Clomipramine
Clomipramine HCl
Also known as: Clomicalm · Anafranil · clomipramini hydrochloridum · G-34586 · monochlorimipramine hydrochloride · Clofranil · Clopram · Clopress · Equinorm · Hydiphen · Maronil · Novo-Clopamine · Placil · Tranquax · Zoiral · Clomipraminum · Clomipramine hydrochloride
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Label directions (Clomicalm) | 2-4 mg/kg | PO | once daily or divided twice daily | — | 🌎 NA |
| Behavioral disorders | 3 mg/kg | PO | q12h | — | 🌎 NA |
| Male dimorphic behaviors, fearful/fear aggression, noise phobias, obsessive/compulsive behaviors | 1 mg/kg PO every 12 hours for 2 weeks; then 2 mg/kg PO q12h for 2 weeks, then 3 mg/kg PO q12h for 4 weeks and maintain | PO | q12h | Maintain after 8 weeks | 🌎 NA |
| Adjunctive treatment of storm phobia | Clomipramine 2 mg/kg PO q12h for 3 months, then 1 mg/kg PO q12h, then 0.5 mg/kg PO q12h for 2 weeks | PO | q12h | 3.5 months | 🌎 NA |
| Separation-related disorders, anxiety, compulsive behaviors, noise fears, cataplexy | 1-2 mg/kg | PO | q12h | Long-term (e.g., 3 months for cataplexy) | 🌍 EU |
- Behavioral disorders: start at a low dose (e.g., 1 mg/kg for 2 weeks, then 2 mg/kg for 2 weeks, then 3 mg/kg)
- Male dimorphic behaviors, fearful/fear aggression, noise phobias, obsessive/compulsive behaviors: May take 4-6 weeks to see apparent improvement.
- Adjunctive treatment of storm phobia: Used with alprazolam (0.02 mg/kg PO as needed 1 hour before anticipated storms and q4h as needed) and behavior modification
- Separation-related disorders, anxiety, compulsive behaviors, noise fears, cataplexy: Licensed for use in association with a behaviour modification plan for separation-related disorders.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Urine marking/spraying; inter-cat aggression; redirected aggression; compulsive grooming/wool sucking | 0.5 mg/kg | PO | once daily | — | 🌎 NA |
| Behavioral disorders | 0.3-0.5 mg/kg | PO | q24h | — | 🌎 NA |
| Behavioral disorders | 0.5-1 mg/kg | PO | once daily | — | 🌎 NA |
| Urine marking | 0.3-0.5 mg/kg PO q24h (2.5-5 mg per cat q24h) | PO | q24h | — | 🌎 NA |
| Anxiety-related disorders, compulsive behaviours, urine spraying | 0.25-1 mg/kg | PO | q24h | — | 🌍 EU |
- Anxiety-related disorders, compulsive behaviours, urine spraying: Monitor for urinary retention.
Birds
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Adjunctive treatment of feather picking | 0.5-9 mg/kg | PO | q12-24h | — | 🌎 NA |
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Clomipramine is a tricyclic antidepressant (TCA) used primarily in veterinary behavioral medicine.
- Dogs: FDA-approved for the treatment of obsessive-compulsive disorders (ritualistic stereotypical behaviors) and separation anxiety. It is also used off-label for dominance aggression and noise phobias.
- Cats: Used off-label for behavioral issues such as urine spraying, psychogenic alopecia, and compulsive grooming.
- Birds: Used to treat feather-picking behaviors.
Clinical Pearl: Like most TCAs and SSRIs, clomipramine requires a prolonged duration of therapy (often 4-8 weeks) before maximal clinical efficacy is observed. It should ideally be used as an adjunct to a comprehensive behavior modification plan rather than a standalone treatment.
Mechanism of action
The exact mechanism of action of tricyclic antidepressants involves the blockade of monoamine reuptake in the central nervous system.
- Primary Action: Clomipramine predominantly inhibits the presynaptic reuptake of serotonin (5-HT) via the serotonin transporter (SERT) → increasing synaptic serotonin concentrations.
- Active Metabolite: Its primary active metabolite, desmethylclomipramine, primarily inhibits the reuptake of norepinephrine (NE) via the norepinephrine transporter (NET).
- Receptor Downregulation: The chronic elevation of these neurotransmitters leads to the gradual down-regulation of post-synaptic receptors, which correlates with the delayed onset of clinical behavioral effects (taking several weeks).
- Off-target Effects: TCAs also exhibit antagonism at muscarinic (cholinergic), histamine (H1), and alpha-1 adrenergic receptors, which are responsible for many of their adverse effects (e.g., dry mouth, sedation, hypotension).
Safety & warnings
Contraindications
- Prior hypersensitivity to clomipramine or other tricyclic antidepressants
- Concomitant use with monoamine oxidase inhibitors (MAOIs) within 14 days
- Concurrent ingestion of aged cheeses (high tyramine content)
- Known sensitivity to tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs)
- Concurrent use of Monoamine Oxidase Inhibitors (MAOIs) or within 2 weeks of their use
- Male breeding animals (due to risk of testicular hypoplasia)
Adverse effects
- Emesis
- Diarrhea
- Sedation, lethargy, and depression
- Anticholinergic effects (dry mouth, tachycardia, urinary retention)
- Elevation of liver enzymes
- Pancreatitis (rarely reported in dogs)
- Birds: Ataxia, drowsiness, regurgitation
- Sporadic vomiting
- Changes in appetite
- Urinary retention (especially in cats)
- Testicular hypoplasia (in male breeding animals)
Precautions
Seizure Warning: TCAs may lower the seizure threshold. Use with extreme caution in animals with preexisting seizure disorders.
- Anticholinergic Risks: Use cautiously in patients with decreased GI motility, urinary retention, cardiac rhythm disturbances, or increased intraocular pressure.
- Hepatic Function: May cause hepatic abnormalities. Baseline and annual monitoring of liver enzymes is recommended for long-term use.
- Thyroid Disease: Use cautiously in hyperthyroid patients or those on thyroid supplementation due to increased risk of cardiac arrhythmias.
- Reproductive Safety: Not a known teratogen, but high doses have demonstrated testicular atrophy. The manufacturer warns against use in breeding male dogs. FDA Category C for human pregnancy.
- Species Sensitivity: Cats may be more sensitive to adverse effects (sedation, anticholinergic signs) due to slower elimination of the desmethyl metabolite.
Drug interactions
Additive anticholinergic effects; use cautiously
Risk of extrapyramidal side effects (reported in a macaw)
May inhibit tricyclic antidepressant metabolism and increase the risk of toxicity
Increased risk for prolonged QT interval
May cause increased blood pressure
Additive CNS depression; use cautiously
Increased risk for serotonin syndrome
Increased risk for QTc interval prolongation and tricyclic adverse effects
May decrease tricyclic blood levels
Increased risk for serotonin syndrome
May increase the risk of cardiac effects (arrhythmias, hypertension, hyperpyrexia)
Concomitant use is generally contraindicated due to high risk of fatal serotonin syndrome
Risk of fatal serotonin syndrome; do not use concurrently or within 2 weeks of each other
Potentiation of anticholinergic effects (e.g., dry mouth, tachycardia, urinary retention)
Potentiation of CNS depressant effects
Potentiation of CNS depressant effects (though noted as safe to use together with care)
Potentiation of sympathomimetic cardiovascular effects
Potentiation of anticoagulant effects
Increased plasma levels of the antiepileptic drug
Increased plasma levels of the antiepileptic drug
Increased risk of serotonin syndrome; use only in exceptional cases with careful monitoring
High risk of fatal serotonin syndrome. Do not use within 2 weeks of each other.
Increased risk of serotonin syndrome. Use with trazodone only in exceptional cases with careful monitoring.
May potentiate anticholinergic effects.
May potentiate CNS depressant effects.
May potentiate sympathomimetic effects.
Plasma levels of the antiepileptic drugs may be increased by co-administration.
Monitoring
- Clinical efficacy (behavioral improvement)
- Baseline and annual liver function tests
- EKG (especially in patients with cardiac risks or hyperthyroidism)
- Clinical efficacy (reduction in anxiety/compulsive behaviors)
- Signs of serotonin syndrome (agitation, tremors, hyperthermia, tachycardia) if used with other serotonergic drugs
- Urinary output and frequency, particularly in cats
- Appetite and gastrointestinal tolerance
Pharmacokinetics
Half-life
Absorption
Dogs: Rapidly converted in the liver to active metabolite desmethylclomipramine. Food decreases AUC for the parent compound by ~25% but not the metabolite. Cats: Oral bioavailability averages 90%. Humans: Well absorbed but substantial first-pass effect reduces systemic bioavailability to ~50%.
Distribution
Highly lipophilic and widely distributed throughout the body (Vd = 17 L/kg). Highly bound to plasma proteins (96%). Crosses the placenta, maternal milk, and the blood-brain barrier.
Metabolism
Metabolized principally in the liver to several metabolites, including the active desmethylclomipramine. Cats metabolize clomipramine more slowly than dogs (male cats slower than females).
Elimination
About two-thirds of metabolites are eliminated in the urine and the rest in the feces.
Overdose
Clomipramine has a narrow margin of safety. Significant clinical signs can be seen at or slightly above the therapeutic range (2-3 mg/kg).
- Lethal Dose: In dogs, lethal doses are approximately 50-100 mg/kg/day PO (12.5-25X recommended dose).
- Clinical Signs (Dogs): Lethargy, tachycardia, ataxia, depression, vocalization, and vomiting.
- Clinical Signs (Cats): Lethargy, mydriasis, tachypnea, ataxia, depression, and tachycardia.
- Severe Toxicity: Overdosage with TCAs can be life-threatening, leading to severe arrhythmias, seizures, and cardiorespiratory collapse.
Action: Because toxicities and therapies are complicated and controversial, contact an animal poison control center immediately in any potential overdose situation.
Available products
Formulations
- Oral tablets
- Oral capsules
- 5 mg tablet
- 20 mg tablet
- 80 mg tablet
Veterinary
- Clomipramine HCl Oral Tablets: 5 mg, 20 mg, 40 mg, & 80 mg (Clomicalm®)
- Clomicalm 5 mg tablets
- Clomicalm 20 mg tablets
- Clomicalm 80 mg tablets
Human-labeled
- Clomipramine Oral Capsules: 25 mg, 50 mg, & 75 mg (Anafranil®)
- Anafranil 10 mg, 25 mg, 50 mg, 75 mg capsules/tablets
Regulatory status
Licensed for separation-related disorders in dogs.
POM-V classification.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Veterinary tablets should be stored in a dry place at controlled room temperature (15-30°C) in the original closed container. Human capsules should be stored at <30°C in tight containers and protected from moisture.
Client information
- Patience is Key: This medication may take several weeks (often 4-8 weeks) before you see beneficial effects in your pet's behavior.
- Training: It is generally most effective when used in combination with a behavior modification plan provided by your veterinarian or a veterinary behaviorist.
- Administration: May be given with or without food. If your pet vomits after taking the medication, try giving it with a meal.
- Do Not Stop Abruptly: Do not stop therapy suddenly without your veterinarian's guidance, as this can cause withdrawal effects or a relapse in behavior.
- Toxicity Warning: Keep this medication strictly out of reach of pets and children. Overdoses can be highly toxic and life-threatening.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.