Anxiolytics, antipsychotics, antidepressants, and mood stabilizers used to treat human behavior disorders are being administered more commonly in veterinary medicine as adjuncts to behavior modification treatment. Few veterinary clinical studies have been reported, and guidelines for veterinary use are grounded on therapeutic applications in human medicine.
For specific therapeutic recommendations, including dosages, refer to the relevant disease chapter.
Anxiolytics
Anxiolytics, including the benzodiazepines and an azaperone (buspirone), have been used to treat generalized anxiety and panic disorder in dogs and cats, as well as urine spraying in cats.
Benzodiazepines—eg, diazepam, alprazolam, oxazepam, and clorazepate—act by binding to gamma-aminobutyric acid (GABA) receptors and enhancing GABA-mediated chloride influx.
Benzodiazepines can cause sedation and muscle relaxation; dependence and withdrawal signs also can occur.
Occasionally, disinhibition (exhibition of typically inhibited behavior, such as excitement or aggression) has been observed in dogs treated with benzodiazepines. In cats, fatal hepatic necrosis has also been reported shortly after initiation of treatment with oral diazepam. Therefore, oral benzodiazepines should be administered with caution in this species.
Buspirone as Anxiolytic for Treatment of Animals
Buspirone differs from the benzodiazepines in its pharmacological properties (ie, it blocks serotonin pre- and postsynaptically and acts as a dopamine agonist), its onset of action (delayed onset of 7–30 days), and its lack of sedative effect. Buspirone appears to offer no greater control of anxiety-related behaviors than do the benzodiazepines; however, it may help treat urine spraying in cats.
Clorazepate as Anxiolytic for Treatment of Animals
Clorazepate has been used to treat anxiety in cats. Diazepam, clonazepam, and clorazepate dipotassium also have anticonvulsant properties (see Anticonvulsants for Treatment of Animals).
Diazepam as Anxiolytic for Treatment of Animals
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 and instead can 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Although diazepam has been reported to diminish urine spraying in cats, most cats resume spraying when the drug is withdrawn.
Gabapentin as Anxiolytic for Treatment of Animals
In veterinary medicine, gabapentin is used mainly for its analgesic, anticonvulsant, and anxiolytic properties. It should be administered 90 minutes before a stressful event, including traveling or visits to the veterinarian. The peak effect was reported at 2–3 hours after administration, and cats showed less stress-related behavior and aggression with this treatment.
In dogs, gabapentin has been used as a temporary adjunct for the treatment of anxiety, phobias, panic disorders, and compulsive disorders when selective serotonin reuptake inhibitors or tricyclic antidepressants are not effective, or as a longer-term add-on. It is recommended to start at the low end of the dose and titrate up to avoid adverse effects (mainly sedation).
Imepitoin as Anxiolytic for Treatment of Animals
In the US, Imepitoin is labeled to treat noise aversion in dogs. Treatment should be started 2 days before the anticipated event (eg, fireworks).
Oxazepam and Alprazolam as Anxiolytics for Treatment of Animals
Oxazepam and alprazolam have been used to treat fears and phobias in both dogs and cats. In addition, alprazolam has been used to treat nighttime anxiety in dogs and refractory house soiling in cats.
Antipsychotics
Antipsychotics are classified as low-potency agents (acepromazine, chlorpromazine, and thioridazine hydrochloride) and high-potency agents (haloperidol, fluphenazine, trifluoperazine hydrochloride, prochlorperazine, thiothixene, and risperidone). Low-potency agents require larger doses and produce more sedation, anticholinergic adverse effects, and cardiovascular effects; however, they have a lower incidence of extrapyramidal adverse effects (parkinsonism, dystonia, dyskinesia, and akathisia) than the high-potency agents have.
All of the antipsychotics are used for nonselective tranquilization and diminishing behavior arousal. Acepromazine is commonly administered for infrequent anxiety episodes; however, it can induce paradoxical excitation (excessive excitement, anxiety, or aggression) in some dogs and cats. In one reported case, aberrant behavior in a dog (tail chewing, growling, snapping, and barking) was controlled with thioridazine (1).
Mood-Stabilizing Drugs
Mood-stabilizing drugs (lithium, carbamazepine, and valproic acid) are unrelated chemical compounds administered in human medicine to treat bipolar disorder, impulsivity, emotional reactivity, and aggression. Carbamazepine and valproic acid are also anticonvulsant drugs.
Carbamazepine as a Mood-Stabilizing Drug for Treatment of Animals
Carbamazepine has been administered to cats to decrease fear-related aggression against people; however, it can paradoxically increase aggression against conspecifics.
Lithium as a Mood-Stabilizing Drug for Treatment of Animals
Lithium is excreted unmetabolized in urine. Serum concentration monitoring is necessary because of lithium's narrow therapeutic index (recommended range: 0.8–1.2 mEq/L). Adverse effects include polyuria/polydipsia, memory problems, weight gain, and diarrhea. Because lithium stimulates granulopoiesis, neutrophilia is also expected on a CBC.
In one reported case, lithium was administered to treat owner-directed aggression and psychotic behavior (random air snapping and pawing) in a Cocker Spaniel (2).
Lithium is not recommended for use in cats.
Valproic Acid as a Mood-Stabilizing Drug for Treatment of Animals
Valproic acid has been used mainly in dogs to treat seizures (see Anticonvulsants for Treatment of Animals). Its use to treat behavior problems remains anecdotal; no dosages have been established for this purpose.
Antidepressants
Antidepressants are classified as tricyclic compounds (tertiary amines, secondary amines), selective serotonin reuptake inhibitors, and atypical antidepressants. They can be used to treat behavior disorders, including obsessive-compulsive behaviors, stereotypies, aggression, and inappropriate elimination.
Their mode of action is to block the reuptake of serotonin or norepinephrine or to decrease neurotransmitter turnover.
All antidepressants have a lag time before a behavioral effect becomes evident.
Selective Serotonin Reuptake Inhibitors for Treatment of Animals
Selective serotonin reuptake inhibitors (SSRIs), 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 can take 7–30 days for these drugs to be effective.
The most common adverse effects of SSRIs are changes in appetite and GI signs; seizures have also been reported. These drugs inhibit hepatic cytochrome P450 enzymes, so drug interactions are possible.
Tricyclic Antidepressants for Treatment of Animals
The tricyclic antidepressants include amitriptyline, imipramine, clomipramine, and doxepin. Case reports indicate that treatment success for behavior disorders is highly variable among drugs within the same chemical class. The antihistaminic effect of these agents can be a useful adjunct in controlling pruritus that is due to atopy and food allergies.
Adverse effects of tricyclic antidepressants include vomiting, diarrhea, hyperexcitability, sedation, arrhythmias including tachycardia, orthostatic hypotension, mydriasis, decreased lacrimation and salivation, urine retention, constipation, and weight gain. Widening of the QRS complex with tachycardia on ECG is an early indicator of toxicosis. It can take 7–30 days for these drugs to be effective.
Amitriptyline as Antidepressant for Treatment of Animals
Amitriptyline hydrochloride has been administered to dogs for separation anxiety, anxiety-related aggression, urination due to submission or excitement, and allergy-related pruritus. In cats, it has been administered for urine marking and hypervocalization.
Clomipramine as Antidepressant for Treatment of Animals
Clomipramine hydrochloride has been administered to dogs to decrease licking behavior for canine lick granuloma and for stereotypies such as circling and tail chasing. It has also been used successfully in cats for urine marking, as well as for anxiety-related and obsessive-compulsive disorders.
In some countries, clomipramine is approved for the treatment of separation anxiety in dogs.
Doxepin as Antidepressant for Treatment of Animals
Doxepin has been used in dogs to treat pruritus.
Imipramine as Antidepressant for Treatment of Animals
Imipramine hydrochloride has been administered to dogs for inappropriate urination due to submission or excitement.
Other Agents and Hormones
Medroxyprogesterone Acetate for Treatment of Animals
Medroxyprogesterone acetate, an injectable, long-acting progestin, has been used to treat aggression, urine marking, and roaming. It is rarely used, however, because of the risk of adverse effects and availability of other, safer behavioral drugs.
Megestrol Acetate for Treatment of Animals
In castrated and sexually intact male dogs, megestrol acetate has been administered to treat aggression, urine marking, and roaming. Likewise, in neutered male cats, megestrol acetate can decrease spraying; however, potential adverse effects (diabetes mellitus, mammary gland hyperplasia and adenocarcinoma, and bone marrow suppression) make its use risky.
Monoamine Oxidase Inhibitors for Treatment of Animals
Monoamine oxidase inhibitors, such as selegiline, are used for cognitive dysfunction in aging dogs. Although no drugs or diets are licensed for feline cognitive dysfunction, selegiline has been used in an extralabel fashion.
Progestin Hormones for Treatment of Animals
The use of progestin hormones to treat behavior problems has been reported but is considered a last-resort treatment because of the risk of adverse effects.
References
Jones RD. Use of thioridazine in the treatment of aberrant motor behavior in a dog. J Am Vet Med Assoc. 1987;191(1):89-90. doi:10.2460/javma.1987.191.01.89
Reisner I. Use of lithium for treatment of canine dominance-related aggression: a case study. In: Proceedings. Annual Meeting of the American Veterinary Society of Animal Behavior, Minneapolis, Minnesota, 19 July 1993.
