PharmaceuticalAntidepressantMelatonin receptor agonist5-HT2C antagonist

Agomelatine

Also known as Valdoxan · Thymanax · S 20098

Written by enwyReviewed 5 Aug 20262 sources0 comments

Antidepressant that combines MT1/MT2 melatonin agonism with 5-HT2C antagonism. Used in Europe for major depression, valued for restoring sleep architecture without sexual dysfunction or dependence, but carries a real risk of hepatotoxicity requiring liver monitoring.

01 Overview

Agomelatine (brands Valdoxan, Thymanax) is an atypical antidepressant approved in the EU (2009) but never approved in the US. Its combined melatonergic agonism and 5-HT2C antagonism resynchronise disrupted circadian rhythms, which makes it attractive for depressed patients with prominent insomnia; it is sometimes used off-label chiefly for its sleep-promoting, non-sedating rhythm effects.

Unlike SSRIs it is largely free of sexual side effects, weight gain, and discontinuation syndrome. The major limitation is dose-dependent hepatotoxicity, including rare cases of liver failure, which mandates liver function testing before and periodically during treatment.

02 Mechanism

Agonist at MT1/MT2 melatonin receptors (resynchronising circadian rhythms) combined with antagonism at 5-HT2C receptors, increasing frontocortical dopamine and noradrenaline.

03 Dosing

Tier	Dose	Route	Notes
Standard	25 mg/day	Oral	25 mg at bedtime; may increase to 50 mg after two weeks if needed.
Higher	50 mg/day	Oral	50 mg at bedtime; higher hepatotoxicity risk mandates LFT monitoring.

04 Effects

Effect	Magnitude	Evidence
Restored sleep architectureImproves sleep continuity and slow-wave sleep without daytime sedation.		Clinical
Antidepressant effectReduces depressive symptoms in major depression.	comparable to SSRIs in trials	Clinical
No sexual dysfunction / minimal discontinuationLargely spares sexual function and lacks the withdrawal syndrome seen with SSRIs.		Clinical

05 Side effects

Effect	Severity	Frequency	Evidence	Countermeasures
Headache and dizzinessHeadache, dizziness, and nausea, especially early in treatment.	Mild	Common	Clinical
HepatotoxicityDose-dependent transaminase elevations and rare cases of hepatitis and liver failure.	Severe	Uncommon but serious	Clinical

06 Legal status

EMA-approved for major depression; not habit-forming. · as of Jan 2026

United States

Not approved

Development discontinued in the US; not marketed. · as of Jan 2026

07 References

Agomelatine in the treatment of major depressive disorder: a meta-analysisCNS Drugs, 2013

Valdoxan (agomelatine) EPAR product informationEuropean Medicines Agency

08 Discussion0 comments

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This page is reference information, not medical advice. Doses and protocols are documented as they appear in the clinical literature and in practice — describing them is not a recommendation to use them. Countermeasures listed here are not a substitute for a physician. Legal status varies by jurisdiction and changes.