OTHER MEDICATIONS

Valproic Acid

This medication is effective in humans with all types of seizures; however, it is metabolized very quickly in dogs and therefore its use is limited.  Valproic Acid is primarily used in combination with other drugs such as Phenobarbital.  Potential side effects include loss of hair and liver disease.

Written by Dr. William Thomas, DVM, MS on Valproic Acid:

Valproate (valproic acid, Depekene) is considered a second line drug for the treatment of epilepsy in dogs. The elimination half-life in dogs is fairly short (approximately 3 hours) compared to people (5 to 15 hours). Thus, unless very high doses are used, blood levels of valproate in dogs are less than concentrations known to be therapeutic in people. However, these blood levels may still be sufficient in dogs, since lower protein binding of valproate in dogs gives rise to higher brain concentrations,
compared to people.

In one short-term study, treatment with valproate alone was effective in reducing seizure frequency by 50% or more in 7 out of 16 dogs (44%) with idiopathic epilepsy. When used in conjunction with other anti-seizure drugs (mostly phenobarbital or primidone), valproate was successful in reducing seizure frequency by at least 50% in 21 of 41 dogs (51%).   Because of the lack of long term studies and concerns about the rapid metabolism in dogs, valproate is currently considered a second line drug for the treatment of canine epilepsy. It is used primarily in dogs whose seizures are not well controlled with phenobarbital or bromide.

Side effects:

Nausea and vomiting. These can usually be avoided by giving valproate with or soon after meals.

Drowsiness and sedation can occur, especially at higher doses or when valproate is combined with other antiseizure drugs.

Hair loss has been observed in dogs and people.

Liver disease has been reported in about 1 in 3700 people (1 in 500 young children) treated with valproate. Although valproate-induced liver disease has not been documented in dogs, there are no large, long-term studies of this drug in dogs with epilepsy.


Loscher W. Plasma levels of valproic acid and its metabolites during
continued treatment in dogs. Journal of Veterinary Pharmacology and
Therapeutics 4:111-119,1981.

Nafe LA. Sodium valproate: A preliminary clinical trial in epileptic dogs
Journal of the American Animal Hospital Association17:131-133,1981.

WB Thomas DVM,MS
Dipl.ACVIM(Neurology)
University of Tennessee

Diazepam (Valium), Clonazepan, Lorazepam and Clorazepate

These medications are all part of the benzodiazepines and are potent anti-seizure drugs, but they all have characteristics that limit their use for maintenance of seizures in dogs.  First, they are only effective for a short time requiring frequent administration to maintain adequate serum levels.  Second, long term use of this category of drug reduces its effectiveness in controlling seizures.  Long term use of any benzodiazepine may prevent effective use of diazepam to treat emergency seizures.   These drugs are effective for the emergency treatment of status epilepticus or cluster seizures.  They can also be useful as temporary therapy when seizures can be predicted, such as seizures precipitated by stress or sleep deprivation.

Clorazepate (Tranxene)
Written by Dr. William Thomas, DVM, MS

Clorazepate (Tranxene) was introduced in the United States in 1981. It is used mostly as add-on therapy in people. It is sometimes used as add-on therapy in dogs unresponsive to first line drugs.

After oral administration, clorazepate is converted to nordiazepam (also called N-desmethyldiazepam), in the stomach. Nordiazepam provides all of the antiseizure effect. The elimination half-life is 2 to 5 hours, tending to be slightly longer with long term administration. A dose of 2 mg/kg every 8 or 12 hours has been suggested.

Sustained release tablets (Tranxene SD) offer no pharmacokinetic advantages over regular-release tablets in dogs. Coadministration of phenobarbital with clorazepate results in lowered blood levels of clorazepate. Tolerance (reduction in anti-seizure effects with long-term use) can occur with clorazepate, as with most other benzodiazepines.

Forrester SD, et al. Disposition of clorazepate in dogs after single- and
multiple-dose oral administration. American Journal of Veterinary Research
51:2001-2005,1990.

Brown SA, Forrester SD. Serum disposition of oral clorazepate from
regular-release and sustained-delivery tablets in dogs. Journal of
Veterinary Pharmacology and Therapeutics. 14:426-429,1991.

Forrester SD, et al. Effects of a 44-day administration of phenobarbital on
disposition of clorazepate in dogs. American Journal of Veterinary Research
54:1136-1138,1993.

Scherkl R, et al. Clorazepate in dogs: tolerance to the anticonvulsant
effect and signs of physical dependence. Epilepsy Research 3:144-150,1989.

Dilantin (Phenytoin)

Although Dilantin is extremely effective in treating human epilepsy, dogs metabolize this drug too quickly to maintain adequate blood levels.  In one clinical study only 1 in 77 epileptic dogs could be controlled with this drug.

Vigabatrin
Written by Dr. William Thomas, DVM, MS

Vigabatrin has been evaluated in a small number of dogs with idiopathic epilepsy. Results were not very encouraging and several dogs developed hemolytic anemia that required stopping the drug.

Speciale-J, et al. Clinical evaluation of gamma-vinyl-gamma-aminobutyric
acid for control of epilepsy in dogs.J.Amer.Vet.Mec.Assoc.1991, 198:
995-1000.

Excerpt from abstract:
The drug was administered to 14 dogs in conjunction with other anticonvulsants, in an attempt to control refractory epilepsy. Four of these dogs had clinically relevant evidence of decreased seizure frequency. In 4 dogs, response to the drug was no better than response to phenobarbital alone. In 2
dogs, seizure control improved, but gamma-vinyl-gamma-aminobutyric acid was withdrawn because of development of haemolytic anemia. For various reasons, the therapeutic effect in the remaining 4 dogs could not be evaluated.

WB Thomas DVM, MS
Dipl.ACVIM(Neurology)
University of Tennessee
Knoxville, TN

Trileptal (Oxcarbarepine)

Question for Dr. William Thomas:
I am interested in the new drug Trileptal. It says monitoring of hepatic enzymes or hematologic tests is not required. It doesn't effect the kidneys or the liver. Sounds like the perfect drug to me for HUMANS. Has it been used on K-9's yet?  It is made by Novartis.

Dr. Thomas' Answer:
I'm not aware of any studies using this drug in dogs with epilepsy. However, it has been studied in normal laboratory dogs. The elimination half-life is approximately 4 hours.   During continued treatment for 8 days, plasma concentrations showed a pronounced decline from day 3, and the half-life decreased to 1 hour. This is considered to be the result of oxcarbazepine inducing its  own metabolism. The very short half-life suggests oxcarbazepine is probably unsuitable as antiseizure medication in dogs.

Pharmacokinetics of oxcarbazepine in the dog.
Schicht-S; Wigger-D; Frey-HH
J-Vet-Pharmacol-Ther. 1996 Feb; 19(1): 27-31.

WB Thomas DVM, MS
Dipl.ACVIM(Neurology)
University of Tennessee
Knoxville, TN

Tegretol (Carbamazepine)
Written by Dr. William Thomas, DVM, MS

Carbamazepine (trade name; Tegretol) is one of the most widely used antiseizure drugs in people. Unfortunately, this drug is eliminated very quickly in dogs, with a half-life of only 1-2 hours (compared to 5-25 hours in people). With long term use, the half-life becomes even shorter because of increased liver metabolism.

I'm not aware of any clinical trials of carbamazepine in dogs, although there is a single case report of successful use in a dog with psychomotor seizures (a form of focal seizures). Clinical experience suggests it is not very effective in dogs, probably because of the difficulty in maintaining adequate blood levels.

Frey HH; Loscher W. Pharmacokinetics of carbamazepine in the dog.
Arch-Int-Pharmacodyn-Ther. 1980 ; 243(2): 180-91

Holland CT. Successful long term treatment of a dog with psychomotor
seizures using carbamazepine. Aust-Vet-J. 1988 Dec; 65(12): 389-92.


WB Thomas DVM, MS
Dipl.ACVIM(Neurology)
University of Tennessee
Knoxville, TN

Keppra (Levetiracetam)
Written by Dr. William Thomas, DVM, MS

Keppra (levetiracetam) is approved in the US for people with focal seizures refractory to other anti-seizure drugs. I'm not aware of any clinical or long-term safety studies in dogs. The elimination half-life in dogs is about 3.6 hours. This compares to 7-10 hours in people.

I have used it in a few dogs with epilepsy refractory to other medication, but experience is still too limited to tell if this will prove to be a useful drug for dogs.

WB Thomas DVM,MS
Dipl.ACVIM(Neurology)
University of Tennessee

Zonisamide (Zonegran)
Written by Dr. William Thomas, DVM, MS Dipl. ACVIM (Neurology)
University of Tennessee

From the annual ACVIM forum in Charlotte, NC:

Curtis Dewey presented an abstract on using zonisamide (Zonegran) in 12 dogs with epilepsy refractory to other drugs (mostly phenobarbital and bromide). Seven dogs (58%) had a decrease in the number of seizures after starting zonisamide, with a mean decrease in seizure frequency of 81%. In 8 of these dogs, it was possible with decrease the dose or withdraw concurrent anti-seizure drugs. Side effects were very mild.

Question on Zonegran for Dr. Thomas:

Zonegran caught my attention and I wondered how this AED is metabolized?

Dr. Thomas answer:

In the dog, zonisamide (Zonegran) we use 10 mg/kg every 12 hours and is metabolized by the liver, with an elimination half-life of 15 hours.

Zonisamide seems to be an effective "second-line" drug in dogs, based on limited clinical experience. It's elimination half-life is 15-20 hours in dogs, so it is usually given twice daily. It's expensive. So far, side effects in dogs seem rare.