Use of medication to treat depression in people with opioid dependence

There is little evidence to support the use of antidepressants for treating people who are dependent on opioids and have clinical depression. Depression is more common in people with substance abuse and dependence than in the general population. The depression experienced is also associated with an increased risk of completed suicide. Depression may represent an independent disorder, the psychosocial stress associated with addictive behavior or it could be a consequence of drug use and drug withdrawal effects. A maintenance program with opioid agonists (methadone, buprenorphine, LAAM) is an effective treatment for people who are dependent on opioids in terms of retention in treatment and reduced use of opioids. Depression is however still prevalent and negatively impacts on treatment outcomes. Treatment with antidepressant drugs has therefore been proposed. These adjunct drug treatments include tricyclic antidepressants (doxepin, desipramine, imipramine) and selective serotonin reuptake inhibitors (SSRIs fluoxetine, sertraline).

Authors included seven randomised controlled studies that involved 482 participants in our review. The studies were conducted in outpatient settings over four to 16 weeks; six were in USA and one in Australia. The mean age of participants was 34 years and 62% were males. No clear difference was found in the number of dropouts from an opioid agonist maintenance program between people receiving antidepressants and those in the placebo groups. Neither was drug use different (two studies). Severity of depression was reduced with the use of antidepressants (two studies), including tricyclic antidepressants. Adverse events were important as more of the participants who received antidepressants withdrew from the studies for medical reasons compared with those participants on placebo (four studies).

The differences between studies in clinical (participant characteristics, the medications used, services and treatments delivered) and methodological characteristics (study design and quality) made it difficult to draw confident conclusions about the efficacy and safety of antidepressants for the treatment of depression in people who are dependent on opioids.

Authors' conclusions: 

There is low evidence, at the present, supporting the clinical use of antidepressants for the treatment of depressed opioid addicts in treatment with opioid agonists. There is a need of larger randomised studies investigating relevant outcomes, safety issues and reporting data to allow comparison of results.

Read the full abstract...

Lifetime prevalence of depression in subjects with opioid dependence is higher than in the general population (44-54% versus 16%) and represents a risk factor for morbidity and mortality. For patients on opioid agonist treatment, current prevalence rates of depression ranges between 10 and 30%, influencing negatively the outcome of the treatment.


To evaluate the efficacy and the acceptability of antidepressants for the treatment of depressed opioid dependents treated with opioid agonists.

Search strategy: 

We searched Pubmed, EMBASE, CINAHL (to October 2009), CENTRAL (The Cochrane Library Cochrane Drug and Alcohol Group Specialised Register, issue 4, 2009), main electronic sources of ongoing trials, specific trial databases and reference lists of all relevant papers.

Selection criteria: 

Randomised and controlled clinical trials examining the efficacy of any antidepressant medication to treat depressed opioid dependents in treatment with opioid agonists.

Data collection and analysis: 

Two authors independently screened and extracted data from studies.

Main results: 

Seven studies, 482 participants, met the inclusion criteria.

- Comparing antidepressant with placebo, no statistically significant results for dropouts. Selecting studies with low risk of bias, 325 participants, results favour placebo, RR 1.40 (Cl 95% 1.00 to 1.96). For severity of depression, results from two studies, 183 participants, favour antidepressants utilising Clinical Global Impression Scale RR 1.92 (CI 95% 1.26 to 2.94), while another study, 95 participants, utilising the Hamilton Depression Rating Scale, did not find a statistically significant difference RR 0.96 (CI 95% 0.54 to 1.71). For adverse events, result favour placebo, four studies, 311 participants, RR 2.90 (Cl 95% 1.23 to 6.86). For drug use, three studies, 211 participants, it was not possible to pool data because outcomes' measures were not comparable. Looking at singular studies, no statistically significant difference was seen.

- Comparing different classes of antidepressants, the results favour tricyclics for severity of depression, two studies, 183 participants, RR 1.92 (Cl 95% 1.26 to 2.94) and favour placebo for adverse events, two studies, 172 participants, RR 3.11 (Cl 95% 1.06 to 9.12).