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Comparative Efficacy and Risk of Harms of Immediate- versus Extended-Release Second-Generation Antidepressants: A Systematic Review with Network Meta-Analysis

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Abstract

Background

Major depressive disorder (MDD) has detrimental effects on an individual’s personal life, leads to increased risk of comorbidities, and places an enormous economic burden on society. Several ‘second-generation’ antidepressants are available as both immediate-release (IR) and extended-release formulations. The advantage of extended-release formulations may be the potentially improved adherence and a lower risk of adverse events.

Objective

We conducted a systematic review to assess the comparative efficacy, risk of harms, and patients’ adherence of IR and extended-release antidepressants for the treatment of MDD.

Data Source

English-language abstracts were retrieved 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.

Eligibility Criteria

We included head-to-head randomized controlled trials (RCTs) of at least 6 weeks’ duration that compared an IR formulation with an extended-release formulation of the same antidepressant in adult patients with MDD. We also included placebo-controlled trials to conduct a network meta-analysis. To assess harms and adherence, in addition to RCTs, we searched for observational studies with ≥1,000 participants and a follow-up of ≥12 weeks.

Study Appraisal and Synthesis Methods

We dually reviewed abstracts and full texts and assessed quality ratings. Lacking head-to-head evidence for many comparisons of interest, we conducted network meta-analyses using Bayesian methods. Our outcome measure of choice was response on the Hamilton Depression Rating Scale.

Results

We located seven head-to-head trials and 94 placebo- and active-controlled trials for network meta-analysis. Overall, our analyses indicate that IR and extended-release formulations do not differ substantially with respect to efficacy and risk of harms. The evidence is mixed with respect to differences in adherence, indicating lower adherence for IR formulations.

Limitations

The lack of head-to-head comparisons for many drugs compromises our conclusions. Network meta-analyses have methodological limitations that need to be taken into consideration when interpreting findings.

Conclusion

Available evidence currently shows no clear differences between the two formulations and therefore we cannot recommend a first choice. However, if adherence or compliance with one medication is an issue, then clinicians and patients should consider the alternative medication. If adherence or costs are a problem with one formulation, consideration of the other formulation to provide an adequate treatment trial is reasonable.

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References

  1. Kessler RC, et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Arch Gen Psychiatry. 2005;62(6):593–602.

    PubMed  Google Scholar 

  2. Wittchen HU, Jacobi F. Size and burden of mental disorders in Europe: a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol. 2005;15(4):357–76.

    CAS  PubMed  Google Scholar 

  3. Wu E, et al. Comparison of treatment persistence, hospital utilization and costs among major depressive disorder geriatric patients treated with escitalopram versus other SSRI/SNRI antidepressants. Curr Med Res Opin. 2008;24(10):2805–13.

    CAS  PubMed  Google Scholar 

  4. Birnbaum HG, Ben-Hamadi R, Greenberg PE, Hsieh M, Tang J, Reygrobellet C. Determinants of direct cost differences among US employees with major depressive disorders using antidepressants. Pharmacoeconomics. 2009;27:507–17.

  5. Olfson M, Marcus SC. National patterns in antidepressant medication treatment. Arch Gen Psychiatry. 2009;66(8):848–56.

    PubMed  Google Scholar 

  6. DeVane CL. Immediate-release versus controlled-release formulations: pharmacokinetics of newer antidepressants in relation to nausea. J Clin Psychiatry. 2003;64(Suppl 18):14–9.

    CAS  PubMed  Google Scholar 

  7. Kondo T, et al. Altered pharmacokinetics and metabolism of valproate after replacement of conventional valproate with the slow-release formulation in epileptic patients. Pharmacol Toxicol. 2002;90(3):135–8.

    CAS  PubMed  Google Scholar 

  8. Kennedy SH, et al. Combining bupropion SR with venlafaxine, paroxetine, or fluoxetine: a preliminary report on pharmacokinetic, therapeutic, and sexual dysfunction effects. J Clin Psychiatry. 2002;63(3):181–6.

    CAS  PubMed  Google Scholar 

  9. Gartlehner G, 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.

    PubMed  Google Scholar 

  10. Sussman N. Venlafaxine XR therapy for major depression and anxiety disorders: the clinical implications that its advantages pose. Postgrad Med. 1999;106(6 Suppl):31–6.

    CAS  PubMed  Google Scholar 

  11. Keene MS, et al. Adherence to paroxetine CR compared with paroxetine IR in a Medicare-eligible population with anxiety disorders. Am J Manag Care. 2005;11(12 Suppl):S362–9.

    PubMed  Google Scholar 

  12. Huskamp HA. Prices, profits, and innovation: examining criticisms of new psychotropic drugs’ value. Health Aff (Millwood). 2006;25(3):635–46.

    Google Scholar 

  13. Gartlehner G, et al. Second-generation antidepressants in the pharmacologic treatment of adult depression: an update of the 2007 comparative effectiveness review. Report no. 12-EHC012-EF. Rockville: Agency for Healthcare Research and Quality; Dec 2011.

  14. 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.

    Google Scholar 

  15. Higgins JPT, Altman DG, Sterne J. Assessing risk of bias in included studies. In: Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated March 2011]. The Cochrane Collaboration; 2011.

  16. Deeks JJ, et al. Evaluating non-randomised intervention studies. Health Technol Assess, 2003;7(27):iii–x, 1–173.

  17. Jansen JP, et al. Bayesian meta-analysis of multiple treatment comparisons: an introduction to mixed treatment comparisons. Value Health. 2008;11(5):956–64.

    PubMed  Google Scholar 

  18. Lu G, Ades AE. Combination of direct and indirect evidence in mixed treatment comparisons. Stat Med. 2004;23(20):3105–24.

    CAS  PubMed  Google Scholar 

  19. Dias S, et al. Evidence synthesis for decision making 2: a generalized linear modeling framework for pairwise and network meta-analysis of randomized controlled trials. Med Decis Mak. 2013;33(5):607–17.

    Google Scholar 

  20. Schmidt ME, et al. The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder. J Clin Psychiatry. 2000;61(11):851–7.

    CAS  PubMed  Google Scholar 

  21. Claxton A, et al. Patient compliance to a new enteric-coated weekly formulation of fluoxetine during continuation treatment of major depressive disorder. J Clin Psychiatry. 2000;61(12):928–32.

    CAS  PubMed  Google Scholar 

  22. Rapaport MH, et al. Efficacy of controlled-release paroxetine in the treatment of late-life depression. J Clin Psychiatry. 2003;64(9):1065–74.

    CAS  PubMed  Google Scholar 

  23. Higuchi T, et al. Paroxetine controlled-release formulation in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled study in Japan and Korea. Psychiatry Clin Neurosci. 2011;65(7):655–63.

    CAS  PubMed  Google Scholar 

  24. Golden RN, et al. Efficacy and tolerability of controlled-release and immediate-release paroxetine in the treatment of depression. J Clin Psychiatry. 2002;63(7):577–84.

    CAS  PubMed  Google Scholar 

  25. 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.

    CAS  PubMed  Google Scholar 

  26. Burke WJ, McArthur-Miller DA. Exploring treatment alternatives: weekly dosing of fluoxetine for the continuation phase of major depressive disorder. J Clin Psychiatry. 2001;62(Suppl 22):38–42.

    CAS  PubMed  Google Scholar 

  27. Feiger A, et al. 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 

  28. Feiger AD, et al. A placebo-controlled study evaluating the efficacy and safety of flexible-dose desvenlafaxine treatment in outpatients with major depressive disorder. CNS Spectr. 2009;14(1):41–50.

    PubMed  Google Scholar 

  29. Boyer P, et al. Efficacy, safety, and tolerability of fixed-dose desvenlafaxine 50 and 100 mg/day for major depressive disorder in a placebo-controlled trial. Int Clin Psychopharmacol. 2008;23(5):243–53.

    PubMed  Google Scholar 

  30. Liebowitz MR, Yeung PP, Entsuah R. A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in adult outpatients with major depressive disorder. J Clin Psychiatry. 2007;68(11):1663–72.

    PubMed  Google Scholar 

  31. Septien-Velez L, et al. A randomized, double-blind, placebo-controlled trial of desvenlafaxine succinate in the treatment of major depressive disorder. Int Clin Psychopharmacol. 2007;22(6):338–47.

    PubMed  Google Scholar 

  32. Brannan SK, et al. Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder. J Psychiatr Res. 2005;39(1):43–53.

    PubMed  Google Scholar 

  33. Detke MJ, et al. Duloxetine 60 mg once daily dosing versus placebo in the acute treatment of major depression. J Psychiatr Res. 2002;36(6):383–90.

    PubMed  Google Scholar 

  34. Detke MJ, et al. Duloxetine, 60 mg once daily, for major depressive disorder: a randomized double-blind placebo-controlled trial. J Clin Psychiatry. 2002;63(4):308–15.

    CAS  PubMed  Google Scholar 

  35. Detke MJ, et al. 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.

    CAS  PubMed  Google Scholar 

  36. Wernicke JF, et al. Low-dose fluoxetine therapy for depression. Psychopharmacol Bull. 1988;24(1):183–8.

    CAS  PubMed  Google Scholar 

  37. Lydiard RB, et al. Fluvoxamine, imipramine, and placebo in the treatment of depressed outpatients: effects on depression. Psychopharmacol Bull. 1989;25(1):68–70.

    CAS  PubMed  Google Scholar 

  38. Cohn CK, et al. Responders to antidepressant drug treatment: a study comparing nefazodone, imipramine, and placebo in patients with major depression. J Clin Psychiatry. 1996;57(Suppl 2):15–8.

    CAS  PubMed  Google Scholar 

  39. Fontaine R, et al. A double-blind comparison of nefazodone, imipramine, and placebo in major depression. J Clin Psychiatry. 1994;55(6):234–41.

    CAS  PubMed  Google Scholar 

  40. Rickels K, et al. A placebo-controlled, double-blind, clinical trial of paroxetine in depressed outpatients. Acta Psychiatr Scand Suppl. 1989;350:117–23.

    CAS  PubMed  Google Scholar 

  41. Reimherr FW, 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.

    PubMed  Google Scholar 

  42. Lydiard RB, et al. A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression. J Clin Psychiatry. 1997;58(11):484–91.

    CAS  PubMed  Google Scholar 

  43. 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.

    Google Scholar 

  44. Olie J, Gunn K, Katz E. A double-blind placebo-controlled multicentre study of sertraline in the acute and continuation treatment of major depression. Eur Psychiatry. 1997;12(1):34–41.

    CAS  PubMed  Google Scholar 

  45. Blumenthal JA, et al. Exercise and pharmacotherapy in the treatment of major depressive disorder. Psychosom Med. 2007;69(7):587–96.

    CAS  PubMed Central  PubMed  Google Scholar 

  46. 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.

    CAS  PubMed  Google Scholar 

  47. 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.

    CAS  PubMed  Google Scholar 

  48. Khan A, et al. Double-blind comparison of escitalopram and duloxetine in the acute treatment of major depressive disorder. Clin Drug Investig. 2007;27(7):481–92.

    CAS  PubMed  Google Scholar 

  49. Lee P, et al. Once-daily duloxetine 60 mg in the treatment of major depressive disorder: multicenter, double-blind, randomized, paroxetine-controlled, non-inferiority trial in China, Korea, Taiwan and Brazil. Psychiatry Clin Neurosci. 2007;61(3):295–307.

    CAS  PubMed  Google Scholar 

  50. Feighner JP, et al. Double-blind comparison of bupropion and fluoxetine in depressed outpatients. J Clin Psychiatry. 1991;52(8):329–35.

    CAS  PubMed  Google Scholar 

  51. Mao PX, et al. Escitalopram in major depressive disorder: a multicenter, randomized, double-blind, fixed-dose, parallel trial in a Chinese population. Depress Anxiety. 2008;25(1):46–54.

    CAS  PubMed  Google Scholar 

  52. Hong CJ, et al. A double-blind, randomized, group-comparative study of the tolerability and efficacy of 6 weeks’ treatment with mirtazapine or fluoxetine in depressed Chinese patients. J Clin Psychiatry. 2003;64(8):921–6.

    CAS  PubMed  Google Scholar 

  53. Rush AJ, et al. Comparative effects of nefazodone and fluoxetine on sleep in outpatients with major depressive disorder. Biol Psychiatry. 1998;44(1):3–14.

    CAS  PubMed  Google Scholar 

  54. Gagiano C. A double blind comparison of paroxetine and fluoxetine in patients with major depression. Br J Clin Res. 1993;4:145–52.

    Google Scholar 

  55. De Wilde J, et al. A double-blind, comparative, multicentre study comparing paroxetine with fluoxetine in depressed patients. Acta Psychiatr Scand. 1993;87(2):141–5.

    PubMed  Google Scholar 

  56. Chouinard G, 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.

    CAS  PubMed  Google Scholar 

  57. Sechter D, et al. A double-blind comparison of sertraline and fluoxetine in the treatment of major depressive episode in outpatients. Eur Psychiatry. 1999;14(1):41–8.

    CAS  PubMed  Google Scholar 

  58. 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 

  59. Dierick M, et al. A double-blind comparison of venlafaxine and fluoxetine for treatment of major depression in outpatients. Prog Neuropsychopharmacol Biol Psychiatry. 1996;20(1):57–71.

    CAS  PubMed  Google Scholar 

  60. Costa e Silva J. Randomized, double-blind comparison of venlafaxine and fluoxetine in outpatients with major depression. J Clin Psychiatry. 1998;59(7):352–7.

    PubMed  Google Scholar 

  61. Alves C, Cachola I, Brandao J. Efficacy and tolerability of venlafaxine and fluoxetine in outpatients with major depression. Prim Care Psychiatry. 1999;5(2):52–63.

    Google Scholar 

  62. Tzanakaki M, et al. Increased remission rates with venlafaxine compared with fluoxetine in hospitalized patients with major depression and melancholia. Int Clin Psychopharmacol. 2000;15(1):29–34.

    CAS  PubMed  Google Scholar 

  63. De Nayer A, et al. Venlafaxine compared with fluoxetine in outpatients with depression and concomitant anxiety. Int J Neuropsychopharmacol. 2002;5(2):115–20.

    PubMed  Google Scholar 

  64. Tylee A, et al. A double-blind, randomized, 12-week comparison study of the safety and efficacy of venlafaxine and fluoxetine in moderate to severe major depression in general practice. Prim Care Psychiatry. 1997;3(1):51–8.

    Google Scholar 

  65. Haffmans PM, Timmerman L, Hoogduin CA. Efficacy and tolerability of citalopram in comparison with fluvoxamine in depressed outpatients: a double-blind, multicentre study. The LUCIFER Group. Int Clin Psychopharmacol. 1996;11(3):157–64.

    CAS  PubMed  Google Scholar 

  66. Hicks JA, et al. Randomised controlled study of sleep after nefazodone or paroxetine treatment in out-patients with depression. Br J Psychiatry. 2002;180:528–35.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  68. Rush AJ, et al. Response in relation to baseline anxiety levels in major depressive disorder treated with bupropion sustained release or sertraline. Neuropsychopharmacology. 2001;25(1):131–8.

    CAS  PubMed  Google Scholar 

  69. Munizza C, et al. A comparative, randomized, double-blind study of trazodone prolonged-release and sertraline in the treatment of major depressive disorder. Curr Med Res Opin. 2006;22(9):1703–13.

    CAS  PubMed  Google Scholar 

  70. Weisler RH, et al. Comparison of bupropion and trazodone for the treatment of major depression. J Clin Psychopharmacol. 1994;14(3):170–9.

    CAS  PubMed  Google Scholar 

  71. van Moffaert M, et al. Mirtazapine is more effective than trazodone: a double-blind controlled study in hospitalized patients with major depression. Int Clin Psychopharmacol. 1995;10(1):3–9.

    PubMed  Google Scholar 

  72. Kasper S, et al. A comparative, randomised, double-blind study of trazodone prolonged-release and paroxetine in the treatment of patients with major depressive disorder. Curr Med Res Opin. 2005;21(8):1139–46.

    CAS  PubMed  Google Scholar 

  73. 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.

    CAS  PubMed  Google Scholar 

  74. Sir A, et al. Randomized trial of sertraline versus venlafaxine XR in major depression: efficacy and discontinuation symptoms. J Clin Psychiatry. 2005;66(10):1312–20.

    CAS  PubMed  Google Scholar 

  75. Shelton RC, 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.

    CAS  PubMed  Google Scholar 

  76. Boulenger JP, et al. A comparative study of the efficacy of long-term treatment with escitalopram and paroxetine in severely depressed patients. Curr Med Res Opin. 2006;22(7):1331–41.

    CAS  PubMed  Google Scholar 

  77. Ventura D, et al. Escitalopram versus sertraline in the treatment of major depressive disorder: a randomized clinical trial. Curr Med Res Opin. 2007;23(2):245–50.

    CAS  PubMed  Google Scholar 

  78. Perahia DG, et al. Duloxetine in the treatment of major depressive disorder: a placebo- and paroxetine-controlled trial. Eur Psychiatry. 2006;21(6):367–78.

    CAS  PubMed  Google Scholar 

  79. Tourian KA, et al. Desvenlafaxine 50 and 100 mg/d in the treatment of major depressive disorder: an 8-week, phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial and a post hoc pooled analysis of three studies. Clin Ther. 2009;31:1405–23.

    CAS  PubMed  Google Scholar 

  80. Nierenberg AA, 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.

    CAS  PubMed  Google Scholar 

  81. Goldstein DJ, et al. Duloxetine in the treatment of major depressive disorder: a double-blind clinical trial. J Clin Psychiatry. 2002;63(3):225–31.

    CAS  PubMed  Google Scholar 

  82. Coleman CC, 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.

    CAS  PubMed  Google Scholar 

  83. Croft H, et al. 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.

    CAS  PubMed  Google Scholar 

  84. Coleman CC, 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.

    CAS  PubMed  Google Scholar 

  85. Fava M, et al. A double-blind study of paroxetine, fluoxetine, and placebo in outpatients with major depression. Ann Clin Psychiatry. 1998;10(4):145–50.

    CAS  PubMed  Google Scholar 

  86. Rudolph RL, Feiger AD. A double-blind, randomized, placebo-controlled trial of once-daily venlafaxine extended release (XR) and fluoxetine for the treatment of depression. J Affect Disord. 1999;56(2–3):171–81.

    CAS  PubMed  Google Scholar 

  87. Nemeroff CB, Thase ME. A double-blind, placebo-controlled comparison of venlafaxine and fluoxetine treatment in depressed outpatients. J Psychiatric Res. 2007;41(3):351–9.

    Google Scholar 

  88. Fava M, et al. 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.

    CAS  PubMed  Google Scholar 

  89. Ou JJ, et al. Efficacy and safety of escitalopram versus citalopram in major depressive disorder: a 6-week, multicenter, randomized, double-blind, flexible-dose study. Psychopharmacology. 2011;213(2–3):639–46.

    CAS  PubMed  Google Scholar 

  90. Barber JP, et al. Short-term dynamic psychotherapy versus pharmacotherapy for major depressive disorder: a randomized, placebo-controlled trial. J Clin Psychiatry. 2012;73(1):66–73.

    PubMed  Google Scholar 

  91. Dunlop BW, et al. Symptomatic and functional improvement in employed depressed patients: a double-blind clinical trial of desvenlafaxine versus placebo. J Clin Psychopharmacol. 2011;31(5):569–76.

    CAS  PubMed  Google Scholar 

  92. Alvarez E, et al. 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.

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Oakes TM, et al. Assessment of depressive symptoms and functional outcomes in patients with major depressive disorder treated with duloxetine versus placebo: primary outcomes from two trials conducted under the same protocol. Hum Psychopharmacol. 2012;27(1):47–56.

    CAS  PubMed  Google Scholar 

  94. Mehtonen OP, et al. 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.

    CAS  PubMed  Google Scholar 

  95. Fabre LF, Putman HP 3rd. A fixed-dose clinical trial of fluoxetine in outpatients with major depression. J Clin Psychiatry. 1987;48(10):406–8.

    CAS  PubMed  Google Scholar 

  96. Elliott AJ, et al. Randomized, placebo-controlled trial of paroxetine versus imipramine in depressed HIV-positive outpatients. Am J Psychiatry. 1998;155(3):367–72.

    CAS  PubMed  Google Scholar 

  97. Fabre L, et al. Fluvoxamine versus imipramine and placebo: a double-blind comparison in depressed patients. Int Clin Psychopharmacol. 1996;11(2):119–27.

    CAS  PubMed  Google Scholar 

  98. Feighner JP, Boyer WF. Paroxetine in the treatment of depression: a comparison with imipramine and placebo. J Clin Psychiatry. 1992;53(Suppl):44–7.

    PubMed  Google Scholar 

  99. Feighner J, et al. A double-blind, placebo-controlled trial of nefazodone in the treatment of patients hospitalized for major depression. J Clin Psychiatry. 1998;59(5):246–53.

    CAS  PubMed  Google Scholar 

  100. Smith WT, Glaudin V. A placebo-controlled trial of paroxetine in the treatment of major depression. J Clin Psychiatry. 1992;53(Suppl):36–9.

    PubMed  Google Scholar 

  101. Muijen M, et al. A comparative clinical trial of fluoxetine, mianserin and placebo in depressed outpatients. Acta Psychiatr Scand. 1988;78(3):384–90.

    CAS  PubMed  Google Scholar 

  102. Smith WT, et al. Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. Psychopharmacol Bull. 1990;26(2):191–6.

    CAS  PubMed  Google Scholar 

  103. Wernicke J, et al. Fixed-dose fluoxetine therapy for depression. Psychopharmacol Bull. 1987;23(1):164.

    CAS  PubMed  Google Scholar 

  104. Rudolph RL, et al. A randomized, placebo-controlled, dose-response trial of venlafaxine hydrochloride in the treatment of major depression. J Clin Psychiatry. 1998;59(3):116–22.

    CAS  PubMed  Google Scholar 

  105. Rickels K, et al. The efficacy and safety of paroxetine compared with placebo in outpatients with major depression. J Clin Psychiatry. 1992;53(Suppl):30–2.

    PubMed  Google Scholar 

  106. Rickels K, et al. Nefazodone and imipramine in major depression: a placebo-controlled trial. Br J Psychiatry. 1994;164(6):802–5.

    CAS  PubMed  Google Scholar 

  107. Roy-Byrne PP, et al. Nefazodone treatment of major depression in alcohol-dependent patients: a double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2000;20(2):129–36.

    CAS  PubMed  Google Scholar 

  108. McGrath PJ, et al. A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression. Am J Psychiatry. 2000;157(3):344–50.

    CAS  PubMed  Google Scholar 

  109. Hegerl U, et al. Effects of pharmacotherapy and psychotherapy in depressed primary-care patients: a randomized, controlled trial including a patients’ choice arm. Int J Neuropsychopharmacol. 2010;13(1):31–44.

    CAS  PubMed  Google Scholar 

  110. Soares CN, et al. Desvenlafaxine and escitalopram for the treatment of postmenopausal women with major depressive disorder. Menopause. 2010;17(4):700–11.

    PubMed  Google Scholar 

  111. Beasley CM Jr, et al. Fluoxetine versus trazodone: efficacy and activating-sedating effects. J Clin Psychiatry. 1991;52(7):294–9.

    PubMed  Google Scholar 

  112. Silverstone PH, Ravindran A. Once-daily venlafaxine extended release (XR) compared with fluoxetine in outpatients with depression and anxiety. Venlafaxine XR 360 Study Group. J Clin Psychiatry. 1999;60(1):22–8.

    CAS  PubMed  Google Scholar 

  113. Lapierre YD, et al. Treatment of major affective disorder with fluvoxamine. J Clin Psychiatry. 1987;48(2):65–8.

    CAS  PubMed  Google Scholar 

  114. Gastpar M, Singer A, Zeller K. Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study. Pharmacopsychiatry. 2006;39:66–75.

    CAS  PubMed  Google Scholar 

  115. Goldstein DJ, et al. Duloxetine in the treatment of depression: a double-blind placebo-controlled comparison with paroxetine. J Clin Psychopharmacol. 2004;24(4):389–99.

    CAS  PubMed  Google Scholar 

  116. Claghorn JL. The safety and efficacy of paroxetine compared with placebo in a double-blind trial of depressed outpatients. J Clin Psychiatry. 1992;53(Suppl):33–5.

    PubMed  Google Scholar 

  117. Corrigan MH, et al. Comparison of pramipexole, fluoxetine, and placebo in patients with major depression. Depress Anxiety. 2000;11(2):58–65.

    CAS  PubMed  Google Scholar 

  118. Clerc GE, Ruimy P, Verdeau-Palles J. A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. The Venlafaxine French Inpatient Study Group. Int Clin Psychopharmacol. 1994;9(3):139–43.

    CAS  PubMed  Google Scholar 

  119. Gulseren L, et al. Comparison of fluoxetine and paroxetine in type II diabetes mellitus patients. Arch Med Res. 2005;36(2):159–65.

    PubMed  Google Scholar 

  120. Wade A, et al. A randomized, double-blind, 24-week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care. Int Clin Psychopharmacol. 2003;18(3):133–41.

    PubMed  Google Scholar 

  121. Eisen SA, Miller DK, Woodward RS, Spitznagel E, Przybeck TR. The effect of prescribed daily dose frequency on patient medication compliance. Arch Intern Med. 1990;150(9):1881–4.

    CAS  PubMed  Google Scholar 

  122. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23(8):1296–310.

    CAS  PubMed  Google Scholar 

  123. Stang P, Young S, Hogue S. Better patient persistence with once-daily bupropion compared with twice-daily bupropion. Am J Ther. 2007;14(1):20–4.

    PubMed  Google Scholar 

  124. Consumer Reports Best Buy Drugs™. Using antidepressants to treat depression. 2013. Available from: http://www.consumerreports.org/health/resources/pdf/best-buy-drugs/Antidepressants_update.pdf. Accessed 9 Apr 2014.

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Acknowledgments

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

Funding

This project was originally funded under Contract No. HHSA-290-2007-10056I from the AHRQ, US Department of Health and Human Services.

Conflicts of Interest

All authors report grants from the US AHRQ during the conduct of the study.

Barbara Nussbaumer, Laura C. Morgan, Ursula Reichenpfader, Amy Greenblatt, Megan van Noord, Linda Lux, Bradley N. Gaynes, and Gerald Gartlehner declare that they have no conflicts of interest.

Richard A. Hansen declares that he has received personal consulting fees from Novartis, personal fees from Daiichi Sankyo, and personal fees from Allergan outside the submitted work.

Systematic Review Registration Number

This systematic review was not registered, but all AHRQ protocols are available online on their website.

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Authors and Affiliations

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

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

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

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

  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, 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

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  1. Barbara Nussbaumer
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  2. Laura C. Morgan
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  7. Linda Lux
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  9. Gerald Gartlehner
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Correspondence to Barbara Nussbaumer.

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Nussbaumer, B., Morgan, L.C., Reichenpfader, U. et al. Comparative Efficacy and Risk of Harms of Immediate- versus Extended-Release Second-Generation Antidepressants: A Systematic Review with Network Meta-Analysis. CNS Drugs 28, 699–712 (2014). https://doi.org/10.1007/s40263-014-0169-z

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