A Double-Blind, Placebo-Controlled Trial Combining Sertraline and Naltrexone for Treating Co-Occurring Depression and Alcohol Dependence

Abstract

BACKGROUND Empirical evidence has only weakly supported antidepressant treatment for patients with co-occurring depression and alcohol dependence. While some studies have demonstrated that antidepressants reduce these patients’ depressive symptoms, most studies have not found antidepressants helpful in reducing excessive drinking in these patients. We provide results from a double blind, placebo-controlled trial that evaluated the efficacy of combining approved medications for depression (sertraline) and alcohol dependence (naltrexone) for treating patients with both disorders. METHODS 170 depressed, alcohol-dependent patients were randomized for 14 weeks to sertraline (200mg/day), naltrexone (100mg/day), the combination, or placebo, while receiving weekly cognitive behavioral therapy. RESULTS The sertraline + naltrexone combination produced a higher alcohol abstinence rate (53.7%; p = .001; odds ratio = 3.7), and a longer delay before relapse to heavy drinking (98 median days; p = .003; d = .54), than the other treatments: naltrexone (21.3% abstinent, 29 days), sertraline (27.5% abstinent, 23 days), or placebo (23.1% abstinent, 26 days). There also was a trend for more patients in the medication combination group not to be depressed by the end of treatment (83.3%; p = .014; odds ratio = 3.6), compared to the other treatments. The serious adverse event rate was 25.9%, with fewer reported by the medication combination group (11.9%; p < .02) than the other treatments. CONCLUSION More depressed, alcohol-dependent patients taking the sertraline + naltrexone combination achieved abstinence from alcohol, delayed relapse to heavy drinking, reported fewer serious adverse events, and tended not to be depressed by the end of treatment.

Multiple possible inaccuracies cast doubt on a recent report suggesting selective serotonin reuptake inhibitors to be toxic and ineffective

“…4. One of the trials included by the authors, Pettinati (20), reports an SAE frequency of 37.5% in the SSRI monotherapy arm and of 28.2% in the placebo arm, hence constituting an extreme outlier with respect to SAE prevalence. The reason for this is obvious: this was a study in patients with depression combined with alcohol dependence, the most frequent SAE being 'requiring inpatient detoxification and/or rehabilitation'.…”

“…Basing our analyses on the data provided in table 2 in the paper by Jakobsen et al, we (i) added the two apparently erroneously non-tabulated studies (see above) (37,38), (ii) excluded studies that we believe should not have been included for reasons mentioned above (20,21,27), (iii) included missing treatment arms (see above), (iv) corrected all identified errors regarding the number of SAEs, (v) consistently used the intention to treat population for the patients at risk statistics and (vi) refrained from subdividing the placebo groups in multi-arm studies; for an annotated list of the changes we made to the data set, see Supplementary File 1. Although the overall result of this analysis reveals no significant difference between SSRI and placebo with respect to SAEs (OR 1.21, 0.94-1.56, p = 0.13; I 2 = 0%), the test for subgroup differences was significant (p = 0.049; I 2 = 74.1%), an increased risk for SAEs being observed in SSRItreated subjects in studies regarding older subjects (OR 1.86, 1.13-3.06, p = 0.01; I 2 = 0%) but no corresponding association found in the non-elderly studies (OR 1.04, 0.78-1.40, p = 0.77; I 2 = 0%).…”

Safety and Tolerability of Pharmacological Treatment of Alcohol Dependence: Comprehensive Review of Evidence

“…The majority of studies have used naltrexone at 50mg daily, though some [50][51][52][53][54][55] have investigated the tolerability of 100mg naltrexone. Use of 150 mg naltrexone daily in patients with comorbid cocaine dependence [56] is discussed below, but a single open label study by Yoon et al [57] evaluated the safety of 150mg daily in patients with alcohol dependence (titrated up from 25mg daily by week 3) over eight weeks.…”

Identification and management of alcohol dependence and withdrawal in alcoholic liver disease

“…It has also been suggested that concurrent treatment of co-occurring psychiatric disorders may also help decrease the risk for relapse. 11 As many patients with alcohol dependence are not offered medication treatment, they could be encouraged to discuss this with their addiction treatment providers.…”