Serotonin syndrome caused

Ferrer-Dufol A, Perez-Aradros C, Murillo EC, Marques-Alamo JM. Fatal serotonin syndrome caused by moclobe-mide-clomipramine overdose. J Toxicol Clin Toxicol 1998 36(l-2) 31-2. 

Dardennes RM, Even C, Ballon N, Bange F. Serotonin syndrome caused by a clomipramine-moclobemide interaction. J Clin Psychiatry 1998 59(7) 382-3. 

Mekler G, Woggon B. A case of serotonin syndrome caused by venlafaxine and lithium. Pharmacopsychiatry 1997 30 263-264. 

Fitzsimmons CR, Metha S Serotonin syndrome caused by overdose with paroxetine and moclobemide. JAccId Emerg MecM999 16(4) 293-295. [PMID 10417944] (Case report.)... 

Spigset O, Mjomdal T, Lovheim O. Serotonin syndrome caused by a moclobemide-clomi-pramine interaction. BM/(1993) 306, 248. 

Fisher AA, Davis MW. Serotonin syndrome caused by selective serotonin reuptake-inhibitors-metoclopramide interaction. Ann Pharmacother (2002) 36,67-71. 

Not understood. The symptoms that developed with eitalopram or paroxetine and dextromethorphan were attributed by the authors of the reports to the serotonin syndrome, caused by the additive effeets of the SSRIs and dextromethorphan on serotonin transmission. It has also been suggested that paroxetine inhibited the cytochrome P450 isoenzyme CYP2D6, by which dextromethorphan is metabolised, resulting in increased dextromethorphan levels. Fluoxetine also inhibits CYP2D6. ... 

Rajapakse S, Abeynaike L, Wickramarathne T. Venlafaxine-associated serotonin syndrome causing severe rhabdo-myolysis and acute renal failure in a patient with idiopathic Parkinson disease. J Clin Psychopharmacol 2010 30(5) 620-2. 

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. 

The risk of potentially serious side effects should be enough to preclude the prescription of antidepressants for their placebo benefit, but this is not the only hazard associated with these medications. On 19 July 2006 the FDA issued a public-health advisory warning that, when taken in conjunction with other drugs that can affect serotonin levels, antidepressants can induce a life-threatening disorder called the serotonin syndrome .5 The serotonin syndrome is caused by an excess of serotonin in a person s body. 

Serotonin syndrome Some TCAs inhibit neuronal reuptake of serotonin and can increase synaptic serotonin levels (eg, clomipramine, amitriptyline). Either therapeutic or excessive doses of these drugs, in combination with other drugs that also increase synaptic serotonin levels (such as MAOIs), can cause a serotonin syndrome consisting of tremor, agitation, delirium, rigidity, myoclonus, hyperthermia, and obtundation. 

Serotonergic drugs - antidepressants maprotUine, monoamine oxidase inhibitors, drug combinations with specific serotonin reuptake inhibitors causing the serotonin syndrome - lithium, LSD, MDMA... 

Excess serotonin in the central nervous system leads to a condition commonly referred to as the serotonin syndrome. There are several drug mechanisms that can cause serotonin toxicity. Serotonin toxicity can be a medical emergency characterised by rapid onset of severe hyperthermia, muscle rigidity and multiple organ failure. 

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. 

Duloxetine is a moderate inhibitor of the CYP 2D6 enzyme and may increase the levels of other medications that use this enzyme (Table 1-1). Because of the risk of serotonin syndrome, duloxetine should not be combined with MAOIs. Because duloxetine is highly bound to plasma protein, combination with another drug that is highly protein bound may cause increased free concentrations of the other drug, potentially resulting in adverse events. 

Inhibition of MAO can cause severe interactions with other drugs, as detailed in the Hypertensive Crisis and Serotonin Syndrome subsections earlier in this section. A list of drugs that interact with the nonselective MAOIs is provided in Table 2-5. 

MAOIs have the most serious pharmacodynamic interactions of any antidepressant class. As discussed earlier, they can cause a hypertensive crisis and the serotonin syndrome. They potentiate the hypertensive effects of most sympathomimetic amines, as well as tyramine, which is the reason for the avoidance of over-the-counter preparations containing such agents, in addition to the tyramine-free diet ( 508, 509). The serotonin syndrome occurs most often when MAOIs are used in combination with SSRIs and venlafaxine but it can also occur when MAOIs are used with tryptophan, 5-hydroxytryptophan, and some narcotic analgesics. In addition, MAOIs can also significantly potentiate the sedative and respiratory depressant effects of narcotic analgesics. 

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. 

HT2 receptors are present on skeletal muscle membranes, but their physiologic role is not understood. Serotonin syndrome is a condition associated with skeletal muscle contractions and precipitated when MAO inhibitors are given with serotonin agonists, especially antidepressants of the selective serotonin reuptake inhibitor class (SSRIs see Chapter 30). Although the hyperthermia of serotonin syndrome results from excessive muscle contraction, serotonin syndrome is probably caused by a central nervous system effect of these drugs (Table 16-4 and Serotonin Syndrome and Similar Syndromes). 

Rasagiline Inhibits MAO-B selectively, higher doses also inhibit MAO-A Increases dopamine stores in neurons may have neuroprotective effects Parkinson s disease adjunctive to levodopa smooths levodopa response Oral Toxicity interactions may cause serotonin syndrome with meperidine, and theoretically also with selective serotonin reuptake inhibitors, tricyclic antidepressants... 

Linezolid Prevents bacterial protein synthesis by binding to the 23S ribosomal RNA of 50S subunit Bacteriostatic activity against susceptible bacteria Infections caused by methicillin-resistant staphylococci and vancomycin-resistant enterococci Oral, IV hepatic clearance (half-life 6 h) dosed twice-daily Toxicity Duration-dependent bone marrow suppression, neuropathy, and optic neuritis serotonin-syndrome may occur when coadministered with other serotonergic drugs (eg, selective serotonin reuptake inhibitors)... 

Newer antidepressants (eg, fluoxetine, paroxetine, citalopram, venlafaxine) are mostly SSRIs and are generally safer than the tricyclic antidepressants and monoamine oxidase inhibitors, although they can cause seizures. Bupropion (not an SSRI) has caused seizures even in therapeutic doses. Some antidepressants have been associated with QT prolongation and torsade de pointes arrhythmia. SSRIs may interact with each other or especially with monoamine oxidase inhibitors to cause the serotonin syndrome, characterized by agitation, muscle hyperactivity, and hyperthermia (see Chapter 16). 

The diagnosis of GHB withdrawal may be difficult because it is similar to sedative or alcohol withdrawal syndromes, as well as to withdrawal from sympathomimetic agents such as cocaine, methamphetamine, and ecstasy. GHB withdrawal may also be confused with serotonin syndrome (a reaction caused by a combination of drugs, one of which increases serotonin levels in the body, such as Prozac) and neuroleptic malignant syndrome (a rare reaction to an antiseizure medication). 

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