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Antidepressants have greater effect in those with severe depression, study finds

Patients with mild to severe depressive symptoms may not benefit from antidepressant medicines although those with very severe symptoms do, according to a study (JAMA 2009;303:47) published last week (6 January 2010)

Patients with mild to severe depressive symptoms may not benefit from antidepressant medicines although those with very severe symptoms do, according to a study (JAMA 2009;303:47) published last week (6 January 2010).

Investigators from the University of Pennsylvania analysed data from six studies, which included 718 patients given antidepressants or placebo.

Analysis of the data from the studies suggests that the magnitude of benefit from antidepressant medication compared with placebo increases with the severity of depression symptoms and may be minimal or non-existent, on average, in patients with mild or moderate symptoms.

Clinically significant differences between antidepressants and placebo, as set by the National Institute for Health and Clinical Excellence, were only seen for severely depressed patients — in the study, those with a baseline Hamilton Depression Rating Scale (HDRS) score of above 25.

The authors say: “What makes our findings surprising is the high level of depression symptom severity that appears to be required for clinically meaningful drug/placebo differences to emerge, particularly given the evidence that the majority of patients receiving antidepressant medicines in clinical practice present with scores below these levels.”

They stress that prescribers and patients should be aware that the efficacy of antidepressants is established on the basis of studies which only include patients with more severe forms of depression.

 Panel: Study findings

The meta-analysis incorporated studies that included patients with varying levels of depression according to the Hamilton Depression Rating Scale. The drugs used were paroxetine and imipramine.

In patients with mild, moderate and severe depression (HDRS scores below 23), the Cohen d effect size — the measure of the strength of the relationship between two variables — for the difference between medication and placebo were estimated to be less than 0.20 (a standard definition of a small effect).

The superiority of antidepressants over placebo was associated with a medium size effect for patients with HDRS scores of 25 or greater (d=0.53, 95 per cent confidence interval 0.19–0.86) and a large effect for patients with HDRS of 27 or greater (d=0.81, CI 0.30–1.32).

Citation: The Pharmaceutical Journal URI: 10992261

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