Serotonin Syndrome



  • Condition associated with skeletal muscle contractions, hyperthermia, hyperreflexia, diarrhea, mydriasis, agitation, myoclonus & coma.
  • Due to excessive serotonin in synapse.


1. Due to 5HT metabolism inhibition:

  • Seen with MAO inhibitor.

2. Due to 5HT release inhibition:

  • Amphetamines
  • Cocaine
  • Fenfluramine
  • MDMA

3. Due to serotonin reuptake inhibition:

  • SSRI’s (High-risk factor):
    • Co-administration of SSRIs with MAO inhibitors.
    • SSRIs should be started at least 14 days after MAO inhibitor discontinuation.
    • To allow sufficient time for MAO regeneration.
  • TCA’s
  • Amphetamines, cocaine, MDMA, pethidine.

4. Due to serotonin receptor agonists

  • Buspirone
  • LSD
  • Sumatriptan

5. Due to non-specific increase in 5HT activity:

  • Lithium.
  • Electroconvulsive therapy.

6. Drug-induced:

  • Carbamazepine.
  • Nefazodone.
  • Tramadol.

Treatment for serotonin syndrome:

  • Cyproheptadine or chlorpromazine

Exam Important

  • The main high-risk factor involved in causing serotonin syndrome is co-administration of SSRIs with MAO inhibitors.
  • To prevent the risk of serotonin syndrome, SSRIs should be started at least 14 days after MAO inhibitor discontinuation.
  • Mechanisms by which serotonin syndrome is precipitated include 5HT metabolism inhibition, 5HT release inhibition, serotonin reuptake inhibition, serotonin receptor agonists, non-specific increase in 5HT activity & also drug-induced serotonin syndrome.
  • Cyproheptadine or chlorpromazine is used for treating serotonin syndrome.


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