In this episode, I’ll discuss the use of cyproheptadine to treat serotonin syndrome.

Serotonin syndrome (SS) can result from an overdose or drug interaction involving one or more of the many drugs that increase serotonergic activity.

The Hunter Criteria is often used for the diagnosis of serotonin syndrome. To fulfill the Hunter Criteria, a patient must have taken a serotonergic agent and meet ONE of the following conditions:

1. Spontaneous clonus

2. Inducible clonus PLUS agitation or diaphoresis

3. Ocular clonus PLUS agitation or diaphoresis

4. Tremor PLUS hyperreflexia

5. Hypertonia PLUS temperature above 38ºC PLUS ocular clonus or inducible clonus

Serotonin syndrome is very similar to neuroleptic malignant syndrome. A thorough review of the patient’s current and recent medications and history of present illness is essential for differentiating between the two syndromes. SS develops over 24 hours, whereas NMS develops over a period of days. SS is accompanied by neuromuscular hyperreactivity (tremor, hyperreflexia, and myoclonus); NMS is accompanied by sluggish neuromuscular responses (rigidity and bradyreflexia).

For mild to moderate cases of serotonin syndrome, cyproheptadine can be used.

Cyproheptadine is an H1 blocking antihistamine, but it also has serotonin receptor blocking activity. Specifically, it acts to block 5-HT1A and 5-HT2A receptors, which are the receptors responsible for the symptoms of serotonin syndrome.

The typical dose of cyproheptadine for serotonin syndrome is 12 mg. This can be given orally or by gastric tube. This dose appears to have been arrived at based on a 1998 case series in which 5 patients with serotonin syndrome were treated. All patients were given 4 to 8 mg of cyproheptadine. Three of the five patients had symptoms resolve. The remaining 2 patients had a partial response, were given a repeat dose of cyproheptadine, and then had a complete response.

If this initial dose of 12 mg is not sufficient, cyproheptadine can be continued at a dose of 2 mg every 2 hours until symptoms completely resolve.

Cyproheptadine can also be given to patients with severe cases of serotonin syndrome. However, patients with severe serotonin syndrome require supportive care first with benzodiazepines, agents to control hypertension/tachycardia, and sometimes airway management. After the supportive care has been established cyproheptadine can be added to the treatment regimen.

While many case reports describe cyproheptadine as effective for serotonin syndrome, it has not been evaluated in a clinical trial. Therefore the effect on patient outcomes when cyproheptadine is used is unknown.

For more on serotonin syndrome, and how to tell the difference between it and neuroleptic malignant syndrome or malignant hyperthermia go to pharmacyjoe.com/episode40.

If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.

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