Thankfully, neonatal seizures are not something that we identify frequently in veterinary medicine. Unfortunately, neonatal seizures are one of the most common reasons for presentation to the ER in human medicine. Among full term infants, seizures account for 1-3.5% of the cases for infant presentation to ER. To date, phenobarbital (PB) has been the anti-epileptic drug (AED) of choice, however levetiracetam (LEV) was evaluated in a meta-analysis in 202. (REF) The findings are interesting…read on to learn more!
Seizures, Quality of Life and Side Effects, oh my!
A study published in JAVMA (Gristina BR et al. JAVMA 2023) just recently caught my eye and I thought, perhaps it might interest you as well. The study evaluated 100 dogs with , with Tier I or Tier II level confidence of idiopathic epilepsy and assessed owner satisfaction, seizure control and adverse effects (the fancy name for side effects) of various drugs.
*Tier I = normal CBC, serum biochemistry, neurologic examination and bile acid test
* Tier II = all of tier I plus normal brain MRI and CSF analysis
How was the Seizure Control?
Improvement in seizure control was reported in 86% of dogs with phenobarbital, 76% in the levetiracetam and 65% in the zonisamide group. Treatment failure, due to inadequate seizure control, was 48% for phenobarbital, 32% for levetiracetam and 35% for zonisamide. Importantly, they didn't corelate seizure control with serum drug concentrations because we don't have target serum concentrations for levetiracetam and zonisamide. HTerefore, some dogs could have been under medicated, and thus poorly controlled. Interestingly, 88% of dogs were still on their original antiepileptic drug (AED) at the time this study was performed. Mean daily doses for phenobarbital, levetiracetam and zonisamide were 4.9 mg/kg, 53.8 mg/kg and 12.4 mg/kg, respectively.
What side effects made a splash?
Phenobarbital had the highest reported adverse effects at 77%, followed by levetiracetam at 59% and zonisamide at 39% of dogs. The most common adverse effects are listed below for each drug:
Phenobarbital: polyphagia, polydipsia, ataxia, sedation and polyuria
Zonisamide: sedation, ataxia, hyporexia
Levetiracetam: Sedation, ataxia, hyporexia, diarrhea, behavioral changes.
What was the perceived Quality if Life?
Owners perceived a significant improvement in quality of life, regardless of the anticonvulsant used, between pre and post treatment assessment. This is important for us to realize: clients can tolerate adverse effects if they perceive improved seizure control and quality of life! Although this retrospective, owner-perception study has limitations (all studies do), I felt it was worth repeating a bit of the information for you to add to your knowledge when addressing seizure management with your clients.
Have a wonderful week! Remember, early bird registration ends May 31st for the July CE event so register soon if you are planning to do so! Details are available on my website.
Reference: doi.org/10.2460/javma.22.10.0469
What do CBD and Phenobarbital Have in Common?
Phenobarbital and CBD are known to both use the Cytochrome P450 system for hepatic metabolism therefore it stands to reason that co-administration could result in altered metabolism of one or both of these drugs.
In a recent study by Doran et al (https://doi.org/10.2460/ajvr.21.08.0120), changes in CBD pharmacokinetics (PK) were discussed, in reference to phenobarbital. Interestingly, no apparent changes in PK of phenobarbital or CBD were noted when each drug was given ONCE (not chronic dosing).
Significant changes in serum ALP were noted during chronic (3 week) CBD dosing at 10 and 20 mg/kg/d. More dogs had a chance in serum ALP concentration at the higher dose, but the sample sizes were very small so it is difficult to extract too much information from that finding.
Also interesting, the maximal concentration of CBD was higher in fed animals, than in those fasted at the time of CBD administration. Food for thought...
What is the take away?
1. CBD alone can cause elevated ALP in dogs. Significance? Not addressed in this study.
2. We don't know how phenobarbital serum concentrations are affected by chronic or single dose exposure to CBD, because this wasn't studied as a separate question.
3. This study didn't tell us anything about dose escalations so if you are using CBD oil in your practice, please look elsewhere for dosing recommendations for efficacy!
**Disclaimer: the State of Wisconsin forbids prescribing or recommending CBD containing products by veterinarians. Please consider this TidBit informative and not a recommendation for treatment with CBD containing products for pets.**
Short and sweet this week! Have a great week and I hope to work with you soon!
Feline Orofacial Pain Syndrome
This is a little bit out of my wheelhouse, but it has come across my radar recently on a few cases so I thought I'd share with you what I know about FOPS.
What is it?
This is not a seizure, we don't think, and shouldn't be confused with orofacial seizures in cats. FOPS is a behavioral disorder in cats with evidence of oral discomfort and occasionally tongue, lip or gum mutilation. There is some suspicion that this is a neuropathy, or neuropathic pain disorder arising from the trigeminal nerve or the ganglion processing from CN V.
How does it present?
This disease is more common in Burmese cats, but can be seen in any breed at any age. Signs are often linked to dental work, tooth eruption or oral surgery. According to data from one study (link below), the median age was 7 years at first onset of signs, with the majority of cats having repeated or ongoing signs.
Can it be diagnosed?
It is a diagnosis of exclusion. Rule out underlying dental disease, oral pain, or diet-related causes for automatisms of the mouth following eating or other activities. Unfortunately no confirmatory test exists at this time.
How is it treated?
Not well.... oh wait, that is not what you mean, is it? Sadly, it is the truth. What treatments have been tried?
Dental procedures: 35/53 cats improved following a dental procedure but it was not sustained in 9 cats.
NSAIDS: 18 cats received NSAIDS of some variety. This was effective in 6 cats
Corticosteroids: 7/17 cats had relief with steroid use.
Antibiotics: 2/12 cats attained improvement with antibiotics (unknown type, dose)
Combination treatment (anti-inflammatory and antibiotic): 9/21 this was effective
Opioids: 4/14 these were effective
Phenobarbital: 14/14 cats, effective (this was combined with a dental 2 cats)
Diazepam oral: 13/14 cats this was effective (combined with a dental in 1 cat)
Gabapentin: only used in 1 cat and was effective (my experience has been that this is not effective)
Chlorpheniramine: 2/4 cats it was effective
Take Home Message
It is very important to read the numbers regarding treatment carefully. This data is reporting a subjective response to treatment, with variable doses and types of drugs within one class, in a small group of cats. This data is suggestive of efficacy with phenobarbital or diazepam use but other treatment choices may be effective. These medications are proposed to be effective because of their anti-allodynic effect, not anticonvulsant effects. Human patients with neuropathic pain that is reported to be burning in sensation find phenobarbital particularly effective. Remember that oral diazepam can cause idiosyncratic hepatic necrosis and therefore should be used with caution in cats.
Have a great week, and thanks for reading!
My hours are changing December 20-January 30th. Please reach out via email or text if you cannot find a suitable time for a consult as I may have some flexibility outside of posted times.
Link to an article for additional information:https://doi.org/10.1016%2Fj.jfms.2010.03.005
What Do You Do With That Phenobarbital Concentration, Anyway?
BREAKING NEWS: Phenobarbital causes side effects in cats!
Phenobarbital and Cats
It comes as no surprise that I'm a super fan of phenobarbital for seizure control in cats. My research at the University of Wisconsin started with the development of a novel transdermal phenobarbital product, and it ended (so far) with a novel oral formulation (not published yet). Phenobarbital works WELL and for many cats. But, it still has some misconceptions which I'll enumerate below.
Misconception.... TRUTH
1) Phenobarbital causes elevated ALP enzymes in cats.....IT DOES NOT. There was one study that reported a few elevations but NONE of the 77 cats in a recent study, nor any of the cats in a prior study my resident and I conducted had elevated ALP enzymes. Elevated ALP is a dog thing!
2) Phenobarbital does not have observable side effects....FALSE! Side effects occur in 46.7%of cats (Marsh et al). Sedation and ataxia were the most common side effects, but not the only ones.
Here are the side effects (called Type A adverse events), and percent of cats affected, as reported in Marsh's study:
a. Sedation 89%
b. Ataxia 53%
c.Polyphagia 22%
d. Polydipsia 6%
e. Polyuria 6%
f. Anorexia 6%
** Perhaps the last 4 are only notable to the observant owner, or in single cat households. Also of note, side effects in cats are reported less often compared with dogs.
Type B adverse events were extremely rare in the recent study, as well as in my experience. Bone marrow suppression did occur in 1 cat (as can be seen with dogs) and it resolved with removal of the phenobarbital. Lymphadenopathy has been linked to phenobarbital use as well.
3) Phenobarbital side effects happen randomly...FALSE! They are dose dependent and predictable. Higher serum concentrations (above 35 ug/ml) result in a higher odds ratio of developing a side effect. Additionally, 20 of the 36 cats in the study by Marsh had transient signs. The majority of side effects only occured in the first 4 weeks of treatment. This is a terrific point to make when discussing the use of this drug with clients.
What is the Take Away Message?
1) Start phenobarbital at a dosage targeted to reach 20-30 ug/ml. This typically means about 3 mg/kg (or a bit less) q12h.The goal is seizure control without concerning side effects.
2) Counsel clients that side effects occur in about 1/2 of cats, and of those, the majority occur within the first 4 weeks of administration AND resolve without any dose adjustments. If side effects are present beyond 4 weeks, consider a dose reduction.
Thanks for your business, especially in these unusual times. I truly enjoy working with you, and your staff. Please stay safe, stay healthy, and keep those consults coming!
*Marsh O, Corsini G, Van Dijk J, Gutierrez-Quintana R, De Risio L. Prevalence and clinical characteristics of phenobarbitone-associated adverse effects in epileptic cats. Journal of Feline Medicine and Surgery. June 2020. doi:10.1177/1098612X20924925
*Finnerty K, Barnes Heller H, Mercier M, et al. Evaluation of therapeutic phenobarbital concentrations and application of a classification system for seizures in cats: 30 cases (2004 -2013). JAVMA 2014: 244(2):195-199.
