Doxepin
Doxepin is a dibenzoxazepine-derivative **tricyclic antidepressant (TCA)** used primarily in veterinary medicine as an adjunctive therapy for psychogenic dermatoses, particularly those with an underlying anxiety component. While it is classified as an antidepressant, it possesses extremely potent **H1-antihistaminic properties**, making it a dual-purpose agent for managing pruritus and behavioral conditions. Its efficacy as a standalone antihistamine for atopic dermatitis is debated, but it is highly valuable when pruritus is exacerbated by or leads to anxiety and compulsive behaviors (e.g., acral lick granulomas, overgrooming). > **Clinical Pearl:** Because of its combined anxiolytic and antihistaminic effects, doxepin is often selected for nervous or highly-strung patients suffering from allergic skin disease.
Mechanism: Doxepin exerts its effects through multiple receptor pathways: * **Monoamine Reuptake Inhibition:** In the central nervous system, doxepin blocks the presynaptic reuptake of **norepinephrine** (moderate inhibition) and **serotonin (5-HT)** (weak inhibition) โ increasing their synaptic concentrations and prolonging their activity, which contributes to its antidepressant and anxiolytic effects. * **Receptor Antagonism:** It exhibits potent **H1-histamine receptor blockade** (providing anti-pruritic and sedative effects), as well as **anticholinergic (muscarinic)** and **alpha-1 adrenergic blocking** activity. These latter receptor affinities are largely responsible for its side effect profile (e.g., dry mouth, urinary retention, hypotension).
Dosing by species
- Treatment of psychogenic dermatoses ยท 0.5-1 mg/kg PO q12-24h. Up to 25-50 mg (total dose) per cat. ยท PO ยท q12-24h ยท Allow 3-4 weeks for initial trial
- Excessive grooming ยท 0.5-1 mg/kg PO q12h. ยท PO ยท q12h
- Treatment of behavior problems (e.g., overgrooming, intercat aggression) ยท 0.5-1 mg/kg PO once to twice daily. ยท PO ยท SID to BID
- Treatment of anxiety, pruritus caused feather plucking in psittacines ยท 1-2 mg/kg PO q12h ยท PO ยท q12h
- Treatment of anxiety, pruritus caused feather plucking in psittacines ยท 0.5-1 mg/kg PO twice daily ยท PO ยท BID
- Treatment of psychogenic dermatoses ยท 3-5 mg/kg PO q12h; maximum dose is 150 mg (per dog) q12h ยท PO ยท q12h
- Treatment of psychogenic dermatoses ยท 3-5 mg/kg, PO q8-12h. Begin at 3 mg/kg PO q12h for 2 weeks, then increase by 1 mg/kg PO q12h for 2 weeks up to the maximum dosage as needed; if no clinical response after at least 3-4 weeks of therapy, decrease dosage by 1 mg/kg PO q12h for 2 weeks until at the initial dosage ยท PO ยท q8-12h ยท Titrated over weeks
- Antihistaminic effects in treatment of atopy ยท 2.2 mg/kg PO three times daily ยท PO ยท TID
- Antihistaminic effects in treatment of atopy ยท 3-5 mg/kg twice daily ยท PO ยท BID ยท Used especially if dog has anxiety or other behavioral condition
Routes of administration
Contraindications
- Prior sensitivity to doxepin or other tricyclic antidepressants
- Concomitant use with Monoamine Oxidase Inhibitors (MAOIs) such as selegiline or amitraz (within 14 days)
- Urinary retention
- Glaucoma
- Severe cardiac disease
- History of seizures
- Concurrent use with MAOIs
Adverse effects
- Hyperexcitability (paradoxical)
- Gastrointestinal distress
- Lethargy and sedation
- Ventricular arrhythmias (particularly in overdose)
- Anticholinergic effects (dry mouth, urinary retention, constipation)
- Altered blood glucose levels
- Sedation
- Lethargy
- Dry mouth (xerostomia)
- Tachycardia
- Urinary retention
- Constipation
Drug interactions
- Anticholinergic Agents ยท Additive anticholinergic effects; use cautiously. ยท moderate
- Cimetidine ยท May inhibit tricyclic antidepressant metabolism and increase the risk of toxicity. ยท moderate
- CNS Depressants ยท Additive CNS depression; use cautiously. ยท moderate
- Meperidine, Pentazocine, Dextromethorphan ยท Increased risk for serotonin syndrome.
- Monoamine Oxidase Inhibitors (MAOIs, e.g., amitraz, selegiline) ยท Concomitant use (within 14 days) is generally contraindicated due to high risk of serotonin syndrome.
- Quinidine ยท Increased risk for QTc interval prolongation and tricyclic adverse effects.
- SSRIs (e.g., fluoxetine, paroxetine, sertraline) ยท Increased risk for serotonin syndrome.
- Sympathomimetic Agents ยท May increase the risk of cardiac effects (arrhythmias, hypertension, hyperpyrexia).
- Monoamine Oxidase Inhibitors (MAOIs) ยท Risk of fatal serotonin syndrome ยท major
- Selective Serotonin Reuptake Inhibitors (SSRIs) ยท Increased risk of serotonin syndrome ยท major
Monitoring
- Efficacy (reduction in pruritus, anxiety, or compulsive behaviors)
- Adverse effects (GI distress, lethargy, hyperexcitability)
- ECG (if arrhythmias are suspected or in cases of overdose)
- Heart rate and rhythm
- Resolution of pruritus or behavioral signs
- Signs of excessive sedation or anticholinergic effects
Overdose
Overdosage with tricyclic antidepressants can be **life-threatening**. * **Clinical Signs:** Severe ventricular arrhythmias, cardiorespiratory collapse, profound CNS depression or seizures. * **Action:** Because the toxicities and therapies for treatment are complicated and controversial, it is highly recommended to contact an **animal poison control center** immediately for further information in any potential overdose situation.
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.