Arndt 1994.

Study characteristics
Methods	Design: placebo‐controlled parallel trial
Participants	Participants: methadone‐maintained male outpatients with cocaine dependency (AsPD subgroup) Sex: male only Age: whole sample mean = 40.5 years (range = 29 to 59 years) Unit of allocation: individual participant Number randomised: 79 (number with AsPD not reported) (see note 1) Number completing: 29 with AsPD (desipramine = 17, control = 12) (see note 1) Setting: outpatient; single site; Philadelphia, USA Inclusion criteria: cocaine dependence lasting at least 3 months (DSM‐III; National Institute Mental Health Diagnostic Interview Schedule); aged 20 to 60 years; cocaine‐positive urine over 1 month prior to being contacted for participation Exclusion criteria: medical condition contraindicating desipramine use; cocaine misuse disorder lasting less than 3 months Ethnicity: whole sample = 90% black American Baseline characteristics: whole sample = male service veterans (100%); on methadone maintenance for at least 1 month (100%); average methadone dose 45 mg/day (range = 15‐85 mg/day); reported using cocaine intravenously (83%); reported 'free basing' (15%); reported intranasal use (11%); employed (79%); educated to high school degree level (53%); some college education (29%); married (35%); never married (35%); separated or divorced (30%)
Interventions	Two conditions: desipramine (oral, 250 to 300 mg/day) + standard methadone treatment (number randomised not reported, n = 17 completed) placebo + standard methadone treatment (number randomised not reported, n = 12 completed) All participants received standard clinical services including weekly drug counselling, social work services as needed, employment counselling, referral psychiatric and medical care Duration of intervention: 12 weeks Duration of trial: 12 weeks Length of follow‐up: participants were not followed up beyond the study period Dose adjustment: desipramine 50 mg/day initially increased by 50 mg every 2 to 4 days as tolerated to a target dose of 250 to 300 mg/day; mean blood levels 185 mg/ml (range 85 to 270 mg/ml)
Outcomes	Primary outcomes Social functioning: days family/social problems in past 30 days (Addiction Severity Index; ASI) Secondary outcomes Substance misuse: urinalysis; days opiate use in past 30 days via the ASI; days cocaine use in past 30 days (ASI); days depressant use in past 30 days (ASI); cocaine craving score (see note 2) Employment status: days worked in past 30 days (ASI); employment income (ASI) Other outcomes Depression (Beck Depression Inventory; BDI); days medical problems in past 30 days (ASI); days illegal activity in past 30 days (ASI); illegal income (ASI); days psychological problems past 30 days (ASI) Timing of outcome assessments Weekly urinalysis; biweekly blood assay; measures such as ASI at baseline, 4,8 and 12 weeks.
Notes	Investigators initially randomised 79 participants of which 59 (36 treatment; 23 control) completed the trial; 49% of completers had AsPD. This review focuses on the data available from the 29 completers with AsPD (17 treatment; 12 control). Cocaine craving score derived from the Cocaine Craving Scale and Quantitative Cocaine Inventory (as described in Arndt 1992) Study funding: National Institute on Drug Abuse (USA) Declaration of interests: none reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information given. Clarification about method of sequence generation has been requested from the trial investigators, but no further information was available at the time this review was prepared.
Allocation concealment (selection bias)	Unclear risk	Comment: no information given. Clarification about method of sequence generation has been requested from the trial investigators, but no further information was available at the time this review was prepared.
Blinding (performance bias and detection bias) of participants	Unclear risk	Comment: Investigators described the study as "double‐blind" and report that an independent researcher "gave directions for changing the dose given to the patients receiving placebo so that the double‐blind condition was maintained" (Arndt 1992, p.889, column 2). No further information given.
Blinding (performance bias and detection bias) of personnel	Low risk	Comment: Investigators reported that "study physicians were blind to the blood level results [which were] provided to an independent research physician who recommended increases or decreases to achieve the desirable blood level" (Arndt 1994, p.152, column 2), and also that the BDI outcome measure was "administered by trained research technicians who were experimentally blind and independent of the treatment program" (Arndt 1992, p.889, column 1). Review authors judged that appropriate care was taken to ensure blinding of study personnel, and that it was unlikely that this blinding could have been broken.
Blinding (performance bias and detection bias) of outcome assessors	Low risk	Comment: Investigators reported that "study physicians were blind to the blood level results [which were] provided to an independent research physician who recommended increases or decreases to achieve the desirable blood level" (Arndt 1994, p.152, column 2), and also that the BDI outcome measure was "administered by trained research technicians who were experimentally blind and independent of the treatment program" (Arndt 1992, p.889, column 1). Review authors judged that appropriate care was taken to ensure blinding of outcome assessors, and that it was unlikely that this blinding could have been broken.
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: Incomplete outcome data arise from participants not completing the study and applies to all measured outcomes. Investigators did not provide numbers of non‐completers for the AsPD subgroup, but supplied the following data for the whole sample. For the desipramine group, 17 out of 53 (32%) discontinued because of side effects (4), non‐compliance with the protocol (4), hospitalisation unrelated to desipramine treatment (3), legal violations (3), or for other reasons (3). For the control group, 3 out of 26 (12%) discontinued (reasons not given). Numbers of missing data are thus not balanced between experimental conditions for the whole sample. Clarification has been requested from the trial investigators but no further information was available at the time this review was prepared. In this review, data from the 29 participants with AsPD who completed the study were included in the analysis (desipramine condition, n = 17; control condition, n = 12).
Selective reporting (reporting bias)	Unclear risk	Comment: The study protocol is not available; however, the published report included all expected outcomes, including those that were pre‐specified in the methods.
Other bias	Low risk	Comment: The study appeared to have no other obvious sources of bias.