http://www.bmj.com/content/331/7509/155?ijkey=26c8afe7ad38424073e7794ec14de137dc7b7616&keytype2=tf_ipsecsha

Efficacy of antidepressants in adults

BMJ 2005; 331 doi: http://dx.doi.org/10.1136/bmj.331.7509.155 (Published 14 July 2005)

Cite this as: BMJ 2005;331:155

• Drugs: musculoskeletal and joint diseases

Most people with depression are initially treated with antidepressants. But how well do the data support their use, and should we reconsider our strategy?

Introduction

The National Institute for Health and Clinical Excellence (NICE) recently recommended that antidepressants, in particular selective serotonin reuptake inhibitors, should be first line treatment for moderate or severe depression.1 This conclusion has broadly been accepted as valid.2 The message is essentially the same as that of the Defeat Depression Campaign in the early 1990s, which probably contributed to the 253% rise in antidepressant prescribing in 10 years.1 From our involvement in commenting on the evidence base for the guideline we believe these recommendations ignore NICE data. The continuing concern that selective serotonin reuptake inhibitors may increase the risk of suicidal behaviour^{w1 w2} means there needs to be further consideration of evidence for the efficacy of antidepressants in adults as there has been in children.

Efficacy

Although the NICE meta-analysis of placebo controlled trials of selective serotonin reuptake inhibitors found significant differences in levels of symptoms, these were so small that the effects were deemed unlikely to be clinically important.1 The conclusion that the drugs had clinically important benefits was based on analysis of response and remission rates. However, in our comments on the draft guidelines, we pointed out that these categorical outcomes were derived from the same continuous data for symptoms scores that were found to show no clinically relevant effects. As NICE notes, “dichotomising scores into remission and non-remission creates an artificial boundary, with patients just over the cut-off score often being clinically indistinguishable from those just under the cut-off.”

In V-Bi statistics there is a paradoxical relationship between significant and insignificant results, if they are over the 95% confidence level then they may be approved but a 94% level may not be. This represents a tipping point that can be chaotic between success and failure, similar boundaries can be manipulated to make it appear a result is more useful. For example a drug might not work but people expecting to be helped might be happier in the earlier stages of a trial. So counting evidence of happiness such as smiles and laughter might give an appearance that the drug is causing this rather than expectations. This problem is compounded with depression scales of measurements that are based on behavior like this, people expect to be helped and a remission can appear to occur from this expectance of this.