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Sexual Dysfunction associated with Second-Generation Antidepressants in Patients with Major Depressive Disorder: Results from a Systematic Review with Network Meta-Analysis

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Abstract

Background

Sexual dysfunction (SD) is prevalent in patients with major depressive disorder (MDD) and is also associated with second-generation antidepressants (SGADs) that are commonly used to treat the condition. Evidence indicates under-reporting of SD in efficacy studies. SD associated with antidepressant treatment is a serious side effect that may lead to early termination of treatment and worsening of quality of life.

Objectives

Our objective was to systematically assess the harms of SD associated with SGADs in adult patients with MDD by drug type.

Methods

We retrieved English-language abstracts from PubMed, EMBASE, the Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980 to October 2012 as well as from reference lists of pertinent review articles and grey literature searches. Two independent reviewers identified randomized controlled trials (RCTs) of at least 6 weeks’ duration and observational studies with at least 1,000 participants.

Study Selection

Reviewers abstracted data on study design, conduct, participants, interventions, outcomes and method of SD ascertainment, and rated risk of bias. A senior reviewer checked and confirmed extracted data and risk-of-bias ratings.

Analyses

Random effects network meta-analysis using Bayesian methods for data from head-to-head trials and placebo-controlled comparisons; descriptive analyses calculating weighted mean rates from individual trials and observational studies.

Results/Synthesis

Data from 63 studies of low and moderate risk of bias (58 RCTs, five observational studies) with more than 26,000 patients treated with SGADs were included. Based on network meta-analyses of 66 pairwise comparisons from 37 RCTs, most comparisons showed a similar risk of SD among included SGADs. However, credible intervals were wide and included differences that would be considered clinically relevant. We observed three main patterns: bupropion had a statistically significantly lower risk of SD than some other SGADs, and both escitalopram and paroxetine showed a statistically significantly higher risk of SD than some other SGADs. We found reporting of harms related to SD inconsistent and insufficient in some trials.

Limitations

Most trials were conducted in highly selected populations. Search was restricted to English-language only.

Conclusion and Implications

Because of the indirect nature of the comparisons, the often wide credible intervals, and the high variation in magnitude of outcome, we rated the overall strength of evidence with respect to our findings as low. The current degree of evidence does not allow a precise estimate of comparative risk of SD associated with a specific antidepressant. In the absence of such evidence, clinicians need to be aware of SD as a common adverse event and should discuss patients’ preferences before initiating antidepressant therapy.

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References

  1. Bromet E, Andrade LH, Hwang I, Sampson NA, Alonso J, de Girolamo G, et al. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med. 2011;9:90.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Lindsley CW. The top prescription drugs of 2011 in the United States: antipsychotics and antidepressants once again lead CNS therapeutics. ACS Chem Neurosci. 2012;3(8):630–1.

    Article  CAS  PubMed  Google Scholar 

  3. Angst J. Sexual problems in healthy and depressed persons. Int Clin Psychopharmacol. 1998;13(Suppl 6):S1–4.

    Article  PubMed  Google Scholar 

  4. Kennedy SH, Dickens SE, Eisfeld BS, Bagby RM. Sexual dysfunction before antidepressant therapy in major depression. J Affect Disord. 1999;56(2–3):201–8.

    Article  CAS  PubMed  Google Scholar 

  5. Rothschild AJ. Sexual side effects of antidepressants. J Clin Psychiatry. 2000;61(Suppl 11):28–36.

    CAS  PubMed  Google Scholar 

  6. U.S. Department of Health and Human Services, Food and Drug Administration. Guidance for Industry and Investigators. Safety reporting requirements for INDs and BA/BE studies. Rockville: U.S. Department of Health and Human Services; 2012.

  7. Gregorian RS, Golden KA, Bahce A, Goodman C, Kwong WJ, Khan ZM. Antidepressant-induced sexual dysfunction. Ann Pharmacother. 2002;36(10):1577–89.

    Article  CAS  PubMed  Google Scholar 

  8. Rosenberg KP, Bleiberg KL, Koscis J, Gross C. A survey of sexual side effects among severely mentally ill patients taking psychotropic medications: impact on compliance. J Sex Marital Ther. 2003;29(4):289–96.

    Article  PubMed  Google Scholar 

  9. Clayton AH, Balon R. The impact of mental illness and psychotropic medications on sexual functioning: the evidence and management. J Sexual Med. 2009;6(5):1200–11 (quiz 12–3).

    Google Scholar 

  10. Serretti A, Chiesa A. Treatment-emergent sexual dysfunction related to antidepressants: a meta-analysis. J Clin Psychopharmacol. 2009;29(3):259–66.

    Article  CAS  PubMed  Google Scholar 

  11. Gartlehner G, Hansen RA, Morgan LC, Thaler K, Lux L, Van Noord M, et al. Comparative benefits and harms of second-generation antidepressants for treating major depressive disorder: an updated meta-analysis. Ann Intern Med. 2011;155(11):772–85.

    Article  PubMed  Google Scholar 

  12. Williams VS, Edin HM, Hogue SL, Fehnel SE, Baldwin DS. Prevalence and impact of antidepressant-associated sexual dysfunction in three European countries: replication in a cross-sectional patient survey. J Psychopharmacol (Oxford, England). 2010;24(4):489–96.

    Article  CAS  Google Scholar 

  13. Kennedy SH, Eisfeld BS, Dickens SE, Bacchiochi JR, Bagby RM. Antidepressant-induced sexual dysfunction during treatment with moclobemide, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry. 2000;61(4):276–81.

    Article  CAS  PubMed  Google Scholar 

  14. Montejo AL, Llorca G, Izquierdo JA, Rico-Villademoros F. Incidence of sexual dysfunction associated with antidepressant agents: a prospective multicenter study of 1022 outpatients. Spanish Working Group for the Study of Psychotropic-Related Sexual Dysfunction. J Clin Psychiatry. 2001;62(Suppl 3):10–21.

    CAS  PubMed  Google Scholar 

  15. Nieuwstraten CE, Dolovich LR. Bupropion versus selective serotonin-reuptake inhibitors for treatment of depression. Ann Pharmacother. 2001;35(12):1608–13.

    Article  CAS  PubMed  Google Scholar 

  16. Cipriani A, Purgato M, Furukawa TA, Trespidi C, Imperadore G, Signoretti A, et al. Citalopram versus other anti-depressive agents for depression. Cochrane Database Syst Rev (Online). 2012;7:CD006534.

  17. Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, Churchill R, et al. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev (Online). 2011;(12):CD006528.

  18. Cipriani A, La Ferla T, Furukawa TA, Signoretti A, Nakagawa A, Churchill R, et al. Sertraline versus other antidepressive agents for depression. Cochrane Database Syst Rev (Online). 2010;(4):CD006117.

  19. Gartlehner G, Hansen RA, Morgan LC, Thaler K, Lux LJ, Van Noord M, et al. Second-generation antidepressants in the pharmacologic treatment of adult depression: an update of the 2007 comparative effectiveness review, Rockville; 2011.

  20. Chapman A, Morgan LC, Gartlehner G. Semi-automating the manual literature search for systematic reviews increases efficiency. Health Inf Libr J. 2009;27(1):22–7.

    Article  Google Scholar 

  21. Higgins JPT, Altman DG, Sterne J. Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, S G, editors. Cochrane handbook for systematic reviews of interventions version 510 [updated March 2011]. The Cochrane Collaboration; 2011.

  22. Deeks JJ, Dinnes J, D’Amico R, Sowden AJ, Sakarovitch C, Song F, et al. Evaluating non-randomised intervention studies. Health Technol Assess. 2003;7(27):iii–x, 1–173.

    Google Scholar 

  23. Owens DK, Lohr KN, Atkins D, Treadwell JR, Reston JT, Bass EB, et al. AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions—agency for healthcare research and quality and the effective health-care program. J Clin Epidemiol. 2010;63(5):513–23.

    Article  PubMed  Google Scholar 

  24. Dias S, Welton NJ, Sutton AJ, Ades AE. NICE DSU Technical Support Document 2: a generalised linear modelling framework for pairwise and network meta-analysis of randomised controlled trials; 2011. http://www.nicedsu.org.uk (last updated March 2013).

  25. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. PLoS Med. 2009;6(7):e1000100.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Alvarez E, Perez V, Dragheim M, Loft H, Artigas F. A double-blind, randomized, placebo-controlled, active reference study of Lu AA21004 in patients with major depressive disorder. Int J Neuropsychopharmacol. 2012;15(5):589–600.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Behnke K, Sogaard J, Martin S, Bauml J, Ravindran AV, Agren H, et al. Mirtazapine orally disintegrating tablet versus sertraline: a prospective onset of action study. J Clin Psychopharmacol. 2003;23(4):358–64.

    Article  CAS  PubMed  Google Scholar 

  28. Benkert O, Szegedi A, Kohnen R. Mirtazapine compared with paroxetine in major depression. J Clin Psychiatry. 2000;61(9):656–63.

    Article  CAS  PubMed  Google Scholar 

  29. Clayton AH, Croft HA, Horrigan JP, Wightman DS, Krishen A, Richard NE, et al. Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies. J Clin Psychiatry. 2006;67:736–46.

    Article  CAS  PubMed  Google Scholar 

  30. Clayton A, Kornstein S, Prakash A, Mallinckrodt C, Wohlreich M. Changes in sexual functioning associated with duloxetine, escitalopram, and placebo in the treatment of patients with major depressive disorder. J Sexual Med. 2007;4(4 Pt 1):917–29.

    Article  CAS  Google Scholar 

  31. Coleman CC, King BR, Bolden-Watson C, Book MJ, Segraves RT, Richard N, et al. A placebo-controlled comparison of the effects on sexual functioning of bupropion sustained release and fluoxetine. Clin Ther. 2001;23(7):1040–58.

    Article  CAS  PubMed  Google Scholar 

  32. Coleman CC, Cunningham LA, Foster VJ, Batey SR, Donahue RM, Houser TL, et al. Sexual dysfunction associated with the treatment of depression: a placebo-controlled comparison of bupropion sustained release and sertraline treatment. Ann Clin Psychiatry. 1999;11(4):205–15.

    Article  CAS  PubMed  Google Scholar 

  33. Croft H, Settle E Jr, Houser T, Batey SR, Donahue RM, Ascher JA. A placebo-controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained-release bupropion and sertraline. Clin Ther. 1999;21(4):643–58.

    Article  CAS  PubMed  Google Scholar 

  34. Delgado PL, Brannan SK, Mallinckrodt CH, Tran PV, McNamara RK, Wang F, et al. Sexual functioning assessed in 4 double-blind placebo- and paroxetine-controlled trials of duloxetine for major depressive disorder. J Clin Psychiatry. 2005;66(6):686–92.

    Article  PubMed  Google Scholar 

  35. Detke MJ, Wiltse CG, Mallinckrodt CH, McNamara RK, Demitrack MA, Bitter I. Duloxetine in the acute and long-term treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Neuropsychopharmacol. 2004;14(6):457–70.

    Article  CAS  PubMed  Google Scholar 

  36. Ekselius L, von Knorring L, Eberhard G. A double-blind multicenter trial comparing sertraline and citalopram in patients with major depression treated in general practice. Int Clin Psychopharmacol. 1997;12(6):323–31.

    Article  CAS  PubMed  Google Scholar 

  37. Fava M, Amsterdam JD, Deltito JA, Salzman C, Schwaller M, Dunner DL. A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression. Ann Clin Psychiatry. 1998;10(4):145–50.

    Article  CAS  PubMed  Google Scholar 

  38. Feiger A, Kiev A, Shrivastava RK, Wisselink PG, Wilcox CS. Nefazodone versus sertraline in outpatients with major depression: focus on efficacy, tolerability, and effects on sexual function and satisfaction. J Clin Psychiatry. 1996;57(Suppl 2):53–62.

    CAS  PubMed  Google Scholar 

  39. Feighner JP, Gardner EA, Johnston JA, Batey SR, Khayrallah MA, Ascher JA, et al. Double-blind comparison of bupropion and fluoxetine in depressed outpatients. J Clin Psychiatry. 1991;52(8):329–35.

    CAS  PubMed  Google Scholar 

  40. Ferguson JM, Shrivastava RK, Stahl SM, Hartford JT, Borian F, Ieni J, et al. Reemergence of sexual dysfunction in patients with major depressive disorder: double-blind comparison of nefazodone and sertraline. J Clin Psychiatry. 2001;62(1):24–9.

    Article  CAS  PubMed  Google Scholar 

  41. Gelenberg AJ, Trivedi MH, Rush AJ, Thase ME, Howland R, Klein DN, et al. Randomized, placebo-controlled trial of nefazodone maintenance treatment in preventing recurrence in chronic depression. Biol Psychiatry. 2003;54(8):806–17.

    Article  CAS  PubMed  Google Scholar 

  42. Gilaberte I, Montejo AL, de la Gandara J, Perez-Sola V, Bernardo M, Massana J, et al. Fluoxetine in the prevention of depressive recurrences: a double-blind study. J Clin Psychopharmacol. 2001;21(4):417–24.

    Article  CAS  PubMed  Google Scholar 

  43. Golden RN, Nemeroff CB, McSorley P, Pitts CD, Dube EM. Efficacy and tolerability of controlled-release and immediate-release paroxetine in the treatment of depression. J Clin Psychiatry. 2002;63(7):577–84.

    Article  CAS  PubMed  Google Scholar 

  44. Guelfi JD, Ansseau M, Timmerman L, Korsgaard S. Mirtazapine versus venlafaxine in hospitalized severely depressed patients with melancholic features. J Clin Psychopharmacol. 2001;21(4):425–31.

    Article  CAS  PubMed  Google Scholar 

  45. Hicks JA, Argyropoulos SV, Rich AS, Nash JR, Bell CJ, Edwards C, et al. Randomised controlled study of sleep after nefazodone or paroxetine treatment in out-patients with depression. Br J Psychiatry. 2002;180:528–35.

    Article  CAS  PubMed  Google Scholar 

  46. Hochstrasser B, Isaksen PM, Koponen H, Lauritzen L, Mahnert FA, Rouillon F, et al. Prophylactic effect of citalopram in unipolar, recurrent depression: placebo-controlled study of maintenance therapy. Br J Psychiatry. 2001;178:304–10.

    Article  CAS  PubMed  Google Scholar 

  47. Burke WJ, Gergel I, Bose A. Fixed-dose trial of the single isomer SSRI escitalopram in depressed outpatients. J Clin Psychiatry. 2002;63(4):331–6.

    Article  CAS  PubMed  Google Scholar 

  48. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John’s wort) in major depressive disorder: a randomized controlled trial. JAMA. 2002;287(14):1807–14.

    Article  Google Scholar 

  49. Keller MB, Kocsis JH, Thase ME, Gelenberg AJ, Rush AJ, Koran L, et al. Maintenance phase efficacy of sertraline for chronic depression: a randomized controlled trial. JAMA. 1998;280(19):1665–72.

    Article  CAS  PubMed  Google Scholar 

  50. Kiev A, Feiger A. A double-blind comparison of fluvoxamine and paroxetine in the treatment of depressed outpatients. J Clin Psychiatry. 1997;58(4):146–52.

    Article  CAS  PubMed  Google Scholar 

  51. Mehtonen OP, Sogaard J, Roponen P, Behnke K. Randomized, double-blind comparison of venlafaxine and sertraline in outpatients with major depressive disorder. Venlafaxine 631 Study Group. J Clin Psychiatry. 2000;61(2):95–100.

    Article  CAS  PubMed  Google Scholar 

  52. Nemeroff CB, Ninan PT, Ballenger J, Lydiard RB, Feighner J, Patterson WM, et al. Double-blind multicenter comparison of fluvoxamine versus sertraline in the treatment of depressed outpatients. Depression. 1995;3(4):163–9.

    Article  Google Scholar 

  53. Perahia DG, Wang F, Mallinckrodt CH, Walker DJ, Detke MJ. Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Psychiatry. 2006;21:367–78.

    Article  CAS  PubMed  Google Scholar 

  54. Schatzberg A, Roose S. A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression. Am J Geriatr Psychiatry. 2006;14:361–70.

    Article  PubMed  Google Scholar 

  55. Segraves RT, Kavoussi R, Hughes AR, Batey SR, Johnston JA, Donahue R, et al. Evaluation of sexual functioning in depressed outpatients: a double-blind comparison of sustained-release bupropion and sertraline treatment. J Clin Psychopharmacol. 2000;20(2):122–8.

    Article  CAS  PubMed  Google Scholar 

  56. Shelton RC, Haman KL, Rapaport MH, Kiev A, Smith WT, Hirschfeld RM, et al. A randomized, double-blind, active-control study of sertraline versus venlafaxine XR in major depressive disorder. J Clin Psychiatry. 2006;67(11):1674–81.

    Article  CAS  PubMed  Google Scholar 

  57. Thase ME. Efficacy and tolerability of once-daily venlafaxine extended release (XR) in outpatients with major depression. The Venlafaxine XR 209 Study Group. J Clin Psychiatry. 1997;58(9):393–8.

    Article  CAS  PubMed  Google Scholar 

  58. Trivedi MH, Pigotti TA, Perera P, Dillingham KE, Carfagno ML, Pitts CD. Effectiveness of low doses of paroxetine controlled release in the treatment of major depressive disorder. J Clin Psychiatry. 2004;65(10):1356–64.

    Article  CAS  PubMed  Google Scholar 

  59. Ventura D, Armstrong EP, Skrepnek GH, Haim Erder M. Escitalopram versus sertraline in the treatment of major depressive disorder: a randomized clinical trial. Curr Med Res Opin. 2007;23(2):245–50.

    Article  CAS  PubMed  Google Scholar 

  60. Wade A, Gembert K, Florea I. A comparative study of the efficacy of acute and continuation treatment with escitalopram versus duloxetine in patients with major depressive disorder. Curr Med Res Opin. 2007;23(7):1605–14.

    Article  CAS  PubMed  Google Scholar 

  61. Yevtushenko VY, Belous AI, Yevtushenko YG, Gusinin SE, Buzik OJ, Agibalova TV. Efficacy and tolerability of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, prospective, randomized, double-blind, active-controlled study in adult outpatients. Clin Ther. 2007;29:2319–32.

    Article  CAS  PubMed  Google Scholar 

  62. Nierenberg AA, Greist JH, Mallinckrodt CH, Prakash A, Sambunaris A, Tollefson GD, et al. Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study. Curr Med Res Opin. 2007;23(2):401–16.

    Article  CAS  PubMed  Google Scholar 

  63. Baldwin DS, Cooper JA, Huusom AK, Hindmarch I. A double-blind, randomized, parallel-group, flexible-dose study to evaluate the tolerability, efficacy and effects of treatment discontinuation with escitalopram and paroxetine in patients with major depressive disorder. Int Clin Psychopharmacol. 2006;21:159–69.

    Article  PubMed  Google Scholar 

  64. Baldwin DS, Loft H, Dragheim M. A randomised, double-blind, placebo controlled, duloxetine-referenced, fixed-dose study of three dosages of Lu AA21004 in acute treatment of major depressive disorder (MDD). Eur Neuropsychopharmacol. 2012;22(7):482–91.

    Article  CAS  PubMed  Google Scholar 

  65. Bennie EH, Mullin JM, Martindale JJ. A double-blind multicenter trial comparing sertraline and fluoxetine in outpatients with major depression. J Clin Psychiatry. 1995;56(6):229–37.

    CAS  PubMed  Google Scholar 

  66. Bielski RJ, Ventura D, Chang CC. A double-blind comparison of escitalopram and venlafaxine extended release in the treatment of major depressive disorder. J Clin Psychiatry. 2004;65(9):1190–6.

    Article  CAS  PubMed  Google Scholar 

  67. Boulenger JP, Huusom AK, Florea I, Baekdal T, Sarchiapone M. A comparative study of the efficacy of long-term treatment with escitalopram and paroxetine in severely depressed patients. Curr Med Res Opin. 2006;22:1331–41.

    Article  CAS  PubMed  Google Scholar 

  68. Chouinard G, Saxena B, Belanger MC, Ravindran A, Bakish D, Beauclair L, et al. A Canadian multicenter, double-blind study of paroxetine and fluoxetine in major depressive disorder. J Affect Disord. 1999;54(1–2):39–48.

    Article  CAS  PubMed  Google Scholar 

  69. Cunningham LA. Once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Venlafaxine XR 208 Study Group. Ann Clin Psychiatry. 1997;9(3):157–64.

    Article  CAS  PubMed  Google Scholar 

  70. Dalery J, Honig A. Fluvoxamine versus fluoxetine in major depressive episode: a double-blind randomised comparison. Hum Psychopharmacol. 2003;18(5):379–84.

    Article  CAS  PubMed  Google Scholar 

  71. Detke MJ, Lu Y, Goldstein DJ, Hayes JR, Demitrack MA. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry. 2002;63(4):308–15.

    Article  CAS  PubMed  Google Scholar 

  72. Fava M, Hoog SL, Judge RA, Kopp JB, Nilsson ME, Gonzales JS. Acute efficacy of fluoxetine versus sertraline and paroxetine in major depressive disorder including effects of baseline insomnia. J Clin Psychopharmacol. 2002;22(2):137–47.

    Article  CAS  PubMed  Google Scholar 

  73. Franchini L, Gasperini M, Perez J, Smeraldi E, Zanardi R. A double-blind study of long-term treatment with sertraline or fluvoxamine for prevention of highly recurrent unipolar depression. J Clin Psychiatry. 1997;58(3):104–7.

    Article  CAS  PubMed  Google Scholar 

  74. Katona C, Hansen T, Olsen CK. A randomized, double-blind, placebo-controlled, duloxetine-referenced, fixed-dose study comparing the efficacy and safety of Lu AA21004 in elderly patients with major depressive disorder. Int Clin Psychopharmacol. 2012;27(4):215–23.

    Article  PubMed  Google Scholar 

  75. Lepola UM, Loft H, Reines EH. Escitalopram (10–20 mg/day) is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol. 2003;18(4):211–7.

    Article  PubMed  Google Scholar 

  76. Lineberry CG, Johnston JA, Raymond RN, Samara B, Feighner JP, Harto NE, et al. A fixed-dose (300 mg) efficacy study of bupropion and placebo in depressed outpatients. J Clin Psychiatry. 1990;51(5):194–9.

    CAS  PubMed  Google Scholar 

  77. Montgomery SA, Huusom AK, Bothmer J. A randomised study comparing escitalopram with venlafaxine XR in primary care patients with major depressive disorder. Neuropsychobiology. 2004;50(1):57–64.

    Article  CAS  PubMed  Google Scholar 

  78. Moore N, Verdoux H, Fantino B. Prospective, multicentre, randomized, double-blind study of the efficacy of escitalopram versus citalopram in outpatient treatment of major depressive disorder. Int Clin Psychopharmacol. 2005;20(3):131–7.

    Article  PubMed  Google Scholar 

  79. Rabkin JG, Wagner GJ, McElhiney MC, Rabkin R, Lin SH. Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial. J Clin Psychopharmacol. 2004;24(4):379–85.

    Article  CAS  PubMed  Google Scholar 

  80. Reimherr FW, Chouinard G, Cohn CK, Cole JO, Itil TM, LaPierre YD, et al. Antidepressant efficacy of sertraline: a double-blind, placebo- and amitriptyline-controlled, multicenter comparison study in outpatients with major depression. J Clin Psychiatry. 1990;51 Suppl B:18–27.

    CAS  PubMed  Google Scholar 

  81. Rush AJ, Armitage R, Gillin JC, Yonkers KA, Winokur A, Moldofsky H, et al. Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder. Biol Psychiatry. 1998;44(1):3–14.

    Article  CAS  PubMed  Google Scholar 

  82. Simon JS, Aguiar LM, Kunz NR, Lei D. Extended-release venlafaxine in relapse prevention for patients with major depressive disorder. J Psychiatr Res. 2004;38(3):249–57.

    Article  PubMed  Google Scholar 

  83. Wade A, Michael Lemming O, Bang Hedegaard K. Escitalopram 10 mg/day is effective and well tolerated in a placebo-controlled study in depression in primary care. Int Clin Psychopharmacol. 2002;17(3):95–102.

    Article  CAS  PubMed  Google Scholar 

  84. Meijer WE, Heerdink ER, van Eijk JT, Leufkens HG. Adverse events in users of sertraline: results from an observational study in psychiatric practice in The Netherlands. Pharmacoepidemiol Drug Saf. 2002;11(8):655–62.

    Article  CAS  PubMed  Google Scholar 

  85. Duenas H, Brnabic AJ, Lee A, Montejo AL, Prakash S, Casimiro-Querubin ML, et al. Treatment-emergent sexual dysfunction with SSRIs and duloxetine: effectiveness and functional outcomes over a 6-month observational period. Int J Psychiatry Clin Pract. 2011;15(4):242–54.

    Article  CAS  PubMed  Google Scholar 

  86. Mackay FR, Dunn NR, Martin RM, Pearce GL, Freemantle SN, Mann RD. Newer antidepressants: a comparison of tolerability in general practice. Br J Gen Pract. 1999;49(448):892–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  87. Clayton AH, Pradko JF, Croft HA, Montano CB, Leadbetter RA, Bolden-Watson C, et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry. 2002;63(4):357–66.

    Article  PubMed  Google Scholar 

  88. Ferguson JM. The effects of antidepressants on sexual functioning in depressed patients: a review. J Clin Psychiatry. 2001;62(Suppl 3):22–34.

    CAS  PubMed  Google Scholar 

  89. Salanti G. Indirect and mixed-treatment comparison, network, or multiple-treatments meta-analysis: many names, many benefits, many concerns for the next generation evidence synthesis tool. Res Synth Methods. 2012;3(2):80–97.

    Article  Google Scholar 

  90. Bahrick A, Harris M. Sexual side effects of antidepressant medications: an informed consent accountability gap. J Contemp Psychother. 2009;39(2):135–43.

    Article  Google Scholar 

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Acknowledgments

This project was originally funded under Contract No. HHSA-290-2007-10056I from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services. The authors of this manuscript are responsible for its content. Statements in the manuscript should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

No sources of funding were used to assist in the preparation of this systematic review. However, this review updates part of a larger comparative effectiveness review on SGAD [19], which was funded by and conducted for the US AHRQ, US Department of Health and Human Services under contract no. HHSA-290-2007-10056I.

Amy Greenblatt has participated in research funded by the US AHRQ during the conduct of the study. Richard Hansen has received consulting fees from Daiichi Sankyo and Novartis for studies on unrelated topics, and has served as an expert witness for Allergan for Botox drug safety. Ursula Reichenpfader, Gerald Gartlehner, Laura C. Morgan, Barbara Nussbaumer, Megan Van Noord, Linda Lux, and Bradley N. Gaynes have no conflicts of interest that are directly relevant to the content of this study.

Network meta-analyses were conducted by Tania Wilkins, PhD (The University of North Carolina at Chapel Hill, Gillings School of Global Public Health Biostatistics, 3101 McGavran-Greenberg Hall, Chapel Hill, NC 27599-7420, USA).

Author information

Authors and Affiliations

  1. Department for Evidence-based Medicine and Clinical Epidemiology, Danube University Krems, Dr.-Karl-Dorrek-Str. 30, 3500, Krems, Austria

    Ursula Reichenpfader, Gerald Gartlehner, Barbara Nussbaumer & Megan Van Noord

  2. RTI International, 3040 East Cornwallis Road, PO Box 12194, Research Triangle Park, NC, 27709, USA

    Gerald Gartlehner, Laura C. Morgan, Amy Greenblatt, Megan Van Noord & Linda Lux

  3. Auburn University, Harrison School of Pharmacy, 022 James E. Foy Hall, Auburn, AL, 36849, USA

    Richard A. Hansen

  4. Department of Psychiatry, University of North Carolina School of Medicine Chapel Hill, Suite 304, Room J, MacNider Building, Chapel Hill, NC, 27599-7160, USA

    Bradley N. Gaynes

  5. Division of Community Medicine, Department of Medical and Health Sciences, Linköping University, SE-581 83, Linköping, Sweden

    Ursula Reichenpfader

Authors
  1. Ursula Reichenpfader
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  2. Gerald Gartlehner
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  3. Laura C. Morgan
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  4. Amy Greenblatt
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  5. Barbara Nussbaumer
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  6. Richard A. Hansen
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  7. Megan Van Noord
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  8. Linda Lux
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  9. Bradley N. Gaynes
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Corresponding author

Correspondence to Ursula Reichenpfader.

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Reichenpfader, U., Gartlehner, G., Morgan, L.C. et al. Sexual Dysfunction associated with Second-Generation Antidepressants in Patients with Major Depressive Disorder: Results from a Systematic Review with Network Meta-Analysis. Drug Saf 37, 19–31 (2014). https://doi.org/10.1007/s40264-013-0129-4

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  • DOI: https://doi.org/10.1007/s40264-013-0129-4

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