Common Painkiller And Antidepressant Combo May Increase Higher Seizure Risk In Older Adults

When older adults surviving successful nursing homes are prescribed nan symptom medicine tramadol alongside definite antidepressants, their consequence of seizures whitethorn spell up, according to a study published October 8, 2025, successful Neurology®, nan aesculapian diary of nan American Academy of Neurology. While this study recovered a nexus betwixt utilizing nan medications together and an accrued consequence of seizures, it does not beryllium 1 causes nan other.

Tramadol is an opioid utilized to dainty mean to terrible symptom successful adults. Some antidepressants that inhibit nan CYP2D6 enzyme, called CYP2D6 inhibitors, tin interfere pinch really nan assemblage metabolizes tramadol. When nan CYP2D6 enzyme is blocked, tramadol is not metabolized decently and whitethorn build up successful nan body, perchance expanding nan consequence of broadside effects for illustration seizures. Common CYP2D6-inhibiting antidepressants see fluoxetine, paroxetine and bupropion.

"We recovered a humble but measurable summation successful nan consequence of seizures erstwhile tramadol was taken pinch antidepressants that inhibit nan CYP2D6 enzyme," said study writer Yu-Jung Jenny Wei, PhD, of The Ohio State University successful Columbus. "This consequence was accordant whether nan antidepressant aliases tramadol was started first."

Researchers analyzed 10 years of Medicare information to place 70,156 nursing location residents property 65 and older who had been prescribed some tramadol and an antidepressant.

They divided participants into 2 groups based connected which narcotics they took first. Of participants, 11,162 group took tramadol first and past an antidepressant pinch it, while 58,994 group took an antidepressant first and past added tramadol.

Seizure rates for group who took tramadol first were 16 seizures per 100 person-years, and for group who took antidepressants first, nan complaint was 20 seizures per 100 person-years. This intends for each 100 group who utilized some tramadol and an antidepressant followed for 1 year, astir 16 aliases 20 received a seizure diagnosis.

In some groups, researchers past compared seizure rates betwixt those who took tramadol pinch CYP2D6-inhibiting antidepressants and those who took tramadol pinch antidepressants that do not inhibit nan enzyme. In those who took tramadol first and added an antidepressant, nan complaint was 18 seizures per 100 person-years for those taking CYP2D6-inhibiting antidepressants compared to 16 seizures per 100 person-years successful group taking different antidepressants. In those who took antidepressants first and added tramadol, nan complaint was 22 seizures per 100 person-years for those taking CYP2D6-inhibiting antidepressants compared to 20 seizures per 100 person-years successful group taking different antidepressants.

To thief guarantee nan differences were not owed to different wellness issues, nan researchers adjusted for factors specified arsenic symptom levels, slump symptoms, beingness usability and cognitive ability.

After adjustments, for group who took tramadol first, seizure consequence was 9% higher erstwhile taking it pinch a CYP2D6-inhibiting antidepressant compared to pinch an antidepressant that did not inhibit this enzyme. For those who took an antidepressant first and added tramadol, nan consequence was astir 6% higher for group who took a CYP2D6-inhibiting antidepressant compared to group who took an antidepressant that did not inhibit nan enzyme.

To trial whether this relationship was circumstantial to tramadol, nan researchers repeated nan study utilizing hydrocodone, different opioid symptom reliever that is improbable to origin seizure consequence erstwhile utilized pinch antidepressants. No accrued seizure consequence was observed pinch hydrocodone and CYP2D6-inhibiting antidepressants.

"These findings underscore nan request for observant prescribing practices, particularly for older adults pinch analyzable wellness conditions," said Wei. "Doctors should beryllium alert of imaginable seizure risks erstwhile prescribing tramadol pinch antidepressants, peculiarly CYP2D6 inhibitors. Given really commonly some are prescribed to older adults, these interactions whitethorn beryllium much important than antecedently thought."

A limitation of nan study was that medicine information came from medicine records, which did not corroborate whether patients took nan narcotics arsenic directed.

This investigation was supported by nan National Institute connected Aging.