Antidepressant Drug Effects and Depression Severity A Patient-Level Meta-analysis

Department of Psychology, University of Pennsylvania, 3720 Walnut St, Philadelphia, PA 19104, USA.
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 01/2010; 303(1):47-53. DOI: 10.1001/jama.2009.1943
Source: PubMed

ABSTRACT Antidepressant medications represent the best established treatment for major depressive disorder, but there is little evidence that they have a specific pharmacological effect relative to pill placebo for patients with less severe depression.
To estimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression.
PubMed, PsycINFO, and the Cochrane Library databases were searched from January 1980 through March 2009, along with references from meta-analyses and reviews.
Randomized placebo-controlled trials of antidepressants approved by the Food and Drug Administration in the treatment of major or minor depressive disorder were selected. Studies were included if their authors provided the requisite original data, they comprised adult outpatients, they included a medication vs placebo comparison for at least 6 weeks, they did not exclude patients on the basis of a placebo washout period, and they used the Hamilton Depression Rating Scale (HDRS). Data from 6 studies (718 patients) were included.
Individual patient-level data were obtained from study authors.
Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with HDRS scores below 23, Cohen d effect sizes for the difference between medication and placebo were estimated to be less than 0.20 (a standard definition of a small effect). Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline depression severity and crossed the threshold defined by the National Institute for Clinical Excellence for a clinically significant difference at a baseline HDRS score of 25.
The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.

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    • "Due to the lack of outpatient psychotherapists, patients with mild to moderate symptoms of depression often receive antidepressant medication (Holzinger et al., 2011). This is in contrast to recommendations of treatment guidelines (Fournier et al., 2010), and contrary to treatment preferences of those afflicted, who mostly prefer psychotherapy (Houle et al., 2013). Furthermore, persons with depression are often reluctant to seek professional help (Cuijpers, 2011). "
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    ABSTRACT: Only a minority of people suffering from depression receive adequate treatment. Psychological Online Interventions (POIs) could help bridge existing treatment gaps and augment the effectiveness of current treatments. Apart from effectiveness, user acceptance of POIs must be achieved if such interventions are to be broadly implemented in existing health-care. Valid measurement tools examining attitudes towards POIs are lacking. Therefore, we examined the dimensionality of attitudes towards POIs, developed a novel questionnaire, the Attitudes towards Psychological Online Interventions Questionnaire (APOI), and gathered data to examine its reliability. We recruited a sample of 1004 adults with mild to moderate depressive symptoms from a range of sources. We constructed a set of 35 items based on literature review as well as expert and patient queries. The initial items were subjected to an exploratory factor analysis (EFA) in a randomly selected subsample. A final set of 16 items was subjected to a confirmatory factor analysis (CFA) to cross-validate the factor structure in a separate subsample. The EFA revealed four dimensions: "Scepticism and Perception of Risks", "Confidence in Effectiveness", "Technologization Threat" and "Anonymity Benefits". The model fit in the CFA was excellent relating to all applied indices (χ(2)=105.816, p=.651; SRMR=.042; RMSEA=.013; CFI=.994) and the APOI total scale showed acceptable to good internal consistency. Further research with the APOI might facilitate the development and dissemination of POIs and, ultimately, help improve the quality of care for people experiencing depressive symptoms. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Affective Disorders 09/2015; 187:136 - 141. DOI:10.1016/j.jad.2015.08.044 · 3.38 Impact Factor
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    • "Antidepressant treatment history may reflect greater illness severity, functional impairment, or suicidal ideation, as well as depressive subtype, duration of prior episodes, and other factors . It has been argued that drug-placebo separation may be more evident in those with more severe depression (Khan et al. 2002; Fournier et al. 2010), and older retrospective studies of melancholic or Bendogenous^ depression have reported that these patients have lesser response to placebo (Peselow et al. 1992). While treatment history in our sample was related to age and to the number of prior episodes, with a trend relationship to current episode length, it predicted outcome over and above these and other illness-related factors. "
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    ABSTRACT: A history of antidepressant treatment may predispose subjects toward placebo nonresponse in randomized controlled trials (RCTs) in major depressive disorder (MDD). The objective of this study is to examine self-reported prior antidepressant treatment and response in relationship to clinical outcome in an 8-week randomized trial of reuptake inhibitor antidepressant medication (MED) versus placebo (PBO) administered along with limited supportive care. Chi-square and MMRM analyses examined MED vs. PBO outcomes in antidepressant-naïve vs. antidepressant-experienced subjects. Linear regression models examined treatment history along with covariates as predictors of clinical improvement. Among completers (n = 56), there was no significant difference in response rate between MED (53.3 %) and PBO (42.3 %) (χ (2) = 0.33, p = 0.28, 1-tailed). The antidepressant-experienced subgroup (n = 37), however, showed a significantly greater response rate to MED (52.4 %) than PBO (25.0 %) (χ (2) = 2.82, p = 0.047, 1-tailed). The full intent-to-treat (ITT) sample (n = 69) did not show a significant difference between MED and PBO group improvement over time, but in the treatment-experienced subgroup (n = 46), MED showed significantly greater improvement than PBO (coefficient = .39, SE = .23, p = .045, 1-tailed). A history of prior antidepressant treatment predicted poorer overall response independent of pretreatment symptom severity, number or length of previous episodes, subject expectations, or family history of MDD. Treatment history appears to constitute a factor that is distinct from other commonly studied illness characteristics or expectancy measures, and that impacts overall response as well as drug-placebo separation in RCTs.
    Psychopharmacology 08/2015; DOI:10.1007/s00213-015-4047-2 · 3.88 Impact Factor
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    • "Thus, it is difficult to distinguish between the placebo and the real effects of DTMS in these studies. There is, however, indirect evidence to suggest that placebo response rates are lower in patients with more resistant depressive episodes (Fournier et al., 2010). Thus, placebo effects might have also been low in the mostly treatment-resistant patients who participated in the primary studies included in this analysis. "
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    ABSTRACT: Deep transcranial magnetic stimulation (DTMS) is a relatively new, non-invasive method of stimulating larger and, presumably, deeper brain regions. The current study investigated if DTMS delivered with H-coils has acute antidepressant effects in major depression using a systematic literature review and a quantitative meta-analysis. Seventeen studies on 'DTMS or H-coil' and 'depression' were identified on Medline, PsycInfo, and Google Scholar (until November 2014). Data from nine open-label studies were meta-analysed using a random-effects model with inverse-variance weights. The outcome measures were the standardised paired mean difference (Cohen's d) in depression scores on Hamilton Depression Rating Scale (HDRS), response, remission, and dropout rates after acute DTMS treatment compared to baseline. There was a large antidepressant effect after 20 acute, high-frequency DTMS sessions compared to baseline according to HDRS change scores (overall mean weighted d=2.04, 95% confidence interval: 1.53-2.55; nine studies; 150 patients). Overall weighted response, remission, and dropout rates were 60%, 29%, and 18% respectively. HDRS change scores and response rates tended to be higher in four studies with 68 patients on concurrent antidepressants compared to two studies with 26 patients who received DTMS as a monotherapy. These results are based on data from a low number of open-label studies. High-frequency DTMS appears to have acute antidepressant effects after 20 sessions in mostly unipolar and treatment-resistant patients. Concurrent treatment with antidepressants might enhance the efficacy of DTMS. Copyright © 2015. Published by Elsevier B.V.
    Journal of Affective Disorders 08/2015; 187. DOI:10.1016/j.jad.2015.08.033 · 3.38 Impact Factor
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