Antidepressant – melatonin agonist and 5-HT2C antagonist
ATC code: N06AX22 (Agomelatine)
A structural melatonin analogue. Agonist at melatonin MT1 and MT2 receptors and antagonist at serotonin 5-HT2C receptors. Restores circadian rhythms and increases dopamine and noradrenaline release in the prefrontal cortex. Does not affect serotonin reuptake – differs from SSRIs by lacking typical side effects (sexual dysfunction, GI complaints, discontinuation discomfort). CYP1A2-metabolized, so smoking and strong CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) significantly affect levels.
Second line
Second-line for major depressive disorder per NG222 (2022) and the Spanish SEP 2024. First-line is SSRIs and SNRIs (, , ). Agomelatine is used with concomitant sleep and circadian rhythm disturbance, with SSRI-related sexual side effects, or in seasonal depression. Dose 25 mg at bedtime; up to 50 mg. Effect develops over 2–4 weeks. Cochrane 2014 meta-analysis showed efficacy comparable to SSRIs.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Agomelatine is an antidepressant that acts as a melatonin receptor agonist. It is prescribed for major depression ( 2022 and NG222 guidelines). For sleep and mood improvement outside a depression indication, agomelatine does not work: no clinical studies of such use exist. The main risk is severe hepatotoxicity up to acute liver failure ( PRAC 2014 mandated baseline liver-enzyme monitoring and rechecks at 3, 6, 12, and 24 weeks, then periodically). The combination of potentially dangerous risk and no benefit outside depression makes this prescription unjustified. If insomnia is a real problem, the foundation is cognitive-behavioral therapy for insomnia (CBT-I), and melatonin 1-5 mg an hour before bed is an accessible and safe option. If agomelatine was prescribed for sleep, consider seeking a second opinion.
Opens the checker prefilled with this drug. Pick the second one from your regimen.
Direct links to regulator labels. Open in a new tab.
Limited pregnancy data. Sertraline with more data is preferred in pregnant patients with depression.
No data. Not recommended during lactation.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Agomelatine is evaluated for the following indications with varying evidence strength: Major depressive disorder (evidence tier B), Insomnia and sleep disorders (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Agomelatine (≥ 1 in 100): Headache, Drowsiness, Dizziness, Nausea, Elevated liver enzymes, Anxiety. See the Safety section for uncommon and serious reactions.
FDA category C. Limited pregnancy data. Sertraline with more data is preferred in pregnant patients with depression.
No data. Not recommended during lactation.
Agomelatine is contraindicated in: Agomelatine hypersensitivity; Active liver disease or transaminase elevation over 3× upper limit; Dementia; Concomitant strong CYP1A2 inhibitors (fluvoxamine, ciprofloxacin); Age under 18. Full list in the Safety section.