Selective serotonin reuptake inhibitors

Editor—Geddes and Cipriani comment that available randomised evidence does not provide reliable estimates of the costs and benefits of treatment with selective serotonin reuptake inhibitors (SSRIs) in patients with varying degrees of severity and laments the decline in non-commercial funding.¹ Recent guidelines from the National Institute for National Excellence (NICE) also lack evidence.² The NHS health technology assessment programme is funding a trial to tackle this very question. Led by the University of Southampton, in partnership with the University of Liverpool and Institute of Psychiatry, the THREAD (threshold for antidepressants) trial is comparing the effectiveness of SSRIs combined with supportive care with supportive care alone in primary care.

Since Paykel said that severity of depression around the threshold of DSM major depressive episode was the level at which antidepressant drugs were more effective than placebo,³ two recent studies have shown that SSRI antidepressants may be effective in patients with depressive symptoms of lesser severity.⁴,⁵ Confusion results from the inexact use of terminology: what is described in NICE guidance as “mild” depression is actually sub-syndromal depression by ICD-10 criteria. THREAD is using a continuous measure of symptom severity, the Hamilton depression rating scale, as its chief predictor variable, and recruiting patients with a score of ≥ 12, likely to lie in at least the “moderate” range.

One finding of the trial already apparent, however, is that patients' and doctors' preferences make randomisation a difficult proposition in this context. As previously observed in trials of counselling and drug treatment in this population, truly randomised evidence may be obtainable only in a group of participants who are unusual in other respects, and we need to learn more about the strengths and weaknesses of randomised and preference designs for investigating the value of treatments in such contexts.