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Table 1 Agomelatine-induced liver injury in pre- and postmarketing clinical trials and non-interventioal studies

From: A systematic review of agomelatine-induced liver injury

Study [reference number]

No. Patients enrolled

Duration (weeks)

Indication

Liver enzymes >3X ULN

Serious hepatic reactions (i.e., hepatitis, liver enzymes >10X ULN and hepatic failure) and deaths due to hepatic reaction

European clinical trials (2008) [8]

40681

up to 52 weeks

All indications (Overall safety set)

Ago25: 1.04%2 Ago50: 1.39%2 Pbo: 0.72%

• >10X ULN: 1:1000-10 0003 1 case hepatitis4

Zajecka et al. (2010) [22,23]

511

8

MDD

Ago25: 0% Ago50: 4.5% Pbo: 0%

0%

Stahl et al. (2010) [24,25]

503

8

MDD

Ago25: 0.6% Ago50: 3.0% Pbo: 0.6%

0%

CAGO178A2303 [26]

503

8

MDD

Ago25: 1.3% Ago50: 0.6% Par20: 0.6% Pbo: 0%

0%

Hale et al. (2010) [27]

515

8

MDD

Ago25/50: 1.6%5 Flx20/40: 0.4%

0%

Kasper et al. (2010) [28]

313

6

sleep in MDD

Ago25/50: 0.7%5 Ser50/100: 0%

0%

CAGO178A2301E1 (2009) [29]

329

52

MDD

Ago25/50: 2.0%

0%

CAGO178A2302E1 (2009) [30]

358

52

MDD

Ago25/50: 2.0%

0%

CAGO178A2303E1 (2010) [31]

334

52

MDD

Ago25: 1.2%6 Ago50: 2.0%6

0%

CAGO178A2304 [32]

633

52

MDD

Ago25/50: 4.6% (open-label phase) Pbo: 2.1% (double-blind continuation phase)7

0%

Calabrese et al. (2007) [33]

21

6, plus optional 46 (total 52)

bipolar I disorder

Ago25: N/A

0%

Olié & Kasper (2007) [34]

238

6

MDD

Ago25/50 and Pbo: N/A

0%

Goodwin et al. (2009) [35]

339

34

MDD

Ago25/50 and Pbo: N/A

0%

Demyttenaere et al. (2013) [36]

8628

up to 24

MDD

Ago25: 1.79% Ago50: 2.61% SSRIs: 0.34%

0%

Bruno et al. (2013) [37]

15

12

Fibromyalgia

Ago25: 0%

0%

Martinotti et al. (2012) [38]

60

8

MDD

Ago25/50 and Vlx75/150: N/A

0%

Stein et al. (2012) [39]

477

43

GAD

N/A

0%

Stein et al. (2014) [40]

412

12

GAD

N/A

0%

Heun et al. (2013) [41]

222

8

MDD

Ago25/50: 1.3%5 Pbo: 0%

0%

Laux and the VIVALDI Study Group (2012) [42]

3356

12

MDD

Ago25/50: 0.2%8

0%

Sparshatt et al. (2013) [43]

110

12

MDD

Ago25/50: -Baseline: 0.9%9 -Week 8: 0%

0%

Karaistos et al. (2013) [44]

40

16

Depression in type II diabetes

Ago25/50 and Ser50/100: N/A

0%

Quera-Slava et al. (2011) [45]

138

24

MDD

Ago25/50 and Esci10/20: N/A

0%

Montejo et al. (2010) [46]

92

8

healthy volunteers

Ago25/50, Par20, and Pbo: N/A

0%

  1. Ago25 = 25 mg agomelatine; Ago50 = 50 mg agomelatine; Ago25/50 = entire agomelatine treatment group; Pbo = placebo; Par20 = 20 mg paroxetine, Flx20/40 = entire fluoxetine treatment group; Ser50/100 = entire sertraline treatment group; Vlx75/150 = entire venlafaxine treatment group; Esci10/20 = entire escitalopram treatment group; SSRIs: selective serotonin reuptake inhibitors; MDD = Major Depressive Disorder; GAD = Generalized Anxiety Disorder; Slp = sleep; N/A = non-vailable.
  2. 1: Number of patients receiving agomelatine; the number of patients receiving placebo is not clear.
  3. 2: Classified as a common event.
  4. 3: Classified as a rare event.
  5. 4: Case did not recover at follow-up (2.5 years after end of study).
  6. 5: Percentage calculated from safety set (i.e., enrolled patients who received at least one dose of the study treatment).
  7. 6: Percentage calculated from all treated patients enrolled in the extension phase.
  8. 7: Percentages calculated from information provided in Novartis Clinical Trial Results Database, 2010—study CAGO178A2.
  9. 304.
  10. 8: It is not mentioned by the authors if other ADs were taken concurrently.
  11. 9: Percentage calculated from information provided in the article.
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Journal of Molecular Psychiatry

ISSN: 2049-9256

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