trained community care workers: part therapist, part housing officer, part pre- scriber. Just what such a real world mental health trooper might look like has been described in detail. 4 The battles that they face will be remote from the world depicted in the latest NICE guidance. Competing interests: None. 1. National Institute for Health and Clinical Excellence. Core interventions in the treatment and management of schizophrenia in primary and secondary care (update). Clinical Guidelines CG82, issued March 2009. http://www.nice.org.uk/guidance/ index.jsp?action=byID&o=11786 (accessed 29 July 2009). 2. Kendell R. The distinction between personality disorder and mental illness. Br J Psychiatry 2002;180:110–15. 3. Killaspy H, Bebbington P, Blizard R, et al. The REACT study: randomised evaluation of assertive community treatment in north London. BMJ 2006;332:815–20. 4. Salter M, Turner T. Community mental health care: a practical guide to outdoor psychiatry. Edinburgh: Churchill Livingstone, 2008. Are all antidepressants equal? G Gartlehner, 1,2 B N Gaynes 3 Primary care physicians and psychiatrists manage the majority of patients suffering from acute phase major depressive dis- order (MDD). For most patients, antide- pressant treatment is the primary choice of care. Second generation antidepressants (SGAs)—developed following the first generation of tricyclic and monoamine oxidase agents—have become the pre- ferred drug choice because of their greater tolerability, lower risk of lethality and similar efficacy compared with first gen- eration agents. Clinicians prescribing SGAs face a multitude of drug choices and are the target of extensive marketing campaigns by the pharmaceutical industry. In 2007, three of the 20 top selling drugs in the USA were antidepressants with annual sales ranging from $2.3 billion (venlafax- ine XR (Effexor XR)) to $1.4 billion (duloxetine (Cymbalta)). 1 At the time of writing, 13 different SGAs have been approved for the treatment of major depression in the USA and Canada and two additional drugs (reboxetine, milna- cipran) are available in some European countries. Some of these drugs are now available as generic medications, others are still patent protected. Economically, drug choice matters. The US Consumers Union found that in 2008 the average monthly costs of treatment with second generation antidepressants in the USA varied from $20 to $400 depending on the medication of choice. 2 The study conducted by Cipriani and colleagues 3 addressed an ongoing challenge for clin- icians: how to choose among antidepres- sant treatments and select the best drug for an individual patient suffering from an episode of major depression (see page 107). WHY SUCH A STUDY IS IMPORTANT The burning question for patients and clinicians is whether differences in costs are substantiated by differences in bene- fits and harms. Evidence based data to answer this question and to guide selec- tion of treatments has been limited. Because of the lack of available direct head to head comparisons, prior systema- tic reviews have been able to say little about differences among the medica- tions. 45 The ideal studies to fill this knowledge gap would be large, pragmatic, randomised controlled trials (RCTs) that directly compare the benefits and harms of SGAs. Unfortunately, out of the more than 70 possible comparisons among SGAs, barely more than half have been investigated in RCTs. 6 Many of the available studies are small or have meth- odological problems that severely limit the ability to draw firm conclusions about the comparative efficacy and safety. In a complex statistical analysis, Cipriani and colleagues 3 compared response rates and discontinuation rates of individual SGAs and offered a simple answer: sertraline (Zoloft) and escitalo- pram (Lexapro) are better than other SGAs followed by venlafaxine (Effexor) and mirtazapine (Remeron). 3 Is this the long sought for answer for clinicians who treat patients with MDD? An accompa- nying editorial in The Lancet ‘‘Antidepressants are not all created equal’’ was jubilant and asserted that ‘‘…a new gold standard of reliable infor- mation has been compiled…’’ 7 Subsequent letters to the editor, however, were less enthusiastic but rather outright critical about the methods and conclu- sions of this study. 8–13 The underlying tenor of the critics was that Cipriani et al failed to acknowledge the methodological limitations of the approach and, by ranking drugs, evoked an unsubstantiated sense of precision based on evidence that is fraught with uncertainty. A closer look at the underlying methods is necessary to understand the controversy. STUDY DESIGN AND METHODS The objective of the study was to provide a clinically useful summary of the effects of SGAs that can be used to guide treatment decisions. 3 To detect relevant studies, authors conducted systematic literature searches in the Cochrane Collaboration depression, anxiety and neurosis trials register. Furthermore, they contacted pharmaceutical companies, reg- ulatory agencies and study investigators to acquire unpublished or missing data. The primary outcomes were response (defined as a 50% improvement of the baseline score) and treatment discontin- uation rates at 8 weeks. Because not all antidepressants have been compared directly in RCTs, Cipriani and colleagues 3 used a statistical tech- nique called multiple treatments meta- analysis to derive estimates of the com- parative efficacy and safety for all possible comparisons among SGAs. Such an approach essentially combines results from trials directly comparing two or more SGAs with estimates of treatment effects based on common comparators. For example, if two drugs exhibit a similar treatment effect relative to a common comparator, the conclusion would be that these drugs have similar efficacy. In the absence of direct comparisons, such an approach is legitimate and find- ings can allow inferences about the relative benefits (or harms) of drugs that have never been compared directly. Nevertheless, results have to be inter- preted cautiously. Such a statistical approach is commonly viewed as observa- tional evidence, even if the statistical 1 Danube University, Department for Evidence-based Medicine and Clinical Epidemiology, Krems, Austria; 2 Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, USA; 3 Department of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, USA Correspondence to: Dr G Gartlehner, Danube University, Department for Evidence-based Medicine and Clinical Epidemiology, Krems, Austria; gerald. gartlehner@donau-uni.ac.at EBMH Notebook 98 EBMH November 2009 Vol 12 No 4 on December 10, 2021 by guest. Protected by copyright. http://ebmh.bmj.com/ Evid Based Mental Health: first published as 10.1136/ebmh.12.4.98 on 23 October 2009. Downloaded from