Amitriptyline
Amitriptyline is a first-generation **tricyclic antidepressant (TCA)**. While newer drugs like clomipramine or SSRIs (e.g., fluoxetine) have largely superseded it for primary behavioral disorders in dogs (such as separation anxiety), amitriptyline remains a highly versatile drug in veterinary medicine. **Clinical Pearl**: Its multimodal receptor activity makes it particularly useful for adjunctive treatment of **neuropathic pain**, **pruritus** (due to its potent antihistamine effects), and **feline idiopathic lower urinary tract disease (FLUTD/FIC)**. It is also occasionally used in avian medicine to manage feather-plucking behaviors.
Mechanism: Amitriptyline and its active metabolite, **nortriptyline**, exhibit a complex pharmacologic profile, affecting multiple receptor systems: * **Serotonin (SERT) & Norepinephrine (NET) Reuptake Inhibition**: Blocks the amine pump โ increases synaptic levels of 5-HT and NE โ mood stabilization and descending pain pathway modulation. * **H1-Receptor Antagonism**: Potent antihistamine effect โ stabilizes mast cells and provides antipruritic action. * **M1-Muscarinic (Anticholinergic) Antagonism**: Causes smooth muscle relaxation (useful in FLUTD) but also leads to side effects like dry mouth and urine retention. * **Alpha-1 Adrenergic Antagonism**: Can cause mild vasodilation and sedation. * **NMDA Receptor & Sodium Channel Blockade**: Contributes to its efficacy in treating chronic, neuropathic pain.
Dosing by species
- Adjunctive treatment of pruritus ยท 1-2 mg/kg PO q12h ยท PO ยท q12h
- Acral pruritic dermatitis ยท 2.2 mg/kg PO twice daily ยท PO ยท q12h ยท 2-4 week trial recommended ยท Only occasionally effective.
- Separation anxiety or generalized anxiety ยท 1-2 mg/kg PO q12h ยท PO ยท q12h ยท Use with behavior modification.
- Behavior disorders amenable to tricyclics ยท 1-4 mg/kg PO q12h. Begin at 1-2 mg/kg PO q12h for 2 weeks, increase by 1 mg/kg up to maximum dosage (4 mg/kg) as necessary. If no clinical response, decrease by 1 mg/kg PO q12h for 2 weeks until at initial dosage. ยท PO ยท q12h
- Behavior disorders amenable to tricyclics ยท 2.2-4.4 mg/kg PO q12h ยท PO ยท q12h
- Behavior disorders amenable to tricyclics ยท 0.25-1.5 mg/kg PO every 12-24h ยท PO ยท q12-24h
- Neuropathic pain ยท 1-2 mg/kg PO q12-24h ยท PO ยท q12-24h
- Adjunctive treatment of pain associated with appendicular osteosarcoma ยท 1-2 mg/kg PO q12-24h ยท PO ยท q12-24h
- Management of chronic anxiety, compulsive disorders, and separation anxiety ยท 1-2 mg/kg ยท PO ยท q12-24h ยท Clomipramine is an authorized preparation for dogs and is claimed to have better anticompulsive properties.
- Adjunctive treatment of feather plucking ยท 1-2 mg/kg PO q12-24 hours. Anecdotal reports indicate some usefulness. Barring side-effects, may be worth a more prolonged course of therapy to determine efficacy. ยท PO ยท q12-24h ยท Prolonged course
Routes of administration
Contraindications
- Prior sensitivity to any tricyclic antidepressant
- Concomitant use with monoamine oxidase inhibitors (MAOIs)
Adverse effects
- Sedation
- Constipation
- Urinary retention
- Hyperexcitability (dogs)
- Seizures (rare)
- Cardiac dysrhythmias
- Bone marrow suppression
- Vomiting
- Diarrhea
- Hypersalivation (cats)
- Anorexia (cats)
- Thrombocytopenia
- Neutropenia
- Unkempt hair coat (cats)
- Ataxia
- Disorientation
Drug interactions
- Anticholinergic agents ยท Increased effects; hyperthermia and ileus possible
- Cimetidine ยท May inhibit tricyclic antidepressant metabolism and increase the risk of toxicity ยท moderate
- Cisapride ยท May have additive effects on QTc interval; possible serious arrhythmias may result
- Monoamine Oxidase Inhibitors (selegiline, amitraz) ยท Potential life-threatening serotonin syndrome; use together not recommended
- CNS Depressants ยท Increased sedative effects
- Diazepam ยท Possible increased amitriptyline levels ยท moderate
- Quinidine ยท Increased risk for QTc interval prolongation and tricyclic adverse effects
- Selective-Serotonin Re-uptake Inhibitors (SSRIs, fluoxetine) ยท Potential increased amitriptyline levels, increased risk for serotonin syndrome; enhanced monitoring suggested if used together
- Sympathomimetic agents ยท May increase the risk of cardiac effects (arrhythmias, hypertension, hyperpyrexia)
- Thyroid agents ยท Increased risk for arrhythmias; monitor closely
- Monoamine oxidase inhibitors (MAOIs) ยท Risk of fatal serotonin syndrome. Requires a minimum 2-week washout period. ยท major
- Chlorphenamine ยท Metabolized by CYP2D6; may alter amitriptyline metabolism. ยท moderate
Monitoring
- Clinical efficacy (behavior, pain, or pruritus improvement)
- Adverse effects
- Baseline cardiac evaluation (ECG) prior to therapy
- Baseline CBC and serum chemistry panel prior to therapy
- Liver enzymes in cats (prior to therapy, 1 month after initial therapy, and yearly thereafter)
Overdose
Overdosage with tricyclics can be **life-threatening** (arrhythmias, cardiorespiratory collapse). Because toxicities and therapies are complicated, it is recommended to contact an animal poison control center immediately in any potential overdose situation. * **Dogs**: Common findings include lethargy and tachycardia. * **Cats**: Common findings include vocalization, ataxia, mydriasis (dilated pupils), tachycardia, disorientation, lethargy, and agitation.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.