"The truth is rarely pure, and never simple"  Oscar Wilde

There has been a lot of media publicity about the article on the value of antidepressants by Irving Kirsch and colleagues which was published in PLoS Medicine last month (Kirsch, Deacon et al. 2008). The authors wrote "We obtained data on all clinical trials submitted to the US Food and Drug Administration (FDA) for the licensing of the four new-generation antidepressants for which full datasets were available. We then used meta-analytic techniques to assess ... effects of initial severity on improvement scores for drug and placebo groups and on drug-placebo difference scores." The four antidepressants studied were fluoxetine, paroxetine, nefazodone and venlafaxine.

They reported that " ... weighted mean improvement was 9.60 points on the HRSD (Hamilton Rating Scale for Depression) in the drug groups and 7.80 in the placebo groups, yielding a mean drug-placebo difference of 1.80 on HRSD improvement scores. Although the difference between these means easily attained statistical significance, it does not meet the three-point drug-placebo criterion for clinical significance used by NICE (UK National Institute for Health and Clinical Excellence). Represented as the standardized mean difference, d, mean change for drug groups was 1.24 and that for placebo 0.92, both of extremely large magnitude according to conventional standards. Thus, the difference between improvement in the drug groups and improvement in the placebo groups was 0.32, which falls below the 0.50 standardized mean difference criterion that NICE suggested."

So the improvement (mean change) for those taking the antidepressants was 1.24 - " ... of extremely large magnitude", and the difference in improvement achieved by antidepressants and placebo " ... easily attained statistical significance ... ." The crunch point made by the authors though was that this drug-placebo difference is small, and they went on to state "... there seems little evidence to support the prescription of antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed to provide benefit."

This seems a strong statement - that antidepressants, a standard primary care treatment for depression - should only be used in extremely severe depression or when other approaches have failed. And this point seems to being taken seriously. The British Medical Journal has set up an online poll asking "Should doctors change their practice in prescribing antidepressants in the light of last month's research?" Visiting the poll today, 77% of the 560 current respondents have voted "Yes".

Key issues are "If I am suffering from depression, when is it sensible for me to consider taking an antidepressant?" and "If I am a health professional trying to help someone suffering from depression, when is it is sensible for me to offer them an antidepressant?". The current NICE guideline (see below) does not recommend using antidepressants, at least initially, for mild depression. It does however state that "In moderate depression, offer antidepressant medication to all patients routinely, before psychological interventions." and "When patients present initially with severe depression, a combination of antidepressants and individual CBT should be considered as it is more cost-effective than either treatment on its own." NICE adds that "For routine care, use an SSRI because they are as effective as tricyclic antidepressants and less likely to be discontinued because of side effects." There is also the sensible general recommendation made by NICE "Consider patient preference and the experience and outcome of previous treatment(s) when deciding on treatment." and they state "Consider CBT (or IPT) for patients with moderate or severe depression who do not take or refuse antidepressant treatment." In a later post I'll look further at whether depression sufferers and doctors should still follow this guideline advice or not.

Kirsch, I., B. J. Deacon, et al. (2008). "Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration." PLoS Medicine 5(2): e45. [Free Full Text]
NICE guidance (2004) "Depression: management of depression in primary and secondary care". Due for review in December 2008. http://www.nice.org.uk/guidance/index.jsp?action=byID&o=10958 Accessed March 11, 2008.