Serotonin Syndrome and SSRI Overdose
Posted by Patrick Lickiss on Jun 11, 2010 in Assessment, Research, Treatment | 0 comments
INTRODUCTION
Selective serotonin reuptake inhibitors (SSRIs) are a common class of anti depressant prescribed in the United States and most of the first world. With the prevalence of SSRI use increasing, so too has the risk for interaction with other prescribed medications (1). One of the most dangerous, and rare, interactions is a condition referred to as “serotonin syndrome” or “serotonin toxicity”. Serotonin syndrome refers to the symptoms associated with an increase in the presence of the neurotransmitter 5-hydroxytryptamine (5-HT) (2).
SEROTONIN SYNDROME
Serotonin syndrome generally presents within hour to days of an initial dose of an SSRI, an increase in dose or an intentional overdose. Intentional overdoses causing serotonin syndrome can result from a single medication but are generally limited to poly-pharmacy overdoses. Serotonin syndrome itself results from increased serotonergic neurotransmission (2).
SSRIs work by decreasing the pre-synaptic uptake of serotonin, a neurotransmitter involved in the regulation of aggression, pain, sleep, depression and anxiety (3). Serotonin syndrome most often occurs as a result of mixing an SSRI with another form of anti-depressant, often a monoamine oxidase inhibitor (MAOI). MAOIs work by decreasing the action of the enzyme responsible for breaking down synaptic serotonin (3). As one may guess, the combination of these two medications would result in an unchecked flood of serotonin into the brain.
As mentioned above, serotonin syndrome is a collection of symptoms resulting from an increase in serotonin and occurs in approximately 16% of intentional overdose cases involving an SSRI (3). Symptoms noted fall into one of three categories: alteration of mental status, neuromuscular hyperactivity and autonomic instability (4). Altered mental status can range from confusion to coma and can include agitation, anxiety, delirium, hallucinations and drowsiness. Neuromuscular hyperactivity includes myoclonus (irregular involuntary contraction of a muscle (5)), hyper-reflexia (overactivity of physiological reflexes (5)), muscle rigidity, shivering and tremors. Lastly, and potentially most serious, autonomic instability can present as hyperthermia, diaphoresis, sinus tachycardia, hypertension/hypotension, flushing of the skin, diarrhea and vomiting. Indications of a life-threatening presentation include coma, seizures, rhabdomyolysis and disseminated intravascular coagulation.
DIFFERENTIAL DIAGNOSIS
The two most common differential diagnoses for serotonin syndrome are neuroleptic malignant syndrome (NMS) and malignant hyperthermia (6). NMS results from ingestion of dopamenergic drugs and symptoms develop over a period of days rather than hours (7). Given this limited pool of drugs from which to draw, a good history and assessment on scene, as well as determining the times of ingestion and onset of symptoms will effectively rule out NMS. Malignant hyperthermia, a potentially life-threatening reaction to anesthetic gasses and certain paralytics used in rapid-sequence induction, can be easily ruled out by responders assuming that none of these medications has been given (8).
Diagnostic diagram for Serotonin Syndrome based on Hunter Toxicity Criteria (3)
TREATMENT
In an emergency room setting, serotonin syndrome is treated by discontinuing the medication(s) in question and by providing supportive care to the patient (2). In the pre-hospital setting, the care is the same.
In order to discontinue the ingestion of medication, activated charcoal is considered indicated if given within 60 minutes of ingestion (1). Supportive care consists of administration of intravenous fluids to combat dehydration from hyperthermia, benzodiazepines to control tremors and delirium, cooling measures to manage hyperthermia, and intubation and respiratory management as appropriate (9).
TAKE HOME LESSONS FOR EMS
In the pre-hospital setting, the key to care for patients with serotonin syndrome is early recognition. A thorough history and physical examination will offer a patient the best opportunity to receive timely treatment. By being aware of the symptoms of serotonin syndrome and knowing the possible causes, pre-hospital practitioners can begin appropriate care as soon as possible.
Similarly to in-hospital care, treatment for serotonin syndrome is largely supportive. Airway management and ventilatory support including OPA/NPA, intubation, use of a rescue airway (such as a King LTD), administration of supplemental oxygen and positive pressure ventilation may all be utilized as appropriate. Fluid resuscitation can help to combat dehydration and active cooling measures can help to manage hyperthermia. Methods of active cooling can include, but are not limited to ice packs in the groin, axillae and behind the neck, moistening the patient’s skin with sterile water or saline and turning the air conditioner on in the back of the ambulance. Care must be taken to reduce shivering which will increase core temperature. Finally, the patient should be rapidly transported to the appropriate receiving facility.
CONCLUSION
Serotonin syndrome is the collection of symptoms resulting from an intrasynaptic increase of the neurotransmitter 5-HT. This increase generally results from a combination of drugs but can rarely be the result of a single overdose. Symptoms of serotonin syndrome include alteration of mental status, neuromuscular hyperactivity and autonomic instability. Serotonin syndrome can range from mild to life-threatening in severity. Care for patients suffering from serotonin syndrome is largely supportive. Presence of serotonin syndrome is determined by a thorough history and physical examination and, due to its potential severity, should be considered in the differential diagnosis of patients who are prescribed psychiatric medications.
NOTE: The opinions expressed here are those of the author alone and do not represent the views of any company or organization. Use common sense and check with your local accrediting agency before making treatment decisions based on anything written here. This article is not a substitute for protocols or policy and procedure manuals.
CITED ARTICLES:
1. Isbister GK, Buckley NA, Whyte IM. “Serotonin toxicity: a practical approach to diagnosis and treatment.” MJA. 2007 Sep;187(6):361-5.
2. Evans CE, Sebastian J. “Serotonin Syndrome.” Emerg Med J. 2007;24:e20
3. Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. “The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity.” Q J Med. 2003;96:635-42.
4. Mills KC. “Serotonin Syndrome: a clinical update.” Crit Care Clin. 1997;13:763-83.
5.
http://www.merriam-webster.com
6. Boyer EW, Shannon M. “The serotonin syndrome.” N Engl J Med. 2005;352:1112-1120.
7. Gupta S, Nihalani ND. “Neuroleptic malignant syndrome: a primary care perspective.” Prim Care Companion J Clin Psychiatry. 2004;6:191-194.
8. Litman RS, Rosenberg H. “Malignant hyperthermia: update on susceptibility testing.” JAMA. 2005;293:2918-2924.
9. Canan F, Korkmaz U, Kocer E, Onder E, Yildirim S, Ataoglu A. “Serotonin Syndrome with Paroxetine Overdose: A Case Report.” Prim Care Companion J Clin Psychiatry. 2008;10(2):165-7.
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