Nadia Iovieno

From The Journal of Clinical Psychiatry: Cognitive deficits are common in depression, but studies suggest that cognitive dysfunction is difficult to treat with antidepressants. Can adding an atypical antipsychotic medication to antidepressant treatment help lessen cognitive dysfunction? Read this article to learn the effect that adjunctive ziprasidone had on cognitive deficits in depressed patients treated with escitalopram.

To investigate the relationship between specific levels of placebo response rates and the drug response rate and the relative risk of response to drug versus placebo in clinical trials of antidepressant monotherapy and adjunctive polypharmacy for MDD. MEDLINE/PubMed databases were searched for studies published in the English language between January 1980 and March 2011 by using the search terms depression, placebo, augmentation, adjunct, adjunctive, and each of the antidepressant agents identified. The search was supplemented by manual bibliographic review and examination of relevant review articles. The analysis included randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for MDD, 4 weeks or longer, and of augmentation/combination treatments for antidepressant partial responders/nonresponders with MDD, 1 week or longer. 169 antidepressant monotherapy studies and 35 adjunctive polypharmacy studies were found eligible for inclusion in our analysis. Data extracted included number of patients enrolled, patient characteristics, drug dosages and scheme (fixed vs flexible dosing), duration of the trial, and response rates. In antidepressant monotherapy studies, a higher placebo response rate correlated with a lower risk ratio of responding to antidepressant versus placebo (P < .001) and correlated with higher antidepressant response rates (P < .001); the number needed to treat (NNT) for response was approximately 4, 6, and 9 in trials with placebo response rates < 30%, ≥ 30% and < 40%, and ≥ 40%, respectively. In adjunctive trials, a higher placebo response rate correlated with a lower risk ratio of responding to the adjunctive drug versus placebo (P < .001) and correlated with a trend toward statistical significance with higher response rates to the adjunctive drug (P = .050); the NNT was approximately 6, 7, 11, and 17 in trials with placebo response rates < 20%, ≥ 20% and < 30%, ≥ 30% and < 40%, and ≥ 40%, respectively. These results suggest that the relative efficacy of the active drug compared to placebo in clinical trials for MDD is highly heterogeneous across studies with different placebo response rates, with a worse performance in showing a superiority of the drug versus placebo for studies with placebo response rates ≥ 30% and ≥ 40%, respectively, for monotherapy and adjunctive trials. It is important to maintain placebo response rates below this critical threshold, since this is one of the most challenging obstacles for new treatment development in MDD.

The authors sought to determine study design factors that may influence clinical trial outcome in augmentation/combination trials for antidepressant partial responders/nonresponders with major depressive disorder (MDD) and to examine whether the use of a prospective treatment phase (lead-in) to assess antidepressant nonresponse may result in a better chance to detect a drug-placebo separation in such trials.

Mood and alcohol use disorders are often co-occurring, each condition complicating the course and outcome of the other. The aim of this study was to examine the efficacy of antidepressants in patients with unipolar major depressive disorder (MDD) and/or dysthymic disorder with comorbid alcohol use disorders and to compare antidepressant and placebo response rates between depressed patients with or without comorbid alcohol use disorders. MEDLINE/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of antidepressants used as monotherapy for the acute-phase treatment of MDD and/or dysthymic disorder in patients with or without alcohol use disorders. The search term placebo was cross-referenced with each of the antidepressants approved by the US, Canadian, or European Union drug regulatory agencies for the treatment of MDD and/or dysthymic disorder. 195 articles were found eligible for inclusion in our analysis, 11 of which focused on the treatment of MDD/dysthymic disorder in patients with comorbid alcohol use disorders. The search was limited to articles published between January 1, 1980, and March 15, 2009 (inclusive). We found that antidepressant therapy was more effective than placebo in patients with comorbid alcohol use disorders (risk ratio of response = 1.336; P = .021). However, this was not the case when selective serotonin reuptake inhibitor (SSRI) antidepressants were examined alone (P > .05). There was no significant difference in the relative efficacy of antidepressants (versus placebo) when comparing studies in MDD/dysthymic disorder patients with or without alcohol use disorders (P = .973). Meta-regression analyses yielded no significant differences in the risk ratio of responding to antidepressants versus placebo in trials with comorbid alcohol use disorders, whether antidepressants were used alone or adjunctively to psychotherapy, whether they were used in patients actively drinking or recently sober, or whether they were used in pure MDD or in combined MDD and dysthymic disorder populations. These results support the utility of certain antidepressants (tricyclics, nefazodone) in treating depression in patients with comorbid alcohol use disorders. More data on the use of newer antidepressants, including the SSRIs, for this select patient population are needed.

Background: Many patients with major depressive disorder (MDD) who achieve full remission after antidepressant treatment still have residual depressive symptoms. In this study, we assess the type and frequency of residual symptoms and their relationship to subsequent depressive relapses after remission of major depression with fluoxetine. Method: Five hundred seventy‐six patients with MDD were openly treated with fluoxetine for 12 weeks. Those who responded underwent random assignment, under double‐blind conditions, to continue taking fluoxetine or to switch to placebo for 52 weeks or until relapse. The presence of residual symptoms in patients who achieved remission at the end of the acute phase (N=203) was assessed using the 28‐item Hamilton Depression Rating Scale. Survival analysis was used to examine the effect of residual symptoms on relapse in remitters. Results: More than 90% of patients who met criteria for remission had at least one residual depressive symptom (median=4). The most common were sleep disturbances (insomnia 48.2%, hypersomnia 35.9%) and anxiety (52.7%). The most common individual symptom was middle insomnia (33.5%). No statistically or clinically significant differences in baseline variables were found between remitters with and without residual symptoms. The presence of residual symptoms, the presence of residual insomnia and the global number of residual symptoms did not predict relapse during the continuation phase of the study. Conclusion: The great majority of patients with remission of MDD after treatment with fluoxetine continue to experience selected residual depressive symptoms. The presence of residual symptoms is not significantly associated with an increased risk of relapse. Depression and Anxiety, 2011.