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Electronic letters published:
![[Read Comment]](/icons/misc/sectionDOWN.gif){kind=icon}
Problem with Short Duration of Studies
Stop your Tunnel Vision and use common sense
Different scales for figures accentuate SSRI benefit
comments on Arroll et al.
Comment on article by Arroll et al
Efficacy of antidepressants in primary care
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Joseph P Arpaia, Eugene, USA psychiatrist, solo practice
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This article was interesting in that it focussed on the treatment of depression in the primary care setting. However, most of the studies were only of 6-8 weeks duration. Most primary care physicians see their patients over a much longer time scale. And many patients who respond initially do not continue to respond after 24 or more weeks (which is why I have so many referrals). Primary care physicians must be aware of the potential for an intial positive response to an antidepressant to be short-lived, and ideally will refer to a psychiatrist if that occurs. Competing interests: None declared |
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Linda V. ONeill, Los Angeles. CA RN, biochemist, psychiatric survivor
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Go to Mindfreedom.org and Alternativementalhealth.com (aka Safe Harbor) for a different view from patients and professionals. Take the challenge! Stop poisoning the minds and bodies of your patients with toxic drugs, especially developing children. There are better ways. Also withdrawal from psychotropic drugs is very real. You are out of the loop. Competing interests: None declared |
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John G. King, Milton, VT Family physician, University of Vermont
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I'm curious why you choose to use different scales for figure 2 and figure 3 and then again for figure 4 and figure 5. In both cases the scales chosen accentuate the superiority of SSRI's which makes me concerned about commercial bias. John G. King, M.D., M.P.H. University of Vermont Competing interests: None declared |
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Joseph J. Gallo, Philadelphia, Pennsylvania University of Pennsylvania
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Arroll and colleagues provided a meta-analysis of placebo-controlled trials of TCAs and SSRIs for depression, with a focus on studies carried out in the primary care setting. The paper focuses on “efficacy” studies and is useful in calling attention to the idea that antidepressants work in primary care; at the same time, I would like to raise several issues related to primary care and depression that were not addressed. The notion of generating evidence from primary care settings compared to specialty mental health settings is important. In effectiveness research (in contrast to efficacy research) we may assume medications have an effect but we need to study the patient, family, and practice factors that relate to the effectiveness of treatment [1]. Such factors may contribute to how well medication works or even if medicine is accepted. In many effectiveness studies, “usual care” is often considered as a “placebo” or “control” group, but clearly usual care means different things in different practices or to different physicians. There is room for improvement in that Arroll and colleagues concluded that only 56 to 60% respond to active treatment. Recognizing that the study focused on whether medications had any effect on depression outcomes as assessed by standardized instruments, our work has drawn attention to other processes in primary care, such as processes involved in identification of depression and acceptance of diagnosis across ethnic groups [2]. Testing in placebo-controlled fashion whether a drug has an effect is one thing, providing the services to accompany the prescription is another. Since physicians, especially primary care physicians, prefer to have depression care integrated into the primary care practice [3], how to design practice to improve depression care will be a critical future need [4]. 1. Bogner HR, Cary MS, Bruce ML, Reynolds CF, Mulsant B, Ten Have T, Alexopoulos GS, and the Prospect Group. The role of medical comorbidity on outcomes of major depression in primary care: The Prospect Study. American Journal of Geriatric Psychiatry. 2005, October. 2. Gallo JJ, Bogner HR, Morales KH, Ford DE. Patient ethnicity and the identification and active management of depression in late life. Archives of Internal Medicine. 2005; Sept 26; 1962-1968. 3. Gallo JJ, Zubritsky, C, Maxwell J, Nazar M, Bogner HR, Quijano LM, Syropoulos H, Cheal KL, Chen H, Sanchez H, Dodson J, Levkoff S, and PRISM-E Investigators. Primary care providers evaluate integrated and referral models of behavioral health care for older adults: results from a multisite effectiveness trial (PRISM-E). Annals of Family Medicine. 2004 July/August;2(4):305-309. 4. Dietrich AJ, Oxman TE, Williams JW Jr, Kroenke K, Schulberg HC, Bruce M, Barry SL. Going to scale: re-engineering systems for primary care treatment of depression. Annals of Family Medicine 2004 Jul- Aug;2(4):301-4. Competing interests: None declared |
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James E. Barrett, Jr., Hanover, NH, USA Professor, Dartmouth Medical School
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Arroll et al are to be congratulated for doing a Cochrane style review of the efficacy of antidepressants (TCAs or SSRIs) for depressed primary care patients. As the authors point out, there is evidence of qualitative differences between depressed patients in primary care and those seen in specialty settings, and one can not assume that the effects of recommended treatments will be the same. The authors' data synthesis thus has particular clinical significance for primary care practice. Refreshingly, their systematic review finds evidence for the effectiveness of both TCAs and SSRIs in primary care depressed patients. The findings support what for many years has been recommended practice (treat with antidepressants) to primary care providers. The findings also lay to rest the notion that this medication treatment must be provided by a psychiatrist to be effective, as treatment effects were present when the medication was provided by primary care providers. All of the above is good news. However, to this reader, the worrisome - or at least thought-provoking - news is that the effect size, although statistically significant, is relatively modest : 55-60% improvement for active medication vs 42-47% for placebo. That 40-45% do not improve on active treatment raises important questions, both for future research and for clinical practice. I for one would accept that the evidence is in that antidepressants work in primary care depressed patients; an additional important question is for whom? What are factors which predict which patients will respond (? particular symptom patterns; ? depression symptom severity; ? family history; ? what else). And, for that matter, what factors relate to improvement for those 42-47% who respond to placebo? Such research, and its subsequent findings, would have considerable clinical utility for primary care practitioners in helping them decide which management would be helpful for which patient. This review highlights the need for such research. A minor point, but puzzling to me: not included in the review was a randomized placebo controlled trial of an SSRI (paroxetine) in primary care patients age 18-59 with dysthymia or minor depression carried out by myself and John Williams and reported in the Journal of Family Practice in 2001. Our results were generally consistent with those in this review - effectiveness of the SSRI for remission in primary care patients with dysthymia and a high remission rate (61-66%) with all treatments for minor depression. Barrett,JE, Williams, JW, Oxman, TE, Frank, E, Katon, W, Sullivan, M, Hegel, MT, Cornell, JE, Sengtupa, AS.Treatment of dysthymia and minor depression in primary care. J Fam Practice 2001; 50: 405-412. Competing interests: None declared |
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Corrado Barbui, Verona, Italy University of Verona
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In recent months there have been many debates regarding the efficacy of antidepressants in adults. In England, for example, Moncrieff and Kirsch criticized how trial data were analyzed, suggesting that methodological artifacts may account for the small effect seen in studies comparing antidepressants with placebo (1). Basically three points are at issue: (1) Transformation of continuous outcome data into categorical data magnifies small differences (a one point difference in mean change of scores between drug and placebo may yield response rates of 50% in the drug condition and 32% in the placebo condition); (2) Data suggesting that the superiority of antidepressants over placebo correlates positively with the severity of depression are controversial; (3) Trial limitations hamper the validity of findings (small samples of patients shortly followed are assessed with outcome measures of uncertain validity). The meta-analysis carried out by Arroll and colleagues (2) expands this debate by investigating whether antidepressants work in primary care patients. My personal interpretation of this well-done study, following the reasoning of Moncrieff and Kirsch, can be summarized as follows: (1) The analysis of continuous outcome measures showed a modest effect for tricyclics (for depression scores the standardized mean difference versus placebo was – 0.42 [95% confidence interval –0.55 to –0.3]) while no data were summarized for selective serotonin-reuptake inhibitors on a continuous outcome. In general, a standardized mean difference of at least 0.5 is required for a claim of medium effect size. (2) The relationship between severity of depression and antidepressant response was not addressed, given that a rather heterogeneous group of patients were considered together. (3) Trial limitations are quite relevant: in total, only 535 patients received treatment with tricyclics and 552 with selective serotonin- reuptake inhibitors (small samples); studies were short-term, with a follow-up too short to show an effect (4 weeks) in 4/12 studies; outcome measures included rating scales with items concerning sleep and anxiety which could have influenced the comparisons; finally, drug company pressures to show a positive effect may have overemphasized the true antidepressant effect (3). Consequently, my understanding is that this study provides inconclusive evidence. Additionally, I suspect that future systematic reviews of antidepressant trials will not shed light on this compelling issue, for the simple reason that, inevitably, systematic reviews cannot overcome trial limitations. 1. Moncrieff J, Kirsch I: Efficacy of antidepressants in adults. BMJ 2005; 331(7509):155-157. Rapid responses: http://bmj.bmjjournals.com/cgi/eletters/331/7509/155 2. Arroll B, Macgillivray S, Ogston S, Reid I, Sullivan F, Williams B, Crombie I: Efficacy and tolerability of tricyclic antidepressants and SSRIs compared with placebo for treatment of depression in primary care: a meta-analysis. Annals of Family Medicine 2005; 3449-456 3. Barbui C, Cipriani A, Brambilla P, Hotopf M: "Wish bias" in antidepressant drug trials? J Clin Psychopharmacol 2004; 24(2):126-130 Competing interests: None declared |
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