Depression and substance abuse are common and costly disorders that
frequently co-occur, but controversy about effective treatment for patients
with both disorders persists.
To conduct a systematic review and meta-analysis to quantify the efficacy
of antidepressant medications for treatment of combined depression and substance
PubMed, MEDLINE, and Cochrane database search (1970-2003), using the
keywords antidepressant treatment or treatment depressed in conjunction with each of the following alcohol dependence, benzodiazepine dependence, opiate dependence, cocaine
dependence, marijuana dependence, and methadone; a search of bibliographies; and consultation
with experts in the field.
Among inclusion criteria used for study selection were prospective,
parallel group, double-blind, controlled clinical trials with random assignment
to an antidepressant medication or placebo for which trial patients met standard
diagnostic criteria for current alcohol or other drug use and a current unipolar
depressive disorder. Of the more than 300 citations extracted, 44 were placebo-controlled
clinical trials, 14 of which were selected for this analysis and included
848 patients: 5 studies of tricyclic antidepressants, 7 of selective serotonin
re-uptake inhibitors, and 2 from other classes
We independently screened the titles and abstracts of each citation,
identified placebo-controlled trials of patients with both substance dependence
and depression, applied the inclusion criteria, and reached consensus. Data
on study methods, sample characteristics, and depression and substance use
outcomes were extracted. The principal measure of effect size was the standardized
difference between means on the Hamilton Depression Scale (HDS).
For the HDS score, the pooled effect size from the random-effects model
was 0.38 (95% confidence interval, 0.18-0.58). Heterogeneity of effect on
HDS across studies was significant (P <.02), and
studies with low placebo response showed larger effects. Moderator analysis
suggested that diagnostic methods and concurrent psychosocial interventions
influenced outcome. Studies with larger depression effect sizes (>0.5) demonstrated
favorable effects of medication on measures of quantity of substance use,
but rates of sustained abstinence were low.
Antidepressant medication exerts a modest beneficial effect for patients
with combined depressive- and substance-use disorders. It is not a stand-alone
treatment, and concurrent therapy directly targeting the addiction is also
indicated. More research is needed to understand variations in the strength
of the effect, but the data suggest that care be exercised in the diagnosis
of depression–either by observing depression to persist during at least
a brief period of abstinence or through efforts by clinical history to screen
out substance-related depressive symptoms.