Anxiolytics, antipsychotics, antidepressants, and mood stabilizers used to treat human behavioral disorders are being used more commonly in veterinary medicine as adjuncts to behavioral modification therapy (also see Principles of Pharmacologic and Natural Treatment for Behavioral Problems). Few veterinary clinical studies have been reported, and guidelines for veterinary use are grounded on therapeutic applications in human medicine.
Anxiolytics, including the benzodiazepines and an azapirone (buspirone), have been used to treat generalized anxiety and panic disorder in dogs and cats, as well as urine spraying in cats. Benzodiazepines, such as diazepam, alprazolam, oxazepam, and clorazepate, act by binding to γ-amino butyric acid (GABA) receptors and enhancing GABA-mediated chloride influx. They may cause sedation and muscle relaxation; dependence and withdrawal signs also can occur.
Diazepam has been recommended to alleviate fear-related behaviors in dogs and social anxiety and urine spraying in cats. However, benzodiazepines may not alleviate fear-related aggression in certain animals, but instead may cause a paradoxical increase in such behaviors. While diazepam has been reported to diminish urine-spraying behavior in cats, most cats resume urine spraying when the drug is withdrawn. There have been rare reports of hepatic failure within 3–5 days of starting diazepam in cats.
Oxazepam (dog, 0.2–0.5 mg/kg, PO, sid-bid; cat 1–2.5 mg/cat, PO, bid) and alprazolam have been used to treat fears and phobias in both dogs and cats. In addition, alprazolam has been used to treat night-time anxiety in dogs (0.01–0.1 mg/kg, PO) and refractory housesoiling in cats (0.1 mg/kg or 0.125–0.25 mg [total dose] per cat, PO, bid-tid). Chlorazepate has been used to treat anxiety in cats (1.75–3.75 mg/cat, PO, sid-bid). Diazepam, clonazepam, and chlorazepate dipotassium also have anticonvulsant properties.
Buspirone differs from the benzodiazepines in pharmacologic properties, (ie, it blocks serotonin pre-and postsynaptically and acts as a dopamine agonist), in onset of action (delayed onset of 7–30 days), and lack of sedative effect. Buspirone appears to offer no greater control for anxiety-related behaviors than the benzodiazepines, but it is useful in treating urine spraying in cats at 2.5–7.5 mg/cat.
Antipsychotics are classified as low-potency agents (acepromazine, chlorpromazine, and thioridazine hydrochloride) and high-potency agents (haloperidol, fluphenazine, trifluoperazine hydrochloride, prochlorperazine, thiothixene, risperidone). Low-potency agents require larger doses and produce more sedation, more anticholinergic side effects, and cardiovascular effects, but they have a lower incidence of extrapyramidal side effects (parkinsonism, dystonia, dyskinesia, and akathisia) compared to the high potency agents. All the antipsychotics are used for nonselective tranquilization and diminishing behavioral arousal. Acepromazine is commonly used for infrequent anxietal episodes, but it may induce a paradoxical hyperactivity in some dogs and cats. In one report, a dog with aberrant behavior (tail chewing, growling, snapping, barking) was controlled with thioridazine at 1.1 mg/kg.
Mood-stabilizing drugs (lithium, carbamazepine, and valproic acid) are unrelated chemical compounds that are used in human medicine to treat bipolar disorder, impulsivity, emotional reactivity, and aggression. Carbamazepine and valproic acid are also antiepileptic. Carbamazepine has been used in cats (25 mg/cat, PO, bid) to decrease fear-related aggression against people, but it may paradoxically increase aggression against conspecifics. Lithium is excreted unmetabolized via the urine. Serum concentration monitoring is necessary due to its narrow therapeutic index (recommended range: 0.8–1.2 mEq/L). Side effects include polyuria, polydipsia, memory problems, weight gain, and diarrhea. In one report, lithium (75 mg total dose, bid) was used to treat owner-directed aggression and psychotic behavior (random air-snapping, pawing) in a Cocker Spaniel.
Antidepressants are classified as tricyclic compounds (tertiary amines, secondary amines), selective serotonin-reuptake inhibitors, and atypical antidepressants. They can be used to treat behavioral disorders, including obsessive-compulsive behaviors, stereotypies, aggression, and inappropriate elimination. The mode of action is to block reuptake of serotonin and/or norepinephrine or to reduce neurotransmitter turnover. All have a lag time until a behavioral effect is seen.
The tricyclic antidepressants include amitriptyline, imipramine, clomipramine, and doxepin. Case reports indicate that treatment success for behavioral disorders is highly variable among drugs within the same chemical class. The antihistaminic effect of these agents may be a useful adjunct in controlling pruritus due to atopy and food allergies. Side effects include vomiting, diarrhea, hyperexcitability, sedation, arrhythmias including tachycardia, orthostatic hypotension, mydriasis, reduced lacrimation and salivation, urine retention, constipation, and weight gain. Widening of the QRS complex on an ECG has been used as an early indication of toxicity. It may take 7–30 days for drugs to be effective. Amitriptyline hydrochloride has been used in dogs at 1–2 mg/kg for separation anxiety, anxiety-related aggression, urination due to submission or excitement, and allergy-related pruritus, and in cats at 0.5–1 mg/kg for urine marking and hypervocalization. Imipramine hydrochloride has been used in dogs at 2.2–4.4 mg/kg, bid-tid, for urination due to submission or excitement. Clomipramine hydrochloride has been used in dogs at 1–3 mg/kg for reducing lick behavior for canine lick granuloma and for stereotypies such as circling and tail chasing, and in cats at 0.5 mg/kg. In some countries it is approved for treatment of separation anxiety in dogs. Doxepine has been used in dogs at 3–5 mg/kg.
Selective serotonin-reuptake inhibitors, including fluoxetine, sertraline, and paroxetine, have been used for treating psychogenic alopecia, allergy-related pruritus, owner-directed aggression, fearful behaviors, obsessive-compulsive behaviors, and urine marking. It may take 7–30 days for these drugs to be effective. The most common side effects are changes in appetite and GI signs, although seizures have been reported. These drugs inhibit liver P450 enzymes so drug interactions are possible. Dosages for fluoxetine are 1 mg/kg, PO, sid for dogs, and 0.5–1.0 mg/kg, PO, sid for cats.
Monoamine oxidase inhibitors, like selegiline, are used for cognitive impairment in dogs.
Last full review/revision March 2012 by Linda Shell, DVM, DACVIM-Neurology