NMVMA listserve Veterinary Behavior Tip #15
February, 2016

Jeff Nichol, DVM – Veterinary Behavior Medicine
Veterinary Emergency and Specialty Centers
Albuquerque and Santa Fe


Drug interaction checker :



The dosages and comments listed here are based on published information along with current uses by members of the veterinary behavior community. This outline should only to be used as a guide. Many of these recommendations involve drugs that are not FDA approved for use in pets. Please remember to inform your clients when you prescribe medications for extra-label uses.

Prior to prescribing:

  • Screen cases with a complete blood count and chemistry panel. Monitor lab work annually in young animals, every 3-6 months in older pets.
  • Behavior medications are to be administered orally. Transdermal absorption has been shown to be diminished resulting in inconsistent serum levels.
  • None of these drugs should be used in animals with a history of sensitivity to any drug in the same class.
  • Until you are familiar with a given drug it is advised that treatment be started at a conservative dose.
  • Remember that medications are often unnecessary and when needed are only part of the solution. Research-based behavior modification and management changes are essential for the best success.
  • This is only a partial list. Residency training in psychopharmacology is helpful in managing cases that require other drugs and combinations.
  • I’m always available to answer questions.


Tricyclic Antidepressants (TCA’s)

  • Generally used to treat anxiety, compulsive behaviors and some cases of aggression. They also have antidepressant effects.
  • Full behavioral benefits are not likely to be seen for several weeks (3-4 weeks in most cases).
  • Must be given daily; not useful on an as-needed basis
  • Bitter tasting when compounded in oral liquids.
  • If the decision is made to withdraw these drugs after several months taper by reducing the dose 25% every 1-2 weeks.
  • More effective than SSRIs for fear-related and anxiety disorders. Less effective than SSRIs for aggression.


Common Side Effects:

  • Lethargy/sedation, vomiting, diarrhea, constipation, increased anxiety, seizures in dogs with a history of epilepsy.


Drug Interactions:

  • Monoamine A Oxidase Inhibitors (MAOI’s) like selegiline, amtraz (some tick collars)
  • CNS depressants, SSRI’s, tramadol
  • Phenylpropanolamine may cause hypertension when given with TCAs.
  • Anticholinergics (such as atropine)
  • Thyroid supplements
  • Other drugs that are metabolized by Cytochrome P450 2D6 (fluoxetine, haloperidol, quinidine, doxepin, and paroxetine).



  • Patients with urine or stool retention, glaucoma, seizure history, or cardiac disease. The concern with all TCAs and SSRIs are conduction interval changes. In dogs they have been shown to be minor and a small to possibly negligible risk. Not so in cats.
  • Avoid in cases with severe liver disease


       Amitriptyline (Elavil)

  • Among the first behavior medications in veterinary use.
  • No longer as popular due to its higher risk of side effects and low clinical efficacy.
  • Useful in the treatment of severe recurrent idiopathic cystitis in cats and neuropathic pain in cats and dogs.
  • A TCA that blocks norepinephrine reuptake, it can help reduce hyper arousal. Amitriptyline has more antihistamine effect than clomipramine.
  • May increase appetite. May be inappropriate for dogs with food-related aggression.
  • Dose:
  • Cats: 0.5-2.0 mg/kg q12-24 h
  • Dogs: 1-6 mg/kg q12 h
  • Available in 10, 25, 50, 75, 100, 150 mg tablets


Clomipramine (Clomicalm)

  • The half life increases with increased dose. Higher doses are sometimes more effective.
  • The most serotonin specific of the TCAs. Also has norepinephrine reuptake properties.
  • Interferes with/decreases tT4 & fT4 on testing,
  • Uses in cats: urine spraying, nocturnal hypervocalization, aggression between familiar cats, anxiety-related owner directed aggression, hyperesthesia, compulsive grooming (psychogenic alopecia), wool sucking (Oriental breeds).
  • Uses in dogs: separation anxiety, compulsive disorders: tail chasing, sky gazing, lick granulomas (with antibiotics), and noise phobias (with a benzodiazepine).
  • 25, 50, 75 mg generic capsules ($$$). Clomicalm chewable 5, 20, 40, 80 mg.
  • Dose:
    • Cats: 0.25-1.3 mg/kg q24h
    • Dogs: 2-4 mg/kg q12h. (can go as high as 6-8 mg/kg-Cirabassi)
    • Approach higher doses gradually to determine effectiveness and reduce risk of side effects.
  • Available as chewable tablets: Clomicalm 5, 20, 40, 80 mg.; generic capsules 25, 50, 75 mg.



  • Helpful for dogs with submissive urination due to its side effect of urine retention.
  • Dose:
    • Dogs 0.5 – 2.0 mg/kg tid – bid
  • Available as 10, 25, & 50 mg. tablets


Selective Serotonin Reuptake Inhibitors (SSRIs)

  • Useful in the treatment of generalized anxiety, aggression, urine marking, inappropriate sexual behavior (reduces libido), and compulsive disorders.
  • Full behavioral benefits are not likely to be seen for at least 3-4 weeks. Administer once daily.
  • It is the agonist actions of serotonin specifically upon 5-HT1A receptors that account for the therapeutic effects of SSRIs/SNRIs
  • Must be given daily; not useful on an as-needed basis
  • If the decision is made to withdraw these drugs after several months taper by reducing the dose 25% every 1-2 weeks.
  • Geriatric dogs: sertraline and fluoxetine are less likely than paroxetine to have cholinergic effects that can affect cognitive function.
  • Fluoxetine first unless there is a good reason not to.
    • Use paroxetine if they are aloof or not great eaters to begin with.
    • More activation with sertraline compared to fluoxetine.
    • Useful for the separation anxiety cases that are eliminating in the house.
    • A broken bond (dog is disinterested in owner) use paroxetine and buspar. In 6 weeks many are dramatically improved.
    • Paroxetine has more anticholinergic activity than fluoxetine and sertraline. Reported as mild.

Common Side Effects:

  • Sedation, tremor, diarrhea, vomiting, hyporexia, irritability, restlessness, seizures, and constipation (especially in cats).
    • Activation as a side effect refers to agitation and increased anxiety.
    • It also means a patient that is very awake and alert which is why it’s recommended to give fluoxetine and sertraline in the morning.
  • Seizures
  • Mild lethargy and reduced appetite are commonly seen during the first 1-2 weeks of treatment.
    • Typically resolves with continued use.
    • Less common at lower doses

Drug Interactions:

  • There are many. Those involving the most commonly used drugs that rely on CYP2D6 for metabolization are:
    • The data suggest that treatment with NSAIDs prevents clinical responses to SSRI antidepressants.
      • Antidepressant effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated by antiinflammatory drugs in mice and humans – Jennifer L. Warner-Schmidta,1, Kimberly E. Vanoverb, Emily Y. Chena, John J. Marshalla, and Paul Greengarda,1
      • The interaction between antidepressants and antiinflammatory agents appears to be specific to the efficacy of SSRIs and not a general effect on all classes of antidepressants.
    • MAOI’s like selegiline, amitraz (some tick collars)
    • Other SSRIs
    • TCAs (clomipramine, amitriptyline)
    • Tramadol
    • NSAIDs
    • Benzodiazepines (reduce dose of SSRI when using in combination)
    • Tryptophan
    • cyproheptadine
    • Dextromethorphan, haloperidol, meperidine
    • Metoclopramide (extrapyramidal effects)
    • Cisapride is a relatively potent inhibitor of CYP2D6


  • Avoid in cases with severe liver or kidney disease.
  • Caution in diabetics (may increase blood glucose).
  • Avoid in pets with narrow angle glaucoma.
  • May reduce platelet function resulting in surgical hemorrhage.
  • The concern with all TCAs and SSRIs are conduction interval changes. In dogs they have been shown to be minor and a small to possibly negligible risk. Not so in cats.


Fluoxetine (Prozac)

  • Useful in many cases of (owner directed and interdog) canine aggression and feline urine spraying.
  • Anxiety related behaviors
  • Lick granuloma/self injurious behavior
  • Transdermal absorption is poor.
  • May reduce T4 in serum.
  • Can taper slowly and consider washout of 4-5 half lives prior to starting a different seritonergic drug.
    • Long half-life compared with other SSRIs.
    • If completely d/c it can be stopped abruptly and, because of its long half life, can be allowed to “self taper”.
  • Dose:
    • Cats: 0. 5-1.5 mg/kg q24h
    • Dogs: 0.5-1.5 mg/kg q24h. (Lower doses are usually quite effective and cause fewer side effects)
  • Generic available in 10, 20, 60 mg tablets; 10, 20, & 40 mg capsules
    • Teva brand may be better absorbed in dogs than other generics


Paroxetine (Paxil)

  • Dogs with generalized anxiety disorder (GAD)
  • Cats with urine spraying and aggression
  • May increase appetite. May be inappropriate for dogs with food-related aggression.
  • Urinary retention property makes it helpful in cases of anxiety-related house soiling.
  • Shorter half-life than other SSRIs, so should taper slowly.
  • Avoid paroxetine in dogs with separation anxiety
  • Paroxetine is the go-to for broken bonds.
  • Fewer side effects than any other SSRIs.
    • Fewer anticholinergic, sedative, and cardiovascular side effects than other SSRIs (except in geriatric dogs).
    • Cats on paroxetine are prone to constipation. After initial response dose can often be reduced to EOD, later to every third day.
    • No preferred for use in geriatric pets.
  • Dose:
    • Cats: 0. 5-1.0 mg/kg q24h
    • Dogs: 0.5-1.0 mg/kg q12h. or 1-3 mg/kg q24h.
  • Available in 10, 20, 30, and 40 mg tablets.


Sertraline (Zoloft)

  • An alternative to clomipramine or fluoxetine for treatment of lick granuloma
  • More dopaminergic than fluoxetine
  • A good alternative in animals with a history of side effects to TCAs.
  • Generally safe in cases of renal impairment
  • Sertraline will suppress thyroid results
  • Dose:
    • Cats: 0. 5-1.0 mg/kg q24h
    • Dogs: 2.5-5.0 mg/kg q24h. can split dose bid
  • Available in 25, 50, & 100 mg tablets; 20 mg/ml liquid.



  • Use it in dogs who become anxious or have persistent GI side effects on fluoxetine.
  • Clinical impression is that I see fewer side effects with it than fluoxetine.
  • Dose the same as fluoxetine, starting low and titrating up. Usually dogs stabilize somewhere between 0.5 and 1 mg/kg.
  • Available in 10, 20, & 40 mg tablets; 20 mg/ml liquid.


Benzodiazepines (BDZs)

  • Anxiety, fears/phobias
  • Rapid acting (30-40 minutes) antianxiety medications.
  • Used preemptively for separation anxiety, noise phobias (thunder, fireworks, hot air balloons).
  • Urine spraying and severely frightened cats.
  • Can improve defensive aggression. In cases of offensive aggression biting can be disinhibited (worsened). Not usually recommended in aggression cases.
  • May increase appetite. May be inappropriate for dogs with food-related aggression.
  • Often used in combination with TCAs or SSRIs for noise phobia or separation anxiety.
  • Withdrawal requires gradual tapering (25% dose reduction every 1-2 weeks).
  • May interfere with learning at higher doses.

Common Side Effects:

  • Increased appetite, paradoxical excitation, lethargy (a normal response at higher doses), and aggression in dogs with a tendency for it.
  • Transient cardiovascular depression.
  • Increased affection especially with cats.
  • Rare hepatic necrosis in cats. Diazepam’s intermediate metabolite, nordiazepam, has been has been implicated. Lorazepam has no intermediate metabolites and is considered a safer choice for cats.

Drug Interactions:

  • Ketoconazole
  • Itraconazole
  • Isoniazid
  • Cimetidine
  • Erythromycin
  • Propranalol
  • Valproic acid
  • Digoxin
  • CNS depressants such as barbiturates


  • Narrow angle glaucoma, severe kidney or liver disease. Reduce dose in obese and geriatric pets.
  • Pregnant or lactating animals
  • Situations of possible owner drug addiction


Alprazolam (Xanax)

  • Panic attacks, extreme fear
  • Best given about 40 minutes prior to anticipated events like storms, fire works, owner departure.
  • Short duration (3-4 hours)
  • Dose:
    • Cats: 0.0125-0.25 mg/kg q8h (lorazepam is a better choice in cats)
    • Dogs: 0.02-0.1 mg/kg q4h.
  • Available in 0.25, 0.5, & 1.0, & 2.0 mg tablets; 1.0 mg/ml liquid.


Diazepam (Valium)

  • May be more effective than alprazolam for panic attacks and extreme fear in some dogs.
  • Avoid use in cats due to potentially toxic intermediate metabolite.
  • T ½ in dogs 2.5 – 3.2 hours
    • Metabolite nordiazepam t ½ is 3.6 – 10 hours
  • Dose:
    • Dogs: 0.5-2.0 mg/kg q4h.
  • Available in 2, 5, & 10 mg tablets; 1.0 mg/ml & 5.0 mg/ml suspension.


Lorazepam (Ativan)

  • No active intermediate metabolites
  • Longer acting in cats than other BDZs.
  • Less prone to paradoxical reactions than other BDZs
  • Dose:
    • Cats: 0.03-0.08 mg/kg BID
    • Dogs 0.02-0.5 mg/kg q8-12h
  • Available in 0.5, 1.0 & 2.0 mg tablets; 2.0 mg/ml solution.


Clorazepate (Tranxene)

  • Longer duration: t ½ in dogs 9 hours.
  • Nordiazepam is an active metabolite
  • Dose:
    • Cats: 0.5-2.0 mg/kg BID
    • Dogs 0.5-2.0 mg/kg q4h
  • Available in 3.75, 7.5, 11.25, & 15 mg tablets; 3.75, 7.5, & 15 mg. capsules



  • A mild antianxiety considered the least likely of all psychotropics to cause side effects.
  • Must be given daily; not useful on an as-needed basis
  • Anxieties and minor phobias
  • Generalized Anxiety Disorder (GAD)
  • Urine marking cats in multicat households
  • “Victim” cats in intercat aggression households
  • Can be used with TCAs and SSRIs.
  • Full behavioral benefits are not likely to be seen for at least 1-3 weeks.
  • Dose:
    • Cats: 2.5–5 mg/cat BID
    • Dogs: 0.5-2.0 mg/kg q8-24h. 25 mg. max for most dogs >50#.
  • Available in 5, 10, 15, & 30 mg tablets; the 15 & 30 mg. tablets are scored.

Rare Side Effects:

  • Paradoxical increased anxiety
  • Sedation
  • Vomiting or diarrhea
  • Aggression in pets who may be prone to it.

Drug Interactions:

  • MAOI’s like selegiline, amitraz (some tick collars).


  • Kidney and liver disease result in higher blood levels of buspirone.
  • Concomitant use of erythromycin or itraconazole.



  • In addition to its anticonvulsant effect may be useful for GAD, mood and panic disorders, and as an adjunct therapy in compulsive disorders.
  • May be useful in self-mutilation disorder.
  • Cats with hyperesthesia-use as a secondary agent
  • Used to treat chronic neuropathic pain.
  • May be good for dogs with amygdalar hyperreactivity. Pet has time to think before reacting.
  • The mechanism of action for gabapentin and pregabalin is uncertain, but both drugs have high binding affinities to the α2δ-1 subunit of presynaptic voltage-gated calcium channels in the CNS
    • Their analgesic effects may be related to calcium influx inhibition as well as inhibition of the release of excitatory neurotransmitters in spinal and supraspinal pathways.
    • It is hypothesized that conditions such as neuropathic pain and epilepsy may involve excessive formation of excitatory synapses. A recent study showed that by binding to this α2δ-1 subunit, gabapentin prevents the binding of thrombospondin, a synaptogenic protein secreted by astrocytes, thereby impeding synapse formation between neurons.
  • May be good with SSRI for explosive aggression. Pet has time to think before reacting.
  • Urinary incontinence can occur with doses above 5mg/kg
  • Eliminated by the kidneys
  • A good general analgesic in geriatric dogs. Start low (5mg/kg q8-12h) and titrate to effect balancing analgesia with sedation.
  • Dose:
    • When dosing 25 mg BID.
    • Cats eat it readily on some favored food followed by regular food.
    • Cats: 12.5 mg/cat BID.
    • Dogs: 25-60 mg/kg divided q 6-8h. Dose can be gradually increased.
  • Available in 100, 300, & 400mg capsules; 600 & 800 mg. tablets.
  • Liquid (Neurontin) has xylitol and is not recommended for dogs and cats.



  • A triazolopyridine, a member of the phenylprerazine class.
  • Classified as a SARI
    • Trazodone’s most potent binding property is 5-HT2A antagonism and inhibition of serotonin reuptake.
    • Trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) also have agonistic affects on serotonin 1 receptors.
    • Its ability to block SERTs is 100 fold less potent than its ability to block 5-HT2A receptors Since both of these actions are considered necessary for antidepressant efficacy, trazodone’s multifunctional actions are sometimes categorized as “serotonin antagonist-reuptake inhibition” (SARI)
    • Unlike SSRIs and SNRIs, trazodone simultaneously blocks 5-HT2A receptors and to a lesser extent, 5-HT2C receptors, a key differentiating feature with major clinical implications, especially in terms of tolerability.
  • An adjunct antianxiety (given with SSRIs or TCAs) with minimal side effects.
  • Can be given q 12-24 h or prn.
  • Anxieties (generalized, separation), noise phobias.
  • Full behavioral benefits are seen 1-2 hours post administration.
  • Dose:
    • <10 kg: < 25 mg. q 12-24 h for 3 days, then < 50 mg. q 8-24 h.
    • 10-20 kg: 50 mg. q 12-24 h for 3 days, then 100 mg. q 8-24 h.
    • 20-40 kg: 100 mg. q 12-24 h for 3 days, then 200 mg. q 8-24 h.
    • >40 kg: 100 mg. q 12-24 h for 3 days, then 200-300 mg. q 8-24 h.
    • Over time many dogs develop tolerance and require increasing doses to a maximum of 20 mg/kg/day.
    • 50mg/cat
    • 25mg/cat for petite cats
    • Give 2 hours prior to trip to veterinary clinic,
      • Jill Orlando research: During examinations, there were no significant reductions in stress scores or aggression, and no differences in measures of heart rate and respiratory rate of cats that received trazodone vs placebo.
    • Dogs: 2-5 mg/kg q12-24 hours.
    • Cats:
  • Available in 50, 100, 150, & 300 mg tablets.

Drug Interactions:

  • MAOI’s like selegiline, amitraz (some tick collars).


  • None known

It will take about 1-2 weeks to see the full behavioral effects of this medication.

Trazodone has not been officially approved for use in pets. While the risks are quite low, like all drugs there is a small chance of side effects.

In the unusual pet we can see:

  • Marked sedation
  • Restlessness
  • Weakness
  • Dizziness
  • Tremors

Rare Side Effects:

  • Gagging
  • Behavioral disinhibition (meaning more fear/anxiety/aggression)
  • Colitis (meaning diarrhea)
  • Marked sedation
  • Restlessness
  • Weakness
  • Dizziness
  • Tremors


50, 100, 150 mg. tablets



  • Classified as an antipsychotic because it decreases emotional arousal and causes relative indifference to stressful situations (Crowell-Davis, Murray 2006).
  • Useful for chemical restraint to temporarily reduce motor activity.
  • Not effective as an antianxiety nor in aggressive animals.
  • Not appropriate in the long term treatment of phobias (loud noises); essentially a “chemical straight jacket”.
  • Sometimes used as an adjunct to SSRIs, BDZs.
  • Dose as sole treatment:
    • Cats: 0.5-2.2 mg/kg prn
    • Dogs: 0.1-2.2 mg/kg TID or prn.
  • Dose as adjunctive treatment:
    • Cats: 0.25-0.5 mg/kg prn
    • Dogs: 0.25-0.5 mg/kg TID or prn.
  • Available in 10 & 25 mg tablets.

Common Side Effects:

  • Difficulty initiating movements, muscle spasms, motor restlessness, tremors or stiffness.
  • Decreased social and exploratory behaviors, reduced avoidance responses.
  • Paradoxical excitability, aggression in dogs with no history of aggression.

Drug Interactions:

  • Additive depressant effects when used in combination with barbiturates and narcotics.


  • Pets with seizure disorders.
  • Hepatic or renal impairment, cardiac disease.
  • Use with caution in young or debilitated animals, geriatric and giant breed dogs, greyhounds, and boxers.
  • Can produce prolonged depression.
  • Aggression.



  • Fear, severe separation anxiety
  • Often used with SSRI + trazodone with a propranolol
  • May need to have owners get up earlier than usual to give to dogs who start to wind-up their arousal very early.
  • Drug interactions
    • Start the beta blockers on the weekends and titrate up.
    • When you do the drug interactions- trazodone and SSRI’s are also contraindicated
  • Dose: Dogs 0.2-1mg/kg q8h (can go as high as 0.4-0.5mg/kg tid for highly aroused dogs)



  • Clonidine can be a good med to use post op for dogs that need to be calm because it has analgesic as well as calming properties.
  • It’s related to dexdomitor, alpha 2 adrenergic. Can be used with SSRIs and TCAs.
  • Works well for dogs who won’t go to sleep. Also good for reactive dogs on leash walks.
  • Can reduce BP and HR
  • Dose: 0.026 mg/kg (0.01-0.05 mg/kg) BID – TID. For large dogs 0.3- 0.9 mg. It takes 2 hours to become effective and lasts 4-6 hours.
  • Administer 1.5 – 2 hours prior to fear provoking event, BID – TID. (median optimal dose 0.019 mg/kg.
  • Can use with serotonergic agents.
  • Rebound hypertension can be avoided by slowly withdrawing treatment.
  • Available as 0.1, 0.2, and 0.3 mg tablets


Possible side effects:

  • feeling dizzy, drowsy, tired, or nervous;
  • dry mouth;
  • nausea, vomiting, constipation, loss of appetite;
  • sleep problems (insomnia);
  • urinating more at night;
  • mild skin rash or itching
  • rapid weight gain can occur in humans


  • fast or pounding heartbeat
  • a very slow heart rate
  • confusion, hallucinations;
  • fever, pale skin


Feline Facial Pheromone (Feliway)

  • A synthetic pheromone modeled after pheromones found in the cheeks of cats.
  • Purported to create a state of familiarity and security for cats, to increase comfort and decrease stress.
  • Available in spray and diffuser form. Feliway multicat is a new formulation said to decrease tension and conflict in multi-cat households.


Feliway Multi Cat

  • This is a social pheromone that can be helpful when there are conflicts between/among cats.
  • It will not solve the problem alone but it can be helpful
  • An in-depth behavioral evaluation will be necessary to help make a lasting difference in these households.


 Dog Appeasing Pheromones (Adaptil)

Also known as DAP, this product is a synthetic pheromone modeled after one emitted from a lactating mother dog. Placebo controlled clinical studies have shown that the Adaptil brand of DAP reduces anxious behaviors such as barking and whimpering. About 60% of dogs showed efficacy, some with profound effects. Adaptil comes in many forms, including collars that last 3-4 weeks, plug in diffusers, and sprays.

In addition, the use of a collar impregnated with a synthetic copy of the dog-appeasement pheromoneb that originates from the intermammary sebaceous glands of lactating bitches after whelping is recommended

as an additional anxiety-reducing measure. The synthetic dog-appeasement pheromoneb has been shown to decrease anxiety in several fear-related conditions, 12–14 including noise phobia related to fireworks,15 although evidence of its efficacy as a single agent may not be sufficiently demonstrated.



  • Mild to moderate fears and anxieties.
  • Can be safely added to TCAs and SSRIs
  • l-theanine (Suntheanine) is metabolized by the kidneys in rats.
  • Anxitane S = 50 mg
  • Anxitane M/L = 100 mg

L-theanine, a nutraceutical, is an amino acid found in green tea leaves that is thought to increase levels of GABA, serotonin, and dopamine in the brain. There is some weak scientific data supporting its use in dogs and cats to treat mild anxiety (Virbac sponsored). Originally used in humans as a relaxant and as an antihypertensive. Available as a chewable tablet for both dogs and cats.

Pike (2015) – Dogs, thunderstorms, open label, no placebo, owner self-reported after 5 thunderstorms.

Decreased drooling, following people, panting, pacing, and hiding, with a high owner satisfaction.

Araujo (2010) – 21 beagle dogs, 14 were anxious based on facial expressions, body postures, and actions including retreat, hiding, and conflict behaviors such as circling. 10 in the study, 5 given anxitane, 5 placebo. Increased levels of human approach and interaction and frequency compared to placebo first period, (touching or sniffing in an arena).

“No side effects up to 5x the recommended dose” – virbac

Dramard (2007) – pilot study, 33 cats administered 25 mg BID for a month. Questionnaires filled out by veterinarians on day 0, 15, 30. 21 cats responded. Reported decrease in physical signs, inappropriate elimination, hypervigilance, and aggressiveness. 27/33 owners were satisfied, no side effects reported.



  • Mild to moderate fears and anxieties.
  • 75mg caps: one capsule for 1-5 kg/ 2 capsules for 5-10 kg once daily.
  • 225mg caps: once capsule 10-20kg once daily.
  • 450mg capsules: 20-40 kg 1 capsule/ over 40 kg once daily.
  • Open the capsule and sprinkling on food gives best absorption.

Alpha-casozepine is nutraceutical that contains fractionated bovine milk protein derived from casein. It is structurally similar to GABA and has an affinity for benzodiazepine receptors. There is some scientific evidence that it can be used for mild anxiety in dogs and cats. It can be used daily in conjunction with Adaptil and comes in various capsule sizes.

Zylkene in Diabetics:

  • Contains maltodextrin, which has a glycemic index of 3 times that of table sugar. It was meant to be a filler, but also somewhat of a flavor enhancer as well.
  • Not recommended in diabetics as it is likely to destabilize treatment.



  • Published clinical applications for SAM-e include its use in liver disease and as a treatment for cognitive dysfunction in dogs.
  • In humans, clinical trials have shown that SAM-e is clinically and statistically better than placebo, and is as effective as tricyclic antidepressants (TCAs) in the treatment of depression.
  • Consider SAM-e in any case that has liver enzyme elevation. May also use SAM-e if a patient has vague nausea or is labeled by the client as being a “picky eater” or as “acting old”.
  • If the patient doesn’t seem to respond well enough to a SSRI or TCA can augment it with SAM-e.
  • The dose of SAM-e that I use is what is typically used for liver disease, 20 mg/kg once daily an hour before or two hours after a meal. SAM-e is supplied in a number of formulations. My initial recommendation is to use a veterinary product because there is no regulation in nutraceutical products.
  • With the exception of a new chewable veterinary SAM-e product, it must have an enteric coating and be packaged individually in a sealed foil strip. It cannot be packaged as a bottle of loose tablets since it can degrade and oxidize in the presence of moisture.
  • Drug interactions and side effects are rare. Since SAM-e may increase serotonin levels there are warnings about its concurrent use with SSRIs or TCAs due to the potential for serotonin syndrome. I have not had a drug interaction and have used it concurrently with fluoxetine 0.5 mg/kg once daily and/or amitriptyline 1-2 mg/kg twice daily.
  • Do not use it in conjunction with a monoamine oxidase inhibitor (MAOI).
  • Rare side effects include nausea and diarrhea.



Tryptophan is a precursor for serotonin and therefore may have some effect on behavior. Some human studies have shown that diets low in tryptophan may cause an increase in anger, depression, and aggression while an increase tryptophan may promote a feeling of well-being.

DeNapoli – 33 dogs completed, dominance aggression, territorial aggression, hyperactivity. For each group, 4 diets were fet for a 1 week period each, in random order, with a transitional period of at least 3 days between. Differences in behavior scores with Trp supplementation, but no significant differences in plasma levels. May reduce aggression in dominance and territorial??

Bosch – 8 weeks fed diet, 66 control, 72 tryp diet with 2.6x more trp. Double blind placebo controlled. 3rd diet with trp, beet pulp, salmon oil, soy lecithin, and green tea extract for 69 dogs. Owner reported scores after 4 and 8 weeks. 34 control dogs and 39 trp dogs were subjected to behavioral tests to measure anxiousness. Blood from 15 control and 15 Trp dogs for plasma AA levels. Blood levels changed but behavioral scores did not differ between diets – placebo effect.

Royal Canin Calm Canine and Feline

This is a veterinary diet and requires a prescription. Contains recommended daily levels of alpha-casozepine and increased L-tryptophan: large neutral amino acid ratio. L-tryptophan is a precursor for serotonin. Meets AAFCO standards for maintenance.

Kato (2012) – Compared RC Calm canine vs. skin care (control) diets and compared UCCR. Tryptophan ratio 0.048 vs. 0.043. Samples collected at home and 2 hours after a vet visit. 28 dogs. Better behavior scores for RC CC except for aggression. Increased post-stress UCCR in control diet.

Miyaji (2015) – Study in cats, showed calm diet had decreased in UCCR but not change in plasma cortisol.