Drugs and natural therapeutics – an evidence-based approach (Proceedings)

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Drugs and natural therapeutics – an evidence-based approach (Proceedings)

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Aug 01, 2009

Psychotropic drugs and natural alternatives might be used to help reduce the signs associated with phobic, panic or chronic anxiety states and to improve trainability especially in situations where the pet is too anxious, fearful or impulsive to control its responses. However, drugs can serve to reduce the underlying anxiety, they do not in themselves change the relationship with the stimulus so that concurrent behavior modification will also be needed to desensitize, countercondition and train desirable responses in the presence of the stimulus. Drugs may also be useful for feline urine marking and as an adjunct to therapy in some cases of aggression. There may also be some pathologic disorders affecting behavior, such as compulsive disorders where drugs might be necessary.

Evidence based decision making is a means of providing the best information and treatment options that evidence has to offer. The validity of the information, the fundamentals of all clinical trials and their trial design and the application of statistics is necessary to properly appraise the evidence. Treatment should be selected using the evidence combined with the clinician's expertise as to the patient, client and problem. In veterinary medicine there is limited availability to the process. Many sources of veterinary information fall in the poorest (D) level including personal experience, colleague opinion, text books, continuing education notes, internet or inconclusive studies. Studies based on in vitro research or from another species also fall into this category. The most desirable evidence (A) is from systematic reviews with homogeneity or randomized controlled clinical trials (RT). Where the assessment of multiple RTs is not possible, then a single RT with high confidence would be the next best option.1

In veterinary behavior, much of the information has been extrapolated from human literature; however, drug metabolism and receptor effects vary between species which can lead to inaccurate assumptions with respect to dose, duration of effect, contraindications and side effects. Those few drugs that are licensed for use in pets should first be considered since there is published data with respect to safety, efficacy, side effects, contraindications, toxicity and pharmacokinetics. In addition, the technical support available from the manufacturer provides additional expertise, especially in the event of adverse events. Psychotropic drugs should be used with informed consent for any off-label use. A physical examination and blood and urine tests should be part of the minimum database prior to dispensing drugs and with continued use. Treatment options for cognitive dysfunction are discussed in a separate seminar.

Antidepressants



Antidepressants cause little or no sedation and are unlikely to inhibit learning or memory. They might help to control anxiety and panic and may decrease the intensity of outbursts. There is extensive evidence on the efficacy of clomipramine and fluoxetine in dogs for anxiety disorders including separation anxiety, compulsive disorders and phobias, and for the treatment of compulsive disorders and urine marking in cats. Selective serotonin reuptake inhibitors (SSRI) such as fluoxetine may also be indicated as an adjunct for the treatment of some forms of aggression including those with anxiety and impulse dyscontrol. Clomipramine and fluoxetine are licensed in the United States for the treatment of separation anxiety in dogs, and clomipramine is also licensed in other countries for separation anxiety, compulsive and anxiety disorders in dogs, and for urine marking in cats.

While antidepressants may achieve peak plasma levels within hours, this does not reflect their therapeutic effect since reuptake inhibition may induce down-regulation of postsynaptic receptors that are responsible for the clinical effects. Therefore, 4 to 8 weeks of therapy is generally recommended to fully assess therapeutic effects. Tricyclic antidepressants (TCA) and SSRIs should not be used concurrently with other antidepressants or MAO inhibitors such as selegiline and amitraz and should be used cautiously in pets with seizures. Since SSRIs inhibit cytochrome P-450 enzymes, they can lead to increased toxicity when combined with drugs that are metabolized by these enzymes.

In dogs, when antidepressants are combined with behavior modification, a faster and greater improvement can be achieved in the treatment of separation anxiety. However, in one study behavior modification alone appeared to be as effective. Participants in this study reported that clomipramine reduced general activity and provided a modest suppression of attachment-related tendency to seek physical contact. In one study where the use of fluoxetine chewable tablets were compared to placebo without concurrent behavior modification, a drug effect was established; however even greater improvement was seen when fluoxetine was combined with a behavior modification plan (BMP).