SSRI antidepressants and tramadol: serotonin and seizure risks

Selective serotonin reuptake inhibitors, or SSRIs, are the most widely used antidepressants, according to the NHS. Sertraline, citalopram, escitalopram, fluoxetine and paroxetine are examples. The NHS explains that sertraline is thought to work by increasing the level of serotonin, a chemical in the brain linked to mood.

Tramadol is a strong painkiller used for moderate to severe pain, as the NHS describes. The BNF notes that tramadol itself might cause serotonin toxicity, which is the reason it appears on the interaction lists of serotonergic antidepressants.

The BNF therefore flags the combinations. For each of sertraline, citalopram, escitalopram, fluvoxamine and venlafaxine, the entry says that both medicines can increase the risk of hyponatraemia and might increase the risk of serotonin toxicity.

Serotonin syndrome, also called serotonin toxicity, is described by the NHS sertraline page as a rare but serious condition that causes a fast heartbeat, sweating, shaking, twitching muscles and feeling confused or agitated. A clinical summary on Patient.info says there is a wide spectrum, from barely noticeable symptoms such as tremor through to life-threatening illness, and that symptoms usually occur within six hours of taking the provoking drug.

The same summary lists tremor, restlessness and diarrhoea as early features, with agitation, muscle stiffness and jerks, and high temperature in severe cases. It says mild cases usually resolve within 24 hours of stopping the offending drug, while severe cases need hospital care. Recognising it early is the point: continuing or increasing the offending medicine can cause progression.

Serotonin toxicity is not the only concern. The BNF flags low sodium (hyponatraemia) as a risk with both medicines, so it is worth mentioning any new confusion or unexplained unwellness to a clinician.

The NHS tramadol side-effects page lists seizure among its most serious effects, and its page on who can take tramadol asks people with a condition that causes seizures or fits to tell their doctor first. The NHS also notes that tramadol can make you sleepy, dizzy or confused, so combining it with other medicines that affect the brain deserves care.

There is also a reduced-effect problem: the BNF says fluoxetine and paroxetine are predicted to decrease the efficacy of tramadol, so pain may be less well controlled and someone may be tempted to increase the dose, which would add to the risk.

Call 999 or go to A&E for a seizure or fit, breathing difficulties or short, shallow breathing, as the NHS says for tramadol. The NHS tramadol page also says to call your doctor or 111 now if you feel dizzy or weak, have hallucinations, feel confused, feel very sleepy, or have trouble peeing.

For symptoms that fit serotonin toxicity, such as a combination of agitation, sweating, shaking, twitching muscles and a fast heartbeat, especially after starting or increasing either medicine, treat it as urgent and get same-day medical advice through 111 or an urgent care service. Say clearly which two medicines you take.

Some people do need both an antidepressant and a strong painkiller. The BNF entries are not prohibitions; they are alerts. A prescriber may choose the lowest effective dose, review it soon, pick a different painkiller, or look at whether the antidepressant is the best fit.

Pain relief alternatives are discussed in NHS guidance on painkillers. The NHS tramadol page says it is safe to take tramadol with paracetamol, ibuprofen or aspirin (aspirin only for those aged 16 and over), but not with medicines that contain codeine. Whether any of those suit you with your antidepressant is for the prescriber and pharmacist to confirm.

Do not stop an antidepressant suddenly because of this interaction. The NHS sertraline page says not to stop suddenly because it may cause withdrawal symptoms.

Keep an up-to-date list of medicines, including those bought over the counter and herbal products. The NHS sertraline page says not to use St John’s wort with sertraline, and the NHS tramadol page notes there is little information on herbal remedies and supplements with tramadol.

Say you take both when you see any new prescriber, dentist or pharmacist, and mention a change in how you feel in the first days after starting or changing a dose. Whether care is NHS or private, the same prescribing references apply.