Trazodone and MAOIs: understanding the serotonin toxicity warning

The NHS describes trazodone as an antidepressant medicine used to treat depression and anxiety. The NHS trazodone page describes side effects that include feeling sleepy, dizzy or tired, headaches, feeling sick, constipation, muscle pain and a dry mouth, and advises not to drive or use machinery until sleepiness has passed.

The NHS says trazodone can be taken at bedtime if you are having trouble sleeping, because it can make you feel sleepy. Antidepressants are sometimes changed over time, so the order and timing of any switch involving an MAOI is the practical reason this interaction is worth understanding.

The BNF interaction entry for trazodone states that both trazodone and isocarboxazid might increase the risk of serotonin toxicity, and gives the same wording for phenelzine. Each entry refers readers to the BNF sections on serotonin toxicity and on monoamine-oxidase inhibitors for more information and for advice on avoiding MAOIs during and after other serotonergic drugs.

The NHS trazodone page uses everyday language. It says there are medicines, remedies and supplements that may not mix well with trazodone, including other antidepressants such as amitriptyline, fluoxetine or moclobemide, as well as antifungals such as itraconazole, epilepsy medicines such as carbamazepine or phenytoin, sleeping pills and other sedatives, erythromycin, levodopa and warfarin.

The NHS therefore treats MAOIs as one example within a longer list. The BNF is the more direct statement about the specific trazodone and MAOI pair.

Serotonin is a chemical messenger involved in mood, sleep and many body functions. Medicines that raise its activity can, in combination, push it too far. The NHS describes serotonin syndrome, in its pages on other antidepressants, as a condition that causes a fast heartbeat, sweating, shaking, twitching muscles and feeling confused or agitated.

Because trazodone is often taken in the evening, early symptoms can be mistaken for a restless night or an unusual reaction to a sleeping tablet. If you notice any of the features above after starting or adding a medicine, tell a clinician promptly.

A switch involving an MAOI is a specialist-guided process. The BNF directs prescribers to specific advice on avoiding MAOIs during and after other serotonergic drugs. The BNF text read for this guide does not list a number of days, so none is given here; the length of the gap depends on the medicines and is set by the prescriber.

Never restart trazodone left over from a previous course while taking, or just after stopping, an MAOI. Equally, do not stop either medicine abruptly without advice. The NHS says not to suddenly stop taking trazodone because it may cause withdrawal symptoms, and that the dose is usually reduced gradually over several weeks or months.

If you have taken trazodone and an MAOI together and feel unwell, call NHS 111 or your prescriber for advice the same day. If you have a very fast heartbeat, heavy sweating, shaking, muscle twitching or confusion, or you have collapsed, call 999 or go to A&E and take your medicines with you.

In the NHS the GP, specialist mental health team and community pharmacist can all review a medicine list. Private clinicians use the same BNF, so the same list of medicines should be shared with them.