Antidepressant (eg, selective serotonin reuptake inhibitors [SSRIs], serotonin agonists, serotonin antagonists) toxicities in veterinary medicine are increasingly common. While serotonin syndrome is possible, signs consist largely of GI upset and CNS depression and stimulation. Limited data about SSRI intoxication exists in the veterinary literature. One study showed the most common signs were lethargy, vomiting, mydriasis, and agitation. A dose-dependent relationship to signs has been proposed, with the most minor signs (salivation, lethargy) noted at 1–3 mg/kg of paroxetine and sertraline and most severe signs (tremors, hyperthermia) at 8–10 mg/kg of fluoxetine and sertraline. Seizure activity was also possible with doses >25 mg/kg of fluoxetine and sertraline and >3 mg/kg of paroxetine.

In 313 dogs with presumed SSRI toxicosis, a dose-dependent relationship between drug and signs was only established for fluoxetine. Metabolic variation and access to veterinary care may impact development of signs. As the liver metabolizes SSRIs through cytochrome P450 isoenzyme, and as fluoxetine, paroxetine, and sertraline are highly protein bound, medications that inhibit the P450 system or the presence of preexisting renal or hepatic disease may increase patient susceptibility. Prognosis is considered very good with supportive care; death is rare.

Commentary
SSRIs and tricyclic antidepressants are used to treat dogs, cats, and humans. Common drugs are fluoxetine (Prozac; Reconcile), sertraline (Zoloft), clomipramine (Clomicalm), and amitriptyline (Elavil). Since many behavioral drugs are often off label, artful dosing and diligent attention to individual variability are important: for example, urine retention in a cat after receiving clomipramine may mean that lower-than-published doses are warranted to balance adverse events with cognitive modification. Practitioners should likewise be aware of all possible adverse events of these medications: urine retention should not be confused with urethral obstruction in a cat on clomipramine. Although there is no standard for evaluating a patient on long-term behavioral medications, full examination, history, and a basic serum biochemistry profile performed q6–12mo are warranted.—Heather Troyer, DVM, DABVP, CVA

Source
Retrospective evaluation of toxicosis from selective serotonin reuptake inhibitor antidepressants: 313 dogs (2005-2011). Thomas DE, Lee JA, Hovda LR. JVECC 22:674-681, 2012.