Nefazodone treatment of major depression in alcohol-dependent patients: a double-blind, placebo-controlled trial.
ABSTRACT Depression is the most common comorbid psychiatric illness in patients with alcohol dependence. This double-blind study tested the efficacy of nefazodone versus placebo for the treatment of depression in actively drinking alcohol-dependent patients who were also participating in weekly group treatment for alcoholism. Sixty-four subjects with major depression disorder and alcohol dependence with a history of at least one prior episode of depression when not drinking were randomly assigned to receive 12 weeks of either nefazodone or placebo and participated in a weekly psychoeducational group on alcoholism. Subjects were assessed every 2 weeks for depression, anxiety, side effects, and drinking frequency. Subjects taking nefazodone were significantly more likely to complete the study (62%) than those taking placebo (34%). Analyses of covariance using drinks per week as a time-dependent covariate showed lower Hamilton Rating Scale for Depression scores at week 8 for end-point analysis and at weeks 8 and 12 for completers. The endpoint analysis demonstrated a significantly greater response in the nefazodone group (48%) than in the placebo group (16%). Both groups showed a similarly significant decrease in the average number of alcoholic drinks consumed per day over the course of the study. Although the number of adverse effects was significantly greater for the nefazodone group, there were no severe adverse events, and nefazodone was well tolerated. Nefazodone is a safe and effective antidepressant to use in a population of alcohol-dependent patients with depression who have a high degree of comorbidity. Nefazodone treatment was superior to placebo in alleviating depression in these patients but did not add any advantage over the psychoeducational group in terms of drinking outcomes.
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ABSTRACT: To review published studies on the effectiveness of combining cognitive-behavioural therapy (CBT) and motivational interviewing (MI) to treat comorbid clinical and subclinical alcohol use disorder (AUD) and major depression (MDD) and estimate the effect of this compared with usual care. We conducted systematic literature searches in PubMed, PsycINFO and Embase up to June 2013 and identified additional studies through cross-references in included studies and systematic reviews. Twelve studies comprising 1721 patients met our inclusion criteria. The studies had sufficient statistical power to detect small effect sizes. CBT/MI proved effective for treating subclinical and clinical AUD and MDD as compared with controls, with small overall effect sizes at post-treatment (g = 0.17, CI: 0.07-0.28, p <.001 for decrease of alcohol consumption and g = 0.27, CI: 0.13-0.41, p <.001 for decrease of symptoms of depression respectively). Subgroup analyses revealed no significant differences for both AUD and MDD. However, digital interventions showed a higher effect size for depression than face to face interventions (g = 0.73 and g= 0.23 respectively p = .030). Combined cognitive-behavioural therapy and motivational interviewing for clinical or subclinical depressive and alcohol use disorders has a small but clinically significant effect in improving outcomes compared with treatment as usual.Addiction 12/2013; · 4.60 Impact Factor
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ABSTRACT: Placebo group improvement in pharmacotherapy trials has been increasing over time across several pharmacological treatment areas. However, it is unknown to what degree increasing improvement has occurred in pharmacotherapy trials for alcohol use disorders or what factors may account for placebo group improvement. This meta-analysis of 47 alcohol pharmacotherapy trials evaluated (1) the magnitude of placebo group improvement, (2) the extent to which placebo group improvement has been increasing over time, and (3) several potential moderators that might account for variation in placebo group improvement. Random-effects univariate and multivariate analyses were conducted that examined the magnitude of placebo group improvement in the 47 studies and several potential moderators of improvement: (a) publication year, (b) country in which the study was conducted, (c) outcome data source/type, (d) number of placebo administrations, (e) overall severity of study participants, and (f) additional psychosocial treatment. Substantial placebo group improvement was found overall and improvement was larger in more recent studies. Greater improvement was found on moderately subjective outcomes, with more frequent administrations of the placebo, and in studies with greater participant severity of illness. However, even after controlling for these moderators, placebo group improvement remained significant, as did placebo group improvement over time. Similar to previous pharmacotherapy placebo research, substantial pretest to posttest placebo group improvement has occurred in alcohol pharmacotherapy trials, an effect that has been increasing over time. However, several plausible moderator variables were not able to explain why placebo group improvement has been increasing over time.Journal of clinical psychopharmacology 07/2013; · 5.09 Impact Factor
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ABSTRACT: Major depressive disorder (MDD) has detrimental effects on an individual's personal life, leads to increased risk of comorbidities, and places an enormous economic burden on society. Several 'second-generation' antidepressants are available as both immediate-release (IR) and extended-release formulations. The advantage of extended-release formulations may be the potentially improved adherence and a lower risk of adverse events. We conducted a systematic review to assess the comparative efficacy, risk of harms, and patients' adherence of IR and extended-release antidepressants for the treatment of MDD. English-language abstracts were retrieved from PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to October 2012, as well as from reference lists of pertinent review articles and grey literature searches. We included head-to-head randomized controlled trials (RCTs) of at least 6 weeks' duration that compared an IR formulation with an extended-release formulation of the same antidepressant in adult patients with MDD. We also included placebo-controlled trials to conduct a network meta-analysis. To assess harms and adherence, in addition to RCTs, we searched for observational studies with ≥1,000 participants and a follow-up of ≥12 weeks. We dually reviewed abstracts and full texts and assessed quality ratings. Lacking head-to-head evidence for many comparisons of interest, we conducted network meta-analyses using Bayesian methods. Our outcome measure of choice was response on the Hamilton Depression Rating Scale. We located seven head-to-head trials and 94 placebo- and active-controlled trials for network meta-analysis. Overall, our analyses indicate that IR and extended-release formulations do not differ substantially with respect to efficacy and risk of harms. The evidence is mixed with respect to differences in adherence, indicating lower adherence for IR formulations. The lack of head-to-head comparisons for many drugs compromises our conclusions. Network meta-analyses have methodological limitations that need to be taken into consideration when interpreting findings. Available evidence currently shows no clear differences between the two formulations and therefore we cannot recommend a first choice. However, if adherence or compliance with one medication is an issue, then clinicians and patients should consider the alternative medication. If adherence or costs are a problem with one formulation, consideration of the other formulation to provide an adequate treatment trial is reasonable.CNS Drugs 05/2014; 28(8). · 4.38 Impact Factor