Adverse Effects of First-Line Pharmacologic Treatments of Major
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Appendix Table of Contents Appendix A. Search Strategy A-1 Appendix B. List of excluded studies B-1 Appendix C. Evidence tables C-1 Appendix D. Risk of bias assessment D-1 Appendix E. Strenght of evidence assessments E-1 Appendix F. Forest plots F-1 Tables Table 1. Study and population characteristics, randomized controlled trials ................................ C-1 Table 2. Study and population characteristics-observational studies ............................................ C-8 Table 3. Study level outcomes ....................................................................................................... C-9 Table 4. Risk of bias assessment.................................................................................................... D-1 Table 5. Risk of bias assessment- observational studies................................................................ D-3 Table 6. Strength of evidence ratings for the comparison of SSRI versus placebo ........................ E-1 Table 7. Strength of evidence ratings for the comparison of SSRI versus TCA ............................ E-3 Table 8. Strength of evidence ratings for the comparison of SSRI versus SSRI ............................ E-4 Table 9. Strength of evidence ratings for the comparison of SNRI versus placebo ....................... E-5 Table 10. Strength of evidence ratings for the comparison of SNRI versus SSRI ......................... E-7 Table 11. Strength of evidence ratings for the comparison of bupropion XR versus placebo ....... E-8 Table 12. Strength of evidence ratings for the comparison of mirtazapine versus no antidepressant use ................................................................................................................................................... E-9 Table 13. Strength of evidence ratings for the comparison of mirtazapine versus paroxetine ..... E-10 Table 14. Strength of evidence ratings for the comparison of trazodone versus no antidepressant use ................................................................................................................................................. E-11 Table 15. Strength of evidence ratings for the comparison of vortioxetine versus placebo ......... E-12 Table 16. Strength of evidence ratings for the comparison of vortioxetine versus duloxetine .... E-13 Figures Figure 1. SSRI vs. placebo on any adverse event, acute treatment ................................................ F-1 Figure 2. SNRI vs. placebo on sustained elevated supine diastolic blood pressure, acute treatment ......................................................................................................................................................... F-1 Figure 3. SNRI vs. placebo on standing diastolic blood pressure, acute treatment ........................ F-1 Figure 4. SNRI vs. placebo on standing systolic blood pressure, acute treatment ......................... F-2 Figure 5. SNRI vs. placebo on supine diastolic blood pressure, acute treatment ........................... F-2 Figure 6. SNRI vs. placebo on supine systolic blood pressure, acute treatment ............................ F-2 Figure 7. SNRI vs. placebo on orthostatic hypotension, acute treatment ....................................... F-2 Figure 8. SNRI vs. placebo on orthostatic diastolic blood pressure, acute treatment..................... F-3 Figure 9. SNRI vs. placebo on orthostatic systolic blood pressure, acute treatment ...................... F-3 Figure 10. SNRI vs. placebo on SDST score, acute treatment ....................................................... F-3 Figure 11. SNRI vs. placebo on 2DCT score, acute treatment ....................................................... F-3 Figure 12. SNRI vs. placebo on falls, acute treatment .................................................................... F-4 Figure 13. SNRI vs. placebo on weight loss 7% or greater ............................................................ F-4 Appendix A. Search Strategy Search for KQ 1 and 2- Medline, Cochrane Central, PsychInfo and Embase all via OVID 1. major depression.mp. or major Depression/ 2. major depressive.mp. 3. 1 or 2 4. elderly.mp. or Aged/ 5. "Aged, 80 and over"/ or late-life.mp. 6. later-life.mp. 7. older.mp. 8. geriatric.mp. 9. 4 or 5 or 6 or 7 or 8 10. (anti-depressant or antidepressant).mp 11. Antidepressant Agents/ 12. paroxetine.mp. or Paroxetine/ 13. sertraline.mp. or Sertraline/ 14. citalopram.mp. or Citalopram/ 15. escitalopram.mp. 16. fluoxetine.mp. or Fluoxetine/ 17. fluvoxamine.mp. or Fluvoxamine/ 18. selective serotonin reuptake inhibitor.mp. or Serotonin Uptake Inhibitors/ 19. venlafaxine.mp. or Venlafaxine Hydrochloride/ 20. desvenlafaxine.mp. or Desvenlafaxine Succinate/ 21. duloxetine.mp. or Duloxetine Hydrochloride/ 22. serotonin norepinephrine reuptake inhibitor.mp. 23. bupropion.mp. or Bupropion/ 24. mirtazapine.mp. 25. trazodone.mp. or Trazodone/ 26. vilazodone.mp. or Vilazodone Hydrochloride/ 27. vortioxetine.mp. 28. milnacipran.mp. 29. levomilnacipran.mp. 30. Serotonin and Noradrenaline Reuptake Inhibitors/ 31. 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 32. 3 and 9 and 31 33. Epidemiologic studies/ 34. exp cohort studies/ 35. exp case controlled studies/ 36. Case control.tw. 37. (cohort adj (study or studies)).tw. 38. Cohort analy$.tw. 39. (Follow up adj (study or studies)).tw. 40. (observational adj (study or studies)).tw. 41. Longitudinal.tw. A-1 42. Retrospective.tw. 43. Cross sectional.tw. 44. Cross-sectional studies/ 45. or/33-44 46. Randomized Controlled Trials as Topic/ 47. randomized controlled trial/ 48. Random Allocation/ 49. Double Blind Method/ 50. Single Blind Method/ 51. clinical trial/ 52. clinical trial, phase i.pt. 53. clinical trial, phase ii.pt. 54. clinical trial, phase iii.pt. 55. clinical trial, phase iv.pt. 56. controlled clinical trial.pt. 57. randomized controlled trial.pt. 58. multicenter study.pt. 59. clinical trial.pt. 60. exp Clinical Trials as topic/ 61. or/46-60 62. (clinical adj trial$).tw. 63. ((singl$ or doubl$ or treb$ or tripl$) adj (blind$3 or mask$3)).tw. 64. PLACEBOS/ 65. placebo$.tw. 66. randomly allocated.tw. 67. (allocated adj2 random$).tw. 68. or/62-67 69. 61 or 68 70. case report.tw. 71. letter/ 72. historical article/ 73. or/70-72 74. 69 not 73 75. 45 or 74 76. 75 and 32 A-2 Appendix B. List of excluded studies 1.A double-blind multi-centre trial of fluoxetine 8.Altamura AC, Mauri MC, Colacurcio F, et al. and dothiepin in major depressive illness. Trazodone in late life depressive states: a South Wales Antidepressant Drug Trial double-blind multicenter study versus Group. Int Clin Psychopharmacol. amitriptyline and mianserin. 1988;3(1):75-81. PMID: 3282004 [Not in Psychopharmacology (Berl). 1988;95 older adults] Suppl:S34-6. PMID: 3133712 [Not in older 2.Ackerman DL, Greenland S, Bystritsky A, et adults] al. Characteristics of fluoxetine versus placebo 9.Altamura AC, Mauri MC, Colacurcio F, et al. responders in a randomized trial of geriatric Trazodone in late life depressive states: A depression. Psychopharmacol Bull. double-blind muticenter study versus 1997;33(4):707-714. PMID: 9493483 [No amitriptyline and mianserin. outcome of interest] Psychopharmacology (Berl). 1988;95 3.Ackerman DL, Greenland S, Bystritsky A, et Suppl:34-36. PMID: 3133712 [Not in older al. Side effects and time course of response in adults] a placebo-controlled trial of fluoxetine for the 10.Altamura AC, Mauri MC, Rudas N, et al. treatment of geriatric depression. J Clin Clinical activity and tolerability of trazodone, Psychopharmacol. 2000;20(6):658-665. mianserin, and amitriptyline in elderly PMID: 11106138 [Not in older adults] subjects with major depression: a controlled 4.Adeoye OM, Sweet RA, Pollock BG, et al. multicenter trial. Clin Neuropharmacol. Bupropion plasma concentration and 1989;12 Suppl 1:S25-7. PMID: 2663151 [Not antidepressant response in elderly patients: A in older adults] prospective, randomized, double-blind study 11.Altamura AC, Novellis FD, Guercetti G, et International Journal of Geriatric al. Fluoxetine compared with amitriptyline in Psychopharmacology. 2000;2(3):132-136. elderly depression: a controlled clinical trial. [Not in older adults] Int J Clin Pharmacol Res. 1989;9(6):391-6. 5.Aguglia E, Casacchia M, Cassano GB, et al. PMID: 2699465 [Acute care setting] Double-blind study of the efficacy and safety 12.Altamura AC, Percudani M, Guercetti G, et of sertraline versus fluoxetine in major al. Efficacy and tolerability of fluoxetine in depression. Int Clin Psychopharmacol. the elderly: A double-blind study versus 1993;8(3):197-202. PMID: 8263318 [Not in amitryptiline. Int Clin Psychopharmacol. older adults] 1989;4(Suppl 1):103-106. PMID: 2783697 6.Alam MY, Jacobsen PL, Chen Y, et al. Safety, [Acute care setting] tolerability, and efficacy of vortioxetine (Lu 13.Ambree O, Bergink V, Grosse L, et al. AA21004) in major depressive disorder: S100B Serum Levels Predict Treatment results of an open-label, flexible-dose, 52- Response in Patients with Melancholic week extension study. Int Clin Depression. Int J Neuropsychopharmacol. Psychopharmacol. 2014;29(1):36-44. PMID: 2015;19(3):pyv103. PMID: 26364276 [Not in 24169027 [Not in older adults] older adults] 7.Allard J, Artero S, Ritchie K. Consumption of 14.Amsterdam JD, Brunswick DJ. Site psychotropic medication in the elderly: a re- variability in treatment outcome in evaluation of its effect on cognitive antidepressant trials. Prog performance.