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Serotonin Syndrome

Serotonin Syndrome is a potentially life-threatening condition that is caused by elevated serotonin concentrations in the body. This condition is brought on by the use of "serotonogenic" drugs, which include several types of antidepressants such as SSRIs, tricyclics and MAOIs. Other substances which may contribute to serotonin syndrome include cocaine, L-tryptophan, Lithium, amphetamines, ecstasy and LSD.

Precipitants of serotonin syndrome include the following:

  1. Drug combinations - serotonin precursors or agonists (tryptophan, LSD, lithium, L-dopa, buspirone [BuSpar]), serotonin-release agents, SSRls (paroxetine [Paxil], fluoxetine [Prozac], sertraline [Zoloft], fluvoxamine [Luvox]), nonse­lective serotonin reuptake inhibitors (clomipramine [Anafranil], imipramine, dextromethorphan, meperidine, venlafaxine [Effexor], nefazodone [Serzone], pentazocine [Talwin], trazodone, fenfluramine), nonspecific inhibitors of serotonin metabolism (cocaine, MAOIs)
  2. Increased serotonin precursors or agonists
  3. Increased release of serotonin (3,4 - methylenedioxy-methamphetamine [Ecstasy], fenfluramine)


Serotonin syndrome is often caused by taking two or more drugs which result in drug interaction where two or more agents which enhance serotonergic neurotransmission by different mechanisms are administered in combination or taken in overdose. Serotonin syndrome can be caused by combining the following drugs:

  • An MAOI combined with Prozac or another SSRI.
  • Combining Lithium with a SSRI has also been reported to be a factor in serotonin syndrome
  • Combing MAOI or SSRI's with fenfluramine may contribute to serotonin syndrome.

Be advised that there may be other factors involved as well. If you suspect you might have serotonin syndrome it is advisable that you contact a physician immediately.


  • Altered mental status +++: mania, hallucinations, and confusion
  • Autonomic dysfunction: diaphoresis ++, diarrhea ++, lacrimation, and shivering ++
  • Neuromuscular abnormalities: akathisia +++ and fever +++


  • Altered mental status: coma, delirium, mutism, and agitation
  • Autonomic dysfunction: mydriasis, hyperthermia, tachycardia, and alteration in blood pressure
  • Neuromuscular abnormalities: myoclonus +++, hyperreflexia ++, tremor ++, incoordination ++, clonus, nystagmus, rigidity
  • Seizure
  • Headache


The first line of treatment is to discontinue all drugs that affect serotonin. Benzodiazepines may be helpful to relieve muscular symptoms, and supportive treatment may be necessary for conditions such as respiratory distress. Drugs that specifically act against serotonin can be useful as well.

In most cases, symptoms subside quickly once this is done and the patient recovers fully. However, it should be emphasized that serotonin syndrome can be fatal, so it is important to seek help immediately if you or a loved one should experience any of the above symptoms shortly after starting a new antidepressant or changing from one to another.


The prevention of serotonin syndrome involves awareness of the toxic potential of serotonergic drugs. The manufacturer's advice about washout periods should be carefully considered when switching antidepressants and patients should also be educated about possible drug interactions.


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