Bupropion and SSRIs: serotonin toxicity and raised antidepressant levels

The BNF interaction list for bupropion has 76 entries. For the SSRIs it says that bupropion might enhance the risk of serotonin toxicity when given with citalopram, fluoxetine, fluvoxamine, paroxetine or sertraline, and in each case that the MHRA advises monitor. The severity label is severe and the evidence type anecdotal.

Two points are worth reading carefully. The word might shows that this is a possibility documented mainly in case reports, not a certainty. And MHRA advises monitor is a different instruction from avoid. It means the combination can be used where there is a reason, with someone watching for effects, and the prescriber decides on that basis.

The SSRI lists in the BNF show the other half of the entry. The citalopram and sertraline interaction lists each contain a bupropion entry with the same wording, so the warning appears whichever medicine the prescriber or pharmacist looks up.

A second type of entry concerns exposure. The BNF says bupropion is predicted to increase the exposure to amitriptyline, nortriptyline, imipramine, clomipramine and trimipramine, with the manufacturer advising monitor for toxicity and adjust the dose. These are tricyclic antidepressants, so a person who takes one of them with bupropion could have higher levels than expected from the dose alone.

The SSRI entries are framed as a serotonin toxicity risk rather than a change in exposure, but the pattern is consistent. Bupropion is a medicine whose use alongside other antidepressants needs thought, which is why the references steer toward monitoring.

The NHS pages for citalopram, sertraline, fluoxetine, venlafaxine and duloxetine list serotonin syndrome among the possible serious side effects. The NHS citalopram and sertraline pages describe it as a rare but serious condition that causes a fast heartbeat, sweating, shaking, twitching muscles and feeling confused or agitated.

Symptoms that come on soon after a new medicine is added or a dose is raised are the pattern to take seriously. If you notice them, tell a clinician the same day. For severe symptoms, or if you feel very unwell or confused, call 999 or go to A&E. This site has a separate overview of serotonin syndrome.

• Fast heartbeat or sweating.

• Shaking or twitching muscles.

• Feeling confused or agitated.

• Symptoms starting soon after a new medicine or a higher dose.

The NHS stop-smoking treatments page read for this guide describes nicotine replacement, varenicline and cytisine and does not mention bupropion, so the BNF is the main source for this page. The BNF entries do not describe why a particular person was prescribed bupropion, so the reason for treatment is something to ask the prescriber or find in the leaflet.

The NHS pages for several SSRIs also advise not to use St John's wort, and the BNF lists St John's wort in the same bupropion serotonin toxicity group, so herbal products belong on the medicine list you share.

Keep an up-to-date list of every medicine and supplement and show it whenever an antidepressant, a painkiller such as tramadol, or any new medicine is prescribed. The BNF also lists tramadol with bupropion in the same serotonin toxicity group, so pain relief is a place where a second serotonergic medicine can be added without much thought.

Do not stop either medicine suddenly. The NHS pages for the SSRIs say not to suddenly stop taking them because it may cause withdrawal symptoms and that the dose is usually reduced gradually over weeks. If you have concerns, ask your GP, pharmacist or the specialist who prescribed the bupropion.