Clomipramine

Clomipramine is a tricyclic antidepressant used in veterinary behavioral medicine. Its best-established role is treatment of separation-related anxiety in dogs alongside behavioral management. It is also used extra-label for selected compulsive disorders and feline behavioral problems. Sustained treatment changes monoaminergic signaling relevant to anxiety and repetitive behavior.

Group

Tricyclic antidepressant

Mechanism of Action

Clomipramine inhibits presynaptic reuptake of serotonin, increasing its availability within central synapses. Its active metabolite, desmethylclomipramine, contributes more strongly to inhibition of norepinephrine reuptake. Adaptation of these neurotransmitter systems during continued treatment underlies the gradual anxiolytic and anti-compulsive effects. The drug also interacts with muscarinic, histamine and alpha-adrenergic receptors.

Dose Rates

Dogs

Use / stage	Dose	Route	Schedule	Instructions
Behavioral disorders	2–4 mg/kg	PO	Every 24 h	Total daily oral regimen. An alternative is division into two daily doses; do not give the entire daily amount twice daily.
Behavioral disorders	1–2 mg/kg	PO	Every 12 h	Arithmetic division of the stated 2–4 mg/kg total daily amount into two equal doses.
Higher-dose behavioral titration	Reference only	PO		Historical escalation: 1 mg/kg orally every 12 hours for two weeks, then 2 mg/kg every 12 hours for two weeks, then 3 mg/kg every 12 hours for four weeks and reassessment. This exceeds some routine label daily ranges and requires an individualized titration plan.
Storm-phobia combination treatment	Reference only	PO		Historical combination: clomipramine 2 mg/kg orally every 12 hours for three months, then reduce through 1 mg/kg and 0.5 mg/kg every 12 hours, the latter for two weeks. Alprazolam 0.02 mg/kg orally one hour before a predicted storm and every four hours as needed is a separate adjunct; use behavior modification.

Cats

Use / stage	Dose	Route	Schedule	Instructions
Behavioral disorders	1–5 mg/animal	PO	Every 12–24 h	Start low and titrate. The source also describes approximately 0.5 mg/kg total daily as an alternative.
Behavioral disorders	0.5 mg/kg	PO	Every 24 h
Urine spraying	5 mg/animal	PO	Every 24 h	Upper fixed dose described; lower doses may be selected during titration.
Behavioral disorders	0.3–0.5 mg/kg	PO	Every 24 h
Behavioral disorders	0.5–1 mg/kg	PO	Every 24 h
Urine spraying	2.5–5 mg/animal	PO	Every 24 h

Birds

Use / stage	Dose	Route	Schedule	Instructions
Feather-picking adjunct	0.5–9 mg/kg	PO	Every 12–24 h	Very broad historical reported range; species, diagnosis and behavior management determine appropriateness. Not a routine starting range.

Indications

Treatment of separation-related anxiety in dogs as part of a behavioral modification program.
Extra-label treatment of canine compulsive behaviors, including selected cases of repetitive licking, tail chasing or stereotypic activity.
Extra-label reduction of anxiety-associated urine spraying in cats.

Contraindications

Use cautiously in cardiac disease.
Use cautiously with seizures, urinary retention, reduced gastrointestinal motility, glaucoma or thyroid disease/supplementation.

Interactions

Do not combine with other serotonergic behavior medicines or MAO inhibitors, including selegiline and amitraz.
Cisapride can add to QT-related arrhythmia risk; cimetidine can reduce tricyclic clearance.
Serotonergic opioids, dextromethorphan and SSRIs increase serotonin-syndrome risk; avoid MAO inhibitors and maintain an appropriate drug-specific washout.
Anticholinergics and CNS depressants add to adverse effects; sympathomimetics or quinidine can increase cardiac risk.
Rifampin can reduce tricyclic exposure.

Adverse effects

Sedation
Reduced appetite and vomiting
Dry mouth, tachycardia and urine retention
Weight gain in cats
Reduced total and free T4

Toxicity

Large overdoses can cause life-threatening cardiotoxicity.

Preparations

Preparation	Form	Strength	Route
Clomipramine 5 mg tablet	Tablet	5 mg / tablet	PO
Clomipramine 20 mg tablet	Tablet	20 mg / tablet	PO
Clomipramine 40 mg tablet	Tablet	40 mg / tablet	PO
Clomipramine 80 mg tablet	Tablet	80 mg / tablet	PO
Clomipramine 25 mg capsule	Capsule	25 mg / capsule	PO
Clomipramine 50 mg capsule	Capsule	50 mg / capsule	PO
Clomipramine 75 mg capsule	Capsule	75 mg / capsule	PO

Monitoring and Administration

Combine drug treatment with behavior management. Benefit can take 2–4 weeks; increase doses gradually, generally no more often than every 14 days.

Monitor heart rate and rhythm. A small amount of food may reduce vomiting. Protect from moisture.

Efficacy has not been shown for dominance aggression or feline psychogenic alopecia.

Obtain baseline hepatic tests and ECG when indicated; reassess liver function during long-term use. Broad behavioral response may require 4–6 weeks, and withdrawal or dose reduction should be gradual.