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: 30.39). 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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Available from: Richard C Shelton, Jan 31, 2015
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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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    • "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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    • "In the Khan et al. (2002) analysis, improvement as a function of baseline severity increased in drug groups but decreased in placebo groups. In Fournier et al. (2010), improvement as a function of severity increased significantly in both drug and placebo groups (as would be predicted by regression toward the mean), but the increase was significantly larger in the drug group. It should be noted that a re-analysis of the Kirsch et al. (2008) data set, which controlled for the effect of structural coupling (this occurs when baseline values and change score are coupled algebraically, thus possibly leading to an inflated association between the variables; Tu et al., 2004) concluded that baseline severity did not influence treatment outcome (Fountoulakis et al., 2013). "
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