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Investigating the potential of the anti-epileptic drug imepitoin as a treatment for co-morbid anxiety in dogs with idiopathic epilepsy

View Article: PubMed Central - PubMed

ABSTRACT

Background: 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 GABAA 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).

Results: 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.

Conclusions: 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.

No MeSH data available.


Related in: MedlinePlus

Box and whisker plot of the five C-BARQ behavioural measures before and after imepitoin treatment in dogs in dogs treated with only imepitoin as a monotherapy (n = 56). The top and bottom lines of the boxes represent the 25th and 75th percentiles, the central line indicates the median, and the whiskers represent the range. Filled circles represent outliers and stars represent extreme outliers
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Fig2: Box and whisker plot of the five C-BARQ behavioural measures before and after imepitoin treatment in dogs in dogs treated with only imepitoin as a monotherapy (n = 56). The top and bottom lines of the boxes represent the 25th and 75th percentiles, the central line indicates the median, and the whiskers represent the range. Filled circles represent outliers and stars represent extreme outliers

Mentions: No significant effect of imepitoin treatment was found on the five behavioural measures, in either the whole population (Table 1) or when only monotherapy cases were considered (p > 0.05) (Fig. 2).Table 1


Investigating the potential of the anti-epileptic drug imepitoin as a treatment for co-morbid anxiety in dogs with idiopathic epilepsy
Box and whisker plot of the five C-BARQ behavioural measures before and after imepitoin treatment in dogs in dogs treated with only imepitoin as a monotherapy (n = 56). The top and bottom lines of the boxes represent the 25th and 75th percentiles, the central line indicates the median, and the whiskers represent the range. Filled circles represent outliers and stars represent extreme outliers
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5383962&req=5

Fig2: Box and whisker plot of the five C-BARQ behavioural measures before and after imepitoin treatment in dogs in dogs treated with only imepitoin as a monotherapy (n = 56). The top and bottom lines of the boxes represent the 25th and 75th percentiles, the central line indicates the median, and the whiskers represent the range. Filled circles represent outliers and stars represent extreme outliers
Mentions: No significant effect of imepitoin treatment was found on the five behavioural measures, in either the whole population (Table 1) or when only monotherapy cases were considered (p > 0.05) (Fig. 2).Table 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: 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 GABAA 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).

Results: 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.

Conclusions: 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.

No MeSH data available.


Related in: MedlinePlus