Comparative Efficacy and Acceptability of 21 Antidepressant Drugs for the Acute Treatment of Adults with Major Depressive Disorder
2018 · paper · Clinical trials
A systematic review and network meta-analysis of 522 trials (116,477 participants) comparing 21 antidepressants for acute adult depression. All outperformed placebo, with differences between drugs smaller in placebo-controlled analyses and more variable in head-to-head trials.
1 finding
Substance "Response rate was imputed in 20 608 (17·7%) of 116 447 cases", while the total sample is "116 477" participants elsewhere (abstract, results, discussion; 87 052 + 29 425).
- p. 4 Results, para 1
Response rate was imputed in 20 608 (17·7%) of 116 447 cases
- p. 4 Results, para 1
116 477 patients) done between 1979 and 2016
- p. 4 Results, para 1
Response rate was imputed in 20 608 (17·7%) of 116 447 cases.
- p. 4 Results, para 1
comprising 116 477 patients
Only the authors can say what is right here.
Judge's note: The page 4 image shows 116 447. The total of 116 477 appears in the abstract and the Discussion, and also equals 87 052 active + 29 425 placebo. No analysis set of 116 447 is defined anywhere. 17·7% is reached with either denominator, so the percentage cannot show which value is meant. A digit transposition is likely, but only the authors can confirm it.
Second check: another model agreed
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7 minor (typos and the like; most checked by the judge only)
Wording "The mean study sample size was 224 participants (SD 186)", but 116 477 participants / 522 trials = 223·1.
- p. 4 Results, para 1
The mean study sample size was 224 participants
- p. 4 Results, para 1
The mean study sample size was 224 participants (SD 186).
Only the authors can say what is right here.
Judge's note: Seen on the page 4 image. 116 477/522 rounds to 223, not 224. The mean could be based on total trial enrolment, which may include arms outside the 21 drugs and placebo, but the paper does not say so. Query the authors on the basis for the mean.
Second check: another model agreed
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Wording Results: "Only levomilnacipran was not directly compared with at least another active drug in any of the networks" vs Figure 5 caption: "Desvenlafaxine, levomilnacipran, and vilazodone ... had only placebo-controlled trials."
- p. 4 Results, para 3
Only levomilnacipran was not directly compared with at least another active drug in any of the networks.
- p. 9 Figure 5 caption
Desvenlafaxine, levomilnacipran, and vilazodone were not included in the head-to-head analysis because these three antidepressants had only placebo-controlled trials.
- p. 5 Figure 1
9 desvenlafaxine vs placebo or another active comparison
- p. 4 Results, para 3
Only levomilnacipran was not directly compared
Only the authors can say what is right here.
Judge's note: Seen on the page 4, 5 and 9 images. Figure 1 lists desvenlafaxine and vilazodone as "vs placebo or another active comparison" and only levomilnacipran as "vs placebo". The head-to-head set is defined as studies "with at least two active groups at licensed dose" (p 5). Desvenlafaxine's and vilazodone's active comparisons may come from placebo-controlled multi-arm trials or fall outside the licensed dose, but the caption's "had only placebo-controlled trials" does not say this. As worded, it conflicts with the Results sentence.
Second check: another model agreed
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Wording Figure 4 title "Head-to-head comparisons for efficacy and acceptability of the 21 antidepressants", but the league table and key show only 18 drugs.
- p. 8 Figure 4 title
Head-to-head comparisons for efficacy and acceptability of the 21 antidepressants
Judge's note: Seen on the page 8 image. The abbreviation key lists 18 drugs (Agom to Vort); desvenlafaxine, levomilnacipran and vilazodone are absent. The Figure 5 caption explains why these three are omitted, but the Figure 4 title still says 21.
Second check: another model agreed
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Typo Unmatched closing parenthesis: "To inform clinical practice globally, we selected the two tricyclics (amitriptyline and clomipramine) included in the WHO Model List of Essential Medicines)."
- p. 3 Methods, first paragraph
included in the WHO Model List of Essential Medicines).
Judge's note: The page 3 image shows "...Essential Medicines).". The sentence starts at the foot of page 2 ("To inform clinical practice globally"), and the extracted text shows no opening parenthesis. The only bracket pair in the sentence closes after "clomipramine".
Second check: none (judge only)
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Typo Contributors: "GS, Ach, JPTH, and ME analysed the data". The same author is "ACh" elsewhere (later in Contributors and in Role of the funding source).
- p. 10 Contributors
GS, Ach, JPTH, and ME analysed the data
- p. 6 Results, GRADE paragraph
nefazadone
- p. 4 Role of the funding source
ACi, TAF, GS, ACh, LZA
Judge's note: The page 10 image shows "Ach", and the next sentence in the same section has "ACh". The 'nefazadone' part of this cluster is covered in C011.
Second check: none (judge only)
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Typo Misspelling: "vortioxetine, nefazadone, clomipramine, bupropion, and amitriptyline" should read nefazodone.
- p. 6 Results, GRADE paragraph
vortioxetine, nefazadone, clomipramine, bupropion
- p. 6 Results, GRADE paragraph
low to very low for most comparisons involving vortioxetine, nefazadone, clomipramine, bupropion, and amitriptyline
- p. 8 Discussion, limitations
low or very low for amitriptyline, bupropion, and venlafaxine
- p. 6
vortioxetine, nefazadone, clomipramine, bupropion, and amitriptyline
Judge's note: The page 6 image shows "nefazadone". Everywhere else the paper has "nefazodone" (Methods, Figure 1, Figure 4 key, Figure 5 key). The second point, that the Discussion's GRADE examples (amitriptyline, bupropion, venlafaxine) differ from the Results list, is not a defect. The Discussion speaks of "many comparisons" and gives examples, not a complete list.
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Typo Declaration of interests names a company as "Geodon Richter"; the pharmaceutical company is presumably Gedeon Richter.
- p. 10 Declaration of interests
Geodon Richter
Only the authors can say what is right here.
Judge's note: Rests on outside knowledge: the company is named Gedeon Richter, and Geodon is a brand name for ziprasidone. The page image (crop C016-a, PDF page 10, Declaration of interests) shows "LB Pharma, Lundbeck, Otsuka, TEVA, Geodon Richter, Recordati," exactly as printed, so this is not an extraction artefact. It looks like a cosmetic misspelling of a company name in the disclosures.
Second check: none (judge only)