Initiating antidepressant therapy? Try these 2 drugs first

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PURLs

Initiating antidepressant therapy? Try these 2 drugs first

J Fam Pract. 2009 July;58(7):365-369

By

Gail Patrick, MD, MPP

Gene Combs, MD

Thomas Gavagan, MD, MPH

For most patients, sertraline and escitalopram are more effective and better tolerated than other antidepressants.

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References

1. Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet. 2009;373:746-758.

2. Murray CJ, Lopez AD. Global Burden of Disease. Cambridge, MA: Harvard University Press; 1996.

3. Williams SB, O’Connor EA, Eder M, et al. Screening for child and adolescent depression in primary care settings: a systematic evidence review for the U.S. Preventive Services Task Force. Pediatrics. 2009;123:e716-e735.

4. Timonen M, Liukkonen T. Management of depression in adults. BMJ. 2008;336:435-439.

5. Gartlehner G, Hansen RA, Thieda P, et al. Comparative Effectiveness of Second-Generation Antidepressants in the Pharmacologic Treatment of Adult Depression. Comparative Effectiveness Review No. 7. (Prepared by RTI International-University of North Carolina Evidence Based Practice Center under Contract No. 290-02-0016.) Rockville, MD: Agency for Healthcare Research and Quality; January 2007. Available at: www.effectivehealthcare.ahrq.gov/reports/final.cfm. Accessed May 18, 2009.

6. Hansen RA, Gartlehner G, Lohr KN, et al. Efficacy and safety of second-generation antidepressants in the treatment of major depressive disorder. Ann Intern Med. 2005;143:415-426.

7. Adams SM, Miller KE, Zylstra RG. Pharmacologic management of adult depression. Am Fam Physician. 2008;77:785-792.

8. Qaseem A, Snow V, Denberg TD, et al. Using second-generation antidepressants to treat depressive disorders: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2008;149:725-733.

9. DeRubeis RJ, Hollon SD, Amsterdam JD, et al. Cognitive therapy vs medications in the treatment of moderate to severe depression. Arch Gen Psychiatry. 2005;62:409-416.

10. deMello MF, de Jesus MJ, Bacaltchuk J, et al. A systematic review of research findings on the efficacy of interpersonal therapy for depressive disorders. Eur Arch Psychiatry Clin Neurosci. 2005;255:75-82.

11. APA Practice Guidelines. Practice guideline for the treatment of patients with major depressive disorder, second edition. Available at: http://www.psychiatryonline.com/content.aspx?aID=48727. Accessed June 16, 2009.

12. Sackett D. An introduction to performing therapeutic trials. In: Haynes RB, Sackett DL, et al, eds. Clinical Epidemiology: How to Do Clinical Practice Research. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2006.

13. Turner EH, Matthews AM, Linardatos E, et al. Selective publication of antidepressant trials and its influence on apparent efficacy. N Engl J Med. 2008;358:252-260.

14. Mathew SJ, Charney DS. Publication bias and the efficacy of antidepressants. Am J Psychiatry. 2009;166:140-145.

PURLs methodology This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) Surveillance System methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed at www.jfponline.com/purls.

Practice changer

When you initiate antidepressant therapy for patients who have not been treated for depression previously, select either sertraline or escitalopram. A large meta-analysis found these medications to be superior to other “new-generation” antidepressants.¹

Strength of recommendation

A: Meta-analysis of 117 high-quality studies.

Cipriani A, Furukawa TA, Salanti G, et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. Lancet. 2009;373:746-758.

ILLUSTRATIVE CASE

Mrs. D is a 45-year-old patient whom you’ve treated for type 2 diabetes for several years. On her latest visit, she reports a loss of energy and difficulty sleeping and wonders if they could be related to the diabetes. As you explore further and question Mrs. D about these symptoms, she becomes tearful—and tells you she has episodes of sadness and no longer enjoys things the way she used to. Although she has no past history of depression, when you suggest that her symptoms may be an indication of depression, she readily agrees.

You discuss treatment options, including antidepressants and therapy. Mrs. D decides to try medication. But with so many antidepressants on the market, how do you determine which to choose?

Major depression is the fourth leading cause of disease globally, according to the World Health Organization.² Depression is common in the United States as well, and primary care physicians are often the ones who are diagnosing and treating it. In fact, the US Preventive Services Task Force recently expanded its recommendation that primary care providers screen adults for depression, to include adolescents ages 12 to 18 years.³ When depression is diagnosed, physicians must help patients decide on an initial treatment plan.

All antidepressants are not equal

Options for initial treatment of unipolar major depression include psychotherapy and the use of an antidepressant. For mild and moderate depression, psychotherapy alone is as effective as medication. Combined psychotherapy and antidepressants are more effective than either treatment alone for all degrees of depression.⁴

The ideal medication for depression would be a drug with a high level of effectiveness and a low side-effect profile; until now, however, there has been little evidence to support 1 antidepressant over another. Previous meta-analyses have concluded that there are no significant differences in either efficacy or acceptability among the various second-generation antidepressants on the market.^5,6 Thus, physicians have historically made initial monotherapy treatment decisions based on side effects and cost.^7,8 The meta-analysis we report on here tells a different story, providing strong evidence that some antidepressants are more effective and better tolerated than others.

STUDY SUMMARY: Meta-analysis reveals 2 “best” drugs

Cipriani et al¹ conducted a systematic review and multiple-treatments meta-analysis of 117 prospective randomized controlled trials (RCTs). Taken together, the RCTs evaluated the comparative efficacy and acceptability of 12 second-generation antidepressants: bupropion, citalopram, duloxetine, escitalopram, fluoxetine, fluvoxamine, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, and venlafaxine. The methodology of this meta-analysis differed from that of traditional meta-analyses by allowing the integration of data from both direct and indirect comparisons. (An indirect comparison is one in which drugs from different trials are assessed by combining the results of their effectiveness and comparing the combined finding with the effectiveness of a drug that all the trials have in common.) Previous studies, based only on direct comparisons, yielded inconsistent results.

The studies included in this meta-analysis were all RCTs in which 1 of these 12 antidepressants was tested against 1, or several, other second-generation antidepressants as monotherapy for the acute treatment phase of unipolar major depression. The authors excluded placebo-controlled trials in order to evaluate efficacy and acceptability of the study medications relative to other commonly used antidepressants. They defined acute treatment as 8 weeks of antidepressant therapy, with a range of 6 to 12 weeks. The primary outcomes studied were response to treatment and dropout rate.

Response to treatment (efficacy) was constructed as a Yes or No variable; a positive response was defined as a reduction of ≥50% in symptom score on either the Hamilton depression rating scale or the Montgomery-Asberg rating scale, or a rating of “improved” or “very much improved” on the clinical global impression at 8 weeks. Efficacy was calculated on an intention-to-treat basis; if data were missing for a participant, that person was classified as a nonresponder.