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Amitriptyline for Veterinary Use
by Barbara Forney, VMD
Amitriptyline is a tricyclic antidepressant drug (TCA). The name of the licensed human drug is Elavil. TCA drugs have their largest effects on serotonin receptors, norepinephrine receptors, some adrenergic receptors and some histamine receptors. Amitriptyline is a relatively nonspecific TCA. It has antihistaminic, anticholinergic, anti-alpha-adrenergic, anti-inflammatory, analgesic and sedative actions.
Some of the other TCA drugs have greater activity on serotonin receptors. Based on studies in laboratory animals, amitriptyline does not affect either memory or learning ability. The active metabolite of amitriptyline is nortriptyline. Nortriptyline is an option for some animals that experience too much sedation with the parent compound.
Dogs and Cats
Cats: Amitriptyline is commonly used for cats that spray or exhibit inappropriate elimination behaviors. It is used for either the victim or the aggressor for non specific anxiety due to social hierarchy. It is also used in the treatment of idiopathic feline urinary tract disease although this use is somewhat controversial due to the lack of controlled studies.
There are some issues with palatability in the cat, particularly for those animals on long term treatment. Transdermal patches are available and may be useful when oral medication is not possible or practical. It should be noted that in at least one study, the plasma levels of amitriptyline were undetectable with transdermal applications.
Dogs: Amitriptyline is used for the treatment of separation anxiety, pruritus, and neuropathic pain. Clomipramine is more commonly used for the treatment of separation anxiety and stereotypic behaviors because it has a higher specificity for serotonin receptors and is FDA approved for this use. Amitriptyline has sufficient anti-histamine properties to be used as an adjunctive treatment for pruritic dogs. There are also citations in the literature of use in dogs with osteoarthritis.
- The most common side effects are sedation, constipation and urinary retention.
- Less common side effects include paroxysmal hyper excitability, or disinhibition of aggression, cardiac arrhythmias, bone marrow suppression, gastro-intestinal disorders including vomiting, diarrhea, anorexia, and ataxia or disorientation.
- Amitriptyline is a relatively nonspecific TCA. It may take 7-10 days to reach full therapeutic effect. Sedation due to the antihistaminic side effects should not be mistaken with treatment response.
- Amitriptyline may lower the seizure threshold.
- Amitriptyline has been shown to cause fetal limb abnormalities. It should not be used during pregnancy unless the benefits outweigh the possible risks.
- Amitriptyline should be used with caution in animals with diabetes or other endocrine disorders, liver disease, kidney disease, KCS, glaucoma and cardiac arrhythmia.
- There are a number of serious potential drug interactions.
- Monoamine oxidase inhibitors (selegiline, amitraz): potential for serotonin syndrome.
- Selective serotonin re-uptake inhibitors (SSRI’s): potential for serotonin syndrome. Although these drugs are used concurrently with TCA’s, increased monitoring and a thorough understanding of the individual drugs is advisable. There are some excellent articles by Dr Karen Overall on behavioral medications and poly-pharmacy.
- Sympathomimetic drugs, cisapride, thyroid medications: increased risk of cardiac side effects.
- Anticholinergic drugs may increase the risk of hyperthermia and ileus.
- CNS depressant drugs may increase the risk of sedation.
- Cimetidine and diazepam may either inhibit metabolism or increase amitriptyline drug levels resulting in potential increased risk of toxicity.
- Overdose with TCA drugs such as amitriptyline can cause life-threatening cardiac arrhythmia and cardio-respiratory collapse.
- If recognized promptly, gut emptying protocols may be of value.
About the Author
Dr. Barbara Forney is a veterinary practitioner in Chester County, Pennsylvania. She has a master's degree in animal science from the University of Delaware and graduated from the University of Pennsylvania School of Veterinary Medicine in 1982.
She began to develop her interest in client education and medical writing in 1997. Recent publications include portions of The Pill Book Guide to Medication for Your Dog and Cat, and most recently Understanding Equine Medications published by the Bloodhorse.
Dr. Forney is an FEI veterinarian and an active member of the AAEP, AVMA, and AMWA.
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