Clomipramine is a tricyclic antidepressant (TCA) available under the veterinary brand name Clomicalm (manufactured by Elanco). It is the first and only FDA-approved medication for the treatment of separation anxiety in dogs when used in conjunction with a behavior modification program. Clomipramine works primarily by inhibiting the reuptake of serotonin and, to a lesser extent, norepinephrine in the brain, which helps regulate mood and reduce anxiety-related behaviors. It has been used in veterinary medicine since the late 1990s and remains a cornerstone treatment for canine anxiety disorders.
What Is Clomipramine Used For?
Clomipramine is prescribed for dogs to treat:
- Separation anxiety (FDA-approved indication) including destructive behavior, excessive vocalization, and house soiling when left alone
- Compulsive disorders such as acral lick dermatitis, tail chasing, and flank sucking (off-label)
- Generalized anxiety and noise phobias (off-label)
- Urine marking and anxiety-related elimination (off-label)
Clomipramine is most effective when combined with a structured behavior modification program. Medication alone is generally insufficient. Consult your veterinarian and consider working with a veterinary behaviorist for the best outcomes.
Dosage
The FDA-approved dose of clomipramine for separation anxiety in dogs is 1 to 2 mg/kg (0.5 to 1 mg/lb) twice daily. Your veterinarian will determine the appropriate dose.
| Dog’s Weight | Starting Dose (1 mg/kg BID) | Maximum Dose (2 mg/kg BID) |
|---|---|---|
| 10 lbs (4.5 kg) | 4.5 mg twice daily | 9 mg twice daily |
| 20 lbs (9 kg) | 9 mg twice daily | 18 mg twice daily |
| 40 lbs (18 kg) | 18 mg twice daily | 36 mg twice daily |
| 60 lbs (27 kg) | 27 mg twice daily | 54 mg twice daily |
| 80 lbs (36 kg) | 36 mg twice daily | 72 mg twice daily |
Clomicalm tablets are available in 5 mg, 20 mg, 40 mg, and 80 mg strengths. Clomipramine may take 4 to 6 weeks to reach full therapeutic effect. Do not increase the dose or discontinue the medication without consulting your veterinarian. Gradual tapering is recommended to avoid withdrawal effects.
Side Effects
| Common Side Effects | Serious Side Effects (Contact Your Vet) |
|---|---|
| Drowsiness or sedation | Seizures |
| Decreased appetite | Rapid or irregular heartbeat |
| Dry mouth | Difficulty urinating |
| Mild GI upset (vomiting, diarrhea) | Severe lethargy or disorientation |
| Elevated liver enzymes | Jaundice (yellowing of gums/skin) |
| Serotonin syndrome (tremors, agitation, hyperthermia) |
Most side effects are mild and often resolve within the first 1-2 weeks of treatment. Your veterinarian may recommend periodic blood work to monitor liver function during long-term use.
Drug Interactions
Clomipramine has significant drug interactions. Always inform your veterinarian of all medications your dog is taking.
- MAOIs (selegiline/Anipryl, amitraz): Concurrent use can cause fatal serotonin syndrome. A minimum 14-day washout period is required.
- SSRIs (fluoxetine, sertraline): Increased risk of serotonin syndrome.
- Tramadol: May increase serotonin syndrome risk.
- Cimetidine: May increase clomipramine blood levels.
- Anticholinergic drugs: May potentiate anticholinergic side effects (dry mouth, urinary retention, constipation).
- CNS depressants: May increase sedation.
Contraindications
Clomipramine should not be used in:
- Dogs with known hypersensitivity to clomipramine or other TCAs
- Dogs currently receiving or recently treated with MAOIs (wait at least 14 days)
- Dogs with a history of seizures (may lower seizure threshold)
- Male breeding dogs (may affect fertility; safety not established)
Use with caution in dogs with cardiac disease, glaucoma, urinary retention, liver disease, or hyperthyroidism. Consult your veterinarian before use.
Storage
- Store at controlled room temperature, 68-77 degrees F (20-25 degrees C).
- Protect from moisture and light.
- Keep in original packaging.
- Keep out of reach of children and pets.
Frequently Asked Questions
How long does clomipramine take to work? Initial mild improvement may be seen within 1-2 weeks, but full therapeutic effect typically takes 4 to 6 weeks. Do not discontinue the medication prematurely if you do not see immediate results. Consult your veterinarian.
Can I stop clomipramine suddenly? No. Abrupt discontinuation may cause withdrawal symptoms including irritability, nausea, and rebound anxiety. Your veterinarian will provide a gradual tapering schedule.
Does my dog still need behavior training? Yes. Clomipramine is FDA-approved specifically as an adjunct to behavior modification, not as a standalone treatment. A structured desensitization and counterconditioning program is essential for long-term success.
Is clomipramine safe for cats? Clomipramine is sometimes used off-label in cats for urine spraying and anxiety, but it is not FDA-approved for feline use. Only use under direct veterinary supervision.
What is the difference between clomipramine and fluoxetine for dogs? Both are used for canine anxiety, but clomipramine (TCA) and fluoxetine (SSRI) have different mechanisms and side effect profiles. Your veterinarian will recommend the most appropriate option based on your dog’s specific condition and health status.
This content is for informational purposes only and is not a substitute for professional veterinary advice. Always consult your veterinarian before starting, changing, or stopping any medication for your dog.