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#7 Are some 2nd generation antidepressants more equal than others?

In adults suffering from depression, are any of the 2nd generation antidepressants better than others?

Among 2nd generation antidepressants, there is little or no reliable difference in the efficacy or frequency of adverse events, but the types of adverse events do vary. Clinicians should select antidepressants based on adverse effects profile and cost, not on efficacy differences.

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Two groups compared the benefits and harms associated with 2nd generation antidepressants.    
  • 2011 systematic review1 (234 trials): 
    • No important difference in efficacy. The few statistical differences found were not clinically important. 
      • E.g. Escitalopram 1.13 points better than citalopram on the 60-point MADRS scale (minimal clinically important difference ≥2). 
      • Sponsorship may have played a role in these subtle differences. 
    • Similar number of patients had adverse events (61% had ≥1), but types varied 
      • E.g. Venlafaxine 11% more nausea and vomiting, sertraline 3% more diarrhea. 
  • 2009 systematic review2 (117 trials): 
    • Identified some small differences in efficacy and acceptability. 
    • Efficacy top four: Mirtazapine, escitalopram, venlafaxine, sertraline. 
    • Acceptability top four: Escitalopram, sertraline, bupropion, citalopram. 
    • Cochrane reviews by the same authors suggested small efficacy advantages for sertraline3 and escitalopram4, whereas other agents (e.g. fluvoxamine5) did not show any benefit over other antidepressants. 
  • Antidepressant evidence suffers from significant bias. For example: 
    • ≤10% are high-quality studies.1,2 
    • Selective publication (and re-publication) of positive trials (publication bias).6,7 
    • Interpretation of results in favor of the sponsor (funding bias).8 
  • The 2009 review2 has important concerns regarding validity, including: 
    • Treated all depression scales as the same (and they are not). 
    • Using odds ratios exaggerated the differences they found. 
    • When they tried to account for sponsorship bias, differences between the drugs were reduced. 
  • Both reviews1,2 performed some indirect comparisons of drugs from different studies, which is less reliable than direct comparison in the same trial. 
  • The 2011 review was more robust overall 
Reviewed: July 13, 2016 by ricky

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  • Adil S Virani BSc(Pharm) PharmD FCSHP
  • G. Michael Allan MD CCFP

1. Gartlehner G, Hansen RA, Morgan LC, et al. Ann Intern Med. 2011; 155:772-85.

2. Cipriani A, Furukawa TA, Salanti G, et al. Lancet. 2009; 373:746-58.

3. Cipriani A, La Ferla T, Furukawa TA, et al. Cochrane Database Syst Rev. 2009; (2):CD006117.

4. Cipriani A, Santilli C, Furukawa TA, et al. Cochrane Database Syst Rev. 2009; (2):CD006532.

5. Omori IM, Watanabe N, Nakagawa A, et al. Cochrane Database Syst Rev. 2010; (3):CD006114.

6. Melander H, Ahlqvist-Rastad J, Meijer G, et al. BMJ. 2003; 326:1171-3.

7. Turner EH, Matthews AM, Linardatos E, et al. N Engl J Med. 2008; 358:252-60.

8. Jureidini JN, Doecke CJ, Mansfield PR, et al. BMJ. 2004; 328:879-83.

Authors do not have any conflicts of interest to declare.