Agomelatine: A Beacon of Light in the MDD & GAD Treatment Landscape

During the 50th Philippine Psychiatric Association’s Annual Convention, a symposium sponsored by Servier Philippines Inc. featured a compelling discussion led by Dr Edgardo Juan Tolentino and Dr Rene Samaniego on a novel treatment approach for major depressive disorder (MDD) and generalized anxiety disorder (GAD).

AGOMELATINE: A BREAKTHROUGH IN MDD & GAD TREATMENT

MDD and GAD affect millions globally, and recent events like the COVID-19 pandemic have made these conditions even more common.¹

The symptoms of these conditions can impact psychosocial functioning and quality-of-life, and managing these symptoms is key to treating MDD and GAD, as well as preventing relapses.^2,3

Given these challenges, there is a pressing need for safe and effective approaches to managing MDD and GAD.

Agomelatine and its synergistic mechanism of action

Dr Tolentino noted two primary challenges affecting existing MDD and GAD treatments that a novel treatment could address: treatment resistance or inadequate symptom relief; and the burden of side effects.

Agomelatine is a novel treatment for GAD and MDD, and the first melatonergic antidepressant.

Dr Tolentino notes that agomelatine has two major benefits. Not only is it clinically efficacious it also supports symptomatic and functional remission, making recovery more likely (See Figure 1).^4-6

The unique mechanism of agomelatine contributes to its efficacy for MDD and GAD. As both a melatonergic (MT1 and MT2) agonist and a serotonergic antagonist (5-HT2c), agomelatine has a synergistic effect.⁷

The melatonergic agonism resulted in better mood, motivation, and sleep quality while the serotonergic antagonism helps normalize serotonergic receptor activity, preventing sexual dysfunction and other side effects commonly associated with antidepressants.⁷

Agomelatine for MDD and GAD: In the clinic and beyond

Depression

Evidence shows agomelatine can significantly improve depression symptoms.⁶ A meta-analysis of 522 clinical trials studying 21 antidepressants also found that agomelatine is generally efficacious for MDD.⁴

Beyond clinical efficacy, agomelatine has also been found to be highly effective at preventing MDD relapse, with one 10-month trial finding it reduced the risk of relapse by 56%.⁸

Agomelatine is also highly effective at improving functional outcomes. A meta-analysis looking at 42 clinical trials found that agomelatine patients had the greatest improvements in day-to-day functioning, as measured by the Sheehan Disability Scale (SDS).⁹

Anxiety

Agomelatine is already an established first-line treatment for GAD, recommended by global and national guidelines.^10-14

The clinical evidence also backs agomelatine’s effectiveness for anxiety. Trials have found it is efficacious in reducing anxiety symptoms and improving functional outcomes as measured by the SDS.^15-18

A 6-month study also found it was able to prevent relapse, with a 41.8% reduction of relapse risk compared to placebo.¹⁹

Evidence also shows that agomelatine is effective for patients with both anxiety and depression. The drug has been shown to affect anxiety in MDD patients greater than some SSRIs.²⁰

Treatment success requires continued treatment: tolerability and adherence

Tolerability is one of agomelatine’s greatest strengths. A meta-analysis by Cipriani, et al. – the largest such analysis to date²¹ – found that among 21 antidepressants, agomelatine has the highest patient acceptability, as measured by dropout rate (See Figure 2).⁴

Evidence also shows that – compared to other antidepressants – agomelatine is associated with lower rates of anxiety during treatment initiation, nausea and vomiting, emotional blunting and sexual dysfunction^22-24

CASE DISCUSSION

After the lecture, Dr Rene Samaniego shared some of his personal case studies highlighting the practical application of agomelatine in managing MDD and GAD.

In conclusion, the symposium highlighted agomelatine as a promising and efficacious MDD and GAD treatment, offering improved functional outcomes, remission rates, and tolerability.

The comprehensive discussion and local case presentations highlighted how agomelatine can give patients new hope for easy and effective treatment.