The objective of this study was to determine if combined psychotherapy and pharmacotherapy reduces reported depressive symptoms compared to an assessment only condition for active drug injectors over nine months. Using a randomized controlled trial at an outpatient academic research office, the researchers applied psychotherapy (eight sessions of cognitive behavioral therapy) plus pharmacotherapy (citalopram) to active injection drug users with a DSM-IV diagnosis of major depression, dysthymia, substance-induced mood disorder with symptoms persisting for at least three months, or major depression plus dysthymia, and a Modified Hamilton Rating Scale for Depression (MHRSD) score greater than 13. The MHRSD scale scores were then assessed at the completion of three, six, and nine months. Participants (n = 109) were 64% male and 82% Caucasian, with a mean baseline MHRSD score of 20.7. Depression subtypes included major depression only (63%), substance-induced depression (17%), and double-depression (17%). Study retention at nine months was 89%. At the completion of three months of acute treatment, 26% of combined treatment patients (n = 53), compared to 12% of control patients (n = 56), were in remission (p = .047). At both six and nine months, the between-group differences in remission rates and mean MHRSD scores were insignificant, although the overall mean MHRSD score decreased from baseline (p < .01). At all follow-up assessments, depression remission was significantly associated with lower heroin use. Among active drug injectors diagnosed with depression, symptoms decline over time. Combined treatment is superior to an assessment-only condition in depression remission rates at the end-of-treatment, but this difference does not persist.