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Reading: Mixing antidepressants with painkiller prescribed to millions could raise risk of disturbing seizures, research sugests
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INFORMATION HUB > Blog > HEALTH > Mixing antidepressants with painkiller prescribed to millions could raise risk of disturbing seizures, research sugests
HEALTH

Mixing antidepressants with painkiller prescribed to millions could raise risk of disturbing seizures, research sugests

Dailymail
Last updated: October 9, 2025 6:08 am
Dailymail
16 hours ago
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Mixing antidepressants with painkiller prescribed to millions could raise risk of disturbing seizures, research sugests
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Doctors were today warned about dishing out two common drugs given to millions at the same time, over fears the combination could raise the risk of seizures. 

It followed research that found the medications could increase by the risk by almost 10 per cent. 

Opioid drug tramadol, widely prescribed for moderate to severe pain to provide short-term relief, was one of the medications scientists raised the alarm over. 

The other, antidepressants that inhibit the liver enzyme CYP2D6, include fluoxetine, paroxetine, bupropion, sertraline, and fluvoxamine. 

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US scientists, who analysed the health records of more than 70,100 nursing home residents, found a ‘modest but measurable increase in the risk of seizures’ when tramadol was taken with such antidepressants. 

And the risk was consistent regardless of which medication was taken first. 

Dr Yu-Jung Jenny Wei, an expert in geriatric pharmacoepidemiology at Ohio State University and study co-author said: ‘Our findings underscore the need for careful prescribing practices, especially for older adults with complex health conditions. 

‘Doctors should be aware of potential seizure risks when prescribing tramadol with antidepressants, particularly CYP26 inhibitors.’

Doctors were today warned about dishing out two common drugs given to millions at the same time, over fears the combination could raise the risk of seizures

Doctors were today warned about dishing out two common drugs given to millions at the same time, over fears the combination could raise the risk of seizures 

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He added: ‘Given how commonly both are prescribed to older adults, these interactions may be more important than previously thought.’

In the study, researchers analyzed 10 years of health record data to identify 70,156 nursing home residents age 65 and older who had been prescribed both tramadol and an antidepressant.

They divided participants into two groups based on which drugs they took first. 

Of participants, 11,162 people took tramadol first and then an antidepressant with it, while 58,994 people took an antidepressant first and then added tramadol.

They found that for every 100 people who took tramadol before the antidepressant, 16 suffered seizures. 

For every 100 people that took the antidepressant first, seizure risk rose to 20. 

After accounting for factors that could skew the results, the researchers calculated that for people who took tramadol first, seizure risk was 9 per cent higher when taking it with a CYP2D6-inhibiting antidepressant compared to with an antidepressant that did not inhibit this enzyme. 

For those who took an antidepressant first and added tramadol, the risk was about 6 per cent higher for people who took a CYP2D6-inhibiting antidepressant compared to people who took an antidepressant that did not inhibit the enzyme. 

Opioids like tramadol, can provide highly effective pain relief when used in the short-term. But doctors have previously warned that patients waiting months for NHS operations are taking the painkillers for dangerously long periods

Opioids like tramadol, can provide highly effective pain relief when used in the short-term. But doctors have previously warned that patients waiting months for NHS operations are taking the painkillers for dangerously long periods 

Your browser does not support iframes.

Writing in the journal Neurology, the scientists cautioned that their findings do not prove the combination of drugs causes seizures and further research would be necessary.

However, they suggested that the risk of seizures may have increased because CYP2D6 inhibitors, can interfere with how the body metabolizes tramadol. 

When the CYP2D6 enzyme is blocked, tramadol may not be metabolized properly and may build up in the body, raising the risk of side effects like seizures. 

It comes as concerning research this week also suggested that tramadol is ‘not that effective’ at treating chronic pain. 

Danish scientists who analysed the health records of over 6,500 patients found the drug increased the risk of serious side effects, including heart disease. 

Publishing their findings in BMJ Evidence Based Medicine, the team from Rigshospitalet in Copenhagen said tramadol’s potential harms ‘likely outweigh’ its modest benefits. 

Tramadol is one of the most commonly prescribed opioid painkillers in the UK, with hundreds of thousands of NHS prescriptions issued every month. 

In the US, it’s the 36th most prescribed drug, with more than 16 million prescriptions issued a year. 

But doctors have long warned that patients waiting months for NHS operations are often left on tramadol and other opioids for dangerously long periods, putting them at risk of addiction.  



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