Pharmacologic support may be necessary to achieve a change in behavior, particularly in cases for which 1) ongoing exposure
to provocative environmental and social stimuli is unavoidable, 2) the animal's degree of arousal is sufficient that behavior
modification alone will be ineffective or difficult to accomplish, or 3) the health or safety of the animal or others is at
risk. But keep in mind that behavior modification and environmental management are integral to managing behavior problems
and may enhance the efficacy of the drugs and effectively reduce the dosage and duration of treatment.12,13 Be sure to consider the animal's motivational or emotional state and the underlying neurophysiology when recommending pharmacologic
support. The types of drugs useful for self-directed behaviors include benzodiazepines, tricyclic antidepressants (TCAs),
selective serotonin reuptake inhibitors (SSRIs), and melatonin (Table 2).
Table2. Psychotropic Medications Commonly Used in the Management of Self-directed Behaviors in Dogs and Cats
The benzodiazepines increase neural inhibition as a result of their agonistic effect upon GABA receptors and produce rapid
calming and sedative effects. The benzodiazepines act as anxiolytics at low doses and hypnotics at high doses. Benzodiazepines
may not only decrease reactivity, but also facilitate social interactions. A primary benefit of benzodiazepines is their immediate
onset of action relative to the TCAs and SSRIs. As such, they can be valuable in initially managing situational and social
anxieties in pets. Benzodiazepines used in veterinary behavioral medicine include diazepam, alprazolam, clonazepam, and lorazepam.
The benzodiazepines may interfere with short-term memory and learning. Ataxia, lethargy, and somnolence may result from high
doses (hypnotic effect) as well as from lower doses, particularly during the initial days of administration or when the dose
is increased. Other side effects include increased appetite, physiological dependency, paradoxical excitement, anxiety, aggression,
excessive vocalization, and sleep disturbances. Although uncommon, idiosyncratic hepatotoxicity has been reported with diazepam
administration in cats.14
TCAs block the reuptake of serotonin and norepinephrine and are variable competitive antagonists at acetylcholine (muscarinic),
histamine, and α1- and α2-adrenergic receptors. Amitriptyline and doxepin both have antihistaminic properties because they block H1 and H2 receptors. Amitriptyline affects H1 and H2 receptors equally, while doxepin is more selective for H1 receptors. These antihistaminic properties may contribute to the efficacy of TCAs in treating pruritic conditions refractory
to traditional antihistamines, and combined with their noradrenergic effects, these drugs may be valuable in managing inflammation,
neuralgia, and pain associated with self-injurious behaviors. Because of the mechanism of action of TCAs in affecting synaptic
receptors, allow a minimum of four weeks to observe the onset of clinical effects.
Clomipramine is relatively more serotonergic and less anticholinergic than amitriptyline and doxepin. The veterinary formulation,
Clomicalm (Novartis), has been approved by the FDA for use in dogs in treating separation anxiety, although it also can be
an effective aid in treating other anxiety-related behaviors. Clomipramine is also the only TCA that has documented efficacy
in treating compulsive behaviors in animals.10,15
Potential side effects of TCAs in veterinary patients include transient sedation, increased appetite, weight gain, gastrointestinal
disturbances, constipation, cardiac conduction disturbances in patients with dysrhythmias, anxiety, and aggression. Concurrent
administration of other TCAs or SSRIs is not advisable, and concurrent administration with monoamine oxidase inhibitors (e.g. amitraz, selegiline) or L-tryptophan is contraindicated. A minimum washout period of two to three weeks is advisable before
and after monoamine oxidase inhibitor administration.16,17
Selective serotonin reuptake inhibitors
SSRIs block the reuptake of serotonin with fewer effects on other receptors than TCAs. Of the SSRIs commonly used in veterinary
behavioral medicine—sertraline, paroxetine, and fluoxetine—paroxetine does produce some muscarinic anticholinergic effects
(primarily constipation, most notable in cats). While TCAs maintain some structural similarity as a group, SSRIs vary substantially
in chemical structure, so they may differ substantially in their pharmacokinetic properties. The metabolism of paroxetine
is unique in that almost no active metabolites are produced. This feature may favor paroxetine administration in elderly patients
or animals with liver or kidney disease. SSRIs are used to treat anxiety disorders, depression, and aggressive behaviors.
Despite the specificity of SSRIs for serotonin in comparison with clomipramine, they appear to be equally effective in managing
compulsive behaviors. Because of SSRIs' mechanism of action in affecting synaptic receptors, allow a minimum of six to eight
weeks to observe the onset of clinical effects.