The effect of sertraline and environmental context on treating depression and illicit substance use among methadone maintained opiate dependent patients: a controlled clinical trial. A randomised, controlled trial of fluoxetine in methadone maintenance patients with depressive symptoms. Doxepin as adjunctive therapy for depressed methadone maintenance patients: a double-blind study. Depression and anxiety in heroin addicts: a placebo-controlled study of doxepin in combination with methadone. Fluoxetine treatment of depressive disorders in methadone-maintained opioid addicts. Imipramine as treatment for depression in addicts. Imipramine treatment of opiate-dependent patients with depressive disorders. A placebo-controlled trial.
Psychiatric comorbidity, particularly depressive disorders, is associated with continued substance use and poor social functioning among methadone maintained patients. Evidence suggests similar neurochemical and environmental pathways may link the two disorders and it is reasonable to hypothesize that pharmacological and environmental factors play important roles in the treating comorbid depression and substance use. The present study tested the efficacy of sertraline for treating syndromally defined depressive disorders among non-abstinent methadone maintained opiate dependent patients. The moderating effects of environmental context on treatment outcome were also examined. Ninety-five patients were randomized in a 12-week, double-blind, placebo-controlled trial of sertraline, a serotonin-selective re-uptake inhibitor. There was no main effect of sertraline on either depression or substance use outcomes. However, sertraline demonstrated significant ameliorative effects on depression among patients with a more positive environment or less negative environment. The odds of being abstinent from heroin and cocaine were greater for patients on sertraline in environments with relatively less adversity. The findings support the hypothesis that contextual factors moderate the efficacy of pharmacological treatment for depression among methadone patients. They also suggest future research should examine a pharmacological treatment that is combined with a behavioral intervention targeting the accessibility of reinforcement or reducing the impact of aversive environmental interactions. Depression and antidepressant use are prevalent in methadone maintenance patients (MMPs). However, antidepressant efficacy is not well established in this population. This study examined the efficacy of fluoxetine in improving depressive symptoms and reducing substance use in MMPs.
                Stabilised MMPs scoring over 21 on the Beck Depression Inventory were randomised to receive fluoxetine or placebo over 12 weeks.
                Forty-nine subjects were randomised. In both groups, significant improvements were observed in depression, life functioning, and social impairment over 12 weeks. Poly-drug use improved in completers only. No fluoxetine effects were observed.
                Little evidence supports use of fluoxetine as a treatment for depressive symptoms in MMPs. Depression and anxiety can contribute to both drug dependence and reduced retention rates in methadone maintenance programs. In a 5-week double-blind study, the effectiveness of doxepin as an adjunctive treatment was compared to placebo in 46 depressed/anxious patients attending a methadone maintenance program. Doxepin was superior to placebo on Clinical Global Impressions and several factors of the Hamilton Rating Scale for Depression and the Profile of Mood States. No clinically significant potentiation of side effects was observed with the combined administration of doxepin and methadone. Narcotic addicts may manifest symptoms of depression that aggravate their addiction. In this double-blind study of 35 mildly depressed patients in a methadone maintenance program, subjects who received doxepin improved significantly more than control subjects. Even in this short-term study, the reduction in depression was associated with a trend toward better performance in other areas of rehabilitation. This study tested the effectiveness of fluoxetine as a treatment for depression in a population of methadone-maintained opioid addicts. Methadone-maintained opioid addicts (44) with depression received fluoxetine or placebo in addition to their methadone, in a double-blind randomized trial, for 12 weeks. Depressive symptoms decreased significantly overall with no significant differences between the groups treated with fluoxetine versus placebo. In addition, drug use outcomes, including cocaine and heroin self-reported use and urine toxicology were measured. There was a significant decrease in heroin use in treatment, but no medication effect. Cocaine use, was unchanged from pre-treatment to endpoint. In separately analyzing data for the subsample of subjects with the most severe depression, there was a significant decrease in depression during treatment and a significant decrease in self-reported cocaine use, but no medication effect on either depressive symptoms or on cocaine use. This study suggests that fluoxetine is not an effective agent in treating depression or cocaine use in this population. This report describes the results of a placebo-controlled double-blind clinical trial evaluating imipramine hydrochloride, a tricyclic antidepressant, as treatment for depression in methadone-maintained opiate addicts. Forty-six subjects were assigned randomly to either the imipramine or placebo group for up to eight weeks. All patients also received mandatory once weekly group therapy as part of the methadone program. Outcome measures included attrition, depressive symptoms, global improvement, side effects, social functioning, and urine specimen results positive for illicit drugs. The therapeutic response in the two conditions was similar. Addicts receiving either imipramine or placebo experienced a substantial reduction of depressive symptoms during the eight weeks of the study. These findings are compared with other studies that treat depression in addicts and nonaddicts. The literature is inconclusive on the role of antidepressant medications in treating drug dependence. Studies have either not focused on depressed patients or have selected patients with depressive disorders based on cross-sectional symptoms rather than a syndromal diagnosis. A clinical trial of an antidepressant was, therefore, conducted on drug-dependent patients with syndromal depression.
                Patients receiving methadone hydrochloride maintenance treatment were selected if they met the criteria for a DSM-III-R depressive disorder that was chronologically primary, had persisted during a past abstinent period or was long-standing, and persisted during at least 1 month of stable methadone treatment. Subjects were randomized to a 12-week, double-blind, placebo-controlled trial of imipramine hydrochloride. A favorable response was defined as a Clinical Global Impression scale score for depression of 2 ("much improved") or 1 ("very much improved") and at least a 75% reduction in self-reported drug or alcohol use or abstinence.
                One hundred thirty-seven patients were randomized, and 84 completed a minimum adequate trial of at least 6 weeks. Among the 84 adequately treated patients, 57% (24/42) receiving imipramine were rated as responders compared with 7% (3/42) receiving placebo (P < .001). On measures of mood, there was a robust effect of imipramine. Imipramine was superior to placebo on some self-reported measures of substance use and craving, and mood improvement was associated with improvement in self-reported substance use. However, few patients achieved urine-confirmed abstinence.
                Imipramine was an effective antidepressant in patients receiving methadone who were selected via syndromal criteria for depressive illness. Imipramine may reduce substance abuse among patients whose mood improves; however, this effect was less robust.
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.