Agomelatine: Melatonin Receptor Agonist Antidepressant
Agomelatine (Valdoxan) is an atypical antidepressant acting as a melatonin MT1/MT2 receptor agonist and 5-HT2C receptor antagonist. Unlike SSRIs, it does not inhibit monoamine reuptake.
Approved in Europe for major depressive disorder (MDD). It improves sleep architecture, resynchronises circadian rhythms, and has antidepressant efficacy without sexual side effects or discontinuation syndrome.
Mechanism of Action
MT1/MT2 agonism resynchronises the sleep-wake cycle and improves sleep quality. 5-HT2C antagonism increases dopamine and noradrenaline release in the frontal cortex, contributing to antidepressant and anxiolytic effects.
Indications & Use
Major depressive disorder in adults. Particularly useful when sleep disturbance is prominent or when sexual dysfunction from SSRIs is problematic. Not approved for anxiety disorders or bipolar depression.
Dosage
25 mg once daily at bedtime. After 2 weeks, may increase to 50 mg/night if insufficient response. Liver function tests (LFTs) must be checked before starting, at 3, 6, 12, and 24 weeks.
Side Effects
Common: headache, dizziness, nausea, somnolence. Important: hepatotoxicity (rare but serious — elevated transaminases in ~1–3%). No sexual dysfunction, no weight gain, no withdrawal syndrome.
Drug Interactions
Fluvoxamine and ciprofloxacin (potent CYP1A2 inhibitors): markedly increase agomelatine levels — contraindicated. Smoking (CYP1A2 inducer): reduces efficacy. Alcohol: increases hepatotoxic risk.
Contraindications
Hepatic impairment (any degree), transaminases >3× ULN, concomitant potent CYP1A2 inhibitors (fluvoxamine, ciprofloxacin), hypersensitivity. Caution in obesity, diabetes, and alcohol use.
Frequently Asked Questions
Why do I need liver tests for agomelatine?
Agomelatine is metabolised by the liver and can rarely cause elevated liver enzymes or hepatitis. Regular LFT monitoring detects this early — stop immediately if transaminases exceed 3× upper normal limit.
Does agomelatine cause sexual dysfunction?
No. Unlike SSRIs/SNRIs, agomelatine does not inhibit serotonin reuptake and is not associated with sexual dysfunction or anorgasmia — a key advantage for many patients.
Is there withdrawal when stopping agomelatine?
No discontinuation syndrome has been reported. You can stop agomelatine without tapering, which is another advantage over SSRIs and SNRIs.
References
- EMEA Valdoxan SPC 2023
- Stahl SM: Stahl's Essential Psychopharmacology, 5th ed.
- Kasper S et al. Lancet 2010
Medical Disclaimer: This information is for educational purposes only and does not replace professional medical advice.