Toxicoses in Animals From Human Antidepressants, Anxiolytics, and Sleep Aids

If the patient is clinically normal, emesis should be induced if antidepressant ingestion happened recently—generally within 2 hours for venlafaxine and selective serotonin reuptake inhibitors (SSRIs); within 15–30 minutes for the tricyclic antidepressants mirtazapine, bupropion, and trazodone, and for the monoamine oxidase inhibitor selegiline.

Emesis induction can be followed by the administration of activated charcoal (even several hours after ingestion) plus a cathartic such as sorbitol or sodium sulfate (magnesium sulfate is contraindicated because it can add to CNS depression). Diazepam can be administered to control seizures.

Clinical signs of serotonin syndrome should be managed as needed. Heart rate and rhythm should be monitored and cardiac arrhythmias treated. Atropine should not be administered to control bradycardia, because it can aggravate the anticholinergic effects of tricyclic antidepressants.

An IV lipid emulsion (20% solution) can also be given to hasten recovery with serious overdoses. The suggested dose is 1.5 mL/kg, IV bolus, followed by 0.25 mL/kg per minute, IV, for 30–60 minutes. This treatment can be repeated after 4 hours if there is no hyperlipemia and no improvement in clinical signs.

The group of clinical signs characterizing serotonin syndrome usually includes at least three of the following features: altered mental status, agitation, nervousness, myoclonus, hyperreflexia, tremors, diarrhea, incoordination, cardiovascular changes (heart rate and blood pressure), and fever.

Serotonin syndrome often occurs because of repeated use or overdose of substances that result in increased free concentrations of serotonin, such as antidepressants or profound stimulants (eg, amphetamines).

Cyproheptadine is a serotonin antagonist often administered for treatment. It is available only as a tablet; however, it can be dissolved in a small amount of saline and administered per rectum at 1.1 mg/kg in dogs or 2 mg/cat in cats. If there is a good response to the initial dose, it can be repeated, but only if clinical signs of serotonin syndrome recur.

Phenothiazines such as acepromazine and chlorpromazine also have antiserotonergic effects and can be administered to control hyperactivity. Benzodiazepines such as diazepam can be administered to control CNS effects. Beta blockers such as propranolol (0.02–0.04 mg/kg, IV) can be administered to control tachycardia.

Other treatment measures might include induction of emesis in clinically normal patients within 2 hours of ingestion, followed by administration of activated charcoal and IV fluids.

Zolpidem, zaleplon, and eszopiclone selectively bind to the omega-1 receptor, which is located within the GABA A receptor complex (as compared with benzodiazepines, which bind to all three omega receptor subtypes). These agents have a very rapid onset (usually < 30 minutes) and a similarly short half-life.

Although the expected result from ingestion of these drugs would be marked sedation, paradoxical excitement also occurs. Doses as low as 0.22 mg/kg have resulted in sedation and ataxia, and dogs have developed tremors, vocalizing, and pacing at doses as low as 0.6 mg/kg.

GI decontamination can be performed if the ingestion happened within 30 minutes and no clinical signs are evident. For mild clinical signs, keeping the patient quiet and in a safe place might suffice.

If paradoxical excitement develops, supportive care should be given and will vary with the signs and their intensity. Hyperexcitation might be controlled with low doses of acepromazine or other phenothiazines. Use of diazepam can aggravate clinical signs of CNS depression.

Flumazenil (0.01 mg/kg, IV) can be administered if clinical signs of toxicosis are severe, and it can be repeated as needed to reverse signs.

Melatonin is a naturally occurring hormone produced in the pineal gland; it can also be synthesized. It is associated with hair growth and regulation of sleep cycles. Melatonin is used to treat insomnia and other sleep disorders and sometimes as a sedative for cancer treatment.

In veterinary medicine, melatonin is used to treat canine alopecia, sleep disorders, and immune-mediated thrombocytopenia and to promote fertility in a variety of species.

Melatonin generally has a wide margin of safety; however, many melatonin products intended for human use contain additional ingredients of concern, particularly 5-hydroxytryptophan (5-HTP; which can pose a risk for serotonin syndrome) or xylitol (which can pose a risk for hypoglycemia and liver failure).

Gummy formulations of melatonin can pose a risk for electrolyte disturbances as well. Melatonin can cause vomiting, lethargy, sedation, and ataxia.

Induction of emesis can be considered when a clinically normal patient has ingested a gummy formulation within approximately 2 hours. For other formulations, decontamination is generally unnecessary or not recommended. Administration of activated charcoal is not necessary. Keeping the patient quiet and in a safe place might suffice in most cases.

For ingestion of melatonin in a gummy formulation, electrolytes (sodium) should be monitored and corrected as needed. The administration of IV fluids might be considered for hydration when a large number of gummies have been ingested.