Serotonin syndrome manifestations

In addition, whenever an antidepressant that blocks serotonin reuptake is discontinued, an unpleasant but harmless discontinuation syndrome manifested by abdominal discomfort, instability, anxiety, and occasionally painful shock-like sensations in the extremities can arise. The risk appears to be greatest with venlafaxine and paroxetine. Consequently, switching from one of these medications to another that does not block serotonin reuptake requires a gradual taper of the first medication over days to weeks. 

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). 

The major clinical applications of cyproheptadine are in the treatment of the smooth muscle manifestations of carcinoid tumor and in cold-induced urticaria. The usual dosage in adults is 12-16 mg/d in three or four divided doses. It is of some value in serotonin syndrome, but because it is available only in tablet form, cyproheptadine must be crushed and administered by stomach tube in unconscious patients. 

Manifestations of serotonin syndrome include altered mental status, restlessness, myoclonus, hyper-reflexia, diaphoresis, shivering, tremor, incoordination, and/or fever. 

Many reports have linked childhood hyperactivity to impaired central serotonin functions.89 In animals, the occurrence of a behavioral syndrome consisting of hyperactivity, stereotyped movements, and increase of temperature has been induced by L-tryptophan, as a serotonin precursor, by serotonin reuptake inhibitors, and by MAOIs.90 Most of these manifestations can be blocked specifically by pretreatment with an inhibitor of serotonin synthesis. In humans, the association of myoclonus, diarrhea, confusion, hypomania, agitation, hyperreflexia, shivering, incoordination, fever, and diaphoresis, when patients are treated with serotoninergic agents, could constitute a "serotonin syndrome." Such cases of serotonin syndrome were reported after treatments with L-tryptophan, MAOIs, serotonin reuptake inhibitors, and tricyclics, alone or in association. 

Information on the reaction between linezolid and the SSRIs, tricyclics, mirtazapine or venlafaxine appears to be limited, but what is known suggests that the interaction is probably rare. The manufacturers of linezolid say that patients taking SSRIs and tricyclic antidepressants should have their blood pressure monitored and be closely observed if given linezolid. They say that if this is not possible, concurrent use should be avoided. If linezolid is used with a drug with serotonergic actions it would seem prudent to monitor for symptoms of the serotonin syndrome, which may take several weeks to manifest. See The serotonin syndrome , (p.9), for further details. 

A small study in healthy subjects found no problems when moclobemide was given 24 hours after clomipramine. However, the serotonin syndrome occurred in 3 patients when clomipramine was replaced by mo-clobemide without a washout period or with only a 24-hour washout period, " and in another patient when moclobemide was replaced by clomipramine after only 12 hours. A fatal case of the serotonin syndrome occurred in a patient taking clomipramine and amitriptyline, with symptoms manifesting within 30 minutes of a 300-mg dose of moclobemide. Two other patients developed fatal serotonin syndrome after taking moderate overdoses of moclobemide and clomipramine. The serotonin syndrome has been reported in at least 8 other cases of moclobemide and clomipramine overdose, one of which also involved tramadol (see also MAOIs + Opioids Tramadol, p.ll41), another fluoxetine (see also MAOIs or RIMAs + SSRIs, p.l 142), and yet another buspirone (see also MAOIs or RIMAs + Buspirone, p.l 133). Conversely, a case of an overdose of moclobemide and clomipramine resulted in no adverse effects except sinus tachycardia. ... 

Serotonin is an important neurotransmitter, a local hormone in the gut, a component of the platelet clotting process, and is thought to play a role in migraine headache. Serotonin is also one of the mediators of the signs and symptoms of carcinoid syndrome, an unusual manifestation of carcinoid tumor, a neoplasm of enterochromaffin cells. In patients whose tumor is not operable, a serotonin antagonist may constitute a useful treatment. 

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