Behavioural medicine - role of drugs, nutraceuticals and pheromones

What are the aims of altering neurochemistry?

• promote biogenic amines

  • catecholamines - dopamine, noradrenaline

  • serotonin

• promote inhibitory (or hyperpolarizing) neurotransmitters

  • e.g. GABA

What are the methods of altering neurochemistry?

• use medication

• use nutraceuticals

• use diet

What can medication be used for, in behavioural medicine?

• management of patients at the veterinary practice

  • for consults - pre vet visit medications

  • hospitalisation

• management and treatment of patients with physical health concerns that are influenced by emotional health

• management and treatment of patients presented with primary behavioural concerns

How can we use medication for patients with primary behavioural concerns?

• short term situational management

• longer term management of emotional state and arousal

What are three scenarios for the use of medication for vet visits?

1. preparation at home before the vet visit

   • give instructions to caregiver to administer before coming to practice - often reduces level of anxiety

2. medication on arrival at the practice

   • given when the animal gets to the practice, may involve level of sedation

3. medication during hospitalisation

What are the aims of vet visit medication?

• to improve welfare during this experience

• to facilitate examination or procedures

• to improve welfare during future visits though influencing potential learning at this visit

What are the aims of pre-vet visit medication?

• to alter emotional bias

• to reduce emotional arousal

• to influence memory formation

Are medications used in pre-vet visit protocols licensed?

• no - used off label

• signed consent form necessary

Why do we no longer use acepromazine?

• was used to make patients easier to interact with

• but make patient unable to respond to their protective emotions

• welfare concerns - ‘chemical straight jacket’

Which cases will benefit from medication support?

• high arousal cases

  • noradrenergic action

• protective emotions

  • fear-anxiety and frustration —> seratonergic action

  • panic-grief —> dopaminergic action

• compulsive responses

  • seratonergic action

What type of drug action would be wanted for high arousal cases?

noradrenergic action

What type of drug action would be wanted for fear-anxiety and frustration protective emotions?

seratonergic action

What type of drug action would be wanted for panic-grief protective emotions?

dopaminergic action

What type of drug action would be wanted for compulsive responses?

seratonergic action

What are the criteria for cases for drug therapy?

• emotional and physical health diagnosis

• duration of problem

• severity of signs

• risk of euthanasia / rehoming and resulting need for quick results

• threat to animals welfare form failing to prescribe medication

What are the possible drug classes used in behavioural medicine?

• antidepressants (TCAs, SARIs and SSRIs)

• monoamine oxidase inhibitors

• beta blockers

• benzodiazepines

• anti-epileptics e.g. imepitoin

• hormonal preparations

• neuroleptics

• azapirones

• opitoid antagonists

• CNS stimulants

• antihistamines

• adrenoreceptor stimulants

• adrenoreceptor antagonists

• xanthine derivatives

What drugs are used for short term management to influence neurotransmitter levels?

• Serotonin

  • SARI - Trazodone

• GABA

  • Benzodiazepines - Alprazolam / Diazepam

• Noradrenaline

  • alpha-2 adrenoreceptor agonist

    • Dexmedetomidine oral mucosal gel

    • Tasipimidine oral solution

What drugs are used for short term management to inhibit neuronal signalling?

• Gabapentin

• Pregabalin

How do Gabapentin and Pregabline inhibit neuronal signalling?

by binding to the alpha2-gamma subunit of voltage gated calcium channels in the CNS

What makes drugs suitable for short term management?

• rapid onset of action

• can influence emotional valence or arousal

What situations may we want to use short term management drugs for?

• situational emotional responses

  • fireworks

  • car travel

  • vet visits

  • visitors

What drugs can be used for long term emotional management?

• serotonin - TCAs, SSRIs and SARIs

• dopamine - MAOBIs

• GABA - Topiramate

• Noradrenaline - Clonidine

What Tricyclic antidepressants (TCAs) are licensed?

• clomipramine - licensed for dogs

• clomicalm - used extra label in cats

What is the lag time to effect for TCAs?

4-6 weeks

What type of action do TCAs have?

• serotonergic action

• noradrenergic action

What Selective serotonic reuptake inhibitors (SSRIs) are licensed?

• fluoxetine licensed in dogs and cats

• sertraline licensed in dogs

what is the lag time to effect for SSRIs?

4-6 weeks

Are serotonic antagonist and reuptake inhibitros (SARIs) licensed?

• no licensed product

• Trazodone used off license

What are the non licensed TCAs?

• amitryptiline

• doxepin

How long does Trazodone take for effects?

1-1.5 hours

Can serotonin drugs be used with MAOBIs?

no

What Monoamine oxidase B inhibitor (MAOBI) is licensed?

• selgian licensed in dogs

• used in cats off license

What is the main action of Selgian (MAOBI)?

• primarily dopaminergic action

• also affects serotonin and noradrenaline

• neuroprotective action towards free radicals and neurotoxic substances

What should we not administer MAOBIs with?

• pethidine

• morphine

• fluoxetine

• phenothiazines

When are anti-epileptics used?

• where limbic epilepsy is involved - conventional epilepsy treatment

• neuoleptics used for behaviour for anxiolytic properties

  • Imepitoin - for sound related fears

  • action is GABAnergic

• neuroleptics used compulsive disorders

  • Toprimate - used for compulsive mutilation disorders

  • exerts actions on voltage-dependent sodium channels, GABA-A receptors and glutamate receptors

When would hormone preparations be used?

in cats - where behavioural signs are directly motivated by hormonal influences

Female hormones

Males hormones

What drugs could be used for situational anxiety?

• Benzodiazepines - alprazolam, loprazolam, diazepam

• dexmedotomidine

• tasipimidine

• gabapentin

• pregabalin

• SARIs - Trazodone

What drugs could be used for generalised anxiety?

• TCAs - amitryptiline, clomipramine, doxepin

• SSRI - fluoxetine

• SARI - trazodone

• anti-epileptics - Pexion / Topiramate

What drugs could be used for compulsive disorders?

• SSRI - fluoxetine

• pain management if appropriate

What drugs can be used for panic disorders related to anxiety?

• SSRI - sertraline, fluoxetine

What drugs could be used for fear?

• MAOBI - selegiline

• Imepitoin - Pexion (fear of sounds)

What drugs could be used for panic-grief related behaviour change

• MAOBI - selegiline

What drugs could be used for cognitive dysfunction?

• MAOBI - selegiline

• xanthine derivative - propentofylline

What are treatments for chronic pain?

• multimodal analgesia

  • NSAIDs - meloxicam , firocoxib, robenacoxib, grapiprant

  • Gabapentin / Pregabalin

  • Paracetamol

  • NDMA receptor antagonists - memantine, amantidine

What are nutraceuticals?

use of dietary supplementation to influence behaviour

What are the two main areas of interest for nutraceuticals?

• use of dietary supplementation to influence cognitive function

• use of dietary supplementation to influence emotional state

How can we support cognitive dysfunction?

• alter oxidative balance

• use nutraceuticals

• change diet

• support brain function through medication

What can be used to alter oxidative balance?

• antioxidants

• essential fatty acids

• phosphotidylserine

What drugs can be used to support brain function?

• dopamine

• superoxide dismutase

• cerebral blood flow

• glial cell modulation

What is the potential influence of nutrients on emotional state?

• tryptophan —> affects serotonin

• L- Theanine / Fish Hydrolysate —> affect dopamine

• Alpha Caesin / Lemon Balm / Fish Hyrolysate —> affect GABA