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Serotonin and norepinephrine reuptake inhibitors: Choosing the right drug (Proceedings)
A practical guide to choosing the right serotonin and norepinephrine reuptake inhibitors
Abbreviations
- SRI-Serotonin Reuptake Inhibitor
- SSRI-Selective Serotonin Reuptake Inhibitor
- SNRI-Serotonin and Norepinephrine Reuptake Inhibitor
- TCA-Tricyclic Antidepressant (a family of SNRI's)
Cost: Old vs. new
- New SSRI's and SNRI's are typically very expensive
- We usually use the older ones in veterinary medicine because of cost issues
Action-SSRI's
- Inhibition of serotonin reuptake. This increases serotonergic neurotransmission by allowing serotonin molecules to act for extended periods of time.
Action-SNRI's
- 5-HT reuptake inhibition
- NE reuptake inhibition
- Chronic administration causes decreased numbers of β-adrenoceptors and serotonin receptors, as well as altered function of various serotonin receptors.
TCA's also
- α-1 adrenergic antagonism
- Anticholinergic
- Antihistaminic
Uses in dogs and cats
- Anxiety and disorders motivated by anxiety, e.g. urine marking
- Aggression
- Compulsive Disorder, e.g. tail-chasing, lick granuloma
SSRI's
- Side Effects: Sedation, Anorexia, Gastrointestinal signs, Anxiety, Irritability, Insomnia, Aggression, Decreased libido
- Slow onset of action
- Metabolized in liver
- Excreted through kidneys
- Reduce dose in patients with hepatic or kidney impairment
- May have 1-4 week latency to effect
- Long t1/2
- Use cautiously with patients with diabetes mellitus (may decrease blood glucose)
- Use cautiously in patients with a history of seizures
- DO NOT use in combination with a MAOI
Citalopram
- DOGS: 0.5-1.0 mg/kg q24h
- Has been used to treat canine acral lick dermatitis
Fluoxetine hydrochloride
- DOGS: 1.0-2.0 mg/kg q24h
- CATS 0.5-1.5 mg/kg q24h
Paroxetine
- CATS: 0.5-1.0 mg/kg
- DOGS: 0.5-1.0 mg/kg
Sertraline
- CATS: 0.5-1.0 mg/kg
- DOGS: 0.5-4.0 mg/kg
TCA's
- Named after chemical structure
- Use in animals as for SSRI's
Tertiary amines
- Have two methyl groups at the end of their side chain.
- More potent inhibition of 5-HT uptake
- More potent α-adrenergic, cholinergic, and histaminergic receptor blockade
- Significant sedative effects
- Amitriptyline, Clomipramine, Doxepin, Imipramine
Secondary amines
- One methyl group at the end of the side chain
- More potent inhibition of NE reuptake
- Desipramine, Nortriptyline
Biochemical activity
Effects - therapeutic
- Norepinephrine
o ↓General arousal
o ↑Attention
o ↓Mood reactivity
o ↑Stress response modulation
- Serotonin
o Regulate mood states
o ↓Fear responses
o ↓↑Feeding behavior
o ↓Stress response
o ↓Impulsive behavior
Effects - α-adrenergic
- Orthostatic hypotension
- Sedation
- Vasoconstriction
- Smooth muscle contraction
Effects - cholinergic
- Urinary retention
- Dry mouth
- Mydriasis
- ↓Tear production
- Impaired visual accommodation
- Bronchodilation
Effects – anti-histaminic
- Anti-pruritic effect
- Sedation
- Anti-ulcer activity
- Weight gain
Cardiovascular effects: Much more profound in humans than in dogs and cats
Gastrointestinal effects
- Vomiting
- Diarrhea
- Anorexia
- Constipation
Behavioral Side effects
- Sedation
- Anxiety
- Restlessness, agitation
- Sleep disorders
- Fatigue
- Headache
- Ataxia
Other effects
- Lowered seizure threshold
- Altered blood glucose levels
- Bone marrow suppression
- Bitter taste
o Difficulty in medicating animals
o Helps prevent overdosing
Dose management
- 2 – 4 week latency to effect, sometimes longer
- Give daily or b.i.d., not "as needed"
- Stabilize for 1 – 2 months
- Gradual withdrawal
- Certain conditions require long-term treatment
- Metabolized in liver
- Cleared primarily through urine
- DO NOT use in combination with a MAOI
Amitriptyline
- DOGS 1-6 mg/kg q12-24 h
- CATS 0.5-2.0 mg/kg q12-24 h
Clomipramine
- DOGS 1-3 mg/kg q12 hr
- CATS 0.25-2.0 mg/kg q24h
Desipramine
- DOGS 1.5-3.5 mg/kg q24h
Doxepin
- CATS 0.5-1.0 mg/kg q12h
- DOGS 3.0-5.0 mg/kg q8-12h
Imipramine
- CATS 0.5-1.0 mg/kg q12-24h
- DOGS 0.5-2.0 mg/kg q8-12h
- Anti-enuretic effect
o Canine submissive urination
o Canine excitement-induced urination
Nortriptyline
- CATS 0.5-2.0 mg/kg q12-24h
- DOGS 1.0-2.0 mg/kg q12h
Serotonin syndrome
- Mental changes
- Neuromuscular changes
- Autonomic changes
- Usually mild and resolves in 24 to 72 hours
- Can cause death
- Mortality rate in humans of 11%
- Especially likely if taking combinations that
o Decrease serotonin metabolism: MAOI's
o Inhibit serotonin uptake: SSRI's, TCA's
o Serotonin receptor agonists: Buspirone
Management
- Discontinue all serotonergic medications
- Benzodiazepines (diazepam or lorazepam) for myoclonus and hypothermia resulting from myoclonus. Clonazepam not effective.
- Severe cases: cyproheptadine, methysergide, propranolol
- Supportive treatment