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When Starting an Antidepressant, Try Either of These 2 Drugs First

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When Starting an Antidepressant, Try Either of These 2 Drugs First When starting an antidepressant, try either of these 2 drugs fi rst Most patients fi nd that sertraline and escitalopram are more effective and better tolerated than other antidepressants Meta-analysis of 117 high-quality studies found Gail L. Patrick, MD, MPP that sertraline and escitalopram are superior to Dr. Patrick is Assistant Professor of Family and Community Medicine, other “new-generation” antidepressants.1 Northwestern University, Feinberg ® Dowden Health MediaSchool of Medicine, Chicago. Gene N. Combs, MD Copyright Dr. Combs is Clinical Associate IN THIS For personal use only Professor in the Department A woman with diabetes who is fatigued but cannot sleep of Family Medicine, University ARTICLE Mrs. D., 45 years old, has been your patient for several years. of Chicago (NorthShore). Antidepressants are She has type 2 diabetes. On her latest visit, she reports a Thomas F. Gavagan, not all equivalent loss of energy and diffi culty sleeping, and wonders if these MD, MPH symptoms could be related to the diabetes. Dr. Gavagan is Vice Chair of the page 32 Department of Family Medicine, As you explore further and question Mrs. D. about her University of Chicago (NorthShore). symptoms, she becomes tearful, and tells you she has epi- “Acceptability” and sodes of sadness and no longer enjoys things the way she The authors report no fi nancial effi cacy of 10 drugs relationships relevant to this article. used to. Although she has no history of depression, when page 35 you suggest that her symptoms may be an indication of depression, she readily agrees. What this evidence Acknowledgment You discuss treatment options, including antidepres- Sofi a Medvedev, PhD, of the University means for practice sants and psychotherapy. Mrs. D. decides to try medication. HealthSystem Consortium, Oak Brook, Ill., analyzed data from the National Ambulatory page 36 But with so many antidepressants on the market, how do Medical Care Survey and the UHC Clinical you choose one? Database as part of the development of the manuscript of this article. ajor depression is the fourth leading cause of dis- Mease globally, according to the World Health Orga- nization.2 Depression is common in the United States as well, and primary care physicians, including ObGyns, are often the ones who are diagnosing and treating it. In fact, ›› SHARE YOUR EXPERIENCE! the US Preventive Services Task Force recently expanded Does your practice afford time its recommendation that primary care providers screen for managing depression? adults for depression, to include adolescents 12 to 18 years E-MAIL [email protected] FAX 201-391-2778 old.3 When depression is diagnosed, physicians must help patients decide on an initial treatment plan. CONTINUED ON PAGE 32 30 OBG Management | November 2009 | Vol. 21 No. 11 For mass reproduction, content licensing and permissions contact Dowden Health Media. 30_OBGM1109 30 10/22/09 8:17:35 AM Antidepressant therapy Not all antidepressants are equal analysis were all RCTs in which one of these Options for initial treatment of unipolar ma- 12 antidepressants was tested against one, or jor depression include psychotherapy and several, other second-generation antidepres- the use of an antidepressant. For mild and sants as monotherapy for the acute treatment moderate depression, psychotherapy alone phase of unipolar major depression. Th e au- is as eff ective as medication. Combined psy- thors excluded placebo-controlled trials in chotherapy and antidepressants are more order to evaluate effi cacy and acceptability of eff ective than either treatment alone for all the study medications relative to other com- degrees of depression.4 monly used antidepressants. Th ey defi ned Th e ideal medication for depression acute treatment as 8 weeks of antidepressant would be a drug with a high level of eff ec- therapy, with a range of 6 to 12 weeks. Th e tiveness and a low side-eff ect profi le; until primary outcomes studied were response to now, however, there has been little evidence treatment and dropout rate. to support one antidepressant over another. Response to treatment (effi cacy) was con- Previous meta-analyses have concluded that structed as a Yes or No variable; a positive there are no signifi cant diff erences in either response was defi ned as a reduction of ≥50% effi cacy or acceptability among the various in symptom score on either the Hamilton second-generation antidepressants on the Depression Rating Scale or the Montgomery- market.5,6 Th erefore, physicians have histori- Asberg Rating Scale, or a rating of “improved” cally made initial monotherapy treatment or “very much improved” on the Clinical decisions based on side eff ects and cost.7,8 Global Impression scale at 8 weeks. Effi cacy Th e meta-analysis we report here tells a dif- was calculated on an intention-to-treat ba- ferent story, providing strong evidence that sis; if data were missing for a participant, that some antidepressants are more eff ective and person was classifi ed as a nonresponder. better tolerated than others. Dropout rate was used to represent accept- ability, because the authors believed it to Combined be a more clinically meaningful measure psychotherapy Two “best” drugs revealed than either side eff ects or symptom scores. 1 and antidepressants Cipriani and colleagues conducted a system- Comparative effi cacy and acceptability were are more effective atic review and multiple-treatments meta- analyzed. Fluoxetine—the fi rst of the second- than either analysis of 117 prospective randomized, generation antidepressants—was used as the controlled trials (RCTs). Taken together, the reference medication. Th e FIGURE (page 35) treatment alone RCTs evaluated the comparative effi cacy and shows the outcomes for nine of the antide- for all degrees acceptability of 12 second-generation anti- pressants, compared with those of fl uoxetine. of depression depressants: bupropion, citalopram, dulox- Th e other two antidepressants, milnacipran etine, escitalopram, fl uoxetine, fl uvoxamine, and reboxetine, were omitted because they milnacipran, mirtazapine, paroxetine, rebox- are not available in the United States. etine, sertraline, and venlafaxine. Th e overall meta-analysis included Th e methodology of this meta-analysis 25,928 individuals, with 24,595 in the effi - diff ered from that of traditional meta-analy- cacy analysis and 24,693 in the acceptability ses by allowing the integration of data from analysis. Nearly two thirds (64%) of the par- both direct and indirect comparisons. (An in- ticipants were women. Th e mean duration of direct comparison is one in which drugs from follow-up was 8.1 weeks. Th e mean sample diff erent trials are assessed by combining the size per study was 110. results of their eff ectiveness and comparing Studies of women with postpartum de- the combined fi nding with the eff ectiveness pression were excluded. of a drug that all the trials have in common.) Escitalopram and sertraline stand out. Previous studies, based only on direct com- Overall, escitalopram, mirtazapine, ser- parison, yielded inconsistent results. traline, and venlafaxine were signifi cantly Th e studies included in this meta- more effi cacious than fl uoxetine or the other 32 OBG Management | November 2009 | Vol. 21 No. 11 32_r1_OBGM1109 32 10/23/09 3:47:16 PM Antidepressant therapy medications. Bupropion, citalopram, escital- FIGURE Sertraline and escitalopram come out on top in opram, and sertraline were better tolerated acceptability and effi cacy than the other antidepressants. Escitalopram and sertraline were found to have the best 1.25 combination of effi cacy and acceptability. 1.20 escitalopramescitalopraam Effi cacy results. Fifty-nine percent of partici- 1.15 sertrsertralinerraline pants responded to sertraline, versus a 52% re- bbupropion sponse rate for fl uoxetine (number needed to 1.10 citalopramit l treat [NNT]=14). Similarly, 52% of participants 1.05 fl uoxetine responded to escitalopram, compared with 1.00 mirtazapine 47% of those taking fl uoxetine (NNT=20). 0.95 venlafaxinevenlafaxine Acceptability results. In terms of the dropout paroxetinen 0.90 rate, 28% of participants discontinued fl uox- Acceptability (odds ratio) 0.85 duloxetine etine, versus 24% of patients taking sertraline. fl vuvoxamine Th is means that 25 patients would need to be 0.80 0.80 0.90 1.00 1.10 1.20 1.30 1.40 treated with sertraline, rather than fl uoxetine, to avoid one discontinuation. In the compar- Effi cacy (odds ratio) ison of fl uoxetine versus escitalopram, 25% discontinued fl uoxetine, compared with 24% Researchers analyzed a number of second-generation antidepressants, using fl uoxetine as the reference medication. Sertraline and escitalopram provided the who discontinued escitalopram. best combination of effi cacy and acceptability.1 Th e effi cacy and acceptability of sertra- line and escitalopram compared with other second-generation antidepressant medica- tions follow similar trends. Our fi nding? An estimated 4 million pa- Generic advantage. Th e investigators recom- tients 18 years and older given a diagnosis of mend sertraline as the best choice for an ini- depression in the course of the study year re- tial antidepressant because it is available in ceived new prescriptions for a single antide- Sertraline is the generic form and is therefore lower in cost. pressant. Six medications accounted for 90% best choice for Th ey further recommend that sertraline, in- of prescriptions, in this order: an initial stead of fl uoxetine or placebo, be the new • fl uoxetine (Prozac) antidepressant standard against which other antidepres- • duloxetine (Cymbalta) because it is sants are compared. • escitalopram (Lexapro) available in generic • paroxetine (Paxil) form • venlafaxine (Eff exor) Choice is now evidence-based • sertraline (Zoloft). We now have solid evidence for choosing ser- Sertraline and escitalopram, the drugs traline or escitalopram as the fi rst medication shown to be most eff ective and acceptable in to use when treating a patient with newly di- the Cipriani meta-analysis, accounted for 11.8% agnosed depression.
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