Serotonin Syndrome

Chapter 91 Serotonin Syndrome



Erica Lynn Reineke, VMD, DACVECC, Kenneth J. Drobatz, DVM, MSCE, DACVIM, DACVECC



KEY POINTS



• Serotonin (5-hydroxytryptamine [5-HT]) syndrome is a drug-induced condition resulting from excess serotonergic agonism of the central and peripheral nervous system serotonin receptors.

• Serotonin syndrome can result from overdoses of serotonin reuptake inhibitors, monoamine oxidase inhibitors, tricyclic antidepressant medications, lithium, dietary supplements, or administration of multiple serotonergic medications.

• Clinical signs reported in companion animals due to accidental ingestion of serotonergic medications include nervous system signs (seizures, depression, tremors, hyperesthesia, ataxia, paresis, disorientation, coma, hyperreflexia, mydriasis, blindness), gastrointestinal tract symptoms (vomiting, diarrhea, abdominal pain, ptyalism, flatulence, bloat), hyperthermia, and death.

• Treatment of symptomatic animals consists primarily of supportive measures, and correction of nervous system and cardiovascular abnormalities, but could also include administration of a 5-HT2A receptor antagonist such as cyproheptadine.


INTRODUCTION


Over the past 10 years, with mental depression and other psychiatric disorders on the rise, numerous drugs have been developed to manipulate neurotransmitters in the brain. With the increasing use of these antidepressant medications in both humans and animals, it is not surprising that both intentional and accidental ingestions of these medications are also on the rise.


The history of antidepressant medications extends as far back as 1951 with the introduction of the drug isoniazid, and its isopropyl derivative iproniazid, to manage tuberculosis.1,2 Doctors quickly discovered that patients treated with this drug exhibited signs of elevated mood. This psychotropic effect was found to result from iproniazid’s ability to inhibit the enzyme monoamine oxidase, responsible for the breakdown of serotonin, resulting in increased amounts of serotonin in the brain.1,2 Since that time, evidence has accumulated that the diminished formation of neurotransmitters, serotonin in particular, may be responsible for mental depression.3 This has led to the development of additional drugs targeted to increase the levels of serotonin in the brain by inhibiting the breakdown of serotonin (monoamine oxidase inhibitors [MAOIs]), increasing serotonin release (amphetamines), and blocking the reuptake of serotonin (selective serotonin reuptake inhibitors [SSRIs] and tricyclic antidepressants [TCAs]).



DEFINITION


Serotonin syndrome refers to a drug-induced condition resulting from excess serotonergic agonism of the central and peripheral nervous system serotonin receptors. This life-threatening syndrome is characterized by a clinical triad of mental status changes, autonomic instability, and neuromuscular abnormalities.4 In humans this syndrome can occur following initial administration of an SSRI or more commonly results from the concurrent administration of two serotonergic medications. One of the most common and lethal interactions is the combination of an SSRI with an MAOI.4,5 In companion animals, this syndrome has been reported only secondary to accidental ingestion but could also occur secondary to therapeutic dosages of serotonergic medications and drug interactions.6



SEROTONIN AND PATHOPHYSIOLOGY OF SEROTONIN SYNDROME


Serotonin exerts its effects in both the peripheral and central nervous systems. Most of the serotonin in the body is synthesized and stored in the enterochromaffin cells and myenteric plexus in the gastrointestinal (GI) tract.7 Serotonin produced by the enterochromaffin cells in the GI mucosa is scavenged and stored by platelets through an active uptake mechanism. Serotonin is also removed from the circulation by the lungs and either stored there or transferred to platelets.7


The effects of serotonin in the peripheral nervous system include vasoconstriction, platelet aggregation, uterine contraction, intestinal peristalsis, and bronchoconstriction.7,8 Because serotonin cannot cross the blood-brain barrier, it must also be produced in the central nervous system. Most serotonin-producing neurons in the brain are located on the midline raphe nuclei of the lower pons and medulla and project fibers to many areas of the brain and spinal cord.3 Centrally serotonin exerts influences on mood, aggression, thermoregulation, sleep, vomiting, and pain perception.3,8


Serotonin is formed in the body by hydroxylation and decarboxylation of the essential amino acid tryptophan. Increased intake of tryptophan in the diet can increase brain serotonin levels because the enzyme, tryptophan hydroxylase, does not normally reach saturation levels.7 Serotonin is synthesized in the cytosol in neurons, stored in vesicles at the nerve terminal, and released into the synaptic cleft where it binds to the postsynaptic receptor, mediating neurotransmission. After release, much of the serotonin is recaptured by an active reuptake mechanism and inactivated by monoamine oxidase to form 5-hydroxyindoleacetic acid. This substance is then eliminated in the urine (Figure 91-1).7


image

Figure 91-1 Mechanisms of serotonin syndrome. (1) Increased L-tryptophan will increase serotonin. (2) Amphetamines and other drugs increase the release of stored serotonin. (3) Inhibition of serotonin metabolism by monoamine oxidase inhibitors (MAOIs) will increase presynaptic serotonin concentration. (4) Impairment of serotonin transport into presynaptic neurons by uptake blockers (i.e. SSRI, TCA) increases synaptic serotonin concentration. (5) Direct serotonin agonists can stimulate postsynaptic serotonin receptors.

Related posts:

  1. Deteriorating Mental Status
  2. Hyperthermia and Fever
  3. Ventilator-Associated Lung Injury
  4. Allergic Airway Disease in Dogs and Cats and Feline Bronchopulmonary Disease

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Sep 10, 2016 | Posted by in SMALL ANIMAL | Comments Off on Serotonin Syndrome

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