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Medical Treatment of Canine Epilepsy in Europe Sofie F.M

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Medical Treatment of Canine Epilepsy in Europe Sofie F.M Bhatti et al. BMC Veterinary Research (2015) 11:176 DOI 10.1186/s12917-015-0464-z CORRESPONDENCE Open Access International Veterinary Epilepsy Task Force consensus proposal: medical treatment of canine epilepsy in Europe Sofie F.M. Bhatti1*, Luisa De Risio2, Karen Muñana3, Jacques Penderis4, Veronika M. Stein5, Andrea Tipold5, Mette Berendt6, Robyn G. Farquhar7, Andrea Fischer8, Sam Long9, Wolfgang Löscher10, Paul J.J. Mandigers11, Kaspar Matiasek12, Akos Pakozdy13, Edward E. Patterson14, Simon Platt15, Michael Podell16, Heidrun Potschka17, Clare Rusbridge18,19 and Holger A. Volk20 Abstract In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible. Keywords: Dog, Epileptic seizure, Epilepsy, Treatment Background drugs in Europe, and 3) reflects the authors’ experience. In Europe, the number of antiepileptic drugs (AEDs) li- With this paper it is aimed to provide a consensus for the censed for dogs has grown considerably over the last management of canine idiopathic epilepsy. Furthermore, years. Nevertheless, the same questions remain, which for the management of structural epilepsy AEDs are in- include, 1) when to start treatment, 2) which drug is best evitable in addition to treating the underlying cause, if used initially, 3) which adjunctive AED can be advised if possible. treatment with the initial drug is unsatisfactory, and 4) At present, there is no doubt that the administration when treatment changes should be considered. In this of AEDs is the mainstay of therapy. In fact, the term consensus proposal, an overview is given on the aim of AED is rather inappropriate as the mode of action of AED treatment, when to start long-term treatment in most AEDs is to suppress epileptic seizures, not epilep- canine epilepsy and which veterinary AEDs are currently togenesis or the pathophysiological mechanisms of epi- in use for dogs. The consensus proposal for drug treatment lepsy. Perhaps, in the future, the term anti-seizure drugs protocols, 1) is based on current published evidence-based might be more applicable in veterinary neurology, a term literature [17], 2) considers the current legal framework of that is increasingly used in human epilepsy. Additionally, the cascade regulation for the prescription of veterinary it is known that epileptic seizure frequency appears to increase over time in a subpopulation of dogs with un- * Correspondence: [email protected] treated idiopathic epilepsy, reflecting the need of AED 1Department of Small Animal Medicine and Clinical Biology, Faculty of treatment in these patients [63]. Veterinary Medicine, Ghent University, Salisburylaan 133, Merelbeke 9820, Belgium In our consensus proposal on classification and termin- Full list of author information is available at the end of the article ology we have defined idiopathic epilepsy as a disease in © 2015 Bhatti et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http:// creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Bhatti et al. BMC Veterinary Research (2015) 11:176 Page 2 of 16 its own right, per se. A genetic origin of idiopathic epilepsy effects) [42, 115]. In people, clear proof exists that there is is supported by genetic testing (when available) and a gen- no benefit initiating AED treatment after a single unpro- etic influence is supported by a high breed prevalence voked seizure [42], but there is evidence to support start- (>2 %), genealogical analysis and /or familial accumulation ing treatment after the second seizure [43, 108]. In dogs, of epileptic individuals. However in the clinical setting long-term seizure management is thought to be most suc- idiopathic epilepsy remains most commonly a diagnosis of cessful when appropriate AED therapy is started early in exclusion following diagnostic investigations for causes of the course of the disease, especially in dogs with a high reactive seizures and structural epilepsy. seizure density and in dog breeds known to suffer from a severe form of epilepsy [12−14]. A total number of ≥ 10 Aims of AED treatment seizures during the first 6 months of the disease appeared The ideal goal of AED therapy is to balance the ability to be correlated with a poor outcome in Australian Shep- to eliminate epileptic seizures with the quality of life of herds with idiopathic epilepsy [132]. Furthermore, recent the patient. Seizure eradication is often not likely in evidence exists that seizure density is a crucial risk factor, dogs. More realistic goals are to decrease seizure fre- experiencing cluster seizures, and being male is associated quency, duration, severity and the total number of epi- with poor AED response [84]. leptic seizures that occur over a short time span, with A strong correlation exists in epileptic people between no or limited and acceptable AED adverse effects to a high seizure frequency prior to AED treatment and maximize the dog’s and owner’s quality of life. Clinicians poor AED response [16, 34, 59]. Historically, this has should approach treatment using the following paradigm been attributed to kindling, in which seizure activity [23, 76, 91, 92, 120]: leads to intensification of subsequent seizures [117]. However, there is little clinical evidence that kindling – Decide when to start AED treatment plays a role in either dogs [54] or humans [111] with re- – Choose the most appropriate AED and dosage current seizures. In humans, a multifactorial pathogen- – Know if and when to monitor serum AED esis is suggested [14, 52]. Recent epidemiologic data concentrations and adjust treatment accordingly suggest that there are differences in the intrinsic severity – Know when to add or change to a different AED of epilepsy among individuals, and these differences in- – Promote pet owner compliance fluence a patient’s response to medication and long-term outcome. Additionally, evidence for seizure-associated When to recommend maintenance AED treatment? alterations that affect the pharmacodynamics and Definitive, evidence-based data on when to start AED pharmacokinetics of AEDs have been suggested [99]. therapy in dogs based on seizure frequency and type is Breed-related differences in epilepsy severity have been lacking. As such, extrapolation from human medicine may described in dogs, with a moderate to severe clinical be possible to provide treatment guidelines. Clinicians course reported in Australian Shepherds [132], Border should consider the general health of the patient, as well Collies [49, 84], Italian Spinoni [24], German Shepherds as the owner’s lifestyle, financial limitations, and comfort and Staffordshire Bull Terriers [84], whereas a less se- with the proposed therapeutic regimen. Individualized vere form of the disease has been described in a different therapy is paramount for choosing a treatment plan. As a cohort of Collies (mainly rough coated) [77], Labrador general rule, the authors recommend initiation of long- Retrievers [7] and Belgian Shepherds [45]. Consequently, term treatment in dogs with idiopathic epilepsy when any genetics may affect the success of treatment and may ex- one of the following criteria is present: plain why some breeds are more predisposed to drug re- sistant epilepsy [3, 77]. – Interictal period of ≤ 6 months (i.e. 2 or more epileptic seizures within a 6 month period) Choice of AED therapy – Status epilepticus or cluster seizures There are no evidence-based guidelines regarding the – The postictal signs are considered especially choice of AEDs in dogs. When choosing an AED for the severe (e.g. aggression, blindness) or last longer management of epilepsy in dogs several factors need to than 24 hours be taken into account (AED-specific factors (e.g. regula- – The epileptic seizure frequency and/or duration tory aspects, safety, tolerability, adverse effects, drug inter- is increasing and/or seizure severity is actions, frequency of administration), dog-related factors deteriorating over 3 interictal periods (e.g. seizure type, frequency and aetiology, underlying pathologies such as kidney/hepatic/gastrointestinal prob- In humans, the decision regarding when to recommend lems) and owner-related factors (e.g. lifestyle, financial cir- AED treatment is based on a number of risk factors cumstances))
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