Packer Rowena M A, De Risio Luisa, Volk Holger A
Department of Clinical Science and Services, Royal Veterinary College, Hatfield, Hertfordshire, AL9 7TA, UK.
Animal Health Trust, Newmarket, Suffolk, CB8 7UU, UK.
BMC Vet Res. 2017 Apr 7;13(1):90. doi: 10.1186/s12917-017-1000-0.
Behavioural changes associated with idiopathic epilepsy (IE) have been identified in dogs, with fear and anxiety-related problems seen in both drug-naïve dogs and dogs treated with anti-epileptic drugs (AEDs). Treating anxiety-related behaviour in dogs with IE may be challenging, as seizures are a contraindication for many conventional anxiolytic drugs. In addition, many dogs with IE are already treated with AEDs to reduce their seizure frequency, which may have negative effects if used in polytherapy. Imepitoin is low-affinity partial agonist at the benzodiazepine (BDZ) site of the GABA receptor, and has been demonstrated to have both anticonvulsant and anxiolytic effects in laboratory rodents. Imepitoin has been developed for the treatment of IE in dogs, with demonstrated anticonvulsant effects and high tolerability and safety. To date, imepitoin's potential to reduce anxiety in dogs with IE has not been investigated. An online survey was conducted to investigate the effect of imepitoin on fear and anxiety-related behaviours in dogs with IE. Eighty-five valid responses were received from owners of dogs with IE currently treated with imepitoin. Anxiety-related behaviour was quantified before and during imepitoin treatment using a validated questionnaire tool (C-BARQ).
No differences were observed in the five fear/anxiety-related measures between the two time periods (before vs. during treatment) for dog directed fear, stranger directed fear, non-social fear, pain sensitivity and separation related behaviour. A median 45% reduction in seizure frequency/month was observed following imepitoin treatment; however, imepitoin did not appear effective in reducing seizure frequency in a minority of cases. Polyphagia was the most common chronic side effect, and more side effects were reported in polytherapy cases.
Imepitoin does not appear to improve anxiety-related behaviour in dogs with IE treated with this medication for its anti-epileptic effects. Investigating the effects of imepitoin upon the behaviour of dogs with recognised behavioural anxiety-related problems (e.g. specific fears and phobias, separation related behaviours), in both healthy dogs and dogs with epilepsy is required to further explore any potential anxiolytic effects of this medication.
犬特发性癫痫(IE)相关的行为改变已被确认,未接受过药物治疗的犬和接受抗癫痫药物(AEDs)治疗的犬均存在恐惧和焦虑相关问题。治疗患有IE的犬的焦虑相关行为可能具有挑战性,因为癫痫发作是许多传统抗焦虑药物的禁忌证。此外,许多患有IE的犬已经在使用AEDs来降低癫痫发作频率,如果用于联合治疗可能会产生负面影响。艾美嘧啶是一种对γ-氨基丁酸(GABA)受体苯二氮䓬(BDZ)位点具有低亲和力的部分激动剂,并且已在实验啮齿动物中证明具有抗惊厥和抗焦虑作用。艾美嘧啶已被开发用于治疗犬的IE,具有已证实的抗惊厥作用以及高耐受性和安全性。迄今为止,尚未研究艾美嘧啶减轻患有IE的犬的焦虑的潜力。进行了一项在线调查,以研究艾美嘧啶对患有IE的犬的恐惧和焦虑相关行为的影响。从目前正在接受艾美嘧啶治疗的患有IE的犬的主人那里收到了85份有效回复。使用经过验证的问卷工具(C-BARQ)在艾美嘧啶治疗前和治疗期间对焦虑相关行为进行量化。
在犬指向性恐惧、陌生人指向性恐惧、非社交性恐惧、疼痛敏感性和分离相关行为这五项恐惧/焦虑相关指标上,两个时间段(治疗前与治疗期间)未观察到差异。艾美嘧啶治疗后观察到癫痫发作频率/月中位数降低了45%;然而,在少数情况下,艾美嘧啶似乎对降低癫痫发作频率无效。多食症是最常见的慢性副作用,联合治疗病例报告的副作用更多。
对于因抗癫痫作用而接受此药物治疗的患有IE的犬,艾美嘧啶似乎并未改善其焦虑相关行为。需要研究艾美嘧啶对健康犬和患有癫痫的犬中已识别的与行为焦虑相关问题(例如特定恐惧和恐惧症、分离相关行为)的犬的行为的影响,以进一步探索该药物的任何潜在抗焦虑作用。