Drug therapy in behavior: case-based discussion (Proceedings)

Overview of presentation

The use of psychoactive medication can be a critical part of the successful treatment of certain behavior problems afflicting companion animals. However, not all cases require their use and they rarely are the exclusive treatment strategy in managing most behavior issues.

The goal of this presentation is to familiarize you with a few commonly used medications in clinical veterinary behavior cases but, more importantly, help you determine which cases would benefit from the use of drug therapy and which would not.

Synapse physiology

• Synapse – a junction between terminal buttons at the ends of axonal branches of one neuron and the membrane of another (axodendritic, axosomatic, axoaxonic)

• Neurotransmitter – remain within the synapse to transmit action potential to post synaptic membrane.

Synapse physiology

• Enzymatic Deactivation – For example, the activation of acetyl cholinesterase to neutralize the activity of acetylcholine

• Reuptake – Reabsorption of neurotransmitter into the pre-synaptic cytoplasm via membrane channels.

Considerations when using psychoactive pharmaceuticals on your patients

• Drugs are rarely the sole treatment method

• Rule out medical issues (pre and post treatment exams and lab work)

• Allow ample time for drug to take effect. Maximum effect for the TCA's, SSRI's, Selegiline and Buspirone can take as long as 6-8 weeks.

• Consider abuse potential

• Safety factors, side effects, lack of FDA approval. Consider signed informed consent

• Clear client communication before and after dispensing medication

• Clear knowledge of a few drugs

• Drug trial

     – Lack of desirable effect then choose drug from alternate drug class

     – If beneficial, but side effects, then alternate drug from same class

• Caution with combination drug therapy particularly with drugs effecting serotonin (SSRI's, TCA's and MAO's)

• Serotonin Syndrome – excessive levels of serotonin causing increased blood pressure, tremors, decreased mental state, hyper-reflexia, hyperthermia and restlessness.

• Dosage form (tablet, liquid, transdermal), frequency, ease of administration

Pharmaceutical classes

• Neuroleptics

• Tricyclic Antidepressants

• Selective Serotonin Reuptake Inhibitors

• Benzodiazepines

• Miscellaneous Agents

• Antihistamines

• Anticonvulsants

• Progestins/Estrogens

• Stimulants

Tricyclic antidepressants

Effect:

o Tricyclic Antidepressants (TCA's) block the reuptake of serotonin and norepinephrine from synapse causing higher levels of these neurotransmitters to remain in the synaptic cleft and to exert greater effect on the postsynaptic receptors. Clomipramine is the most serotonin specific of the TCA's.

o Clomipramine – Most significant amount of serotonin re-uptake blocking activity

Dose:

o 1-3 mg/kg bid (dog) 0.5 mg/kg sid (cat)

o Allow at least 2-4 weeks for onset of action

o Sedation, anorexia, increased anxiety, phobic behavior, aggression, hepatic disturbances

Selective serotonin reuptake inhibitors

Effect:

o Selectively blocks the reuptake of serotonin into the pre-synaptic neuron causing an elevation of the hormone and increased binding to the post-synaptic receptors. This results in changes in protein production and receptor structure and alteration in learning potential.

o Fluoxetine (Prozac, Reconcile)

Dose:

o 0.5-2 mg/kg sid (dog) 0.5-1.0 mg/kg (cat)

o Allow at least 6-8 weeks for onset of action

o Sedation, anorexia, increased anxiety, phobic behavior, aggression, hepatic disturbances

Benzodiazepines

Effect:

o Accentuates the effect of GABBA as an inhibitory neurotransmitter

o Several examples used in veterinary medicine (diazepam, alprazolam and lorazepam most commonly used). Dosing can have a wide range and are often dosed to effect.

Case Number 1

"Rocco" 4 yr old M/N Cocker Spaniel 11.4 kg

Presenting Complaint:

     • Aggression towards owners, strangers, other dog in home

Diagnosis:

     • Conflict Aggression and Sibling Rivalry (Anxiety Based)

Psychoactive Medication

     • High level of "reactivity" in these situations

     • Fluoxetine - 10 mg sid as well as possible use of sedation for veterinary visits

Case Number 2

"Biggs" 2 yr old M/N English Bulldog 36.0 kg

Presenting Complaint:

     • Aggression towards other dog in home (Gunny)

Diagnosis:

     • Sibling Rivalry (Owner Interference with Hierarchy)

Psychoactive Medication

     • None Used

Case Number 3

"Augie" 4 yr old M/N Cockapoo 23.5 kg

Presenting Complaint:

     • Aggression towards guests to the home

Diagnosis

     • Fear/Territorial Based Aggression

Psychoactive Medication

     • Fluoxetine - 32 mg sid

Case Number 4

"Maya" 3 yr old F/S Pitbull X 26 kg

Presenting Complaint:

     • Destructive Behavior and Housesoiling when alone

Diagnosis

     • Separation Anxiety

Treatment (Maya)

     • Clomipramine and Trazodone

Case Number 5

"Felix" 8 yr old M/N DSH 9 kg

Presenting Complaint:

     • Urination outside the litter box

Diagnosis (Felix)

     • Urine Marking

Psychoactive Medication:

     • 4 mg Fluoxetine (Reconcile) SID

Case Number 6

"Odessa" 7 yr old F/S Dalmatian 22.0 kg

Presenting Complaint:

     • Fear of Thunderstorms and Fireworks

Diagnosis (Odessa)

     • Thunderstorm and Noise Phobia

Psychoactive Medication

     • Clomipramine 80 mg BID (3.5 mg/kg)

     • 20 mg Diazepam (1 mg/kg

Case Number 7

"Cerval" 2 yr old M/N DSH 6.2 kg

Presenting Complaint

     • Aggression directed towards owner and other cat (Zazi) in home

Diagnosis for Aggression Towards Zazi:

     • Play Based Aggression

Diagnosis for Aggression Towards Jarod (owner's son):

     • Defensive Aggression

Treatment (Cerval)

     • Lorazepam 0.125 mg bid (1/4 tab)

     • Clonidine

          o Classified as an alpha 2 antagonist functioning by decreasing levels of catecholamines such as norepinephrine and dopamine

          o Commonly used to cause "quieting of the brain" and reduce reactivity in dogs with problems such as fear based aggression

          o Often used in conjunction with a TCA or SSRI

          o I commonly use this in managing fear based interdog aggression

          o 0.01-0.05 mg/kg prn 2 hours before needed