Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA
Introduction
Traditionally, veterinary medicine has predominantly focused on physical health more than psychological/mental health. However, recent developments in veterinary medicine, including FDA approved psychotropic medications, has revealed possible underlying pathologies in psychological/mental health in animals. Like humans, anxiety and/or psychological stress can contribute to physical conditions. It is also not uncommon for some behavior problems to manifest from anxiety disorders. Therefore, it is the clinician's responsibility to carefully evaluate behavior signs to establish a behavioral diagnosis. The goal of behavioral psychopharmacological interventions is to modulate the causal state of the patient without negatively impacting the animal's welfare as well as the client's quality of life.
There are six key neurotransmitter systems targeted by psychotropic medications.
Serotonin
Norepinephrine
Dopamine
Acetylcholine
Glutamate
GABA (γ-aminobutyric acid)
Long-term Medications
This group of medications is orally administered every day to treat primarily underlying anxiety.
Long-term medications that influence serotonin activity have been used the most in veterinary behavior medicine.
Current FDA (US Food and Drug Administration) approved psychopharmacology medications for dogs that fall into this category are clomipramine (for canine separation anxiety), fluoxetine (for canine separation anxiety) and selegiline (for canine cognitive dysfunction syndrome). FDA has approved no psychopharmacology medications for cats.
Selective Serotonin Reuptake Inhibitors (SSRIs)
Clinical indications for the use of SSRIs in humans range from anxiety disorders, premenstrual dysphoric disorder, eating disorders, major depressive disorders and beyond. Clinical usage for SSRIs in companion animals is usually limited to anxiety-related conditions.
When using SSRIs it is important to know that the clinical effect is delayed after an SSRI is introduced, although side effects can be observed relatively rapidly, if they occur.
There are six SSRIs. Most commonly used in veterinary medicine are fluoxetine, sertraline and paroxetine.
Tricyclic Antidepressants (TCAs)
Most TCAs inhibit, to some extent, both serotonin and norepinephrine reuptake.
All TCAs are antagonists at H1-histaminic, α1-adrenergic, muscarinic cholinergic receptors and voltage-sensitive sodium channels.
While TCA is as effective as SSRIs for similar clinical indications, its major limitation compared to SSRI is its side effects.
There are several agents in TCAs but amitriptyline and clomipramine are clinically used the most in veterinary behavior medicine.
Monoamine Oxidase Inhibitors (MAOIs)
MAO exists in two subtypes, A and B. FDA approved medication, selegiline, is subtype B (MAO-B).
Selegiline may enhance dopamine transmission and the release of norepinephrine.
Clinical indication for the use of selegiline is cognitive dysfunction syndrome.
Selegiline should not be used concurrently with MAO inhibitors such as amitraz, narcotics, or α-adrenergic agents such as phenylpropanolamine or serotonergic drugs such as SSRIs or TCAs.
A 2-week washout is needed following most TCAs and 5 weeks following fluoxetine before starting selegiline.
Azapirones
Buspirone is used in veterinary behavior medicine both as a long-term medication and short-term medication.
It is a partial serotonin receptor agonist.
It is used in combination with an SSRI or TCA for anxiety treatments, or is used alone as an anxiolytic for short-term management such as car rides.
Short-Term Medications
This group of medications is orally administered on an as-needed basis for an anxious/fearful event (e.g., thunderstorms) or in combination with long-term medication.
Neurotransmitters that regulate anxiety/fear symptoms are serotonin, glutamate, GABA, norepinephrine, corticotropin-releasing factor and voltage-gated ion channels.
Most anxiolytic actions target these neurotransmitter actions.
Benzodiazepines
The most widely used anxiolytics in humans and animals. It works by enhancing GABA actions.
In general, decreased anxiety, hyperphagia, muscle relaxation, decreased locomotor activity and varying degrees of sedation are observed with benzodiazepine administration.
Low doses cause mild sedation. Moderate doses cause anxiolytic effects. High doses cause hypnosis.
Paradoxical excitability is known to occur in some patients, therefore, testing the drug in the owner's presence is important.
Disinhibition of aggression can occur under the influence of these medications so caution is advised.
It is important to note that the onset of action, duration of effect, intensity of effect and metabolism differ depending on the agent and the individual patient.
Benzodiazepines are controlled substances and have potential for human abuse.
Although there are several agents in this group, mostly alprazolam, clonazepam, clorazepate, diazepam, lorazepam and oxazepam are clinically used in veterinary behavior medicine.
Atypical Antidepressants
Trazodone is used in veterinary behavior medicine both as a long-term medication and short-term medication.
It is used in combination with an SSRI or TCA for anxiety treatment, or is used alone as an anxiolytic for short-term management such as after surgery.
High doses can cause aggression, anxiety, tachycardia and ataxia.
Close monitoring is required when it is combined with other serotonergic medications.
Alpha-2 adrenergic receptor agonists
Clonidine is used in veterinary behavior medicine in combination with an SSRI or TCA for anxiety treatment.
Clinical indications for the use of clonidine in humans range from antihypertensive agent to analgesics. It is also used for the treatment of attention deficit hyperactive disorder (ADHD), posttraumatic stress disorder (PTSD) and impulsivity. Clinical usage of clonidine in companion animals is used for similar conditions such as anxiety-related conditions and impulsivity.
It is used in combination with a long-term medication.
It should be used cautiously in animals with cardiac disease, and medications that might increase or decrease norepinephrine levels.
Conclusion
Psychopharmacology intervention is definitely helpful if it is applied to an appropriate case. Since most medications used in veterinary behavioral medicine are extra-label use, clinicians should be familiar with specific indications, contraindications and side effects before it is used. Otherwise they should refer the cases to a specialist who is knowledgeable its usage.
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Class
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Drug
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Indications
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Dosage (dog)
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Dosage (cat)
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SSRIs
- Aggression
- Compulsive disorder
- Urine marking
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Fear, anxiety
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Fluoxetine
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1–2 mg/kg q 24 h
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0.5–1 mg/kg q 24 h
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Sertraline
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1–3 mg/kg q 24 h
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0.5–1.5 mg/kg q 24 h
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Paroxetine
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0.5–2 mg/kg q 24 h
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0.5–1 mg/kg q 24 h
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TCAs
- Fear, anxiety
- Compulsive disorder
- Urine marking
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Varies between drugs in this class
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Amitriptyline
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1–2 mg/kg q 12 h
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0.5–1 mg/kg/day
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Clomipramine
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1–2 mg/kg q 12 h
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0.25–1 mg/kg q 24 h
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MAOIs
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Cognitive dysfunction
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Selegiline
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0.5–1 mg/kg q 24 h
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0.5–1 mg/kg q 24 h
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Azapirones
- Urine marking
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Fear, anxiety
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Buspirone
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0.5–2 mg/kg q 8–12 h
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7.5 mg/cat q 12 h
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Benzodiazepines
- Sleep/hypnosis
- Urine marking
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Anxiety
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Alprazolam
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0.02–0.1 mg/kg PRN to q 6 h
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0.125–0.25 mg/cat q 8–24 h
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Clonazepam
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0.1–1 mg/kg q 8–12 h,
0.02 mg/kg before sleep (sleep disorder)
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0.05–0.25 mg/kg q 8 h–24 h,
0.02 mg/kg before sleep (sleep disorder)
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Clorazepate
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0.5–2 mg/kg q 8–12 h
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0.2–0.5 mg/kg q 12–24 h
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Diazepam
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0.5–2.2 mg/kg PRN to q 4 h
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0.2–0.5 mg/kg q 8–12 h
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Lorazepam
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0.02–0.1 mg/kg q 8–24 h
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0.125–0.25 mg/cat q 12–24 h
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Oxazepam
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0.2–1 mg/kg q 12–24 h
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0.2–0.5 mg/kg q 12–24 h
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Atypical antidepressants
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Anxiety
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Trazodone
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2–3 mg/kg PRN to q 8 h
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50 mg/cat PRN
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Alpha-2 adrenergic receptor agonists
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Anxiety, panic
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Clonidine
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0.01–0.05 mg/kg PRN up to q 12 h
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References
1. Landsberg G, Hunthausen W, Ackerman L. Behavior Problems of the Dog and Cat. 3rd ed. St. Louis, MO: Saunders Elsevier; 2013:113–138.
2. Overall KL. Manual of Clinical Behavioral Medicine for Dogs and Cats. St. Louis, MO: Mosby; 2013:458–512.
3. Crowell-Davis S, Muray T. Veterinary Psychopharmacology. Ames, IA: Wiley-Blackwell; 2005.