Behaviour Modifying Drugs - Overview

Although many drugs are used to treat behavioural conditions in animals, there are only three psychoactive drugs specifically licensed for use in companion animals to treat behavioural problems. These are:

• Clomipramine (EU and USA license for the treatment of separation related problems in dogs).
• Selegiline (EU License for the treatment of behavioural problems with an emotional underlying origin).
• Fluoxetine (EU and USA license for the treatment of separation anxiety in dogs, when used in combination with behavioural therapy. Subsequently withdrawn from European market).

A range of other drugs are used to treat behavioural conditions, including beta-adrenoceptor antagonists, benzodiazepines, azapirones, anticonvulsants and triazolopyridines. Some of these drugs are licensed for use in a companion animal species for another condition, but many are not licensed for use in any companion animal species. Examples are listed in the table below, however, most uses listed are unapproved, care should therefore be taken with their use:

Class of Drug	Drugs	Uses	Side Effects
Tranquillisers	Acepromazine	Sedation/restraint (no specific indication in behavioural therapy)	Hypotension, CNS stimulation, contradictory responses. Caution in boxers and greyhounds
Benzodiazepines	Alprazolam, Clonazepam, Clorazepate, Diazepam, Lorazepam, Oxazepam	Acute anxiety, panic, short-term management of noise phobias	Hepatic necrosis after oral dosing (potentially fatal), Sedation, ataxia, increased appetite, paradoxical excitation
Tricyclic Antidepressants (TCAs)	Amitriptyline, Clomipramine	Anxiety, separation anxiety, canine and feline fear aggression, feline urine marking, feline compulsive grooming, stereotypy, some narcoleptic disorders	Sedation, gastrointestinal (GI) effects, dry mouth, increased thirst, urinary retention
Selective Serotonin Reuptake Inhibitors (SSRIs)	Fluoxetine, Fluvoxamine, Paroxetine, Sertraline	Aggression, canine separation anxiety, compulsive disorders, feline urine marking	Lethargy, inappetence, anorexia, GI effects
Beta Blockers	Propranolol	Canine fear aggression, noise phobia	Bradycardia, lethargy, hypotension, syncope
Azapirones	Busiprone	Phobia, anxiety, feline urine marking, interact aggression	Uncommon, not sedating
Triazolopyridines	Trazodone
Anticonvulsants	Carbamazepine, Gabapentin, Levetiracetam, Phenobarbital, Potassium bromide	Canine and feline compulsive tail chasing, unprovoked canine rage aggression	Lethargy, ataxia, polyuria, polydipsia, polyphagia
Hormones	Medroxyprogesterone acetate, Megestrol acetate	Last resort for aggression and feline urine marking	Polyphagia, polydipsia, sedation, diabete mellitus, pyometra, mammary hyperplasia, endometrial hyperplasia, carcinoma
Glial Modulators	Propentofylline
Monoamine Oxidase Inhibitors (MAO-Is)	Selegiline	Canine and feline cognitive dysfunction syndrome, fear related problems, spraying, hyperactivity, compulsive/stereoptypical disorders, specific phobias	GI effects, restlessness or lethargy, anorexia

Benzodiazepines are the only class of drug that consistently succeeds in all models, but this may be why they have a dangerous disinhibitory effect on aggression. These drugs eliminate avoidant responses to many kinds of aversive events, increasing confidence in a number of exploratory tests. This is why benzodiazepines can cause dangerous levels of disinhibition in aggressive dogs. Benzodiazepines also inhibit memory formation by affecting NMDA (glutamate) receptors in the hippocampus, which limits their usefulness in behavioural therapy where any kind of learning is required, which is in most situations. They are useful for memory blocking if given at sub-sedative doses prior to or during a predicted traumatic event such as a thunderstorm. When used at low doses, they act as mild tranquillisers, this can help moderate excitement. At medium doses they lessen anxiety, which can encourage social interaction in a constructive way .

Drugs such as Acepromazine (ACP), which act on dopamine receptors, and synthetic hormone analogues like megestrol acetate (Ovarid), have little or no rational use in behavioural therapy for reasons of non-specificity, and adverse effects which make their use unjustifiable.

Phenothiazines such as ACP have a very varied level of effect and duration of action and dull both normal and abnormal behaviours which is an out of date approach to behavioural therapy.

The first port of call when using medication for behavioural problems should be drugs licensed for veterinary use. These drugs have established data about their efficacy, side effects, contraindications and toxicity, which makes expected outcomes more reliable.