These reports have been too frequently accepted because there is a generally insufficient understanding of the spectrum concept of SS, which explains the progression of dose-related effects that result from synaptic serotonin concentration-related phenomena.9 The spectrum concept provides
both a framework for understanding the subject, and the disparate literature, and makes testable (and proven) predictions about the frequency and severity of toxicity. There will be only rare exceptions to the statement that case reports will not contribute much more to the literature, because large prospective Napabucasin nmr case series (eg, Professor Whyte’s data) provide much more reliable evidence concerning the typical picture of toxicity with individual drugs, with the additional advantage that the signs
ZD1839 research buy and symptoms have been consistently collected and evaluated by an experienced team of toxicologists. Ergots are indolealkylamines, mostly derived directly from ergotamine and its many natural analogs.27,28 There seem to be no cases of typical or hyperthermic SS resulting from ergotamine in the literature. Mathew’s cases31 related to IV use of dihydroergotamine and were atypical (and rightly reported as only “suggestive” of SS) and do not meet the HSTC for SS. Eadie reviewed “Convulsive ergotism: epidemics of the serotonin syndrome,”32 in which he suggests that SS “. . . may therefore have been a public-health problem long before it was recognized as a complication of modern psychopharmacology.” The features, described from old sources (particularly the studies by Barger and Tissot33,34), were: “. . . distortion of the trunk and limbs, painful involuntary flexion of the fingers
and wrists, . . . drowsy, sometimes delirious, lethargic, and melancholic or manic and [patients] could have hallucinations and double vision. Some affected individuals developed profuse sweating, fever, muscle stiffness, and twitching. . . . It seems likely that some of the involuntary postures would now be classified as torsion dystonia or other dyskinesias, . . . .” to It is known that ergot alkaloids also have dopaminergic properties, which are more likely to be the cause of these signs and symptoms.35 Lysergic acid diethylamide is a potent compound; the typical active dose is between only 0.05 and 0.20 mg in humans. It does not seem to be associated with serotonergic symptoms or features of SS, either in “usual” doses or in “over-doses.” There appear to be no cases of SS in more than 50 years of use, and Fantegrossi states, “Indeed, there are no documented cases of death due to LSD overdose, . . . .”36 The absence of mortality or documented SS with LSD is particularly interesting because it is probably the indolealkylamine with the greatest agonist potency at the 5-HT2A receptor.37 The only case reports of toxicity in the literature are not typical SS38,39 although one case exhibited severe hyperthermia.