6 May 2025
Mark Lowrie
Job Title
Image: Eric Isselée / Adobe Stock
Epileptic seizures rank among the most prevalent neurological presentations in dogs, affecting an estimated 0.6% to 0.75% of the canine population (Berendt et al, 2007).
As a chronic condition with acute manifestations, epilepsy necessitates significant clinical attention and management. Notably, a strong inverse correlation exists between seizure frequency and an owner’s perception of their dog’s quality of life (QOL), with higher seizure frequencies associated with poorer QOL (Nettifee et al, 2017).
Compounding this, declines in a dog’s QOL have been directly linked to reduced QOL in their owners, underscoring the broader impact of the disease (Wessmann et al, 2016). Therefore, optimising seizure control is paramount not only for the affected patient, but also for their human caregivers.
For these patients, the challenges are multifaceted, encompassing diagnostic limitations, complex pathophysiology, and the need for tailored management strategies.
This article provides an in-depth review of refractory canine epilepsy, offering insights into its mechanisms, evidence-based treatments and promising future therapies.
Pharmacoresistance, commonly referred to as drug-resistant epilepsy, represents a significant challenge in veterinary neurology, affecting up to 30% of epileptic dogs (Schwartz-Porsche et al, 1985).
It is characterised by the persistence of seizures despite the administration of anti-epileptic drugs (AEDs), such as phenobarbital or potassium bromide at appropriate dosages confirmed by therapeutic serum concentrations. This form of epilepsy not only exacerbates the morbidity and mortality associated with the condition, but also necessitates ongoing innovation in anti-epileptic therapies. Furthermore, it imposes substantial emotional and financial burdens on dog owners, complicating long-term disease management.
Refractory epilepsy arises from various mechanisms that disrupt the efficacy of AEDs, including the following.
The variability in pharmacoresistance between breeds underscores the role of genetics in this condition, though pharmacogenomic studies in humans remain inconclusive, highlighting the multifactorial nature of this challenge.
Understanding these mechanisms is critical for developing targeted therapies and improving outcomes in refractory cases.
Owners often begin consultations with the assertion: “My pet has had a seizure.” However, this presumption warrants careful scrutiny.
Paroxysmal episodes, by their very nature, are challenging to characterise due to their episodic occurrence interspersed with extended periods of normal behaviour. The sporadic presentation of these episodes, coupled with potential prodromal or postictal signs, frequently leads owners to suspect a neurological basis, often concluding the event was a seizure.
Nevertheless, the widespread use of smartphones has transformed the diagnostic process, allowing veterinarians to directly observe recorded events.
Despite a description appearing to confirm an epileptic seizure, the actual diagnosis often reveals an alternate cause.
Key indicators that differentiate epileptic seizures from other paroxysmal disorders include:
Autonomic signs such as urination, defecation, and salivation.
Loss of awareness, and the presence of prodromal or postictal behavioural changes.
Additional features, while not definitive, may strengthen the suspicion of an epileptic seizure. These include stereotypical presentation (that is, episodes consistently appearing identical), increased muscle tone, abrupt onset and termination (excluding reflex seizures), and brevity of the event (generally lasting less than a few minutes).
Conversely, paroxysmal episodes characterised by decreased muscle tone, prolonged duration (for example, 30 minutes or longer), or the absence of postictal signs are more indicative of non-epileptic conditions.
The aetiology of epilepsy is diverse and includes underlying conditions such as brain tumours, inflammatory brain diseases, and degenerative disorders. Approximately 0.75% of dogs are affected by epilepsy, with idiopathic epilepsy (IE) being the most prevalent form.
In cases of IE, no identifiable brain pathology explains the recurring seizures, and the condition’s underlying cause remains unknown. However, certain breeds exhibit a predisposition to IE, suggesting a genetic component based on epidemiological evidence.
Seizures can involve both cerebral hemispheres simultaneously, known as generalised seizures, or may localise to specific regions within one cerebral hemisphere, referred to as focal seizures. Focal seizures have the potential to evolve into generalised seizures.
Among dogs with IE, generalised tonic-clonic seizures are the most frequently observed. The tonic phase is marked by loss of consciousness, opisthotonus and rigid limb extension, followed by the clonic phase, characterised by limb paddling, jerking movements and chewing motions.
This refined understanding of epileptic seizures highlights the importance of thorough evaluation and careful distinction between epileptic and non-epileptic paroxysmal episodes to guide accurate diagnosis and effective management.
IE is most commonly diagnosed in dogs that experience their first seizure between six months and six years of age, though it can occur at any age; for example, in juvenile epilepsy (onset before one year of age), no identifiable brain disease is found in approximately 75% of cases. Similarly, late-onset epilepsy (onset after five years of age) remains idiopathic in 35% of cases.
The diagnosis of IE relies on ruling out other possible causes of seizures through a combination of clinical evaluation, laboratory tests, imaging and cerebrospinal fluid (CSF) analysis. Dogs with IE typically exhibit normal findings on neurological examination, blood tests, brain MRI and CSF analysis.
The diagnostic process often begins with routine blood tests to assess for extracranial metabolic causes.
For optimal results, fasting for 12 hours prior to blood sampling is recommended, so rescheduling the blood test for a more suitable time may be necessary in some cases. Specific tests that provide key insights include the following.
Liver function markers: albumin, urea, cholesterol and glucose are produced by the liver, and can help evaluate liver health. Liver enzymes alone may be insufficient – especially in dogs receiving phenobarbital, as increased alkaline phosphatase is a common finding. When liver dysfunction is suspected, a bile acid stimulation test offers a more comprehensive evaluation.
Renal function markers: if kidney disease is suspected, urea, creatinine, phosphate concentration, and urinalysis should be assessed.
Fasting glucose: this is a critical test to rule out hypoglycaemia as a seizure trigger. Low glucose concentrations in middle-aged or older dogs may indicate an insulinoma, necessitating further investigations such as a blood glucose to insulin ratio.
Blood pressure: measuring blood pressure is essential to rule out hypertensive encephalopathy as a potential cause.
Identifying intracranial causes involves a combination of thorough owner questioning and a focused neurological examination.
Collecting a detailed history from the owner can reveal signs of forebrain dysfunction. These may include altered mentation, central blindness, incessant pacing or circling, head pressing and loss of learned behaviours (such as housetraining).
Such signs, if present between seizures (interictal period), are indicative of forebrain disease. Observing the dog’s gait during the consultation may also reveal subtle abnormalities unnoticed by the owner.
Examination should focus on identifying deficits consistent with forebrain dysfunction, such as changes in mentation, central blindness (reduced menace response with an intact pupillary light reflex), and general proprioceptive ataxia (a “drunken” gait).
It is crucial to distinguish these findings from postictal signs, which may persist for 24 to 48 hours following a seizure and tend to be symmetrical.
Repeating the neurological examination at least 48 hours after a seizure is, therefore, recommended.
If any neurological abnormalities are detected, advanced imaging such as MRI is recommended. However, it is important to note that a normal neurological examination does not exclude brain pathology – especially in refractory epileptic patients.
When initiating treatment for canine epilepsy, the primary AEDs include phenobarbital, imepitoin, and potassium bromide; all are approved for monotherapy. Selection depends on individual case factors, and the American College of Veterinary Internal Medicine (ACVIM) consensus triangle offers a valuable framework, ranking AEDs based on clinical evidence and expert recommendations.
Phenobarbital and imepitoin are highly recommended as first-line treatments, occupying the apex of the ACVIM triangle. Both demonstrate strong efficacy, though their indications differ.
These findings, combined with clinical experience, often position phenobarbital as the preferred first-line AED due to its superior efficacy and reduced likelihood of early cluster seizures.
Both phenobarbital and imepitoin are contraindicated in severe hepatic insufficiency, making potassium bromide a suitable alternative, as it bypasses liver metabolism.
Potassium bromide occupies the second tier of the ACVIM triangle and has shown a reduction of more than or equal to 50% in seizure frequency in 74% of dogs when used as monotherapy. In dogs with severe renal insufficiency, all three first-line AEDs may pose risks, requiring a detailed risk-benefit assessment by the attending veterinarian.
When phenobarbital monotherapy proves insufficient, further evaluation is essential to identify underlying causes, address improper dosing or determine if the patient falls into the 25% of cases classified as refractory epilepsy. Unrealistic owner expectations often contribute to perceived treatment failure (Pergrande et al, 2020).
For polytherapy, potassium bromide is the most strongly recommended adjunctive AED, as it is the only licensed medication for this purpose in dogs. Potassium bromide works synergistically with phenobarbital, making it an optimal choice for patients already on phenobarbital.
Unlicensed AEDs, such as levetiracetam and zonisamide, are additional options for adjunctive use. Although these drugs lack robust clinical evidence, they can provide benefits in refractory cases.
Levetiracetam is well-tolerated and useful as an adjunct AED for refractory epilepsy. It is excreted primarily by the kidneys, making it suitable for dogs with liver dysfunction.
In cases of cluster seizures with prolonged seizure-free intervals, a pulse therapy protocol may be effective: an initial dose of 60mg/kg, followed by 20mg/kg every eight hours during the cluster period, and discontinuation once the dog is seizure free for 48 hours.
A practical at-home treatment for dogs prone to cluster seizures, owners can administer a dose of rectal diazepam 0.5mg/kg to 2mg/kg, repeated up to three times within 24 hours, to manage acute episodes effectively.
Options such as gabapentin, felbamate, topiramate and zonisamide may be considered for severe refractory cases. However, these AEDs often lack substantial clinical evidence, can be expensive for large breeds and are unlikely to produce dramatic improvements in severe epilepsy cases.
For dogs with refractory epilepsy, where AEDs are insufficient or limited in efficacy, many owners seek alternative management strategies. While these approaches vary in evidence and application, some have shown promise in reducing seizure frequency.
Cannabidiol (CBD), a non-psychoactive compound from cannabis, has attracted attention for its potential role in managing epilepsy in dogs.
Unlike tetrahydrocannabinol (THC), the psychoactive element in cannabis, CBD is primarily sought for its therapeutic effects without producing a “high”. Medicinal cannabis formulations often aim for high CBD content with minimal THC to maximise efficacy while minimising psychoactive effects.
Several studies have explored CBD’s antiepileptic potential in dogs. In a clinical trial, CBD oil administered alongside AEDs resulted in a 33% reduction in seizure frequency compared to placebo. However, interestingly, 50% of dogs in both groups (CBD and placebo) were considered responders, showing a reduction in seizures more than or equal to 50%. Side effects in this study included ataxia and a significant increase in serum alkaline phosphatase concentrations (McGrath et al, 2019).
A second study found that 6 of 14 dogs treated with CBD achieved a reduction in seizure frequency more than or equal to 50%, a response not observed in the placebo phase for the same dogs (Morrow and Belshaw, 2020).
In a third double-blinded, crossover trial focused on drug-resistant IE, dogs receiving CBD alongside their standard AEDs showed a 24.1% decrease in seizure days, while the placebo group experienced a 5.8% increase. Although total seizure frequency increased in both groups, the increase was notably lower in the CBD group (3.31% versus 30.72%).
However, when defining success as a reduction in seizures more than or equal to 50%, no significant difference was reported between the CBD and placebo groups (Rozental et al, 2023).
Adverse effects associated with CBD included somnolence in 3 out of 14 dogs and ataxia in 4 out of 14 dogs in one study (Garcia, 2022), as well as ataxia and increased ALP concentrations in another (McGrath et al, 2019). Further adverse effects in a third study included increased liver enzyme activity (alkaline phosphatase, alanine aminotransferase), decreased appetite, and vomiting (Rozental et al, 2023).
Regarding pharmacokinetics, no significant changes in AED concentrations were noted, although phenobarbital concentrations increased by 11% during the CBD phase (Rozental et al, 2023), suggesting a potential pharmacokinetic interaction that warrants further investigation.
While early findings are promising, additional research is needed to standardise CBD dosing, confirm its safety and evaluate its long-term efficacy as an adjunctive or primary treatment for epilepsy in dogs.
The ketogenic diet, long used in humans to manage epilepsy, inspired the development of the medium-chain triglyceride (MCT) diet as a more palatable alternative.
This diet replaces some long-chain fatty acids with MCTs, which are more readily absorbed and ketogenic, allowing for greater carbohydrate inclusion while maintaining therapeutic efficacy.
One study demonstrated that dogs with chronic IE fed a diet containing 5.5% MCTs had a significant reduction in seizure frequency compared to dogs on a standard diet (Law et al, 2015).
In another, a branded diet containing 6.5% MCTs achieved a 32% reduction in monthly seizure frequency in dogs with IE which did not experience cluster seizures (Molina et al, 2020).
These findings highlight the potential of MCT-based diets as an adjunctive therapy in canine epilepsy management, though individual responses may vary.
Vagal nerve stimulation (VNS) is another avenue explored for its antiepileptic effects in dogs, employing two distinct methods.
Surgical implantation: a pacemaker-like device is surgically implanted to deliver intermittent electrical stimulation to the vagus nerve. While promising, this method has limited clinical use due to its high cost, invasiveness and restricted availability.
Ocular compression: a less invasive technique involves manual digital pressure applied to the eyes, stimulating the vagus nerve indirectly. This method has shown anecdotal success in aborting or preventing seizures in some dogs.
While VNS remains underutilised, advancements in accessibility and technology could expand its application in the future.
The placebo effect, though poorly understood, is well documented in epilepsy studies. It involves a psychological or physiological response to an intervention lacking specific therapeutic activity.
In a placebo-controlled trial, more than 50% of dogs receiving placebo experienced a decrease in seizure frequency compared to baseline, and nearly 30% were classified as responders with a reduction in seizures more than or equal to 50% (Muñana et al, 2010). These findings emphasise the importance of placebo-controlled studies in accurately assessing the efficacy of new anti-epileptic therapies.
One of the most under-discussed but essential aspects of managing canine epilepsy is the prognosis and communication with clients.
In a field often dominated by clinical treatment protocols, the emotional, psychological and social implications of caring for a dog with epilepsy can sometimes be overlooked.
A key component of successful epilepsy management is setting realistic expectations from the outset, ensuring that both the pet and the owner understand the long-term nature of the condition and the challenges that lie ahead.
Before starting any medical intervention, it is crucial to manage client expectations regarding treatment outcomes.
The primary goal of therapy is to reduce the frequency, intensity and severity of seizures, ideally with manageable side effects, thereby improving the quality of life for both the dog and its owner. However, it must be communicated early on that complete seizure eradication is highly unlikely and lifelong therapy will most likely be necessary.
When evaluating the success of treatment, clinical trials often define success as a 50% reduction in seizure frequency. For some dogs, this level of improvement might be transformative, while for others it may feel insufficient, depending on their individual seizure patterns. Client education is essential here: they need to understand that the goal is not a cure, but a more manageable condition where seizures are less frequent and less severe.
Furthermore, the therapy is likely to require regular adjustments, making it a long-term financial and emotional commitment for the owners.
A practical tool to assist in assessing the effectiveness of treatment is the seizure diary. By encouraging owners to keep a detailed record of their dog’s seizures, the veterinarian can more accurately track the response to medication and guide future treatment decisions.
This diary also helps ensure that the dog’s AEDs are administered correctly, fostering better compliance and understanding of treatment schedules.
Effective communication from the initial consultation is essential in managing the client’s emotional and psychological needs. It is important to acknowledge the emotional strain that caring for a dog with epilepsy can cause.
Historically, the focus has been on the medical management of the dog’s condition, but the emotional and social impact on owners is now being recognised as equally significant.
The World Health Organization’s definition of health as “a state of complete physical, mental and social well-being, and not merely the absence of disease”, is a pertinent lens through which to view the challenges faced by dog owners managing chronic conditions like epilepsy. The burden of care for owners of dogs with epilepsy is substantial. In addition to the stress of witnessing seizures, owners must also navigate medication side effects and manage the challenging postictal period. This burden can be emotionally draining and sometimes isolating. Furthermore, the success of seizure control does not always correlate with the owner’s commitment or effort, which can lead to feelings of frustration and helplessness.
Recent research – particularly a study by Pergrande et al (2020) – has shed light on the psychosocial impact of living with a dog suffering from IE. Unlike previous studies that relied on surveys, this study used semi-structured interviews to delve deeper into the emotional, financial and social challenges faced by owners.
These challenges include the financial burden, the time commitment, the lack of sleep and the social isolation that many owners experience. The emotional toll is profound, often intensifying when seizures are poorly controlled.
A critical point highlighted by this research is the emotional bond between the dog and its owner. This bond can be a powerful motivator for owners to continue seeking the best possible care for their pets. It is often further intensified when dogs exhibit neurobehavioral comorbidities, such as increased fear and anxiety, common in dogs with epilepsy. Owners of dogs with these issues often report a closer emotional connection with their pets, which, while strengthening their commitment, also increases the psychological burden of care.
Given the emotional impacts, it is clear that owners need more than just medical advice – they require emotional and social support, as well. Veterinary professionals have a unique opportunity to empower clients with information about potential challenges, even when these conversations may be difficult. Clear communication about the realities of epilepsy management can help owners prepare mentally and emotionally for the long road ahead.
However, the use of online support groups and resources should be approached with caution. While they can provide a sense of community and understanding, they can also be overwhelming and full of negativity. It is essential for owners to be directed toward reliable, balanced resources, where they can find both support and constructive advice.
Ultimately, managing the care of a dog with epilepsy requires an holistic approach that addresses not only the medical needs of the dog, but also the emotional and psychological well-being of the owner.
By fostering open, empathetic communication and setting realistic expectations, veterinarians can help mitigate the stress that accompanies the management of this chronic condition, ultimately improving both the dog’s and the owner’s quality of life.
