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Background: Antidepressants are commonly prescribed for depression, but it is unclear whether treatment efficacy depends on severity and duration of symptoms and how prescribing might be targeted cost-effectively. Objectives: We investigated the cost-effectiveness of the antidepressant sertraline compared with placebo in subgroups defined by severity and duration of depressive symptoms. Methods: We undertook a cost-effectiveness analysis from the perspective of the NHS and Personal and Social Services (PSS) in the UK alongside the PANDA (What are the indications for Prescribing ANtiDepressants that will leAd to a clinical benefit?) randomised controlled trial (RCT), which compared sertraline with placebo over a 12-week period. Quality of life data were collected at baseline and at 2, 6, and 12 weeks post-randomisation using EQ-5D-5L, from which we calculated quality-adjusted life years (QALYs). Costs (in 2017/18£) were collected using patient records and from resource use questionnaires administered at each follow-up interval. Differences in mean costs and mean QALYs and net monetary benefits were estimated. Our primary analysis used net monetary benefit regressions to identify any interaction between the cost-effectiveness of sertraline and subgroups defined by baseline symptom severity (0–11; 12–19; 20+ on the Clinical Interview Schedule—Revised) and, separately, duration of symptoms (greater or less than 2 years duration). A secondary analysis estimated the cost-effectiveness of sertraline versus placebo, irrespective of duration or severity. Results: There was no evidence of an association between the baseline severity of depressive symptoms and the cost-effectiveness of sertraline. Compared to patients with low symptom severity, the expected net benefits in patients with moderate symptoms were £24 (95% CI − £280 to £328; p value 0.876) and the expected net benefits in patients with high symptom severity were £37 (95% CI − £221 to £296; p value 0.776). Patients who had a longer history of depressive symptoms at baseline had lower expected net benefits from sertraline than those with a shorter history; however, the difference was uncertain (− £27 [95% CI − £258 to £204]; p value 0.817). In the secondary analysis, patients treated with sertraline had higher expected net benefits (£122 [95% CI £18 to £226]; p value 0.101) than those in the placebo group. Sertraline had a high probability (> 95%) of being cost-effective if the health system was willing to pay at least £20,000 per QALY gained. Conclusions: We found insufficient evidence of a prespecified threshold based on severity or symptom duration that GPs could use to target prescribing to a subgroup of patients where sertraline is most cost-effective. Sertraline is probably a cost-effective treatment for depressive symptoms in UK primary care. Trial Registration: Controlled Trials ISRCTN Registry, ISRCTN84544741.

Original publication




Journal article


PharmacoEconomics - Open

Publication Date





427 - 438