Serotonin Syndrome symptoms

MDMA overdose as well as the concomitant consumption of selective serotonin reuptake inhibitors (SSRI) with other dmgs that exert serotoninergic effects (such as inhibitors of monoamine oxidase) can rapidly lead to the serotonin syndrome. Its symptoms, which are reversible upon cessation, of the drug include confusion, muscle rigidity in the lower limbs, and hyperthermia suggesting an acute reaction to serotonin overflow in the CNS. Blocking the function of SERT outside the brain causes side effects (e.g., nausea), which may be due to elevated 5HT however , impairment of transporter function is not equivalent to direct activation of 5HT recqrtors in causing adverse effects such as fibrosis and pulmonary hypertension. 

Although many patients believe that dietary supplements will not interact with medications, recent literature suggests otherwise. Recently, many St. John s wort-drug interactions have been reported in the literature. Cases of patients developing symptoms of serotonin syndrome have been reported with St. John s wort alone and in concomitant therapy with other antidepressants such as monoamine oxidase inhibitors, serotonin reuptake inhibitors, and venlafaxine. St. John s wort may exacerbate the sedative effects of benzodiazepines, alcohol, narcotics, and other sedatives. St. John s wort may decrease the levels of protease inhibitors, cyclosporine, digoxin, and theophylline. 

The combination of an SSRI with another 5-HT augmenting agent can lead to the serotonin syndrome, which is characterized by symptoms such as clonus, hyperthermia, and mental status changes. 

Add tryptophan to a standard antidepressant (usually an SSRI). There is a danger that the serotonin syndrome may occur however and occasionally the eosinophilia myalgia syndrome. The symptoms that occur with increasing severity are restlessness, diaphoresis, tremor, shivering, myoclonus, confusion, convulsions, death. 

Serotonin syndrome (sibutramine) The rare, but serious, constellation of symptoms also has been reported with the concomitant use of selective serotonin reuptake inhibitors and agents for migraine therapy (eg, sumatriptan, dihydroergotamine), certain opioids (eg, dextromethorphan, meperidine, pentazocine, fentanyl), lithium, or tryptophan. Because sibutramine inhibits serotonin reuptake, it should not be administered with other serotonergic agents. 

A life-threatening condition, when selective serotonin reuptake inhibitors (SSRIs) and 5-hydroxytryptamine receptor agonists (triptans) are used together. However, many other drugs have been implicated (see below). Signs and symptoms of serotonin syndrome include the following ... 

Central Serotonin Syndrome is manifest by autonomic, neuromuscular, and cognitive symptoms. Mild symptoms can include tremor, incoordination, and confusion. Moderate symptoms can manifest as shivering, sweating, hyperreflexia, and agitation, and severe symptoms include fever, myoclonus, and diarrhea. This syndrome is usually associated with two or more drugs that increase central serotonin transmission and affect the 5-HTia receptor (see Table 5.4). 

Sternbach (1991) originally defined the clinical symptoms of the serotonin syndrome (Table 22.4). Table 22.5 lists medications that have been implicated in causing serotonin syndrome. 

Other etiologies need to be ruled out because many of the symptoms of serotonin syndrome overlap with those of early sepsis or neuroleptic malignant syndrome, conditions associated with significant mortality. It is critical to evaluate for sepsis and to determine that a neuroleptic has not been started or increased prior to the onset of... 

Medications with serotonergic activity may also have other monaminergic or sympathomimetic activity. Combining MAOIs with these medications may result in a complex side effect profile. For example, combining meperidine or dextromethorphan with MAOIs may result in respiratory depression, in addition to symptoms of serotonin excess. Furthermore, interactions between MAOIs and tricyclic antidepressants (TCAs) more commonly result in potentiating shared adverse events such as othostatic hypotension, as opposed to hyperadrenergic crises or the serotonin syndrome. 

M. Lejoyeux, J. Ades, F. Rouillon (1994). Serotonin syndrome incidence, symptoms and treat-... 

Hypertensive crisis often occurs as a result of the interaction of two or more drugs acting via different mechanisms to potentiate the cardiovascular effects of NE. It can also occur as a result of a drug-food interaction involving MAOIs and tyramine-containing foods. Like the serotonin syndrome, hypertensive crisis can be fatal. Prodromal symptoms include the following ... 

There were two cases of hypertension from the United States, or possible serotonin syndrome reported with fluvoxamine while on St. John s wort concomitantly. A 44-year-old male with obsessive-compulsive disorder received fluvoxamine and experienced severe hypertensive crisis (160-170/ 120mmHg) after two tablets of St. John s wort. The physician stated that the reaction was probably due to the combination of fluvoxamine and St. John s wort, which has MAOI activity. A 38-year-old male was on fluvoxamine for approximately two months and hypericum 600 mg daily for approximately two weeks before reporting possible serotonin syndrome with severe bitemporal headache. He was hospitalized to rule out myocardial infarction. There were no electrocardiogram (EKG) changes or apparent causative pathology. Symptoms resolved on discontinuation of both drugs. 

Five cases (ages 36, 48, 48 and 60 and one unknown three males and two females) reported intermittent ineffectiveness with sertraline, including complaints of does not seem to be working, anxiety attack, or worsening depression. In four cases, symptoms occurred after sertraline was added to the continuing St. John s wort therapy. In contrast to reports with other antidepressants, these cases did not report hypertension or possible serotonin syndrome. It is uncertain if the occasional events were possibly associated with the patients unstable psychiatric status following sertraline therapy, or due to potential sertraline-related adverse events. 

Concentrations of nefazodone and its metabolites can be increased by fluoxetine and paroxetine (SEDA-20, 9). Combinations of serotonin agents produce serotonin toxicity, and a case of serotonin syndrome occurred when nefazodone (200 mg/day) was combined with fluoxetine (40 mg/day) in a 50-year-old man (109). The toxic symptoms settled 3 days after withdrawal of both antidepressants. 

Serotonin syndrome occurred in an 88-year-old woman who took sertraline 50-100 mg/day and tramadol 200-400 mg/day for 10 days the symptoms subsided 15 days after withdrawal of tramadol (124). 

A 23-year-old Japanese woman with major depression took a single dose of paroxetine (20 mg) and 1 hour later had agitation, myoclonus, mild hyperthermia (37.5°C), sweating, and diarrhea, symptoms that meet the criteria for the serotonin syndrome she recovered with supportive treatment over 3 days (2). 

A 49-year-old man had major adverse effects 11 days after taking a combination of sertraline, buspirone, and loxapine (25). The adverse effects were characteristic of the serotonin syndrome, which is characterized by a constellation of symptoms, including hypomania, agitation, seizures, confusion, restlessness, hyper-reflexia, tremor, myoclonus, ataxia, incoordination, anxiety, double vision, fever, shivering, variable effects on blood pressure, nausea and vomiting, sweating, and diarrhea. 

The tendency for MAO inhibitors to produce symptoms related to neuromuscular excitability, the serotonin syndrome, has been recognized in cases of overdose (SEDA-10, 18) and in interactions with other antidepressants or tryptophan (SEDA-10, 16, 17) (20). The authors of a thorough review of the preclinical and clinical literature have drawn attention to these phenomena, which occur at therapeutic doses with a MAO inhibitor alone, and have speculated that the mechanism is related to a combination of increased serotonergic tone and central disin-hibition of alpha motor neuron-mediated spinal activity (21). They discussed ten previous reports of myoclonus, hyper-reflexia, muscle twitching, and increased muscle tone in patients taking MAO inhibitors. These neuromuscular effects appear to occur in up to 15% or more of patients, and are more likely when tryptophan is given in combination. They usually appear after 10-14 days. Tolerance does not occur, but the effects may abate or... 

The serotonin syndrome occurred in a 60-year-old woman when the addition of trazodone 50 mg/day to nefazodone 500 mg/day caused confusion, restlessness, sweating, and nausea after the third day of treatment (75). The symptoms settled quickly on withdrawal of both antidepressants. 

A 44-year-old man developed the serotonin syndrome after taking moclobemide and alprazolam for 1 year (23). The symptoms developed after 4 days of extreme heat, which was thought to have contributed. 

A 27-year-old married woman developed symptoms of generalized anxiety disorder and was given buspirone 30 mg/day (32). During treatment she felt depressed and decided to take St John s wort. Two months later she started to have nervousness, aggressiveness, hyperactivity, insomnia, blurred vision, and very short periods of confusion and disorientation. The symptoms were consistent with serotonin syndrome. St John s wort was withdrawn and her symptoms resolved after 1 week. 

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