes containing study medication identification provided to investigators, who were instructed that this envelope could be opened only if specific emergency treatment would be dictated by knowing participants’ treatment assignments |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Inferential testing conducted on all randomly assigned participants returning for at least one double‐blind visit and receiving at least one medication dose. Methods applied to account for missing data |
| Blinding of participants and personnel (performance bias) all outcomes | Low risk | Participants and investigators blinded to treatment assignment. Topiramate and matching placebo tablets used |
| Blinding of outcome assessment (detection bias) subjective | Low risk | Outcome assessors blinded to treatment assignment |
| Blinding of outcome assessment (detection bias) objective | Low risk | Outcome assessors blinded to treatment assignment |