Review of the cardiovascular toxicity of amitriptyline treatment for canine neuropathic pain

Abstract

Nowadays, the lifespan of pets has been increased by improvements in veterinary practice but age-related
disorders are also increasing. Several nervous system attenuations are well-known to be the result of aging and/or
pathological lesions. In many cases, neuropathic pain (NP) can develop and cause a significant impact on the clinical
outcome and quality of life. With the difficulty in identification of the specific cause of NP, most NP management is
planned according to clinical manifestations and recommended trial therapy. The drug of choice for trial therapy seems
to be amitriptyline, a tricyclic antidepressant with multiple effects on neurotransmitter receptors and ion channels.
However, the pharmacological effects of amitriptyline depend on several pathophysiological factors, including the level
of drug exposure, drug metabolism capacity, concurrent disease and cellular responsiveness. In addition to its
therapeutic effects, amitriptyline also possesses several adverse effects, especially cardiovascular toxicity. However, the
information on its toxicity in veterinary clinical practice is very limited. In this article, we review the use of amitriptyline
in NP management and its cardiovascular attenuation using both human medicine and veterinary publications. The
aim of this review is to highlight the importance of routine cardiovascular monitoring and to provide a list of
parameters that are associated with amitriptyline cardiovascular toxicity.