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Objective: To report a case of serotonin syndrome associated with interaction between fentanyl and citalopram, as evidenced by medication history, clinical features and reversal following discontinuation of fentanyl., Case Summary: A 65-year-old patient chronically treated with the selective serotonin reuptake inhibitor (SSRI) citalopram developed confusion, agitation, tachycardia, tremors, myoclonic jerks and unsteady gait, consistent with serotonin syndrome, following initiation of fentanyl, and all symptoms and signs resolved following discontinuation of fentanyl. Based on the Naranjo probability scale, serotonin syndrome was a probable adverse reaction associated with co-administration of citalopram and fentanyl., Discussion: Serotonin syndrome is a potentially lethal pharmacodynamic interaction between medications that increase serotonergic transmission at the synaptic junction. The development of new pharmacological agents with varied properties and actions has increased the risk of serotonin syndrome as a clinical diagnosis. SSRIs and fentanyl are commonly co-administered, especially in the setting of chronic or malignant pain, as underlying depression may contribute to the pathogenesis of pain., Conclusion: Healthcare professionals should be aware of the possible development of serotonin syndrome as a complication of initiation of fentanyl and other phenylpiperidine opioids in patients treated with SSRIs.

Escitalopram is the newest selective serotonin reuptake inhibitor (SSRI) available for use in the United States. It has been approved for the treatment of major depression and generalized anxiety disorder. It is the S-enantiomer of the SSRI citalopram and is highly serotonin specific as it has minimal effect on the reuptake of dopamine or norepinephrine. It is also a well-tolerated medication, with a side-effect profile comparable to the other SSRIs. While a number of side effects have been seen during escitalopram therapy, such as insomnia, nausea, and increased sweating, there are no reported cases of serotonin syndrome associated with escitalopram therapy to date. We present the case of a 24-year-old woman who developed serotonin syndrome after an increase in her escitalopram to 30 mg/day. We will review the diagnostic criteria of serotonin syndrome and the clinical scenarios in which serotonin syndrome can develop. We will also discuss the proposed treatments and role that polypharmacology may play in the development of this clinical entity.

A 65-year-old female patient with major depressive disorder suffered from clonus, shivering and impaired visual acuity after 20 mg/day of paroxetine administration. The symptoms were initially regarded as further manifestations of her somatic symptoms of depression, and paroxetine was increased to 30 mg/day resulting in frequent clonus, increased shivering, serious dysarthria, ongoing impairment in visual acuity and agitation. These symptoms subsided upon paroxetine discontinuation. Ten mg/day of paroxetine rechallenge provoked dysarthria, tremor and headache, but these symptoms improved again upon paroxetine discontinuation. These findings indicate that the patient's symptoms were not somatic in origin but were in fact the symptoms of serotonin syndrome. In conclusion, the present case suggests the difficulty in diagnosing serotonin syndrome in a patient with somatic symptoms.

Lithium therapy can cause a confusional state by direct toxicity, precipitation of nonconvulsive status epilepticus, or by interplay with other neuroleptic medications to produce neuroleptic malignant syndrome or serotonin syndrome. These conditions resemble each other clinically, but EEG may help differentiate among them. We reviewed the EEG patterns with triphasic waves or rhythmic delta activity in lithium toxic patients and discuss clinical and EEG differentiation among syndromes. Lithium toxicity poses significant diagnostic challenges from EEG and clinical perspectives.

Background: Serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS) are medical emergencies associated with psychotropic administration. Differentiation and treatment can be complex, especially when features of both syndromes are present and the patient has taken both serotonergic and neuroleptic agents., Method: Case analysis of a poly-drug overdose (venlafaxine, topiramate, divalproex sodium, risperidone, and carbamazepine) presenting with mixed SS/NMS features and whose clinical management suggests a practical algorithm for treatment of undifferentiated SS/NMS in critical care settings., Results: The suggested algorithm includes: 1) Supportive care and withdrawal of all potentially offending agents; 2) Laboratory evaluation with prompt initiation of treatment for both disorders--cyproheptadine for SS and dantrolene for NMS; 3) Do not use bromocriptine (contraindicated in SS) or chlorpromazine (contraindicated in NMS) initially; 4) Add bromocriptine when clinical presentation becomes consistent with NMS (SS can be prolonged if serotonergic agent has long half-life)., Conclusions: Prompt and appropriate identification and intervention are essential for successful management of SS and NMS. The suggested treatment algorithm allows for specific treatment of both disorders and avoids potentially exacerbating either one. The algorithm derived from this case could serve as both a practical guideline and impetus for further investigation in light of increasing psychotropic co-administration.

A 72-year-old man presented to the emergency clinic with motor restlessness and diminished consciousness 24 hours after he had mistakenly been given venlafaxine. He was referred from the psychiatric clinic where he was treated with tranylcypromine. Shortly after arrival, a severe serotonin syndrome developed with generalised myoclonic seizures, hyperreflexia, hypertonia, a rapid increase in temperature to 40.9 degrees C, hypertension, tachycardia, respiratory insufficiency, hyperkalaemia and metabolic acidosis. The patient was treated with the sedative propofol and the muscle relaxant rocuronium, followed by intubation and artificial respiration. He was cooled on a cooling mattress. Twenty-four hours later the airway tube could be removed and after 48 hours he was returned to the psychiatric ward in good condition. Tranylcypromine is a monoamine oxidase inhibitor and venlafaxine is a serotonin and noradrenaline reuptake inhibitor. When two serotoninergic agents are combined, the serotonin syndrome may develop, and this may be life-threatening. The treatment of this syndrome with propofol and rocuronium can be given quickly and safely in practically every hospital.

Serotonin syndrome is a preventable, drug-related complication that results from increased brainstem serotonin activity, usually precipitated by the use of one or more serotonergic drugs. Its clinical presentation consists of autonomic dysfunction, alteration in mental status, and neuromuscular disorder. Early recognition and treatment is important, because this condition is potentially fatal. Management includes withdrawal of causative agents and supportive measures such as hemodynamic stabilization, sedation, temperature control, hydration, and monitoring for complications. Serotonin antagonists, specifically cyproheptadine, have been used, but the documented benefits are purely anecdotal.

Linezolid, a novel antimicrobial with activity against gram-positive bacteria including pathogens resistant to traditional antimicrobials, also inhibits monoamine oxidase. This latter property can cause potentially lethal adverse interactions with antidepressant medications. Long known to psychiatrists, monoamine oxidase inhibitors (MAOIs) and complications of their use may be unfamiliar to medical and surgical practitioners who may thus unwittingly precipitate a hypertensive crisis or serotonin syndrome. We review the pharmacology of MAOis and describe 3 clinical situations In which linezolid-selective serotonin inhibitor (SSRI) interactions, actual or potential, figured prominently.

Anticonvulsants, neuroleptics, and antispasticity agents are used with increasing frequency in the pediatric population. Each of the drugs discussed in this article has serious but potentially reversible adverse effects. Pediatric primary care providers must be aware of the potential emergencies associated with the use of these neurologic medications to provide prompt and effective treatment.

The serotonin-syndrome is a possible side-effect in the treatment with serotonergic drugs. There are diagnostic criteria for diagnosis of this syndrome. After discontinuation of administering the serotonergic drug is fully reversible.

We report a case of neonatal symptoms of irritability, increased tonus and convulsions after in-utero exposure to paroxetine 30 mg/day. The infant's symptoms commenced on the first day after birth and persisted for 10 days. Paroxetine levels were undetectable on day 6. Extensive investigations excluded infective and metabolic causes. Serotonin toxicity due to paroxetine seems the most likely mechanism, though an important differential diagnosis is a paroxetine discontinuation (withdrawal) syndrome. Differentiating between these two syndromes in the neonate presents a dilemma for clinicians. Irrespective of the mechanism, we recommend that all neonates exposed to antidepressants, particularly serotonin reuptake inhibitors (SSRIs), during the last trimester should be followed-up closely for adverse symptoms commencing in the first 10 days after birth. The possibility of such symptoms needs to be discussed with women who are considering starting or continuing antidepressant treatment in pregnancy. All neonatal adverse drug events should be reported to a pharmacovigilance centre. Further research is warranted.

Serotonin toxicity (or serotonin syndrome) has become an increasingly common and important clinical problem in medicine over the last 15 years with the introduction of many new antidepressants that can cause increased levels of serotonin (5-HT) in the central nervous system (CNS). Severe and life-threatening cases are almost exclusively a result of combinations of antidepressants (usually monoamine oxidase inhibitors and selective serotonin reuptake inhibitors). Unfortunately, the term serotonin syndrome has a number of quite different meanings, and many people writing on this subject have failed to differentiate them. This has led to false conclusions regarding the 5-HT receptor subtypes responsible for the life-threatening effects in animal and human toxicity, and suggestions of ineffective treatment strategies. This review primarily addresses the serotonin receptor subtypes that underlie the clinical manifestations of excess CNS serotonin in humans and animals, and their implications for diagnosis and treatment. More specific diagnostic criteria for serotonin toxicity are required to identify situations when specific antidotes are likely to be useful. However, the mainstay of treatment of severe cases is good supportive care and early intubation and paralysis in life-threatening serotonin toxicity.

Serotonin syndrome is a rare but potentially fatal complication of drugs that have effects on central nervous system serotonin. It is characterized by sudden onset of altered mental status, increased neuromuscular activity and autonomic instability. The author reports a child with suprasellar region tumor who presented with depression and obsessive-compulsive disorder and received a combination of sertaline (selective serotonin reuptake inhibitor) and clomipramine (tricyclic antidepressant). Symptoms of serotonin syndrome occurred within 24 hours after increasing the dose of sertaline. The patient's symptoms resolved rapidly with discontinuation of the offending drugs and supportive care.

Serotonin syndrome is a disorder resulting from excess stimulation of serotonin and is associated with drug interaction, single-drug therapy, and overdose. We report a case involving a 32-year-old man who developed sudden agitation, diaphoresis, subjective fever, tremor, and insomnia. These symptoms were related to doubling the dose of citalopram in combination antidepressant therapy. Discontinuation of the agent resulted in early notable clinical resolution after 1 week. This is a rare report of serotonin syndrome induced by citalopram polytherapy. Although serotonin syndrome is rare, clinicians need to recognize it early.

Selective serotonin reuptake inhibitors (SSRI's) are increasingly being used as the first line therapeutic agent for the depression. It is therefore not unusual to see a case of overdose with these agents. More commonly an adverse drug reaction may be seen among the older patients who are particularly vulnerable to the serotonin syndrome due to multiple co-morbidity and polypharmacy. The clinical picture of serotonin syndrome (SS) is non-specific and there is no confirmatory test. SS may go unrecognized because it is often mistaken for a viral illness, anxiety, neurological disorder or worsening psychiatric condition.

Serotonin syndrome results from excessive activation of serotonin (5-hydroxytryptamine; 5-HT) receptors in the nervous system, on the surface of platelets, and on the vascular endothelium. The clinical manifestations are a triad of altered conscious state, autonomic dysfunction, and neuromuscular excitability. Clinical diagnostic criteria remain poorly defined and unvalidated, and there are no available investigations to confirm the diagnosis. The syndrome is caused by the administration of one or more drugs possessing serotonergic activity. Severe forms of the syndrome usually result from overdose, but can be induced by monotherapy. The exact incidence of serotonin syndrome remains unknown, but is likely to be increasing due to increased prescription of selective serotonin reuptake inhibitor antidepressants and tramadol, as well as recreational use of amphetamine-like substances. Serotonin syndrome may complicate the administration of drugs frequently used in anaesthetic practice, including pethidine and tramadol. Although the majority of cases improve with symptomatic and supportive care, severe cases need intensive care and frequently require mechanical ventilation. Neuromuscular excitability is likely to be the cause of rhabdomyolysis seen in severe cases and should be treated with benzodiazepines and muscle relaxants. Supportive therapies are required to treat hyperthermia and autonomic dysfunction. Cyproheptadine is the most commonly administered serotonergic antagonist, but is unavailable in parenteral form.

Objective: To test the ability of a novel super high-flux (SHF) membrane with a larger pore size to clear myoglobin from serum., Setting: The intensive care unit of a university teaching hospital., Subject: A patient with serotonin syndrome complicated by severe rhabodomyolysis and oliguric acute renal failure., Method: Initially continuous veno-venous hemofiltration was performed at 2 l/hour ultrafiltration (UF) with a standard polysulphone 1.4 m2 membrane (cutoff point, 20 kDa), followed by continuous veno-venous hemofiltration with a SHF membrane (cutoff point, 100 kDa) at 2 l/hour UF, then at 3 l/hour UF and then at 4 l/hour UF, in an attempt to clear myoglobin., Results: The myoglobin concentration in the ultrafiltrate at 2 l/hour exchange was at least five times greater with the SHF membrane than with the conventional membrane (>100,000 microg/l versus 23,003 microg/l). The sieving coefficients with the SHF membrane at 3 l/hour UF and 4 l/hour UF were 72.2% and 68.8%, respectively. The amount of myoglobin removed with the conventional membrane was 1.1 g/day compared with 4.4-5.1 g/day for the SHF membrane. The SHF membrane achieved a clearance of up to 56.4 l/day, and achieved a reduction in serum myoglobin concentration from >100,000 microg/l to 16,542 microg/l in 48 hours., Conclusions: SHF hemofiltration achieved a much greater clearance of myoglobin than conventional hemofiltration, and it may provide a potential modality for the treatment of myoglobinuric acute renal failure.

Movement disorders may present acutely, and failure to recognize and exclude important differential diagnoses can result in significant morbidity or mortality. Unfortunately, much of the literature pertaining to this topic is scattered and not easily accessible. This review aims to address this deficit. Movement disorder emergencies are discussed according to their most likely mode of presentation. Diagnostic considerations and early management principles are reviewed, along with appropriate pathophysiology where relevant., (2004 Movement Disorder Society.)

Introduction: Serotonin is a neurotransmitter synthesized from tryptophan. It is implied in the regulation of mood, cognition, sleep cycle, synthesis of cerebrospinal fluid, and other processes. Generally, it is implied in human pathology by hypofunction. However, there is a complication of unknown incidence related to treatment with drugs that increase the stimulation of 5-HT1A serotonin receptors, called serotonin syndrome (SS). Clinically, it is characterised by the presence of a triad of mental and autonomic disorders, and motor hyperactivity. This entity has not biological markers and its diagnosis could be done verifying the proposed criteria., Case Reports: Two cases of SS are presented, one of them related to the combination of risperidone and sertraline, as first report in the literature. Both cases had a favourable outcome employing support measures., Conclusions: The physiopathology, the diagnosis, the differential diagnosis, and the treatment are reviewed. We emphasize the potentially high frequency of this disorder, given the growing use of serotonin activity modifying drugs, and the typically benign course of the SS once the support measures are started.

The symptoms and signs of carisoprodol intoxications do not resemble those caused by its metabolite meprobamate. Meprobamate most probably produces its effects through the GABAergic neurotransmitter system. The signs and symptoms of carisoprodol intoxications, however, are not easily explained by interaction with this neurotransmitter system. In the present study, four cases of carisoprodol intoxications are presented with emphasis on the presence of serotonergic signs and symptoms. All four cases fulfilled three different sets of criteria for the diagnosis of serotonin syndrome. These findings could indicate that an increased serotonin level in the central nervous system could explain some of the symptoms and signs of carisoprodol intoxications. This may have implications for the clinical evaluation and treatment of such intoxications. Since few laboratories routinely screen for carisoprodol it is important to keep this drug in mind when encountering intoxications displaying serotonergic symptoms.

Objective: To report a case of quetiapine/venlafaxine intoxication associated with multiple complications and to review their possible relationship with these 2 drugs., Case Summary: A 53-year-old white man was admitted to the hospital for loss of consciousness secondary to voluntary intoxication with venlafaxine and quetiapine. Several complications were attributable to this intoxication including seizures, prolonged coma, respiratory depression, neuroleptic malignant syndrome, prolonged QRS and QTc intervals, and a possible venlafaxine withdrawal syndrome., Discussion: Quetiapine could be responsible for the neuroleptic malignant syndrome presented in this case. Moreover, venlafaxine intoxication, fever, autonomic instability, and myoclonus presented serotonin syndrome as a differential diagnosis. Potential causes of seizures and prolongation of the QRS and QTc intervals are reviewed. Finally, prolonged coma and late venlafaxine withdrawal are discussed with regard to the pharmacodynamics and pharmacokinetics of drug elimination in the context of intoxication., Conclusions: Clinicians should be aware of possible complications following intoxication with atypical antipsychotics and anti-depressants, including protracted altered mental status.

We report a case of serotonin syndrome that occurred in a patient with chronic heart failure associated with a panic disorder. The 39-year-old Japanese man had been treated with paroxetine at 20 mg/d for 1 1/2 years. He presented with rhabdomyolysis, renal failure, fulminant liver failure, cardiac conduction disturbance, and disseminated intravascular coagulation, as well as conventional symptoms of serotonin syndrome including alterations in cognition (disorientation, confusion) and behavior (restlessness), autonomic nervous system dysfunction (fever, shivering), and abnormal neuromuscular activity (ataxia, hyperreflexia, myoclonus). All medications prescribed before hospital admission were discontinued. After 24 hours of continuous venovenous hemofiltration, diuresis resumed and renal and liver function improved rapidly. Disorientation, restlessness, hyperreflexia, and myoclonus abated slowly over the next 72 hours. The patient's anxiety subsided more slowly, and he recovered completely 1 week later. The plasma concentration of paroxetine was elevated far above the upper limit of the therapeutic range. The patient had cytochrome P-450 (CYP) 2D6*1/*5, a heterozygosity of an inactivated allele of CYP2D6, which metabolizes paroxetine. The patient was determined to be an intermediate metabolizer who was potentially vulnerable to paroxetine, a major inhibitor of CYP2D6. Heart failure is often accompanied by psychiatric disorders. A wide range of drugs commonly prescribed for these conditions, including beta-blockers, antiarrhythmics, and antidepressants, are metabolized by CYP2D6. Genetic screening for CYP2D6 in patients with these conditions may prevent life-threatening drug intoxication.

The serotonin syndrome is a complex of symptoms that are thought to be largely attributable to changes in sensitivity in the serotonin receptor systems in the brainstem and the spinal cord due to drugs. Severe cases are almost always caused by a combination of two or more 'serotonergic' drugs, of which at least one is a selective serotonin reuptake inhibitor or a monoamine oxidase inhibitor. Usually, the syndrome heals spontaneously after withdrawal of the medication. Cessation of 'serotonergic' medication is the preferred treatment as well as supportive care.

Acute right heart failure in a young person is an unusual presentation and drug overdose is a rare cause. A case is described where the patient presented with striking clinical signs of acute pulmonary hypertension and right heart failure, which were confirmed by transthoracic echocardiography. The precipitating event appeared to be poisoning by tramadol. There were features in keeping with tramadol toxicity and serotonin syndrome. The possible pathophysiology behind the process is discussed.

NMS is a rare but fatal syndrome that needs to be considered in the perioperative period. Although many aspects remain unexplored and controversial, with greater awareness of the condition, new concepts are coming into light. Definitive treatment guidelines remain an important issue to be addressed. Efforts have been initiated in that direction and all cases can be reported on a toll-free hotline ( 1-888-667-8367) or online (www.nmsis.org).

Until now, only three patients with Huntington's disease (HD) and a neuroleptic malignant syndrome (NMS) have been reported in the literature. We describe four cases with advanced stage Huntington's disease who within a period of one year developed drug-induced hyperthermia, either the neuroleptic malignant syndrome, or the serotonin syndrome. Possible contributing factors that may have been specific for HD patients could be identified and included advanced neurological disease with severe illness, occurrence in summer, with possible infectious disease, dehydration, and pre-existing extra-pyramidal signs that may mask incipient NMS/serotonin syndrome. Measures to avoid these potentially lifethreatening conditions are discussed.

Nurses need to become more aware of serotonin syndrome to avoid its development and to ensure a therapeutic response when early symptoms emerge. While polypharmacy tends to put individuals at greatest risk for the syndrome, use of a single serotonergic agent may also provoke an adverse response. Because the onset and progression of serotonin syndrome are rapid, prompt action may be needed to avoid potentially life-threatening consequences.

Although SSRIs are widely used and generally considered safe, an abrupt cessation of SSRI use may result in a discontinuation syndrome that can mimic serious illness and can be distressing and uncomfortable. Several pharmacokinetic and pharmacodynamic factors influence the frequency and onset of these symptoms. Rapid identification of SSRI discontinuation syndrome and reinstitution of the medication can provide rapid symptom relief. Ongoing education and discussion about the illness and its treatment can promote medication compliance and thus minimize the potential for sudden cessation of the SSRI, the uncomfortable experience of discontinuation symptoms, and unnecessary medical expenditures.

Background: Selective serotonin reuptake inhibitors (SSRIs) have gained wide acceptance in the treatment of mental disorders in pregnant women, but there seems to be an increased risk for neonatal adaptation problems after exposure to SSRIs in late pregnancy. We aimed to investigate the perinatal sequelae of infants exposed to SSRIs during their fetal life and the relationship of these symptoms to the cord blood monoamine and prolactin concentrations., Methods: We conducted a prospective, controlled, follow-up study with 20 mothers taking 20 to 40 mg/d of either citalopram or fluoxetine for depression (n = 10) or panic disorder (n = 10) and their infants and 20 matched controls not receiving psychotropic medication for confounding obstetric characteristics. Maternal cord blood and infant citalopram, fluoxetine, and norfluoxetine, cord blood monoamine and metabolite, and prolactin concentrations were measured. The newborns underwent standard clinical examination and specific assessment of serotonergic symptoms during the first 4 days of life and at the ages of 2 weeks and 2 months., Results: There was a statistically significant (P =.008, V = 15, n = 20 for both groups), 4-fold difference in the serotonergic symptom score during the first 4 days of life between the SSRI group and the control group. The SSRI-exposed infants had significantly lower cord blood 5-hydroxyindoleacetic acid (5-HIAA) concentrations (P =.02, t31 = 2.57) compared with the control group. A significant inverse correlation (rs = -0.66, P =.007, n = 15) was seen between the serotonergic symptom score and the umbilical vein 5-HIAA concentrations in the SSRI-exposed but not the control infants., Conclusions: Infants exposed to SSRIs during late pregnancy are at increased risk for serotonergic central nervous system adverse effects, and the severity of these symptoms is significantly related to cord blood 5-HIAA levels.