How can I distinguish serotonin syndrome from neuroleptic malignant syndrome in my patient with fever and mental status changes?

Although there is often an overlap between the clinical presentation of serotonin syndrome (SS) and neuromuscular malignant syndrome (NMS), start out with the physical exam. The presence of hyperreflexia, tremors, clonus, hyperactive bowel sounds, and dilated pupils should make you think of SS, whereas hyporeflexia, “lead-pipe” rigidity in all muscle groups, normal pupils, and normal or decreased bowels sounds suggest NMS in the proper context.1-3 The most sensitive and specific sign of SS is clonus.1

Aside from physical exam findings, symptom onset in relation to the implicated drug may also be important. Onset of symptoms within 12-24 h of the initiation or change of an implicated drug suggests SS, whereas a more delayed onset (often 1-3 days) is more supportive of NMS.1-3  SS also tends to resolve within a few days after discontinuation of the offending agent, while NMS usually takes 9-14 days to resolve. 1-3 Although both SS and NMS can be associated with leukocytosis, elevated CK and low serum iron levels are more common in NMS.2

SS is caused by excess serotonin due to a variety of mechanisms—therefore medications— including inhibition of serotonin uptake ( eg, serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, metoclopramide, ondansetron), inhibition of serotonin metabolism (seen with monoamine oxidase inhibitors , including linezolid, methylene blue), increased serotonin release (eg stimulants, including amphetamines, cocaine), and activation of serotonin receptors (eg, lithium), among others. 2

As for medications that can cause NMS, look for neuroleptic agents (eg, haloperidol, olanzapine, quetiapine, risperidone), as well as antiemeics, such as metoclopramide and promethazine.2

 

Bonus Pearl: Did you know that several supplements/herbal products have been associated with serotonin syndrome, including L-tryptophan, St. Jon’s wort and ginseng?1

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References

  1. Bienvenu OJ, Neufeld K, Needham DM. Treatment of four psychiatric emergencies in the intensive care unit. Crit Care Med 2012;40: 2662-70. https://insights.ovid.com/crossref?an=00003246-201209000-00017
  2. Turner AAH, Kim JJ, McCarron RM, et al. Differentiating serotonin syndrome and neuroleptic malignant syndrome. Current Psychiatry 2019;18: 36. https://www.mdedge.com/psychiatry/article/193418/schizophrenia-other-psychotic-disorders/differentiating-serotonin-syndrome
  3. Dosi R, Ambaliya A, Joshi H, et al. Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary. BMJ Case Rep 2014. Doi:10.1136/bcr-2014-204154. https://casereports.bmj.com/content/2014/bcr-2014-204154

 

How can I distinguish serotonin syndrome from neuroleptic malignant syndrome in my patient with fever and mental status changes?

What common drugs may exacerbate urinary retention in my patient with spinal cord injury?

Anticholinergics (including tricyclic antidepressants-TCAs), selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, opioids, alpha-adrenergics, and non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common agents associated with urinary retention1.  This adverse reaction is particularly observed in patients with pre-existing hypoactive bladder, including those with spinal cord injury (SCI).  Unfortunately, patients with SCI also often require pharmacologic management of neuropathic pain with one or more of these agents (eg, TCAs, opioids, and NSAIDs).

The mechanism of urinary retention may vary depending on the agent. Anticholinergics (eg, TCAs, diphenhydramine) decrease detrusor muscle contraction via blockade of the parasympathetic pathway.1 Opiates may increase the sphincter tone of bladder via sympathetic stimulation, as well as decrease the sensation of bladder fullness by partial inhibition of the parasympathetic nerves that innervate the bladder.2 SSRIs increase external sphincter tone by inhibiting serotonin reuptake.3 Alpha-adrenergics (e.g. ephedrine) can lead to detrusor relaxation and sphincter contraction.3 NSAIDs are thought to inhibit prostaglandin-mediated detrusor contraction.5

Although most patients with SCI have urinary incontinence due to detrusor hyperactivity, some will have urinary retention due to detrusor hyporeflexia.6

Final Fun Fact: Did you know that medications may account for up to 10% of urinary retention episodes? 

 

References

  1. Verhamme KM, Sturkenboom MC, Stricker BH, Bosch R. Drug-induced urinary retention. Drug Saf 2008;31(5):373-88. https://www.ncbi.nlm.nih.gov/pubmed/18422378
  2. Elsamra SE, Ellsworth P. Effects of analgesic and anesthetic medications on lower urinary tract function. Urologic Nursing 2012;32: 60-68. https://www.suna.org/download/education/2014/article320260067.pdf
  3. Thor KB. Serotonin and norepinephrine involvement in efferent pathways to the urethral rhabdosphincter: implications for treating stress urinary incontinence. Urology 2003; 62:3-9. https://www.ncbi.nlm.nih.gov/pubmed/14550831
  4. Glidden RS, DiBona FJ. Urinary retention associated with ephedrine. J Pediatr 1977; 90:1013-4. https://www.ncbi.nlm.nih.gov/pubmed/859049
  5. Verhamme KM, Dieleman JP, Van Wijk MA, et al. Nonsteroidal anti-inflammatory drugs and increased risk of acute urinary retention. Arch Intern Med. 2005;165:1547–1551. https://www.ncbi.nlm.nih.gov/pubmed/16009872
  6. Fowler CJ, O’Malley KJ. Investigation and management of neurogenic bladder dysfunction. J Neurol Neurosurg Psychiatry 2003;74(Suppl IV):iv27–iv31. http://jnnp.bmj.com/content/jnnp/74/suppl_4/iv27.full.pdf

 

Contributed by Alice Choi, Medical Student, Harvard Medical School, Boston, MA.

 

What common drugs may exacerbate urinary retention in my patient with spinal cord injury?