Antidepressants

Selective serotonin reuptake inhibitors (SSRIs)

Citalopram

Escitalopram

Fluoxetine

Fluvoxamine

Paroxetine

Sertraline

• Block activity of serotonin receptors at presynaptic membranes, with little effect on other neurotransmitters.

• In addition to the clinical signs described in the text, nystagmus can occur.

• Many SSRIs are used therapeutically to treat behavioral disorders in dogs and cats.

Tricyclic antidepressants

Amitriptyline

Clomipramine

Doxepin

Nortriptyline

• Structurally similar to phenothiazines, with similar anticholinergic, adrenergic, and alpha-blocking properties.

• Block the amine pump and stop neuronal reuptake of norepinephrine, serotonin, and dopamine.

• Also have slight alpha-adrenergic blocking effect.

• Can exert their major toxicity via nonspecific membrane-stabilizing effect.

• In addition to the clinical signs described in the text, cardiac arrhythmias, hypertension, myoclonus, nystagmus, metabolic acidosis, urinary retention, dry mouth, mydriasis, and constipation can occur. These signs might be followed by CNS depression (lethargy), ataxia, hypothermia, respiratory depression, cyanosis, hypotension, and coma.

Monoamine oxidase inhibitors

Selegiline

• Irreversibly inhibit monoamine oxidase.

• Increase synthesis and release of dopamine into the synapse, and inhibit reuptake of dopamine.

• Metabolites of selegiline include amphetamine and methamphetamine. Its half-life in dogs is approx. 1 h.

• In addition to the clinical signs described in the text, hypertension or hypotension, as well as hyperthermia, can occur.

Miscellaneous/novel antidepressants

Bupropion

• Inhibits reuptake of dopamine and norepinephrine.

• Blocks central nicotinic acetylcholine receptors.

• In addition to the clinical signs described in the text, hypertension or hypotension, tachypnea, and nystagmus can occur.

Duloxetine

• Inhibits reuptake of serotonin and norepinephrine.

• Weakly inhibits dopamine reuptake.

• In addition to the clinical signs described in the text, mydriasis can occur.

Mirtazapine

• Antagonizes presynaptic alpha-adrenergic receptors to increase norepinephrine.

• Antagonizes postsynaptic serotonin (5-HT₂ and 5-HT₃) receptors.

• Inhibits histamine (H₁) receptors and antagonizes muscarinic receptors.

• Clinical signs might occur in both dogs and cats even at therapeutic dosages (when used to treat decreased appetite and unwanted behaviors).

Trazodone

• Selectively inhibits neuronal reuptake of serotonin at low doses and acts as an agonist at high doses.

• Shows some antagonism of alpha-1 adrenergic receptors.

• Sedation usually occurs early in the course of toxicosis, followed by stimulatory signs.

Venlafaxine

• Inhibits reuptake of serotonin and norepinephrine.

• Weakly inhibits dopamine reuptake.

• In addition to the clinical signs described in the text, muscle rigidity, hypertension, and nystagmus can occur.