Serotonin Syndrome and Neuroleptic Malignant Syndrome

Author: Rachel Gonzalez

Serotonin Syndrome

Serotonin syndrome is a toxicity caused by increased serotonergic activity in the CNS. Common presentations include mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. Causes of serotonin syndrome include drug interactions, self-poisoning, and even therapeutic medication use of serotonergic drugs. Serotonin syndrome symptoms develop quickly (between 6 – 24 hours) after initiation of causative agent.

The most common causes of serotonin syndrome include SSRIs (citalopram, escitalopram, sertraline, fluoxetine, paroxetine); however other agents can contribute to serotonin syndrome like MAOIs, TCAs, SNRIs, linezolid, triptans, and antiemetics. Any medication that increases serotonin neurotransmission carries the risk of serotonin syndrome and patients on more than one agent should be monitored for this potentially life-threatening condition.

Patients who present with serotonin syndrome can have a variety of symptoms and presentations. Neuromuscular abnormalities such as ocular clonus (continuous horizontal eye movements), tremors, Babinski signs, deep tendon hyperreflexia, and spontaneous muscle clonus may occur. Patients may present with hyperthermia and hypertension and then experience dramatic swings in blood pressure. It is important to do a complete medication history to ensure a patient is experiencing serotonin syndrome and rule out other causes.

The primary treatment for serotonin syndrome is to discontinue all serotonergic drugs and provide supportive care. Benzodiazepines can be utilized to provide chemical sedation, and if these fail to improve agitation, the antidote cyproheptadine may be used. Duration of serotonin syndrome is related to the offending agent’s half-life. Medications with longer half-lives such as fluoxetine, will prolong the effect of serotonin syndrome.

Neuroleptic Malignant Syndrome (NMS)

Neuroleptic malignant syndrome is a serious neurologic emergency caused by antipsychotics. First generation antipsychotics (haloperidol for example) are more likely to precipitate NMS; however, all antipsychotics carry the risk. Antiemetics (promethazine, metoclopramide) additionally carry this warning and lithium can contribute as well. Onset of NMS is slow, and usually develops 2 weeks after initiation of an antipsychotic or at any time during treatment.

Patients with NMS experience a mental status change such as delirium and agitation. They also will experience extreme muscular rigidity, hyperthermia, and autonomic disturbances like tachycardia, hypertension, and diaphoresis. A patient’s CK level will likely be extremely elevated (>1000 IU/L).
Treatment involves discontinuing the offending agent or contributing agent, provide supportive care, utilize benzodiazepines if necessary, and initiation of dantrolene. Dantrolene is typically reserved for more severe cases or patients who are not responding to supportive care and benzodiazepines. Dantrolene should be avoided in patients with abnormal liver function. 

Serotonin syndrome and NMS have similar presentations but there are a few distinct features to differentiate the two. Serotonin syndrome patients often experience hyperreflexia that is not seen in NMS and NMS patient’s rigidity and hyperthermia is often more severe. A detailed medication history can also help differentiate between these two syndromes.

References:

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