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Better—but good enough? The first randomised controlled trial of psychostimulants for depressive symptoms in advanced cancer
  1. Lauren Rayner and
  2. Matthew Hotopf
  1. Department of Psychological Medicine, Institute of Psychiatry, Weston Education Centre, 10 Cutcombe Road, Denmark Hill, London SE5 9RJ, UK
  1. Correspondence to Dr Lauren Rayner, Department of Psychological Medicine, Institute of Psychiatry, Weston Education Centre, 10 Cutcombe Road, Denmark Hill, London SE5 9RJ, UK; Lauren.Rayner{at}

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Depression is common in palliative care, and its adverse impact on quality of life, function and physical symptom severity is well documented.1–3 Alleviating low mood mitigates the emotional, social and physical impact of advanced illness—but for patients with a short prognosis the options are limited. Most psychotherapeutic approaches require a series of sessions delivered over several weeks, and antidepressant medication may take 1–6 weeks to have full therapeutic effect. Recently, there has been a resurgence of interest in the use of psychostimulants for treating depression, especially in patients with advanced disease. The potential for psychostimulants to enhance mood, energy and arousal within hours holds particular promise for palliative patients. Though the evidence base is scant and methodologically shaky,4 several authorities have recommended psychostimulants for patients with a short life expectancy,5 ,6 and they are increasingly being used, particularly in the USA.

This issue presents the results of METIORON—a multicentre, double-blind, randomised placebo-controlled trial of the effect of methylphenidate on depressive symptoms in advanced cancer. Centeno and colleagues’ randomised controlled trial (RCT) is, to our knowledge, the first to evaluate the effect of psychostimulants on palliative patients’ mood as the primary outcome. The study investigators compared response with methylphenidate versus placebo over a 28-day period. In common with many RCTs undertaken in this setting, poor accrual and high attrition undermined the power of the study to provide a definitive answer to the question posed. Nevertheless, the observed non-significant trend towards improved mood with methylphenidate versus placebo is an important finding.

Studies assessing the impact of psychostimulants on depression in non-palliative populations have yielded mixed results, with no clear indication of efficacy. A Cochrane review by Candy et al7 in 2008 identified 24 trials …

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  • Contributors LR planned, drafted and revised the manuscript. MH conceived, and critically revised the manuscript. LR is guarantor.

  • Competing interests None.

  • Provenance and peer review Commissioned; internally peer reviewed.