SSRIs and MAOIs: why this antidepressant combination is dangerous

The NHS lists the main types of antidepressant as SSRIs, SNRIs, tricyclics and MAOIs, and says SSRIs are the most widely used. Examples of SSRIs include sertraline, citalopram, escitalopram, fluoxetine and paroxetine. MAOIs, which the NHS says are now rarely used to treat depression, include medicines such as phenelzine and moclobemide.

The NHS says SSRIs such as sertraline are thought to work by increasing the level of serotonin. Both classes act on serotonin, and the BNF warns that using them together might increase the risk of serotonin toxicity.

The reaction is called serotonin syndrome or serotonin toxicity. Because the two classes both act on serotonin, the combination is not used in the ordinary way, and a switch between them is something to plan with a prescriber.

The NHS page for sertraline lists MAOIs, such as moclobemide and selegiline, among the medicines it may not mix well with, and describes serotonin syndrome as a rare but serious condition that causes a fast heartbeat, sweating, shaking, twitching muscles and feeling confused or agitated.

The BNF entries for sertraline with phenelzine and with moclobemide say that both might increase the risk of serotonin toxicity, and direct prescribers to the sections on serotonin toxicity and monoamine-oxidase inhibitors for specific advice on avoiding MAOIs during and after serotonergic drugs. A clinical summary on Patient.info is blunter: it says the most common causative combinations include an MAOI, and that an SSRI should not be prescribed together with an MAOI.

The Patient.info summary says symptoms usually occur within six hours of taking the provoking drug and range from mild, such as tremor, to life-threatening. Early features it lists include tremor, restlessness and diarrhoea, with agitation, muscle jerks or rigidity and high temperature in more severe cases, and temperatures that may rise as high as 41°C in severe disease.

Because mild cases can be overlooked, and continuing the medicines can lead to progression, the practical rule is to treat any new combination of agitation, sweating, shaking and fast heartbeat after a medicine change as a possible emergency. In the NHS, that means calling 999 or going to A&E if the symptoms are severe, and calling NHS 111 for urgent advice if they are milder.

A person who needs to change from an SSRI to an MAOI, or the reverse, cannot simply swap tablets overnight. The BNF refers prescribers to specific guidance on the intervals needed during and after serotonergic drugs. For the MAOI itself, its entry states that tyramine-rich foods should be avoided with, or for 2 to 3 weeks after stopping, the MAOI.

This is a prescribing decision made by a psychiatrist or GP with access to those references. Anyone considering switching should not attempt it independently. The NHS says to talk to your doctor if you want to stop taking an antidepressant, and that stopping suddenly can cause withdrawal symptoms, so a plan is needed in both directions.

The category of MAOI is wider than antidepressants. The NHS tramadol page gives rasagiline and selegiline, used to treat Parkinson’s disease, as MAOIs, and it says not to take MAOIs with tramadol because the combination can cause serious side effects such as anxiety, confusion and hallucinations. Several other medicines also act on serotonin, including some painkillers and cough remedies.

The NHS depression guidance adds that St John’s wort, a herbal remedy, can cause problems with antidepressants, and the NHS sertraline page says not to use it with sertraline. Always mention supplements and over-the-counter products when you see a prescriber.

If you take an MAOI, carry information that says so, and tell any new prescriber, pharmacist or dentist before accepting a new medicine. Do not self-medicate for coughs, colds or pain without checking. The BNF dietary advice for phenelzine, which names foods and drinks such as mature cheese, salami, meat or yeast extracts and some beers, lagers or wines, is worth keeping on hand.

The NHS and private services use the same prescribing references, so there is no difference in what is advised. What differs is whether your records are visible, so bring a written list of what you take. If you are ever unsure whether two antidepressants were meant to be taken together, check with a pharmacist the same day.