The Efficacy of Mirtazapine in the Treatment of Cocaine Dependence with Comorbid Depression

Abstract

Background Prior findings concerning the use of mirtazapine in the treatment of a variety of substance use disorders and its antagonistic actions at the serotonin 5-HT2A receptor suggest that this drug may have efficacy in the treatment of cocaine dependence in the presence of a depressive disorder. Methods Depressed cocaine-dependent subjects received either mirtazapine (target dose 45 mg daily) or placebo for 12 weeks. Urine concentrations of benzoylecgonine and self-report were used to assess cocaine consumption. Depression and sleep quality were evaluated using the Hamilton Depression Rating Scale (HAM-D) and the Pittsburgh Sleep Quality Index, respectively. Results Cocaine consumption during the treatment period did not differ significantly between the mirtazapine (n = 11) and placebo (n = 13) groups in this study. In week 4 sleep latency was significantly lower in the active medication than in the placebo group. Positive effects of mirtazapine treatment on early insomnia were suggested by an item analysis of the HAM-D. Conclusions and Scientific Significance The results of this study suggest that mirtazapine is superior to placebo in improving sleep in patients with comorbid depression and cocaine dependence, but is not more effective than placebo in reducing cocaine use.

Mirtazapine, and mirtazapine-like compounds as possible pharmacotherapy for substance abuse disorders: Evidence from the bench and the bedside

“…However, this study used a small sample size (13 patients on mirtazapine) with a focus on acute withdrawal states, which are often characterized by anxiety and hypersomnolence. Similarly, a more recent double-blind placebo-controlled study found that mirtazapine is not superior to placebo at decreasing cocaine use in cocaine-dependent subjects comorbid with depression (Afshar et al, 2012); although, similar to the study by Cruickshank et al, the sample size was small with only 11 patients on mirtazapine. Thus, despite two reports where mirtazapine fails to perform as a substance abuse pharmacotherapy, the bulk of the clinical observations suggest that mirtazapine therapy may improve outcomes across a number of SUDs as well as benefit patients with comorbid conditions, including depression, anxiety and/or HIV/AIDS.…”

Effects of quetiapine treatment on cocaine self-administration and behavioral indices of sleep in adult rhesus monkeys

“…In the present study, the high baseline measures of sleep efficiency most likely precluded any significant improvements following quetiapine administration. A study examining the efficacy of mirtazapine (a sleep-promoting agent) in patients with comorbid depression and cocaine dependence showed that mirtazapine was superior to placebo in improving sleep, however it was not more effective than placebo in reducing cocaine use (Afshar et al 2012). Importantly, the present findings indicated that following discontinuation of chronic quetiapine administration there was evidence of disruptions in sleep efficiency, suggesting development of physical dependence over two weeks of treatment.…”

A randomized, double‐blind, placebo‐controlled trial of venlafaxine for the treatment of depressed cocaine‐dependent patients

“…Instead, the results are reminiscent of other small, open pilot studies not replicating in larger controlled trials, and of negative trials of serotonin reuptake inhibitors, nefazodone, or mirtazapine among alcohol, 24,25 or drug-dependent patients. 7,8,12,13,25,26 …”

“…8 Trials with nefazodone and mirtazapine were also negative. 12,13 A trial of the norepinephrine reuptake inhibitor desipramine found a modest beneficial effect of desipramine on depression symptoms, no direct effect of the medication on cocaine use outcome, but mood improvement was associated with cocaine use improvement; poor tolerability limited adherence. 14 An uncontrolled pilot trial of venlafaxine, a mixed serotonin-norepinephrine reuptake inhibitor, with a more benign side effect profile, showed promise for combined cocaine dependence and depression.…”