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Valdoxan (Agomelatine) Tapering Guide

Agomelatine (Valdoxan) is an atypical antidepressant that acts on melatonin receptors and 5-HT2C receptors. It is licensed in the UK and EU (not the US) for major depression. This guide and medication taper calculator help you plan how to stop agomelatine safely with your prescriber.

Dosage

Agomelatine is typically a single 25 mg tablet strength (usual doses 25 mg or 50 mg at night). There is no lower licensed tablet; any step below 25 mg needs a compounded liquid.

It lacks classic SSRI/SNRI discontinuation syndrome, but liver-function monitoring is required during treatment, and you should still watch for relapse of depression when stopping.

Agomelatine taper schedule

Choose a common starting dose to preview the full hyperbolic schedule — free, no email required. This schedule has 12 steps and takes about 22 weeks in total; your prescriber may adjust the pace based on how you feel.

Starting dose

Selected start: 25 mg/day · 1× daily
Taper speed: Moderate
Region (formulations): US; Tablet/liquid products used for dosing tips — not your location. Example uses US formulary; change region in the custom builder.
Modelled occupancy at start: ~53.3%

Limited / derived PET anchor — curve is indicative

Swipe sideways to see every column.

Step	Daily (mg)	How to take it	Per dose × 1/day	Hold (weeks)
0	25	Your current dose — hold steady before step 1.	25 mg × 1	—
1	21.8	GPSee liquid / compounding note below	21.8 mg × 1	2
2	19.1	GPSee liquid / compounding note below	19.1 mg × 1	2
3	16.8	GPSee liquid / compounding note below	16.8 mg × 1	2
4	14.8	GPSee liquid / compounding note below	14.8 mg × 1	2
5	13.05	GPSee liquid / compounding note below	13.05 mg × 1	2
6	11.5	GPSee liquid / compounding note below	11.5 mg × 1	2
7	10.15	GPSee liquid / compounding note below	10.15 mg × 1	2
8	8.95	GPSee liquid / compounding note below	8.95 mg × 1	2
9	7.85	GPSee liquid / compounding note below	7.85 mg × 1	2
10	6.85	GPSee liquid / compounding note below	6.85 mg × 1	2
11	6.25	GPSee liquid / compounding note below	6.25 mg × 1	2

Steps that cannot be made from whole or half licensed tablets point to the liquid / compounding note below — ask your prescriber before changing how you take your dose.

Want a copy to keep?

The full agomelatine schedule is already shown below. Enter your email to also receive a PDF and HTML copy you can save or share with your prescriber — optional, and we never gate the schedule behind it.

It's not a substitute for medical advice. This calculator can help you visualise a tapering schedule but before making any changes to your medication plan it's necessary to consult a medical professional. Ask a psychiatrist — available after you request your protocol.

Dose vs occupancy

This taper is spread across 12 gradual steps. The curve below shows why the last few milligrams matter most: at low doses, small dose changes produce large drops in serotonin-transporter occupancy.

What this shows: the non-linear relationship between dose and serotonin transporter (SERT) occupancy. The curve is flat at high doses — most transporters are already blocked, so a dose cut has little biological impact — and much steeper at low doses, where even a 1–2 mg reduction causes a disproportionately large drop in occupancy. Your taper steps are spaced along this curve so each step removes a similar amount of occupancy.

Modelled Hill-curve occupancy — illustrative only. PET-derived parameters vary by study; your prescriber may use different clinical targets. Small mg changes near zero can still produce large occupancy shifts.

How to Taper Off Agomelatine (Valdoxan) Safely

How to taper off agomelatine (Valdoxan) safely is different again: it is a melatonin MT1/MT2 agonist and 5-HT2C antagonist, not a serotonin-reuptake inhibitor, with a very short half-life (~1–2 hours). Classic SSRI withdrawal syndromes are uncommon, but sleep-timing and mood changes can still appear when you stop. Coming off agomelatine should be planned with your prescriber, including LFTs where monitoring is required.

People searching how to wean off Valdoxan or get off antidepressants with a chronobiotic mechanism should still prefer a short staged exit over an unannounced stop after long use. Follow local label guidance alongside Maudsley/NICE deprescribing caution.

What coming off agomelatine actually feels like, week by week

Because the pharmacology targets circadian and 5-HT2C pathways, the main issues after stopping are often sleep-phase shifts, vivid dreams, or a mood dip rather than brain zaps and dizziness.

A brief Valdoxan taper (for example 50 → 25 → stop, or a short hold at 25 mg) is enough for many people, but those with fragile sleep may prefer a slower exit.

“Stopping Valdoxan was a non-event physically — no zaps, no dizziness. What I watched for was whether my sleep and mood held up.”

— paraphrased from patient forums

“My prescriber kept checking my liver bloods throughout, which was the main practical thing about being on it.”

— paraphrased from patient forums

Withdrawal or relapse — how to tell them apart

Discontinuation-related sleep disruption is early; depressive relapse evolves over weeks. Agomelatine lacks the typical SSRI sensory withdrawal signature (Cosci & Chouinard, 2020 timing logic still applies).

Agomelatine taper schedules by starting dose (50, 25 mg)

Tablets are commonly 25 mg; 50 mg is usually two tablets. Notes high → low.

From 50 mg: how to taper off agomelatine 50 mg typically steps to 25 mg for one to several weeks while watching sleep timing.

From 25 mg: how to taper off Valdoxan 25 mg is often a supervised stop, or a short alternate-night phase if insomnia appears — agree the plan if sleep is fragile.

Build your schedule from your dose →

If it gets worse: pausing and reinstatement

If sleep collapses or mood dips sharply after a cut, reinstate the previous dose briefly and slow the exit. Maintain LFT monitoring rules if you restart.

Resume with a longer hold at 25 mg before stopping fully.

Practical notes on finishing agomelatine

There is little need for micro-milligram liquids compared with SSRIs; the 25 mg tablet is the usual final unit.

Protect sleep hygiene while you come off Valdoxan — circadian rebound is the main practical risk.

The bottom line

Agomelatine is genuinely different from SSRI/SNRI tapers: fewer classic withdrawal syndromes, more sleep-timing risk. A short staged plan is usually enough — wean off Valdoxan with liver-monitoring awareness and a plan for nights.

Milligram scale guidance (advanced — prescriber/pharmacist approval required)

When a dose is below what you can split from a licensed tablet, some people weigh crushed tablet powder. This is not exact chemistry — it is a last resort. Liquid or compounded formulations are safer when available.

Resolution: at least 0.001 g (1 mg) — not a kitchen scale.
Include a calibration weight and use a draft shield if possible.
Weigh on a stable surface; tare your container first.
Crushed tablet weight ≠ exact active ingredient — drug may not be evenly distributed; prefer liquid or compounded specials when available.
Never split enteric-coated (EC) or extended-release (XR) products — discuss with your pharmacist.

Example searches (confirm specs before buying):

Key facts about hyperbolic antidepressant tapering

The calculator algorithm is based on peer-reviewed research and has been reviewed by our medical advisors to ensure the accuracy of the tapering model.

72%
discontinued their antidepressant using hyperbolic tapering strips in a real-world study
71% of the same people had previously tried to stop at least once and been unsuccessful; the study did not record which method those earlier attempts used. Figures come from tapering-strip research and may not generalise to every taper.
Source: Groot et al., Therapeutic Advances in Psychopharmacology 2021
56 days
median taper length in that tapering-strip study — not a target; many people taper over 6–12 months or longer
This median reflects tapering-strip use in one study. Your timeline depends on how long you have taken the medication, your withdrawal symptoms, and previous attempts — slower is often safer.
Source: Groot et al., Therapeutic Advances in Psychopharmacology 2021
10%
serotonin transporter occupancy per tapering step
This linear reduction prevents withdrawal. Slower, more gradual tapering over several months has shown greater success in reducing withdrawal symptoms than short tapers.
Source: Horowitz et al., The Lancet Psychiatry 2019

Claro — tapering companion

A protocol isn’t enough — you need support.

Tapering can take months, sometimes years. Claro helps you track each step, log symptoms, and spot when a reduction was too fast — with psychiatrist-reviewed guidance. Join early access while we launch the app.

Why an AI companion for tapering? →

Frequently asked questions about agomelatine

Common questions about how to taper off agomelatine, hyperbolic schedules, and withdrawal — written for people who want to come off antidepressants safely with their prescriber.

How do you taper off agomelatine (Valdoxan)?

Agomelatine works on melatonin receptors rather than serotonin reuptake, so it has essentially no classic discontinuation syndrome. Because only a 25 mg tablet exists, a step from 50 to 25 mg is straightforward, and any smaller steps need a compounded liquid. The main task when stopping is watching for a return of depression or insomnia, with liver-function monitoring continuing while you take it.

Does agomelatine cause withdrawal symptoms?

Agomelatine is unusual in having little or no withdrawal syndrome, because it does not block serotonin reuptake — brain zaps and the usual discontinuation cluster are not expected. Most people stop it with few physical symptoms. The change to watch for over the following weeks is relapse of the depression or sleep problem it was treating, rather than withdrawal.

What is an antidepressant tapering calculator?

An antidepressant tapering calculator is a free online medication taper calculator that turns your current dose into a step-by-step plan for reducing it over time. The Claro calculator uses the hyperbolic method: each step removes a similar percentage of receptor occupancy rather than the same number of milligrams. The result is a personalised schedule you can review with your prescriber when you decide to wean off antidepressants.

Why use a tapering calculator?

A medication taper calculator turns receptor-occupancy research into a concrete hyperbolic taper schedule you can read in minutes. It is especially useful when you want to come off antidepressants gradually, because the last few milligrams cause the largest change in modelled occupancy. Use it to preview steps, plan liquid or split-tablet doses, and bring a printable plan when you wean off antidepressants with your prescriber.

How does an antidepressant taper calculator work?

The calculator models how much of your serotonin (or noradrenaline) transporter is occupied at each dose using a Hill-equation curve fitted to published PET studies. It then chooses dose reductions so that each step removes a roughly equal amount of occupancy — the hyperbolic method described by Horowitz and Taylor (2019). The schedule is then rounded to doses you can actually achieve with available tablets, capsules, or liquids in your region.

What is hyperbolic tapering and why is it recommended?

Hyperbolic tapering means reducing your dose by smaller and smaller milligram amounts as you get lower, so the change in receptor occupancy at each step stays about the same. It is recommended because antidepressants follow a hyperbolic dose-response curve: at low doses, small milligram changes have outsized effects. Hyperbolic tapering is endorsed in the Maudsley Deprescribing Guidelines (2024), the UK NICE NG222 guideline, and the Dutch multidisciplinary deprescribing document.

What is the safest way to taper off antidepressants?

The safest way is gradual, supervised, and individualised. Work with a prescriber, hold each dose for at least 2-4 weeks before reducing again, and use liquid or compounded formulations once tablets cannot be split small enough. If symptoms become severe, return to the previous stable dose, allow time to settle, then resume with smaller steps. This calculator is educational; do not change medication without clinical supervision.

How slowly should antidepressants be reduced?

Most people benefit from reductions of around 5-10% of the previous dose every 2-4 weeks, and even more slowly toward the end of the taper. Higher-risk drugs — paroxetine, venlafaxine, and duloxetine — typically need slower steps and longer holds. There is no fixed timeline: many people take 6-12 months to fully get off antidepressants and some take longer, especially after years of treatment.

What are common antidepressant withdrawal symptoms?

The most commonly reported antidepressant withdrawal symptoms include dizziness, "brain zaps" (brief electric-shock sensations), nausea, fatigue, insomnia, vivid dreams, headaches, irritability, anxiety, and mood swings. A 2024 Lancet Psychiatry meta-analysis (Henssler et al.) estimated discontinuation symptoms in around 31% of people, with about 2.8% experiencing severe symptoms. Earlier work (Davies & Read, 2019) reported higher rates of 56% across surveyed populations.

What is the difference between antidepressant withdrawal and relapse?

Withdrawal usually starts within days of a dose reduction, includes physical symptoms like dizziness or brain zaps, and improves when you reinstate the previous dose. Relapse of the original condition typically appears weeks later, is dominated by your original symptoms, and is not relieved within hours by reinstating. The Cosci & Chouinard (2020) framework is the standard taxonomy clinicians use to tell the two apart.

Is it dangerous to stop antidepressants cold turkey?

Stopping antidepressants cold turkey is widely discouraged. Sudden discontinuation increases the risk of severe withdrawal symptoms, including dizziness, brain zaps, and emotional changes, and can trigger reinstatement. Short half-life drugs such as paroxetine and venlafaxine carry the highest risk. If you have already stopped abruptly and feel unwell, contact your prescriber; reinstating the previous dose and then tapering more gradually is the standard recommendation.

Why are the last antidepressant dose reductions often the hardest?

Because the dose-occupancy curve is hyperbolic. At low doses, a 1-2 mg change can produce as much receptor change as a 10-20 mg change at higher doses. This is why people often feel fine for most of the taper and then struggle at the end. A medication taper calculator addresses this by making the final steps in tenths of a milligram, which usually requires a liquid formulation or compounded preparation.

Which antidepressants are hardest to taper off?

Paroxetine (Paxil/Seroxat) and venlafaxine (Effexor) are most often reported as the hardest antidepressants to come off, followed by duloxetine (Cymbalta). They share short half-lives and steep dose-occupancy curves, so missed doses or sharp reductions can trigger withdrawal symptoms within days. Fluoxetine (Prozac), with its very long half-life, is generally the easiest and is sometimes used as a "bridge" when switching off shorter-acting drugs.

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Use the guided builder to enter your current dose, region, and taper preset — then email your personalised protocol.

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Clinical references

[1]Horowitz MA, Taylor D. Tapering of SSRI treatment to mitigate withdrawal symptoms. The Lancet Psychiatry 2019.doi:10.1016/S2215-0366(19)30032-XProposes hyperbolic dose reduction based on receptor-occupancy curves; the methodological basis of every modern taper calculator.
[2]Horowitz MA, Taylor D. The Maudsley Deprescribing Guidelines. Wiley 2024.doi:10.1002/9781394291052Per-drug operational manual for hyperbolic tapering across SSRIs, SNRIs, benzodiazepines, gabapentinoids, and antipsychotics.
[3]Davies J, Read J. A systematic review into the incidence, severity and duration of antidepressant withdrawal effects. Addictive Behaviors 2019.doi:10.1016/j.addbeh.2018.08.027Systematic review: 56% of people who discontinue antidepressants experience withdrawal effects; 46% rate them as severe.
[4]Henssler J et al. Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis. The Lancet Psychiatry 2024.doi:10.1016/S2215-0366(24)00133-0Meta-analysis of 79 studies (≈21,000 patients): pooled incidence of discontinuation symptoms ~31%; severe symptoms ~2.8%.
[5]Groot PC, van Os J. Successful use of tapering strips for hyperbolic reduction of antidepressant dose: a cohort study. Therapeutic Advances in Psychopharmacology 2021.doi:10.1177/2045125321103932772% of patients successfully discontinued antidepressants after switching to the hyperbolic model; 71% had previously failed to come off without tapering strips.
[6]Groot PC, van Os J. Antidepressant tapering strips to help people come off medication: real-world outcomes. Therapeutic Advances in Psychopharmacology 2023.doi:10.1177/20451253231171518Of 1,194 patients using hyperbolic taper strips after previous failed attempts, ~71% successfully discontinued their antidepressant.
[7]Framer A. What I have learnt from helping thousands of people taper off antidepressants and other psychotropic medications. Therapeutic Advances in Psychopharmacology 2021.doi:10.1177/2045125321991274Describes the "windows and waves" pattern of withdrawal recovery and supports patient-led pacing.
[8]Hengartner MP et al. Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives. Therapeutic Advances in Psychopharmacology 2020.doi:10.1177/2045125320967183Descriptive analysis of 69 protracted withdrawal cases: median duration 79 weeks; 47% report suicidality during withdrawal.
[9]Cosci F, Chouinard G. Acute and persistent withdrawal syndromes following discontinuation of psychotropic medications. Psychotherapy and Psychosomatics 2020.doi:10.1159/000506868Taxonomy distinguishing new withdrawal symptoms, rebound, and persistent post-withdrawal disorder; the standard framework for withdrawal vs. relapse.
[10]Kalfas M et al. Incidence and Nature of Antidepressant Discontinuation Symptoms. JAMA Psychiatry 2025.doi:10.1001/jamapsychiatry.2025.1362Recent meta-analysis: dizziness was the most common discontinuation symptom in the first 2 weeks after stopping antidepressants, followed by nausea, vertigo, and nervousness.
[11]Gabriel M, Sharma V. Antidepressant discontinuation syndrome. Canadian Medical Association Journal 2017.doi:10.1503/cmaj.160991Clinical review of antidepressant discontinuation syndrome: onset within days of dose reduction, typical symptom course, and management.
[12]Papp A, Onton J. Brain Zaps: An Underappreciated Symptom of Antidepressant Discontinuation. The Primary Care Companion for CNS Disorders 2018.doi:10.4088/pcc.18m02311Characterises "brain zaps" — brief electric-shock sensations — as a common antidepressant discontinuation symptom.
[13]Wang J, Cosci F. Acute and persistent withdrawal syndromes following discontinuation of antidepressants in children and adolescents: a systematic review. Therapeutic Advances in Psychopharmacology 2025.doi:10.1177/20451253251404780Systematic review of acute and persistent antidepressant withdrawal syndromes; reinforces reducing only when stable and under supervision.
[14]Horowitz M, Taylor D. Distinguishing relapse from antidepressant withdrawal: clinical practice and antidepressant discontinuation studies. BJPsych Advances 2022.doi:10.1192/bja.2021.62Frames how clinicians can distinguish antidepressant withdrawal from relapse of the underlying condition.
[15]Sørensen A, Ruhé HG, Munkholm K. The relationship between dose and serotonin transporter occupancy of antidepressants — a systematic review. Molecular Psychiatry 2021.doi:10.1038/s41380-021-01285-wSystematic review of dose–SERT-occupancy relationships across antidepressants; confirms the hyperbolic curve underlying proportional tapering.
[16]Reeve R, Turner JR. Pharmacodynamic models: parameterizing the Hill equation, Michaelis-Menten, the logistic curve, and relationships among these models. Journal of Biopharmaceutical Statistics 2013.doi:10.1080/10543406.2012.756496Explains how the Hill equation, Michaelis-Menten, and logistic models relate — the mathematical basis for the occupancy curve used here.
[17]Preskorn SH. The use of biomarkers in psychiatric research: how serotonin transporter occupancy explains the dose-response curves of SSRIs. Journal of Psychiatric Practice 2012.LinkShows how SERT occupancy explains the non-linear dose–response curves of SSRIs.
[18]Cohrs D, Shapiro B. The relationship between SERT occupancy and extracellular serotonin concentration is hyperbolic, not linear: implications for safely tapering SRI antidepressants. SSRN (preprint) 2026.doi:10.2139/ssrn.6176553Argues the SERT-occupancy to serotonin relationship is itself hyperbolic, reinforcing proportional (hyperbolic) tapering.
[19]Moncrieff J et al. Evidence on antidepressant withdrawal: an appraisal and reanalysis of a recent systematic review. Psychological Medicine 2025.doi:10.1017/S0033291725100652Reappraisal of recent withdrawal-incidence evidence; relevant to how withdrawal rates are interpreted.
[20]Wilson E, Lader M. A review of the management of antidepressant discontinuation symptoms. Therapeutic Advances in Psychopharmacology 2015.doi:10.1177/2045125315612334Practical review of how to manage antidepressant discontinuation symptoms, including tapering and reinstatement.
[21]Groot PC, van Os J. Outcome of antidepressant drug discontinuation with tapering strips after 1–5 years. Therapeutic Advances in Psychopharmacology 2020.doi:10.1177/2045125320954609Long-term follow-up (1–5 years) of patients who discontinued antidepressants using hyperbolic taper strips.
[22]Gury C, Cousin F. Pharmacokinetics of SSRI antidepressants: half-life and clinical applicability. L'Encéphale 1999.LinkHalf-life data for SSRIs — explains why short-half-life drugs (paroxetine, venlafaxine) provoke faster withdrawal.
[23]Mayo Clinic. Antidepressant withdrawal: Is there such a thing?. Mayo Clinic — Expert Answers 2024.LinkPatient-facing explainer on antidepressant discontinuation symptoms and gradual tapering.
[24]NHS Scotland — Right Decision Service. Antidepressants — quality prescribing: difficulty withdrawing from an SSRI/SNRI. NHS Scotland 2024.LinkNHS Scotland guidance on recognising and managing difficulty withdrawing from SSRIs/SNRIs.
[25]The Carlat Psychiatry Report. Clinical pearls for hyperbolic tapering of psychiatric medications in older adults. The Carlat Report 2024.LinkPractical clinical pearls for applying hyperbolic tapering, including in older adults.
[26]Royal College of Psychiatrists. Stopping antidepressants — information for patients and carers. Royal College of Psychiatrists 2024.LinkRCPsych patient-facing guidance on coming off antidepressants safely.
[27]National Institute for Health and Care Excellence (NICE). Depression in adults: treatment and management. NICE guideline [NG222]. NICE 2022.LinkUK national guideline endorsing proportional (hyperbolic) tapering and the use of liquid formulations to enable small final doses.
[28]Royal College of Psychiatrists. Stopping antidepressants — position statement (CR225). Royal College of Psychiatrists 2020.LinkRCPsych acknowledges withdrawal can be severe and long-lasting; recommends slow, individualised tapers.
[29]NHG et al. Multidisciplinary document: Discontinuation of SSRIs and SNRIs (2018; revised 2023). Multidisciplinary Document (Netherlands) 2018.LinkFirst national guideline to explicitly endorse hyperbolic tapering and the use of taper strips (compounded by Regenboog Apotheek).
[30]Medicines and Healthcare products Regulatory Agency (MHRA). Summary of Product Characteristics — SSRI and SNRI products (UK). electronic Medicines Compendium (emc) 2023.LinkAuthoritative UK formulary data (tablet strengths, oral solutions) used to validate the UK region in the calculator.
[31]U.S. Food and Drug Administration. Prescribing information (Structured Product Labeling) for SSRI/SNRI products. FDA / DailyMed 2024.LinkAuthoritative US formulary data (tablet strengths, oral solutions/concentrates) used to validate the US region in the calculator.
[32]Health Canada. Health Canada — Drug Product Database. Health Canada 2024.LinkAuthoritative Canadian formulary data used to validate the Canada region in the calculator.
[33]Therapeutic Goods Administration (TGA). Therapeutic Goods Administration — Australian Register of Therapeutic Goods (ARTG). TGA / ARTG 2024.LinkAuthoritative Australian formulary data used to validate the Australia region in the calculator.
[34]College ter Beoordeling van Geneesmiddelen (CBG-MEB). CBG-MEB — Medicines Information Bank (Netherlands). CBG-MEB 2024.LinkAuthoritative Dutch formulary data; cross-checked with Regenboog Apotheek taper-strip availability.
[35]Regenboog Apotheek, Cinetto. Taperingstrip.com — Regenboog Apotheek. Patient resource (NL) 2024.LinkPioneer of standardised taper strips referenced in the Dutch national guideline.

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