Psychotropic Agents

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. Although diazepam has been reported to diminish urine spraying in cats, most cats resume spraying when the drug is withdrawn. There have been rare reports of hepatic failure within 3–5 days of starting diazepam in cats.

Oxazepam (dogs 0.2–0.5 mg/kg, PO, once to twice daily; cats 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). Clorazepate has been used to treat anxiety in cats (1.75–3.75 mg/cat, PO, once to twice daily). Diazepam, clonazepam, and clorazepate 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), 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 helps treat 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 adverse effects, and cardiovascular effects, but they have a lower incidence of extrapyramidal adverse effects (parkinsonism, dystonia, dyskinesia, and akathisia) than 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 used in human medicine to treat bipolar disorder, impulsivity, emotional reactivity, and aggression. Carbamazepine and valproic acid are also antiepileptic drugs. 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 because of its narrow therapeutic index (recommended range: 0.8–1.2 mEq/L). Adverse 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. Adverse 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 to reduce 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 to treat 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 adverse 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/day, PO, for dogs, and 0.5–1 mg/kg/day, PO, for cats.

Monoamine oxidase inhibitors, such as selegiline, are used for cognitive impairment in aging dogs. The use of progestin hormones to treat behavioral problems is currently considered a "last resort" therapy because of the risk of adverse effects. In castrated and intact male dogs, megestrol acetate has been used to treat aggression, urine marking, and roaming. Likewise, in neutered male cats, megestrol acetate can reduce spraying, but potential adverse effects of inducing diabetes mellitus, mammary gland hyperplasia and adenocarcinoma, and bone marrow suppression make it risky to use. Medroxyprogesterone acetate, an injectable, long-acting progestin, has been used to treat aggression, urine marking, and roaming; however, it is rarely used because of the risk of adverse effects and availability of other, safer behavioral drugs.