Non-Environmental Cost-Benefit News

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.

Robert Peveler, professor of liaison psychiatry
University of Southampton, Royal South Hants Hospital, Southampton SO14 0YG rcp@soton.ac.uk
Tony Kendrick, professor of primary medical care
University of Southampton, Aldermoor Health Centre, Southampton SO16 5ST

References

1. Geddes JR, Cipriani A. Selective serotonin re-uptake inhibitors remain useful drugs which need careful monitoring. BMJ 2004;329: 809-10. (9 October.)[Free Full Text]
2. National Institute for Clinical Excellence. Depression:management of depression in primary and secondary care. Clinical guideline 23. London: NICE, 2004. www.nice.org.uk/pdf/CG023quickrefguide.pdf (accessed 11 Feb 2005).
3. Paykel ES, Hollyman JC, Freeling P, Sedgwick P. Predictors of therapeutic benefit from amitriptyline in mild depression: a general practice placebo-controlled trial. J Affective Dis 1988;14: 83-95[CrossRef][ISI][Medline]
4. Judd LL, Rapaport MH, Yonkers KA, Rush AJ, Frank E, Thase ME, et al. Randomized placebo-controlled trial of fluoxetine for acute treatment of minor depressive disorder. Am J Psychiatry 2004;161: 1864-71.[Abstract/Free Full Text]
5. Barrett JE, Williams JW, Oxman TE, Frank E, Katon W, Sullivan M, et al. Treatment of dysthymia and minor depression in primary care: a randomized trial in patients aged 18 to 59 years. J Fam Pract 2001;50: 405-12.[ISI][Medline]

BMJ 2005;330:420-421 (19 February), doi:10.1136/bmj.330.7488.420-b
http://bmj.bmjjournals.com
http://bmj.bmjjournals.com/cgi/content/full/330/7488/420-b