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Antidepressant interactions

SNRIs and MAOIs: a serotonin toxicity interaction that needs specialist advice

SNRI antidepressants such as venlafaxine and duloxetine and MAOI antidepressants such as phenelzine, isocarboxazid, tranylcypromine and moclobemide should not be combined casually. The BNF warns that the pairs might increase the risk of serotonin toxicity. This guide explains what that means and what to do when switching.

Last checked: 2026-10-10

Key facts

At a glance.

  • BNF wording

    For venlafaxine and duloxetine with isocarboxazid, phenelzine, tranylcypromine and moclobemide, the BNF says both medicines might increase the risk of serotonin toxicity.

  • Specific advice

    The BNF points readers to its Serotonin Toxicity and Monoamine-Oxidase Inhibitors sections for advice on avoiding MAOIs during and after other serotonergic drugs.

  • NHS lists it too

    The NHS venlafaxine and duloxetine pages name MAOIs, such as moclobemide and selegiline, among medicines that may not mix well with them.

  • MAOIs are rare now

    The NHS says MAOIs are now rarely used to treat depression, which makes accidental overlap with an SNRI uncommon but important.

  • Serotonin syndrome signs

    The NHS describes serotonin syndrome as a condition causing a fast heartbeat, sweating, shaking, twitching muscles and feeling confused or agitated.

The two groups of antidepressant

Serotonin and noradrenaline reuptake inhibitors, usually called SNRIs, include venlafaxine and duloxetine. The NHS pages for both medicines place them among antidepressants, and duloxetine is also used for some types of nerve pain and anxiety. They work on chemical messengers in the brain.

Monoamine-oxidase inhibitors, or MAOIs, are an older type of antidepressant. The NHS overview of antidepressants lists MAOIs as one of the main types and says they are now rarely used to treat depression. They remain in use for some people for whom other treatments have not worked, usually under specialist care.

Because both groups increase the activity of serotonin by different routes, their combined effect is the concern. This is why the interaction is described in terms of serotonin toxicity rather than just general side effects.

What the BNF and NHS say

In the BNF interaction entries read for this guide, the statement for each pair is the same: both medicines might increase the risk of serotonin toxicity. The pairs listed include venlafaxine with isocarboxazid, tranylcypromine, phenelzine and moclobemide, and duloxetine with the same group. The entries refer readers to the BNF sections on serotonin toxicity and on MAOIs for more information and for specific advice on avoiding MAOIs during and after administration of other serotonergic drugs.

The NHS venlafaxine and duloxetine pages each include MAOIs such as moclobemide and selegiline in their lists of medicines that may not mix well. The NHS citalopram, sertraline and fluoxetine pages say the same for SSRIs, so the caution is shared across antidepressant groups.

What serotonin toxicity looks like

The NHS lists serotonin syndrome among the possible serious side effects of venlafaxine, duloxetine, citalopram, sertraline and fluoxetine. It describes it as a condition that causes a fast heartbeat, sweating, shaking, twitching muscles and feeling confused or agitated.

Symptoms appearing soon after a new medicine is added, or after a dose increase, are the pattern to watch for. Mild symptoms can look like a bad reaction to a new tablet, so it is worth asking early rather than waiting. This site has a separate overview of serotonin syndrome for readers who want the condition in more depth.

  • Fast heartbeat, sweating or shaking.

  • Twitching muscles.

  • Feeling confused or agitated.

  • Symptoms that start soon after a new medicine or a higher dose.

Switching between the groups safely

Moving from an SNRI to an MAOI, or the reverse, is a planned process. The BNF entries point to specific advice on avoiding MAOIs during and after other serotonergic drugs, which signals that there is a gap to be left between stopping one and starting the other. The BNF text read for this guide does not give a number of days, so this page does not either; the length of the gap depends on the medicines involved and is set by the prescriber and the product information.

Do not start any antidepressant that you have left over from before, or one prescribed for another person, while taking or recently stopping an MAOI. If you have been told to carry an MAOI alert card, show it to every prescriber and pharmacist.

Other things to mention

The NHS pages for these antidepressants advise not to use the herbal supplement St John's wort with venlafaxine, duloxetine and several other antidepressants. Over-the-counter cough and cold products and some painkillers are also worth checking with a pharmacist when you take any antidepressant.

A related guide on this site covers MAOIs, food and medicine interactions, because MAOIs have dietary considerations in addition to medicine interactions.

When to get help

If you have taken both types of medicine and feel unwell, with a racing heart, heavy sweating, shaking or confusion, treat it as urgent. Call NHS 111 for advice, and call 999 or go to A&E if you are very unwell, confused or have collapsed. Take the medicine packets with you.

For planning, speak to the prescriber or a pharmacist before any change. In the NHS this is usually the GP or the specialist mental health team, and a community pharmacist can check combinations when a prescription is handed over.

Frequently asked

Questions people ask.

Quick, plain-English answers to the questions we hear most.

  • Can I take venlafaxine and an MAOI together?

    The BNF says both medicines might increase the risk of serotonin toxicity, and directs prescribers to specific advice on avoiding MAOIs. Never combine them on your own initiative.

  • Does the same warning apply to duloxetine?

    Yes. The BNF uses the same wording for duloxetine with isocarboxazid, phenelzine, tranylcypromine and moclobemide, and the NHS duloxetine page lists MAOIs among medicines that may not mix well.

  • How long is the gap between stopping one and starting the other?

    The sources read for this guide do not state a number, and the gap depends on the specific medicines. Your prescriber will give you instructions based on the product information and the BNF advice.

  • What are the signs of serotonin syndrome?

    The NHS describes a fast heartbeat, sweating, shaking, twitching muscles and feeling confused or agitated. Seek urgent help if these appear after starting or changing medicines.

  • Are MAOIs commonly prescribed in the UK?

    The NHS says MAOIs are now rarely used to treat depression. They are generally reserved for people who have not responded to other treatments and are managed by specialists.

  • Is St John's wort a problem with these medicines?

    The NHS pages for venlafaxine and duloxetine advise not to use St John's wort with them. Always ask a pharmacist before adding a herbal product.

  • Do I need to tell my dentist or hospital team?

    Yes. Any prescriber, including dentists, hospital doctors and out-of-hours services, should know which antidepressant you take, especially before pain relief or antibiotics are prescribed.

  • Can a pharmacist check this for me?

    Yes. A community pharmacist can check your medicine list against the BNF and the product information when you collect a prescription or buy a medicine.

Where this comes from

Sources and checking.

This guide is for information, not medical advice.

Your GP or consultant knows your history and can tell you which parts apply to you. If your symptoms are severe, rapidly worsening, or come with red-flag features, seek urgent medical care. Figures and availability change, so treat them as a guide and confirm with the provider.

Published 2026-10-10, next review 2027-10-10.

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