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Agomelatine (valdoxan), a novel therapeutic option for the management of irritable bowel syndrome (J Clinical Pharm Ther)

Jeffrey Roberts

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Jeffrey Roberts

Agomelatine, a novel therapeutic option for the management of irritable bowel syndrome

Qin Xiang Ng, Alex Yu Sen Soh, Donovan Yutong Lim, Wee-Song Yeo

PMID: 30014556 DOI: 10.1111/jcpt.12749


What is known and objective: Irritable bowel syndrome (IBS) is a complex and chronic, relapsing gastrointestinal condition that affects more than 10% of the population worldwide. There is a pressing need for new therapeutic strategies in the management of IBS. Increasing research has shed light on the modulatory functions of melatonin on pain, local inflammation and motility in the gastrointestinal tract. However, melatonin's effects are limited by its extensive first-pass metabolism and short half-life.

Comment: Agomelatine, a naphthalene analog of melatonin, is a novel melatonergic drug with a longer half-life and a comparatively greater affinity for MT1 and MT2 melatonin receptors than melatonin itself. Agomelatine also shows serotonin 5-HT3 receptor antagonist activity, which is theoretically of benefit for patients with IBS with diarrhoea (IBS-D) as it regulates gastrointestinal motility and visceral sensory mechanisms. Although only one clinical study of agomelatine use in patients with IBS exists, we believe that agomelatine is a safe and efficacious multimodal agent with untapped potential in the management of IBS.

What is new and conclusion: Numerous comorbidities are associated with IBS, including chronic pain syndromes and psychiatric disorders. Coupled with its antidepressant actions, agomelatine could serve as an effective adjunct therapeutic. Agomelatine should be considered in our therapeutic armamentarium for IBS management.

© 2018 John Wiley & Sons Ltd.

>> Abstract on PubMed

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Jeffrey Roberts

Agomelatine: is it really a firstline drug?


Vol 3 #2 March 2018

Agomelatine is listed as a firstline medication for the treament of depression in a number of guidelines including Canadian Guidelines. This is the case eventhough Agomelatine is not approved for use in Canada or the USA.

Agomelatine is structurally similar to melatonin and was felt to be a novel antidepressant that works on melatonergic, MT1 and MT2, 5-HT 2B and 5-HT2C receptors. Agomelatine was developed by  Servier Laboratories in France and was approved for clinical use in Europe in 2009. In the United States Novartis was not been able to get approval for clinical use from the FDA.

To answer the question as to whether Agomelatine should be considered firstline in the treatment of depression JPR has included key points from a Cochrane review carried out by Guaiana and others at the Department of Psychiatry, Western University, Saint Thomas Elgin General Hospital, St Thomas, Ontario.

This Cochrane review was conducted in order to:

  • determine the efficacy of agomelatine in alleviating acute symptoms of major depressive disorder in comparison with other antidepressants;
  • to review the acceptability of agomelatine in comparison with other antidepressant drugs;
  • to investigate adverse effects of agomelatine effects in adults.

The authors searched the Cochrane Collaboration’s Depression, Anxiety and Neurosis Review Group’s Specialised Register to 31 July 2013. This includes randomised controlled trials from the following databases:

CENTRAL (the Cochrane Central Register of Controlled Trials),  EMBASE (1974 onwards), MEDLINE (1950 onwards) and PsycINFO (1967 onwards).

Regulatory agency reports were included. No restrictions on date, language or  publication status were applied to the search. Servier Laboratories (developers of agomelatine) and other experts in the field were contacted for supplemental data.

Randomised controlled trials allocating adult participants with major depression to agomelatine versus any other antidepressive agent were selected for analysis.

Two authors independently extracted data and a double-entry procedure was employed. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability and tolerability.

A total of 13 studies (4495 participants) were included. Agomelatine was compared to selective serotonin reuptake inhibitors (SSRIs), namely paroxetine, fluoxetine, sertraline, escitalopram, and to the serotonin-norepinephrine reuptake inhibitor (SNRI), venlafaxine. Participants were followed up for six to 12 weeks.

Agomelatine did not show any advantage or disadvantage over the other antidepressants for our primary outcome, response to  treatment (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.95 to 1.08, P value 0.75 compared to SSRIs, and RR 1.06; 95% CI 0.98 to 1.16, P value 0.16 compared to venlafaxine). Also, agomelatine showed no advantage or disadvantage over other antidepressants for remission (RR 0.83; 95% CI 0.68 to 1.01, P value 0.07 compared to SSRIs, and RR 1.08; 95% CI 0.94 to 1.24, P value 0.73 compared to venlafaxine).

Overall, agomelatine appeared to be better tolerated than venlafaxine in terms of lower rates of drop outs (RR 0.40; 95% CI 0.24 to 0.67, P value 0.0005), and showed the same level of tolerability as SSRIs (RR 0.95; 95% CI 0.83 to 1.09, P value 0.44). Agomelatine induced a lower rate of dizziness than venlafaxine (RR 0.19, 95% CI 0.06 to 0.64, P value 0.007).With regard to the quality of the body of evidence, there was a moderate risk of bias for all outcomes, due to the number of included unpublished studies.

There was some heterogeneity, particularly between published and unpublished studies. The included studies were conducted in inpatient and outpatient settings,

limiting the generalisability of the results to primary care settings. The efficacy outcomes were precise, but the tolerability outcomes were mostly imprecise.

Publication bias was variable and depended on the outcome of the trial. The review included unpublished studies and this may have reduced the impact of publication bias. 

 The overall methodological quality of the studies was not very good. Almost all of the studies were sponsored by the pharmaceutical company that manufactures agomelatine (Servier), and some of these were unpublished. Attempts to contact the pharmaceutical company Servier for additional information on all unpublished studies were unsuccessful.

Cochrane Authors’ Conclusions:

Agomelatine did not seem to provide a significant advantage in efficacy over other antidepressive agents for the acute-phase treatment of major depression.

Agomelatine was better tolerated than paroxetine and venlafaxine in terms of overall side effects, and fewer participants treated with agomelatine dropped out of the trials due to side effects compared to sertraline and venlafaxine, but data were limited because the number of included studies was small. the authors found that agomelatine was compared with only a small number of other active antidepressive agents.

There were only a few trials for each comparison, limiting the generalisability of the results. The overall methodological quality of the studies was low, and, therefore, no firm conclusions could be drawn about the efficacy and tolerability of agomelatine.


Guaiana G, Gupta S, Chiodo D, Davies SJ, Haederle K, Koesters M. Agomelatine versus other antidepressive agents for major depression. Cochrane Database Syst Rev. 2013 Dec 17.

DOI: 10.1002/14651858.CD008851.pub2

>> Journal of Psychiatry Reform

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Jeffrey Roberts

Efficacy and safety of valdoxan in patients with irritable bowel syndrome

I V Balakina, T Ia Mironova, E N Golovanova

Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova 2014, 114 (4): 90-2

OBJECTIVES: To evaluate the efficacy and safety of the antidepressant valdoxan in irritable bowel syndrome (IBS) with comorbid mild and moderate depression.

METHODS: Twenty-eight patients with IBS and depression without psychotic symptoms were studied using clinical examination and psychometric scales.

RESULTS: A significant reduction in psychopathological symptoms, along with the improvement of health status, was recorded for most patients treated with valdoxan (25-50 mg/night) in the end of the 1st week.

CONCLUSION: Valdoxan has a good tolerability and safety profile, does not exert any negative effect on the IBS course and provides a high level of compliance.

>> https://read.qxmd.com/read/24874326/-efficacy-and-safety-of-valdoxan-in-patients-with-irritable-bowel-syndrome

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  • Jeffrey Roberts changed the title to Agomelatine (valdoxan), a novel therapeutic option for the management of irritable bowel syndrome (J Clinical Pharm Ther)

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