Psychotropic substances are poisoning pets

Many individuals use medications for various diseases and conditions of the brain. Unfortunately, our dogs and cats sometimes get into our pharmaceutical supply and suffer the consequences. In fact, over 30% of calls received by the helpline involve exposures to human medications and supplements, many of them psychotropic, according to Renee D. Schmid, DVM, DABT, DABVT, manager of veterinary medicine and professional services and senior veterinary toxicologist at Pet Poison Helpline, a division of SafetyCall International.

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Dogs corner the market on pharmaceutical poisonings at about 65% of cases, she added, while presenting a lecture at the 2022 Fetch dvm360^® Conference in Kansas City, Missouri. Although feline cases account for only one-third as much of this amount, Schmid warned attendees that they should not be counted out. “Cats really love the taste of these medications,” she said.

But whether it be in cat or dog, decontamination is rule number one in a toxic situation. For ridding either animal of most toxins, however, emesis is only effective within an hour of ingestion.¹

Safety should be kept in mind, Schmid noted. “It’s instinctive for us, when an animal has ingested something, to try to get it back out. But when that animal is lateral recumbent, or when it’s bouncing off the walls, it is not a candidate for inducing vomiting,” she said. Furthermore, each class of psychiatric medication has its very own toxic stamp and specific recommended fix.

ADHD drugs

Medications used to treat attention deficit/hyperactivity disorder (ADHD) are ubiquitous in American households. According to the Centers for Disease Control and Prevention (CDC), over 60% of children aged 2 to 17 years with an ADHD diagnosis are using medication to treat the condition.² ADHD drugs fall into a few different categories: stimulants, α-2 adrenergic agonists, and selective norepinephrine reuptake inhibitors (SNRIs).¹

Stimulants

Prescription stimulants are used in children and adults to address ADHD, narcolepsy, and occasionally obesity. These include amphetamines and methylphenidate preparations.

Like many psychiatric medications, these generally come in immediate-release (IR) and extended-release (ER) versions.¹ To ease administration, particularly in children, formulations other than the standard oral tablet are available. These include patches, as well as tasty chews, solutions, powders, and beads. The flavorings, which may incorporate xylitol, render them appealing to pets.

In dogs and cats, amphetamines are generally toxic at 1 mg/kg (0.8 mg/kg for ER formulations). Methylphenidates are toxic at 0.5 mg/kg. Clinical signs of stimulant intoxication stem from central nervous system (CNS) excitement and sympathomimetic agonism: agitation, hyperactivity, vocalization, tachycardia, hypertension, head bobbing, tremors, seizures, mydriasis, and hyperthermia.¹

A pet that has ingested an IR formulation can experience clinical signs within 20 to 30 minutes that may persist for 12 to 24 hours. “If the animal is asymptomatic after 3 to 4 hours, it probably did not actually get into the medications,” said Schmid. For ER formulations and ingested patches, onset of signs may be delayed by 4 to 6 hours, and clinical effects can last a day or 2.¹

The first step in treating these pets is decontamination. If the animal is neurologically appropriate, emesis should be induced. Chewable and oral disintegrating products are absorbed very quickly, leaving little time to induce emesis. If a dog or cat has ingested an IR product and lives far away, the owner should induce vomiting prior to transporting the pet to the hospital.

For ER products, metabolism is slower, and decontamination can be performed with slightly less urgency. So if an animal who has swallowed ER drugs lives near the clinic, emesis usually can be delayed until it arrives. “Time is on our side,” Schmid said.

If a patient is neurologically intact, attempts to scavenge any remaining drug can be made by feeding the animal-activated charcoal. But once clinical signs have set in, most of the drug will have been absorbed and activated charcoal will not be very effective.

Schmid also addressed the hazards of drug patches. “Dogs do like to ingest patches,” she said.

Unfortunately, the majority of the drug is still active long after patches are discarded. A dog that has swallowed one may exhibit significant clinical signs that last until the patch is completely gone.¹

Patch removal can be achieved via endoscopy or by feeding the animal multiple meals until the patch has been expelled. Activated charcoal can then be used to bind any free-floating drug that has leached from the patch.

Extended hospitalization is generally required for pets that have ingested patches and other ER products with slow drug absorption. Emesis and catharsis should be followed by sedation. “Acepromazine is your friend in just about any toxin case that shows signs of agitation,” Schmid noted.

She recommended a dose of 0.02 mg/kg to 0.04 mg/kg intravenous (IV), intramuscular (IM), and subcutaneous (SQ) acepromazine (0.05-0.1 mg/kg if patient is already manifesting signs). Butorphanol (0.2-0.4 mg/kg IV, IM, SQ), for its cardiac-sparing properties, is safer for some heart disease and geriatric patients. Benzodiazepines should be avoided, as they can cause dysphoria and other CNS effects.

If a patient is experiencing serotonin syndrome, characterized by CNS and autonomic and neurobehavioral signs such as dysphoria, vocalizing, and muscle rigidity,¹ cyproheptadine (dogs, 1.1 mg/kg; cats, 2-4 mg/kg) can be given by mouth or as a slurry per rectum to ease signs. Methocarbamol (55-220 mg/kg IV) is useful for animals experiencing tremors, and anticonvulsants such as phenobarbital or levetiracetam can address seizures.

Α-2 adrenergic agonists

Guanfacine and clonidine are α-2 adrenergic agonists that act centrally to modulate the symptoms of ADHD in children and adults.¹ Clonidine is also used for autism, Tourette syndrome, and insomnia in humans, and to treat behavioral issues such as phobias and separation anxiety in dogs.

These drugs have a narrow margin of safety in pets,¹ and clinical signs—which include depression, sedation, ataxia, vomiting, bradycardia, hypotension, tremors, and seizures in dogs—can develop in doses as low as 0.01 mg/kg to 0.02 mg/ kg. Onset occurs within 4 hours of ingestion, and effects can persist for 24 to 72 hours.

Emetics (within 30 minutes of ingestion) and activated charcoal can be administered to asymptomatic patients. If the patient is symptomatic, the α-2 adrenergic antagonist atipamezole (50 mcg/ kg IM, redosed as needed) can be used to reverse signs of poisoning. (Anticonvulsants are indicated in the rare case of seizures.) IV fluids should be given to maintain blood pressure, perfusion, and hydration. Vital signs, particularly heart rate, must be monitored frequently.

Selective norepinephrine reuptake inhibitors

Atomoxetine, a nonstimulant SNRI used as a second-line treatment for ADHD,1 can cause sedation or agitation and anorexia at low doses in dogs and cats. It can also cause hypertension, tachycardia, and tremors at high doses.

Treatment is with emesis induction for recent ingestion, followed by a single dose of activated charcoal. Further support may include sedation for agitation, antiemetics for nausea or vomiting, β-blockers for persistent tachycardia, methocarbamol for tremors, and IV fluids for cardiovascular support.

Antidepressants

Some 25 million American adults have experienced a major depressive episode in the past few years, according to the CDC. The population most affected— at a rate of 21%—are those aged 18 to 29 years.³

This is important, said Schmid, because “a lot of times, [these patients may not store medications in their original packaging or] may leave medications lying around, increasing the ability of their pets to get to them.”

Selective serotonin reuptake inhibitors

Used in both people and pets to address anxiety-based behaviors, selective serotonin reuptake inhibitors (SSRIs) bathe the CNS with “feel-good” serotonin by blocking its reuptake in the presynaptic membrane.^1,4 Common SSRIs include fluoxetine, citalopram, escitalopram, paroxetine, and sertraline. Trazodone, although not a true SSRI, also blocks serotonin reuptake to produce a calming effect.

The toxicity profile for SSRIs varies by species, with cats being more sensitive than dogs.¹ Small overdoses of 2 to 3 times the therapeutic dose result in sedation or agitation, hypersalivation, vomiting, mydriasis, tremors, and hyperthermia. Larger overdoses can cause ataxia, dysphoria, aggressive behavior, nystagmus, and seizures. Amounts that are even greater may produce serotonin syndrome.

Treatment is generally supportive and involves routine decontamination, IV fluids, tranquilizers, methocarbamol, cyproheptadine in the case of serotonin syndrome, and benzodiazepines for seizures absent serotonin syndrome. It also involves phenobarbital or levetiracetam for seizures associated with higher ingested doses and/or serotonin syndrome.

Tricyclic antidepressants and other agents

Like SSRIs, tricyclic antidepressants (TCAs) can combat depression and anxiety in both humans and animals.⁴ Common TCAs include amitriptyline, clomipramine, nortriptyline, and doxepin.

TCAs differ from SSRIs in their narrow margin of safety.¹ Overdoses produce anticholinergic effects: constipation, urine retention, mydriasis, hypertension, tachycardia, and disorientation. Vomiting, seizures, and serotonin syndrome may also result.

Toxicities involving bicyclic antidepressants, venlafaxine, serotonin, and other SNRIs such as duloxetine, cause sympathomimetic effects, similar to those seen with SSRI intoxication. Toxicities associated with TCAs, bicyclics, and SNRIs are treated similarly to cases of SSRI overdose; for TCA overdoses, careful cardiovascular monitoring is also advised.

Benzodiazepines and nonbenzodiazepines sleep aids

Benzodiazepines are effective anxiolytics, anticonvulsants, muscle relaxants, and sedatives; 3 nonbenzodiazepine hypnotics induce sleep in individuals whose brains fight it.⁵ Both benzodiazepines and nonbenzodiazepines operate through the inhibitory neurotransmitter γ-aminobutyric acid (GABA).^1,4

Benzodiazepines used in humans and in veterinary medicine include alprazolam, diazepam, midazolam, and clonazepam.⁴ Nonbenzodiazepine hypnotics include zolpidem, eszopiclone, and zaleplon.⁵ Of these, clonazepam and zolpidem account for the most Pet Poison Helpline calls.

Because of the wide safety margins of benzodiazepines and nonbenzodiazepines, poisonings rarely cause fatality in animals.^1,5 Clinical signs of acute toxicity, occurring within 30 to 60 minutes after ingestion, are vomiting, ataxia, disorientation, and either sedation or paradoxical CNS stimulation. In cats, chronic oral use of diazepam can lead to hepatic failure, although acute exposures do not carry the same risk.⁶

Treatment for these overexposures is much the same as that for the other psychotropics: decontamination and supportive care. If paradoxical agitation occurs, sedation can be achieved with acepromazine or butorphanol. In rare cases of severe CNS or respiratory depression, the antidote flumazenil (0.01 mg/kg IV, as needed to effect) can reverse signs.

The dietary supplement 5-hydroxytryptophan has become popular for inducing sleep, enhancing mood, and promoting a sense of well-being. As it is an OTC medication, Schmid explained, “owners think it’s safer and won’t be a problem for pets.”

Nonetheless, she warned of this serotonin precursor’s narrow margin of safety in dogs and cats: At just 3 mg/ kg—a single 100-mg capsule in a medium-sized dog—agitation, tachycardia, hypertension, vomiting, diarrhea, and transient blindness can occur within 2 to 4 hours of consumption. Treatment is by decontamination, IV fluids, sedation, cyproheptadine, methocarbamol, and maropitant citrate.

Bipolar disorder medications

Lithium, lamotrigine, and antipsychotic drugs such as olanzapine, risperidone, aripiprazole, and ziprasidone are used to treat bipolar disorder in humans. Like other drugs, they sometimes end up in canine and feline stomachs.

Signs of overdose vary with the compound, but generally encompass lethargy, hypotension, heart rhythm disturbances, tremors, and seizures. Acute overdoses of lithium are well tolerated, with only lethargy, mild vomiting, and anorexia.¹

Management is by decontamination, supportive care, and medications to address each clinical sign. For lamotrigine overdose, cardiovascular function should be monitored closely and any ventricular arrhythmias treated.

Takeaway

How each case of poisoning is managed depends on the compound, formulation, ingested amount, and time elapsed following consumption of the agent. However, the epidemic of psychological drug toxicities in pets can only be reined in by client education regarding the safe storage of medications.

Joan Capuzzi, VMD is a small animal veterinarian and journalist based in the Philadelphia, Pennsylvania, area.

References

1. Hovda LR, Brutlag A, Poppenga RH, Peterson K, eds. Blackwell’s Five-Minute Veterinary Consult Clinical Companion: Small Animal Toxicology. 2nd ed. Wiley-Blackwell; 2016.
2. Data and statistics about ADHD. CDC. Updated August 9, 2022. Accessed September 26, 2022. https://www.cdc.gov/ncbddd/adhd/data.html
3. Plumb DC. Plumb’s Veterinary Drug Handbook. 9th ed. Wiley-Blackwell; 2018.
4. Symptoms of depression among adults: United States, 2019. CDC. Updated September 23, 2020. Accessed September 26, 2022. https://www.cdc.gov/nchs/products/databriefs/db379.htm
5. Lancaster AR, Lee JA, Hovda LR, et al. Sleep aid toxicosis in dogs: 317 cases (2004-2010). J Vet Emerg Crit Care (San Antonio). 2011; 21(6):658-665.doi:10.1111/j.1476-4431.2011.00694.x
6. Center SA, Elston TH, Rowland PH, et al. Fulminant hepatic failure associated with oral administration of diazepam in 11 cats. J Am Vet Med Assoc. 1996;209(3):618-625.