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Question Posted January 23, 2007
I have a question about using tramadol in patients with a history of seizures or taking medications which lower the seizure threshold.
There are numerous reports in the human literature about tramadol and seizures, including de novo incidents for people taking the recommended dose in addition to those described above.
Is this a concern for our veterinary patients?
Melissa M Hayes
Response 1
I don't have any hard documentation, but the lecturer I have heard that addressed this said that it has not been documented in vet med. I use enough of it to see other side effects, but never seizures. I am cautious, in fact deferred use today in a dog that has had seizures potentiated by other meds (several herbals from alternative vet elsewhere), but have used in other seizure dogs after cautioning the owners.
Bianca Shaw
Response 2
Great question. Brings up a question of my own (see end). In the middle is just some anecdotal info from my experiences with Tramadol.
We do use caution prescribing Tramadol to seizure patients, although we have used it in multiple seizure patients without problems (so far) as part of a multimodal approach to pain (usually along with gabapentin for its pain and anticonvulsant properties). These are patients whose seizures are well-controlled and do not have a hx of status epilepticus or clusters, etc. We do explore drug combinations without Tramadol first.
I do warn the owners of tramadol's potential for lowering the seizure threshold, and describe what to watch for. In general, that means dealing with break through seizures, whereby they are instructed to follow the typical protocol (an extra dose of anticonvulsant), stop the Tramadol, and call in the morning as long as control is achieved. They are instructed to go to the E-clinic if the seizure(s) don't respond. Again, so far, this has not happened in the seizure patients I've put on Tramadol.
In addition, if it has been awhile since their last phenobarbitol (or KBr, etc) level, I recommend the appropriate test prior to starting Tramadol.
I remind the owners that it is all about weighing the pros and cons of each option. We are obviously exploring the option of Tramadol due to inadequate pain control, which is very debilitating. The opposite side of the coin is potentially much better pain control, but possibly increased seizure frequency and/or severity. Which is more debilitating? Depends on the case. And, why not try the Tramadol and see if it actually causes reduced seizure control? You can always discontinue the medication.
Maybe someone on this list can also provide some insight on another facet of Melissa's question. What about pain itself contributing to a lower seizure threshold? Has any research been performed on that question? I just think of my own childhood dog who would reliably seize on the vet's stoop due to anxiety/stimulation. We assume pain contributes to anxiety (possibly panic?) in animals. Could that lead to a reduced seizure threshold?
Just food for thought. Any knowledge on the subject would be appreciated.
Amy Leach
Response 3
Could you please tell me what is the tramadol dose that you suggest for regular patients and what for patients with seizures?
Eduardo Gutierrez-Blanco
Response 4
Can someone give the reference for the lowering of the seizure threshold for tramadol?
Lisa Parshley
Response 5
Here is some info on tramadol and seizures from Medline:
1: Clin Toxicol (Phila). 2006;44(2):143-6. Links Seizures associated with intoxication and abuse of tramadol.
a.. Jovanovic-Cupic V,
b.. Martinovic Z,
c.. Nesic N.
Institute on Addictions, Belgrade , Serbia and Montenegro .
PURPOSE: To assess the frequency of seizures and patient characteristics associated with tramadol intoxication and abuse in young addicts.
METHODS:Patients with history of tramadol abuse and intoxication were prospectively studied during a 3-year period. The characterstics of patients with seizures and those without seizures were compared. RESULTS: Fifty-seven patients (mean age 22.3 years [range 16-43 years], 47 males) were included.
Tonic/clonic seizures occurred in 31 (54.4%) patients, (26 males and 5 females): single in 14 (45%), multiple in 17 (55%) patients after a tramadol dose ranging from 250-2500 mg. Seizures occurred within 24 h after tramadol intoxication in 26 (84%) patients, and later in 5 (16%) patients. Compared to addicts without seizures, the abusers with seizures were younger (p < 0.05). Both epileptiform and nonepileptiform electroencephalographic patterns were more common in patients with seizures than in patients without seizures, but the differences did not reach statistical significance.
CONCLUSION: The neurotoxicity of tramadol commonly manifests as generalized tonic-clonic seizures occurring most frequently within 24 h after tramadol intake. Seizures were more common in younger abusers with a longer duration of exposure to tramadol and with the combined use of tramadol with alcohol.
PMID: 16615669 [PubMed - indexed for MEDLINE]
And another:
1: Pharmacotherapy. 2000 Dec;20(12):1423-31. Links Tramadol and seizures: a surveillance study in a managed care population.
a.. Gardner JS,
b.. Blough D,
c.. Drinkard CR,
d.. Shatin D,
e.. Anderson G,
f.. Graham D,
g.. Alderfer R.
Department of Pharmacy, University of Washington , Seattle 98195 , USA .
STUDY OBJECTIVE: To investigate the occurrence of tramadol-associated seizures. DESIGN: Retrospective cohort and case-control studies.
SETTING: UnitedHealth Group-affiliated independent practice model health plans, from different regions of the United States , contracting with large networks of physicians. INTERVENTION: Analysis of administrative data from a large U.S. managed care population. PATIENTS: A cohort of 9218 adult tramadol users and 37,232 concurrent nonusers. MEASUREMENTS AND MAIN RESULTS: Fewer than 1% of users (80) had a presumed incident seizure claim after the first tramadol prescription. Risk of seizure claim was increased 2- to 6-fold among users adjusted for selected comorbidities and concomitant drugs. Risk was highest among those aged 25-54 years, those with more than four tramadol prescriptions, and those with history of alcohol abuse, stroke, or head injury. A case-control study among users was conducted to validate incident seizure outcomes from medical records. Only eight cases were confirmed, and all had cofactors associated with increased seizure risk. CONCLUSION: In a general population, risk of seizure may be associated with long-term therapy with tramadol or the presence of cofactors, or confined to a small sensitive population subset.
PMID: 11130214 [PubMed - indexed for MEDLINE]
FWIW, there are also some reports of tramadol having some anticonvulsant activity (studied in mice thus far) as well.
Russ Star
Response 6
As I read this abstract I was impressed by the fact that these seizures were the result of long term use (or rather abuse) of tramadol. Was the lowering of the seizure threshold a factor of the long term use and abusive use as opposed to one time use lowering seizure threshold?
We in veterinary medicine generally use tramadol for short duration (week maybe two weeks) and at doses of 1-2mg/kg PO BID to TID (rarely above 100mg per dose). Can we compare the abstract presented with our uses?
From the abstract:
"Seizures were more common in younger abusers with a longer duration of exposure to tramadol and with the combined use of tramadol with alcohol"
Lisa Parshley