What is it?
What Agomelatine is
2Agomelatine is a synthetic prescription antidepressant and melatonin analogue, not a nutrient or botanical supplement. EMA lists Valdoxan for major depressive episodes in adults and as prescription-only in the European Union.
Individual trials can be mixed
11In one eight-week placebo-controlled trial in 511 adults with major depressive disorder, the higher-dose arm improved the primary depression score while the lower-dose arm did not separate from placebo. Transient liver-enzyme elevations also occurred. This clinical population and treatment window cannot establish a same-day nootropic benefit.
Names, aliases and forms
Mechanisms of action
Melatonin receptors plus 5-HT2C blockade
2Agomelatine stimulates MT1 and MT2 receptors and blocks 5-HT2C receptors. EMA says this may increase dopamine and noradrenaline signalling and help normalise sleep patterns in depression; this is psychiatric-drug pharmacology, not a supplement mechanism.
Potential effects and evidence map
Agomelatine has regulatory and clinical evidence for major depressive episodes in adults, but the effect is condition-specific and the trial record is not uniformly positive. EMA notes mixed placebo-controlled results and says benefits may be lower than with some other antidepressants; a large 2018 network meta-analysis nevertheless found agomelatine and the other included antidepressants more efficacious than placebo, with certainty ranging from moderate to very low across comparisons. No comparable evidence establishes memory, focus, productivity, or acute mood enhancement in healthy users. Liver monitoring and prescription oversight are inseparable from the evidence-based use case.
Adult depression trials show an antidepressant effect on average; these findings do not establish healthy-user mood enhancement.
Sleep-pattern outcomes have been studied in adults with depression; this does not establish use as a standalone sleep supplement.
No reliable human evidence establishes a focus, concentration, or productivity benefit in healthy users.
Typical dosages and timing
The EU label describes 25 mg once daily at bedtime, with a possible prescriber-managed increase to 50 mg after two weeks without improvement and an individual benefit-risk review. These are prescription-label figures, not a consumer serving recommendation. The required liver-test schedule is detailed in Safety.
Timing & effect horizon
Peak plasma concentration and mean plasma The time for blood levels to fall by half during the final elimination phase.Source are each about 1-2 hours. Those pharmacokinetic figures do not establish an acute nootropic effect, a same-night clinical onset, or a therapeutic-effect duration; depression outcomes were assessed over weeks.
Safety, side effects and risk profile
Baseline and repeated liver-function testing are required; hepatic impairment and baseline transaminases above three times normal are contraindications, and rare serious hepatic outcomes are reported.
Potent CYP1A2 inhibitors such as fluvoxamine and ciprofloxacin are contraindicated; moderate inhibitors, smoking, rifampicin, alcohol, and hepatotoxic medicines require clinician review.
Agomelatine is a prescription medicine where authorised, not a dietary supplement; approved uses, import rules, and lawful dispensing vary by jurisdiction.
Headache is very common and dizziness and nausea are common in the EU label; early adverse effects can affect tolerability and safety-sensitive activity.
Dizziness and somnolence are common, while insomnia can also occur; caution is needed for driving and operating machinery.
Human pregnancy data are limited; the EU label prefers avoidance during pregnancy and requires a treatment-versus-breastfeeding decision during lactation.
Depression evidence does not establish memory, focus, productivity, acute mood enhancement, or healthy-user safety.
The EU label requires liver tests before treatment, around weeks 3, 6, 12 and 24, after dose increases, and later when clinically indicated. Treatment should not start, or should stop, when ALT or AST exceed three times the upper limit of normal.
The EU label reports liver-enzyme elevations above three times normal in 1.2% at the lower labelled dose and 2.6% at the higher dose, versus 0.5% with placebo. These are trial-patient rates, not healthy-user incidence estimates. Rare hepatitis and hepatic failure, with exceptional fatal or transplant cases in patients with hepatic risk factors, establish potential severity. Most reported injury was reversible after discontinuation, but severe outcomes may not be. High rather than moderate reflects this attributable oral-dose hazard and mandatory testing for all patients; it does not rest on prescription status, interactions, pregnancy or overdose alone.
The EU label says agomelatine should not be used at age 75 or older and is not recommended under 18. Prescribing also requires caution with bipolar disorder or mania and close monitoring for worsening depression, suicidal thoughts, or behavioural changes, especially early and after dose changes.
Human pregnancy data are limited, and the EU label says it is preferable to avoid Valdoxan during pregnancy. During lactation, a clinician must weigh the benefit of treatment against breastfeeding because infant risk cannot be excluded.
Interactions and cautions
Agomelatine is metabolised mainly by CYP1A2. Fluvoxamine and ciprofloxacin are contraindicated; moderate CYP1A2 inhibitors such as propranolol or enoxacin require caution, and rifampicin or heavy smoking may reduce exposure. Medication and smoking changes belong with the prescriber.
The EU label says combining agomelatine with alcohol is not advisable. Alcohol use disorder, substantial alcohol intake, obesity or fatty-liver disease, diabetes, and other potentially hepatotoxic medicines raise the need for careful benefit-risk review and surveillance.
Legal and regulatory status
As of 19 October 2026, the EMA lists Valdoxan as a prescription-only medicine authorised in the European Union for major depressive episodes in adults. EU authorisation does not establish U.S. approval or lawful import in any other jurisdiction.
On 19 October 2026, an FDA openFDA Drugs@FDA generic-name search for agomelatine returned no matches; the corresponding label dataset search also returned no matches. This is a dated database observation, not a comprehensive legal determination or evidence that an online listing can lawfully be imported.
Practical buying and quality notes
- For Agomelatine, Valdoxan, Thymanax or Agoprex listings, check the stated active ingredient, tablet strength, pack size, manufacturer, dispensing route and prescription requirements in the relevant jurisdiction. Product availability alone does not establish approval, quality or individual suitability.10
- Compare the same stated tablet strength and number of units before comparing pack prices. Current product titles describe tablets while the catalog form filter says capsules, so confirm the actual dosage form on the merchant page. A loose-powder listing is not equivalent to the labelled finished tablet; price per gram alone cannot establish equivalence or quality.10
FAQ
Is Agomelatine a nootropic?
5Not in the supplement sense. It is a prescription antidepressant where authorised, and its depression and sleep-pattern evidence does not establish memory, focus, or productivity benefits in healthy users.
What is the Agomelatine dose?
3The dosage section gives the EU prescription-label range. It is not an established healthy-user nootropic dose; label use includes prescriber assessment and liver testing rather than a self-directed supplement serving.
What do duration and cycling claims mean?
3Plasma peak and half-life describe drug concentration, not the duration of a cognitive or antidepressant effect. Clinical outcomes were measured over weeks; a reliable single-dose nootropic duration or evidence-based consumer cycle is not established.
Does high risk mean serious injury is common?
3No. The rating describes the potential severity of an established oral liver hazard and its required monitoring, rather than claiming severe harm in most users. Healthy-user nootropic safety is not established, and depression-trial adverse-event rates should not be presented as healthy-user incidence.
References
- PubChem. Agomelatine (CID 82148). Accessed 2026-10-19.
- European Medicines Agency. Valdoxan EPAR overview, revision 27. Accessed 2026-10-19.
- European Medicines Agency. Valdoxan: EPAR product information, revision 27. Updated 2025-04-15; accessed 2026-10-19.
- Medicines and Healthcare products Regulatory Agency. Agomelatine (Valdoxan): risk of liver toxicity. GOV.UK Drug Safety Update. Published 2014-12-11.
- Cipriani A, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder. Lancet. 2018;391(10128):1357-1366.
- Carney RM, Shelton RC. Agomelatine for the treatment of major depressive disorder. Expert Opin Pharmacother. 2011;12(15):2411-2419.
- Freiesleben SD, Furczyk K. A systematic review of agomelatine-induced liver injury. J Mol Psychiatry. 2015;3:4.
- FDA openFDA Drugs@FDA generic-name search for agomelatine. Checked 2026-10-19.
- U.S. Food and Drug Administration. National Drug Code Database Background Information. Accessed 2026-07-14.
- NootropicsIndex Agomelatine product inventory. Checked 2026-10-19.
- Zajecka J, et al. Efficacy and safety of agomelatine in the treatment of major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled trial. J Clin Psychopharmacol. 2010;30(2):135-144.