Pediatric Selective Serotonin Reuptake Inhibitor Toxicity Clinical Presentation

Updated: Apr 12, 2022
  • Author: Mohamed K Badawy, MD, FAAP; Chief Editor: Stephen L Thornton, MD  more...
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Because the enteric nervous system is richly innervated by serotonin, acute toxicity frequently manifests as altered gastrointestinal (GI) motility and nausea. The most serious drug-related adverse effect of selective serotonin reuptake inhibitors (SSRIs) is the potential to produce serotonin syndrome.

Serotonin syndrome typically develops within hours or days of the addition of a new serotonergic agent to a medication regimen that already includes serotonin-enhancing drugs. Serotonin syndrome may also develop when a new serotonergic agent is started following the recent discontinuation of another serotonergic drug without allowing an adequate washout period. Isolated overdoses of SSRIs can also cause the syndrome. [9]

Symptoms attributed to serotonin excess may include the following:

  • Restlessness
  • Hallucinations
  • Shivering
  • Diaphoresis
  • Nausea
  • Diarrhea
  • Headache

Following an extensive review of the literature, Sternbach defined the following criteria for the diagnosis of serotonin syndrome [10] :

  • Symptoms must coincide with the initiation or increase in dose of a known serotonergic agent
  • At least 3 of the following symptoms and signs should be present: altered mental status, agitation, tremor, shivering, diarrhea, hyperreflexia, myoclonus, ataxia, or hyperthermia
  • Other etiologies (infections, metabolic disturbances, substance abuse, withdrawal) must be excluded
  • A neuroleptic agent should not have been initiated or increased in dose prior to the onset of the symptoms and signs

Physical Examination

Signs of serotonin excess vary and can be subdivided into the following 3 categories:

  • Mental status changes - Confusion, agitation, and coma
  • Neuromuscular findings - Myoclonus, rigidity, tremors, hyperreflexia (tends to be more prominent in the lower extremities than in the upper ones), clonus, and ataxia
  • Autonomic instability - Hyperthermia (excessive heat generation may develop secondary to prolonged seizure activity, rigidity, or muscular hyperactivity), mydriasis, tachycardia, and blood pressure alterations (hypertension, hypotension)