In this VETgirl online veterinary continuing education blog, Dr. Justine Lee, DACVECC, DABT reviews Selective Serotonin Re-uptake Inhibitor (SSRIs) antidepressant toxicity. Because the holidays are approaching, COVID-19 is still going on, we’re still curbside, and life is really rough right now. You can also listen to a similar VETgirl podcast on SSRI toxicosis HERE.

Selective serotonin re-uptake inhibitors (SSRIs) are a class of medications that are commonly used in human medicine for depression. Common examples include the following drugs:

• Fluoxetine (Prozac® in human beings; Reconcile™ in veterinary medicine)
• Citalopram (Celexa®)
• Paroxetine (Paxil®)
• Sertraline (Zoloft®)

Other similar drugs include selective norepinephrine re-uptake inhibitors (SNRIs), which include common drugs like duloxetine (Cymbalta®), nefazodone (Serzone®), and venlafaxine (Effexor®). SNRI and SSRI drugs result in similar clinical signs of toxicosis, and therefore are treated the same. In veterinary medicine, SSRIs are used for a wide array of behavioral problems, including feline urine spraying, canine separation anxiety, lick granulomas, etc. These SSRI drugs work by blocking the reuptake of serotonin in the pre-synapse, thereby increasing the levels of serotonin in the pre-synaptic membrane. In small animal patients, common clinical signs from SSRIs include the following:

• Sedation or central nervous system (CNS) stimulation
• Anorexia
• Lethargy
• Serotonin syndrome

Clinical signs of serotonin syndrome include: gastrointestinal (GI) signs (e.g., hypersalivation, vomiting, diarrhea, abdominal pain) and CNS signs (e.g., stimulation, mydriasis, tremors, seizures, hyperthermia secondary to tremoring and seizuring). Treatment for antidepressants includes decontamination (ideally done at a veterinarian, due to the rapid onset of clinical signs), sedation (e.g., with acepromazine or chlorpromazine), intravenous (IV) fluid therapy, blood pressure and electrocardiogram (ECG) monitoring, thermoregulation, muscle relaxants (for tremors; methocarbamol 22-55 mg/kg, IV, PRN), anticonvulsants (e.g., phenobarbital 4-16 mg/kg, IV, PRN; diazepam 0.25-0.5 mg/kg, IV, PRN), serotonin antagonists [e.g., cyproheptadine (1.1 mg/kg for dogs or 2-4 mg total per cat) PO or rectally q. 6-8], and supportive and symptomatic care. In general, the prognosis for antidepressant toxicosis is excellent.

Thankfully, the prognosis is excellent based on two publications where I retrospectively evaluated survival in both dogs and cats. However, appropriate decontamination, treatment and monitoring are imperative. When in doubt, contact the ASPCA Animal Poison Control Center for life-saving advice.

ASPCA Animal Poison Control Center

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