Sertraline
Sertraline hydrochloride
Also known as: Zoloft · Altruline · Anilar · Aremis · Atenix · Besitran · Bicromil · Gladem · Insertec · Irradial · Lustral · Novativ · Sealdin · Serad · Sercerin · Serlain · Serta · Tatig · Tolrest · Tresleen · Sertraline HCl · CP-51974-01 · Sertralinum
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 |
|---|---|---|---|---|---|
| Treatment of compulsive disorders | 2-4 mg/kg PO once daily or divided twice daily | PO | q24h or q12h | — | 🌎 NA |
| Behavioral diagnoses | 1-2 mg/kg PO q24h (once daily) | PO | q24h | allow 6-8 weeks for initial trial | 🌎 NA |
| Behavioral diagnoses | 1-3 mg/kg PO once daily | PO | q24h | 3-6 months | 🌎 NA |
| Treatment of behavioral diagnoses | 0.25-0.5 mg/kg PO q24h (once a day) | PO | q24h | Minimum 4-6 months | 🌎 NA |
| Compulsive disorder, anxiety | 1-4 mg/kg PO q24h (once daily) | PO | q24h | — | 🌎 NA |
| Behavioral diagnoses | 0.5-4 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Generalized anxiety disorder | 0.5-4 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Anxiety-related behaviours (including compulsive type behaviour such as acral lick) | 1-3 mg/kg | PO | q24h | Long-term | 🌍 EU |
- Behavioral diagnoses: Plan is to use the drug for a limited time during which behavioral modification is employed. Wean off over 2-4 weeks by halving the dose weekly.
- Treatment of behavioral diagnoses: Treat for 3-5 weeks minimum to assess effects; treat until 'well' (minimum another 1-2 months), then treat another 1-2 months minimum. Wean off over 3-5 weeks or longer.
- Anxiety-related behaviours (including compulsive type behaviour such as acral lick): Higher doses are described in the literature.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Treatment of compulsive disorders | 0.5 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Urine marking (spraying), aggression, anxiety-including anxiogenic house soiling, phobias, fears | 0.5-1 mg/kg PO q24h (once daily) | PO | q24h | — | 🌎 NA |
| Treatment of behavioral diagnoses | 1 mg/kg PO q24h (once a day) | PO | q24h | Minimum 4-6 months | 🌎 NA |
| Treatment of fear, affective or dominance aggression | 0.5-1 mg/kg PO once daily | PO | q24h | — | 🌎 NA |
| Generalized anxiety disorder | 0.5-1.5 mg/kg PO q24h | PO | q24h | — | 🌎 NA |
| Treatment of compulsive disorder, anxiety | 0.5-1 mg/kg PO q24h (once daily) | PO | q24h | — | 🌎 NA |
| Behavioral diagnoses | 0.25-1.3 mg/kg PO q24h | PO | q24h | — | 🌎 NA |
| Increase inhibitory control (e.g., play-related aggressive behaviour) | 0.5-1.5 mg/kg | PO | q24h | Long-term | 🌍 EU |
- Treatment of behavioral diagnoses: Treat for 3-5 weeks minimum to assess effects; treat until 'well' (minimum another 1-2 months), then treat another 1-2 months minimum. Wean off over 3-5 weeks or longer.
- Increase inhibitory control (e.g., play-related aggressive behaviour): Suggested use, but there are no good empirical studies published to support this.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Sertraline is a widely used human antidepressant that is utilized off-label in veterinary medicine to manage a variety of behavior-related diagnoses in dogs and cats.
Key Clinical Applications:
- Dogs: Aggression, generalized anxiety, and obsessive-compulsive behaviors (e.g., acral lick dermatitis, tail chasing).
- Cats: Urine marking (spraying), affective or dominance aggression, anxiogenic house soiling, phobias, and compulsive disorders.
Clinical Pearls:
Like other SSRIs, sertraline requires a prolonged duration of therapy (typically 4 to 8 weeks) before full clinical efficacy is observed. This delay is due to the time required for neuroreceptor down-regulation. It is relatively inexpensive due to the availability of generic formulations, making it an attractive option for long-term behavioral management.
Mechanism of action
Sertraline is a highly selective inhibitor of the presynaptic reuptake of serotonin (5-hydroxytryptamine or 5-HT) in the central nervous system.
- Mechanism: Blocks the serotonin transporter (SERT) → prevents the reuptake of serotonin into the presynaptic neuron → increases the concentration of serotonin in the synaptic cleft → prolongs stimulation of postsynaptic 5-HT receptors.
- Receptor Specificity: Sertraline has minimal to no effect on the reuptake of dopamine or norepinephrine, and lacks significant affinity for adrenergic, cholinergic, or histaminergic receptors, which minimizes the side effects typically seen with tricyclic antidepressants (TCAs).
- Delayed Onset: The initial increase in synaptic serotonin stimulates presynaptic 5-HT1A autoreceptors, which temporarily decreases serotonin release. Over several weeks, these autoreceptors down-regulate, allowing for enhanced serotonin release and the onset of full therapeutic effects.
Safety & warnings
Contraindications
- Known hypersensitivity to sertraline or other SSRIs
- Concurrent use of Monoamine Oxidase Inhibitors (MAOIs) such as selegiline or amitraz
- Concurrent use of cisapride
- History of seizures or epilepsy
- Concurrent use of MAOIs (e.g., selegiline)
Adverse effects
- Anorexia (common in dogs, usually transient)
- Lethargy or sedation
- Gastrointestinal effects (vomiting, diarrhea)
- Anxiety or irritability
- Insomnia or hyperactivity
- Panting (dogs)
- Changes in elimination patterns (cats)
- Paradoxical aggressive behavior in previously non-aggressive animals
- Decreased appetite
- Trembling
- Restlessness
- Gastrointestinal disturbance
- Paradoxical increase in anxiety
- Potential increase in aggression
Precautions
Hepatic Impairment: Use with caution in patients with severe hepatic disease; dosages may need to be decreased or the dosing interval increased due to extensive hepatic metabolism. Geriatric Patients: Use with caution; dose adjustments may be necessary. Pregnancy: FDA Category C in humans. Animal studies (rats/rabbits) showed delayed ossification and decreased pup survival. Use only if benefits outweigh risks. Weaning: Avoid abrupt discontinuation; taper the dose gradually over several weeks to prevent withdrawal signs.
Drug interactions
Increased risk for serotonin syndrome
May increase sertraline levels
May decrease or reverse the effects of SSRIs
Sertraline may decrease diazepam clearance
Increased risk for serotonin syndrome
High risk for serotonin syndrome; use contraindicated. A 5-week washout period is required after discontinuing sertraline before starting an MAOI, and a 2-week washout if discontinuing an MAOI before starting sertraline.
Serotonin syndrome-like adverse effects possible
SSRIs can inhibit the metabolism of tramadol to active metabolites, decreasing efficacy and increasing the risk of toxicity (serotonin syndrome, seizures)
Sertraline may increase TCA blood levels and increase the risk for serotonin syndrome
Sertraline may increase the risk for bleeding
High risk of fatal serotonin syndrome. Do not use sertraline within 2 weeks of an MAOI, and do not use an MAOI within 6 weeks of stopping sertraline.
Sertraline antagonizes the effects of anticonvulsants and lowers the seizure threshold.
May lower the seizure threshold when used concurrently.
Increased risk of bleeding in the case of tissue trauma.
Increased risk of bleeding.
Increased risk of serotonin syndrome.
Increased risk of serotonin syndrome. Use only in exceptional cases with careful monitoring.
Monitoring
- Efficacy (resolution or improvement of behavioral signs)
- Adverse effects, particularly changes in appetite and body weight
- Baseline liver function tests (consider re-testing as needed)
- Baseline ECG (consider re-testing as needed)
- Behavioral response (efficacy and paradoxical aggression/anxiety)
- Signs of serotonin syndrome (tremors, hyperthermia, agitation)
- Seizure activity
Pharmacokinetics
Half-life
Absorption
In humans, peak levels occur 30-45 minutes after oral dosing.
Distribution
In dogs, the volume of distribution is 25 L/kg. It is highly protein-bound (97% in dogs, 98% in humans).
Metabolism
Undergoes high first-pass metabolism in the liver. Primarily metabolized to N-desmethylsertraline, which is an active metabolite.
Elimination
In dogs, clearance is greater than 35 mL/min/kg, and bile is the major route of excretion.
Overdose
Toxicity Profile: Most exposures in dogs below 20 mg/kg are not considered serious. However, massive overdoses can be life-threatening.
Clinical Signs of Overdose:
- Mild to Moderate: Vomiting, diarrhea, hypersalivation (especially in cats), lethargy, tachycardia, somnolence, and vocalization.
- Severe (Serotonin Syndrome): Muscle tremors, rigidity, agitation, hyperthermia, vocalization, hypertension or hypotension, tachycardia, seizures, coma, and potentially death.
Management: Handle aggressively with supportive and symptomatic treatment. Contact an animal poison control center (e.g., ASPCA APCC) for specific guidance.
Available products
Formulations
- Tablets
- Oral Solution Concentrate
- 50 mg oral tablet
- 100 mg oral tablet
Human-labeled
- Sertraline HCl Tablets: 25 mg, 50 mg & 100 mg (as base); Zoloft® (Pfizer); generic
- Sertraline HCl Oral Solution Concentrate: 20 mg/mL in 60 mL; Zoloft® (Pfizer); generic
- Lustral 50 mg tablets
- Lustral 100 mg tablets
Regulatory status
Prescription Only Medicine (POM). Used under the cascade as no veterinary formulation is currently authorized.
Prescription Only Medicine (POM). Used under the cascade.
No regulatory data for: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store commercially available tablets and oral solution at controlled room temperature (25°C; 77°F); excursions permitted to 15-30°C (59-86°F). The oral solution must be diluted only in water, orange juice, ginger ale, lemonade, or lemon/lime soda, and used immediately after dilution.
Client information
What to Expect:
- Patience is Key: This medication does not work immediately. It typically takes 4 to 8 weeks of consistent daily dosing to see noticeable improvements in your pet's behavior.
- Commitment: You must commit to using the drug for several months to accurately determine if it is helping.
Important Guidelines:
- Do Not Stop Abruptly: Never suddenly stop giving this medication unless directed by your veterinarian, as it can cause withdrawal symptoms. If the medication needs to be stopped, your vet will provide a tapering schedule.
- Appetite Changes: A decrease in appetite is common, especially in dogs, when starting the medication. This is usually temporary. You can try hand-feeding or making the food more palatable. If your pet stops eating entirely, contact your vet.
- Monitor Behavior: Because this drug alters brain chemistry, watch for any unusual behavior, such as increased anxiety, restlessness, or unexpected aggression. Report any significant abnormal findings to your veterinarian immediately.
- Liquid Medication: If using the oral solution, it must be diluted before giving it to your pet. Only mix it with water, orange juice, ginger ale, lemonade, or lemon/lime soda, and give it immediately after mixing.
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.