Melatonin Receptor Agonist / 5-HT2C Antagonist Pregnancy: §4.6: there are no or limited data (fewer than 300 pregnancy outcomes) from use in pregnant women; animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. As a precautionary measure, it is preferable to avoid the use of agomelatine during pregnancy. Breast-feeding: it is not known whether agomelatine/metabolites are excreted in human milk; animal data show excretion in milk and a risk to newborns/infants cannot be excluded — decide whether to discontinue breast-feeding or agomelatine therapy taking account of the benefit of each. Fertility: reproduction studies in rat and rabbit showed no effect on fertility.

Agomelatine

Brand names: Valdoxan

Agomelatine is an antidepressant licensed for major depressive disorder in adults, with a mechanism distinct from conventional serotonergic antidepressants.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: 25 mg once daily

Route: Oral

Frequency: Once daily at bedtime (with or without food)

Max: 50 mg once daily (two 25 mg tablets taken together at bedtime)

Source: UK SPC (eMC) for Agomelatine neuraxpharm 25 mg film-coated tablets, §4.2 (https://www.medicines.org.uk/emc/product/10819/smpc). The recommended dose is 25 mg once daily taken orally at bedtime. After two weeks of treatment, if there is no improvement of symptoms, the dose may be increased to 50 mg once daily (two 25 mg tablets together at bedtime); the decision to increase must be balanced against a higher risk of transaminase elevation and made on an individual benefit/risk basis with strict respect of liver function test monitoring. LIVER FUNCTION MONITORING: LFTs should be performed in all patients before starting treatment; treatment should NOT be initiated if transaminases exceed 3 x the upper limit of normal; during treatment monitor transaminases periodically at around three weeks, six weeks (end of acute phase), twelve weeks and twenty-four weeks (end of maintenance phase) and thereafter when clinically indicated; DISCONTINUE treatment if transaminases exceed 3 x the upper limit of normal; when increasing the dose, repeat LFTs at the same frequency as when initiating treatment. TREATMENT DURATION: patients with depression should be treated for a sufficient period of at least 6 months to ensure they are free of symptoms. SWITCHING FROM AN SSRI/SNRI: patients may experience discontinuation symptoms after cessation of an SSRI/SNRI — consult that product's SmPC on how to withdraw; agomelatine can be started immediately while tapering the SSRI/SNRI dosage. DISCONTINUATION: no dosage tapering is needed on treatment discontinuation. ELDERLY: efficacy and safety (25 to 50 mg/day) established in elderly depressed patients under 75 years; no effect is documented in patients aged 75 years and over, so agomelatine should not be used in that age group; no dose adjustment is required in relation to age. HEPATIC IMPAIRMENT: contraindicated. PAEDIATRIC (not expressed as a per-kg dose in the SPC): safety and efficacy in children from 2 years onwards for treatment of major depressive episodes have not yet been established and no data are available; there is no relevant use in children from birth to 2 years. Verify any under-18 use against a children's formulary. METHOD OF ADMINISTRATION: for oral use; film-coated tablets may be taken with or without food. §4.5 Interactions was not retrieved in this bundle — the interaction listed below is taken from the §4.3 Contraindications text; verify the full §4.5.

Dose adjustments

Renal

No relevant modification in agomelatine pharmacokinetic parameters has been observed in patients with severe renal impairment. However, only limited clinical data are available in depressed patients with severe or moderate renal impairment, so caution should be exercised when prescribing to these patients.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients
Hepatic impairment (i.e. cirrhosis or active liver disease) or transaminases exceeding 3 x the upper limit of normal
Concomitant use of potent CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin)

Side effects

Very common: headache. Common: dizziness, somnolence, insomnia
Common: nausea, diarrhoea, constipation, abdominal pain; uncommon vomiting
Common: increased ALAT and/or ASAT (increases >3 x the upper limit of normal seen in 1.2% of patients on 25 mg daily and 2.6% on 50 mg daily vs 0.5% on placebo); uncommon increased GGT; rare hepatitis, increased alkaline phosphatase, hepatic failure (a few cases exceptionally reported with fatal outcome or liver transplantation in patients with hepatic risk factors), jaundice
Common: anxiety, abnormal dreams; uncommon suicidal thoughts or behaviour, agitation and related symptoms (irritability, restlessness), aggression, nightmares, confusional state; rare hallucinations
Common: back pain, fatigue, weight increased; uncommon blurred vision, paraesthesia, restless leg syndrome, migraine, tinnitus, eczema, hyperhidrosis, pruritus, urticaria; rare akathisia, urinary retention, angioedema

Interactions

Potent CYP1A2 inhibitors (e.g. fluvoxamine, ciprofloxacin) — concomitant use is contraindicated (§4.3; the full §4.5 interactions section was not retrieved in this bundle)

Clinical monograph

How it works

It is an agonist at melatonergic MT1 and MT2 receptors and an antagonist at serotonin 5-HT2C receptors, an action associated with antidepressant effects and resynchronisation of circadian rhythms.

Prescribing in practice

Agomelatine can cause dose-related hepatotoxicity, so liver function must be checked before starting and monitored during treatment, and it is contraindicated in hepatic impairment.
It is taken at bedtime and should be stopped if transaminases rise significantly or symptoms of liver injury develop.
Avoid co-administration with potent inhibitors of its hepatic metabolism and use cautiously with other interacting drugs, following current prescribing references.

Monitoring

Check liver function before treatment and periodically thereafter, and review mood, response and any symptoms of liver injury during therapy.

Counselling the patient

Explain that this antidepressant is taken at night and that blood tests are needed to check the liver.
Advise reporting jaundice, dark urine, abdominal pain, fatigue or unusual itching promptly.
Advise not to stop suddenly without discussion and to attend liver-monitoring blood tests.

Evidence & guidelines

Agomelatine is licensed for major depression with mandatory liver-function monitoring reflected in MHRA advice and current prescribing references because of the risk of hepatotoxicity.

Reference: EMA Agomelatine Assessment Report; NICE CG90 (Depression); Confirm identity and dosing against the manufacturer SPC (eMC) and NICE. Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Myasthenia Gravis Activities of Daily Living (MG-ADL) Scale · Neuromuscular

Pathways