The use of psychotropic drugs to alter behavior of humans and animals has dramatically increased in the last decade. The behaviors
that these types of drugs are intended to alter include depression, anxiety, obsessive or compulsive behavior, and undesirable
impulses (e.g. smoking in humans). With the increased usage of these drugs, the potential for accidental overdosage in companion
animals has increased; this is especially true for dogs, who due to their inquisitive nature and often indiscriminate eating
habits, may ingest entire prescriptions of psychotropic drugs in one sitting. Table 1 gives examples of the various classes
of psychotropic drugs used in human and veterinary medicine.
Table 1. Classes and examples of antidepressant drugs
Serotonin and serotonin syndrome
Early psychotropic drugs were non-selective and frequently targeted a variety of areas of the central nervous system (CNS)
to exert their effect. Over time, it became apparent that certain neurotransmitters in the CNS were more influential in altering
undesirable behaviors, and drugs that more selectively targeted those neurotransmitters were developed. Serotonin is one neurotransmitter
that appears to be extremely important in managing these types of behaviors and older drugs that targeted a variety of neurotransmitters
(e.g. tricyclic antidepressants) have, in human medicine, largely given way to drugs that more selectively alter CNS serotonin
levels, including selective serotonin reuptake inhibitors (SSRIs) and non-selective serotonin reuptake inhibitors (NSSRIs).
Enhancing serotonin levels in the CNS can result in dramatic and favorable alterations in behaviors of humans and animals.
However, excessive levels of serotonin can result in a severe and potentially life-threatening condition termed serotonin
syndrome. In humans, serotonin syndrome is most commonly seen when two different serotonergic drugs are administered simultaneously,
or when insufficient time has elapsed between discontinuation of one class of serotonergic drug and institution of therapy
with a different class of serotonergic drug. Serotonin syndrome is characterized by a variety of effects including altered
mental status (agitation or depression, aggression, vocalization, seizures, etc.), altered neuromuscular activity (rigidity,
myoclonus, tremors, hyperreflexia, ataxia, etc.), hyperthermia, autonomic derangements, and diarrhea. In dogs, serotonin syndrome
has been associated with excessive ingestion of 5-hydroxytryptophan as well as a variety of serotonergic drugs.
Table 2. Dosages of concern for selected antidepressants (dogs)
Management of serotonin syndrome includes managing any severe CNS effects with diazepam or a phenothiazine; refractory seizures
may require general anesthesia. Due to its serotonin-blocking effects, cyproheptadine (1.1. mg/kg PO or rectally q 6 hr prn)
may be beneficial in managing the agitation, hyperthermia, and vocalization. Once animals have been stabilized and severe
signs managed (or in asymptomatic animals), decontamination should be attempted. If the animal has not already vomited, induction
of emesis or gastric lavage might be performed. Administration of activated charcoal is recommended in most cases, and is
especially important if extended- or sustained-release products have been ingested. Severe tachycardia may be managed with
beta-blockers such as propranolol (0.02 mg/kg slow IV, titrate up as needed). Fluid therapy is important to provide cardiovascular
support and protect the kidney from hypotension-related injury. Acid/base status should be monitored and managed as needed.
Serotonin syndrome resulting from ingestion of prompt release products generally lasts 12-18 hours; with extended- or sustained-release
products, signs might persist up to 48-72 hours.