Serotonin Syndrome: Fairly Common but Frequently Forgotten (original) (raw)
Related papers
New England Journal of Medicine, 2005
he serotonin syndrome is a potentially life-threatening adverse drug reaction that results from therapeutic drug use, intentional self-poisoning, or inadvertent interactions between drugs. Three features of the serotonin syndrome are critical to an understanding of the disorder. First, the serotonin syndrome is not an idiopathic drug reaction; it is a predictable consequence of excess serotonergic agonism of central nervous system (CNS) receptors and peripheral serotonergic receptors. 1,2 Second, excess serotonin produces a spectrum of clinical findings. 3 Third, clinical manifestations of the serotonin syndrome range from barely perceptible to lethal. The death of an 18-year-old patient named Libby Zion in New York City more than 20 years ago, which resulted from coadminstration of meperidine and phenelzine, remains the most widely recognized and dramatic example of this preventable condition. 4 The serotonin syndrome is often described as a clinical triad of mental-status changes, autonomic hyperactivity, and neuromuscular abnormalities, but not all of these findings are consistently present in all patients with the disorder (Fig. 1). 5,6 Signs of excess serotonin range from tremor and diarrhea in mild cases to delirium, neuromuscular rigidity, and hyperthermia in life-threatening cases. The difficulty for clinicians is that mild symptoms may be easily overlooked, and an inadvertent increase in the dose of the causative agent or the addition of a drug with proserotonergic effects may provoke a dramatic clinical deterioration. The incidence of the serotonin syndrome is thought to mirror the increasing number of proserotonergic agents being used in clinical practice. 7 In 2002, the Toxic Exposure Surveillance System, which receives case descriptions from office-based practices, inpatient settings, and emergency departments, reported 26,733 incidences of exposure to selective serotonin-reuptake inhibitors (SSRIs) that caused significant toxic effects in 7349 persons and resulted in 93 deaths. 8,9 The assessment of the serotonin syndrome in therapeutic drug dosing has relied on post-marketing surveillance studies, one of which identified an incidence of 0.4 case per 1000 patient-months for patients who were taking nefazodone. 10 Performing a rigorous epidemiologic assessment of the serotonin syndrome, however, is difficult, since more than 85 percent of physicians are unaware of the serotonin syndrome as a clinical diagnosis. 10 The syndrome occurs in approximately 14 to 16 percent of persons who overdose on SSRIs. 8 Although the serotonin syndrome has occurred in a broad range of clinical environments, several barriers limit the ability of clinicians to diagnose the condition. First, the syndrome may be missed because of its protean manifestations. Clinicians and patients may dismiss symptoms such as tremor with diarrhea or hypertension as inconsequential or unrelated to drug therapy; anxiety and akathisia may be misattributed to the patient's mental state. 5,10 Second, a strict application of the diagnostic criteria proposed t definition and epidemiology
Serotonin syndrome: a complex but easily avoidable condition
General Hospital Psychiatry, 2008
Serotonin syndrome is a potentially life-threatening adverse drug reaction caused by excessive serotonergic agonism in central and peripheral nervous system serotonergic receptors (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120. Symptoms are characterized by a triad of neuron-excitatory features, which include (a) neuromuscular hyperactivitytremor, clonus, myoclonus, hyperreflexia and, in advanced stages, pyramidal rigidity; (b) autonomic hyperactivitydiaphoresis, fever, tachycardia and tachypnea; (c) altered mental statusagitation, excitement and, in advanced stages, confusion (Gillman PK. Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. Br J Anaesth 2005;95:434-441). It arises when pharmacological agents increase serotonin neurotransmission at postsynaptic 5-hydroxytryptamine 1A and 5-hydroxytryptamine 2A receptors through increased serotonin synthesis, decreased serotonin metabolism, increased serotonin release, inhibition of serotonin reuptake or direct agonism of the serotonin receptors (Houlihan D. Serotonin syndrome resulting from coadministration of tramodol, venlafaxine, and mirtazapine. Ann Pharmacother 2004;38:411-413). The etiology is often the result of therapeutic drug use, intentional overdosing of serotonergic agents or complex interactions between drugs that directly or indirectly modulate the serotonin system (Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120. Due to the increasing availability of agents with serotonergic activity, physicians need to more aware of serotonin syndrome. The following case highlights the complex nature in which serotonin syndrome can arise, as well as the proper recognition and treatment of a potentially life-threatening yet easily avoidable condition.
Multiple drug interactions - induced serotonin syndrome: a case report
Journal of Clinical Pharmacy and Therapeutics, 2009
Serotonin syndrome is a potentially life-threatening disorder of excessive serotoninergic activity often due to drug interactions. We report a case of serotonin syndrome induced by pharmacokinetic and pharmacodynamic interactions between three different selective serotonin-reuptake inhibitors (SSRI) and possibly ciprofloxacin. Extreme caution is necessary in patients treated with serotonin-reuptake inhibitors who need to be switched to another antidepressant or when they require the addition of concomitant drugs, especially serotoninergic drugs and isoenzimes of cytochrome P450 inhibitors.
Serotonin syndrome: a brief review
2003
Case 1 A 50-year-old man was admitted to hospital with hyperhidro- sis, nausea, vomiting and diarrhea. He had been taking fluoxe- tine (120 mg/d), meprobamate (400 mg/d) and aceprometazine (13.55 mg/d). The dose of fluoxetine had just been increased. The patient was agitated and had insomnia and hyperreflexia, but there were no focal neurological findings. His blood pres- sure was
Serotonin Syndrome: The Role of Pharmacology in Understanding Its Occurrence
Cureus
Serotonin syndrome (SS) is a potentially fatal adverse drug reaction characterized by an exaggerated increase in serotonergic activity in the central and peripheral nervous systems. It presents a constellation of signs and symptoms related to behavioral changes, neuromuscular excitability, and autonomic instability. These symptoms can occur in both mild and severe forms. SS can be triggered by the therapeutic use of a drug that increases serotonin (5-HT) availability in the synaptic cleft or by the co-administration of two or more drugs that provide this increase. With the escalating use of antidepressants by the world's population, this adverse reaction may be more recurrent. However, SS is often overlooked by patients or not diagnosed by doctors. This review aims to improve awareness about SS and provide a pharmacological perspective to explain its occurrence. Evidence shows that other neurotransmitters may also be involved with the pathology of SS. Furthermore, SS and neuroleptic malignant syndrome (NMS) seem to be part of the same pathological spectrum, especially in atypical NMS cases. The emergence of the syndrome's symptoms may be closely related to pharmacokinetic and/or pharmacodynamic polymorphisms that lead to an increase in the 5-HT available to or 5-HT signaling by specific receptors, thus constituting an important area for future investigations.
The central nervous system serotonin syndrome
Clinical Pharmacology & Therapeutics, 1993
The class of drugs known as monoamine oxidase (MAO) inhibitors is often used in patients with depression that is refractory to treatment with simpler-touse drugs such as tricyclic antidepressants or fluoxetine. The hypertensive response caused by the interaction between MAO inhibitors and tyramine or sympathomimetic agents has been well described, and most physicians are aware of this potential problem. However, many physicians may not be aware of the potential for severe drug interactions between a variety of types of medications and MAO inhibitors. In this article, we describe two patients recently referred to our medical center who had life-threatening interactions involving phenelzine (an MAO inhibitor) and either clomipramine or dextromethorphan.
Serotonin Syndrome - A Focused Review
Background: Serotonin syndrome is a potentially life-threatening syndrome with manifestations spanning from mild adverse effects to life-threatening toxicity. The syndrome is caused by overstimulation of serotonin receptors by serotonergic drugs. Since the use of serotonergic drugs is increasing, primarily due to the widespread use of selective serotonin reuptake inhibitors, cases of serotonin syndrome have likely seen a parallel increase. The true incidence of serotonin syndrome remains unknown due to its diffuse clinical presentation. Objectives: This review aims to provide a clinically focused overview of serotonin syndrome, covering its pathophysiology, epidemiology, clinical manifestations, diagnostic criteria, differential diagnosis, and treatment as well as classifying serotonergic drugs and their mechanism of action. The pharmacological context is emphasized, as it is crucial for detection and management of serotonin syndrome. Methods: Focused review based on a literature se...
Serotonin Syndrome and Other Serotonergic Disorders
Pain Medicine, 2003
Serotonin syndrome is an iatrogenic disorder induced by pharmacologic treatment with serotonergic agents that increases serotonin activity. In addition, there is a wide variety of clinical disorders associated with serotonin excess. The frequent concurrent use of serotonergic and neuroleptic drugs and similarities between serotonin syndrome and neuroleptic malignant syndrome can present the clinician with a diagnostic challenge. In this article, we review the pathophysiology, diagnosis, and treatment of serotonin syndrome as well as other serotonergic disorders.