7,8 This review focuses on the relationships between the 3 classes of drugs known to be involved in severe SS, and the relative degrees of toxicity they characteristically precipitate. A key point to be emphasized is the spectrum concept of SS. SS is a synaptic serotonin (5-HT) concentration-related phenomenon.9 Readers are referred to recent selected reviews of SS for a broader perspective. There have been advances in the quantification of the frequency

and severity of SS with different drugs,9-14 in the definition of SS in animals and humans,15-17 in the pathophysiology,15 in the clinical presentation,18 and in its management and treatment.19-21 Serotonin syndrome can be diagnosed with accuracy and confidence, but few reports classify it using recognized diagnostic criteria, hence diminishing their value. It is not, as far as Talazoparib cost current human and animal evidence indicates, an idiosyncratic response, but a predictable and inevitable selleck chemicals result of

toxicity (mediated via the final common pathway of elevated intra-synaptic serotonin). If a case history were to appear reporting SS following an overdose of vitamin C, it would be parsimonious to assume that there had been a failure to ascertain or recognize the simultaneous ingestion of a potently serotonergic drug, cf. the Stanford case report.22 It would not be logical to make an initial assumption that vitamin C had previously unknown serotonergic properties, especially as we have good reasons to predict that it does not affect serotonin. That is Bayesian reasoning, ie, considering the prior probability when

estimating the likelihood of an outcome. Without such frameworks of knowledge and understanding of SS, case reports are often difficult to interpret, and the type of information they can yield reliably requires cautious consideration.23 The uncertainty and debate surrounding triptans demonstrates this problem clearly. The FDA alert was based on case reports, most of them informal, or “second-hand” and not peer-reviewed, and interpreted with an imperfect notion of Inositol oxygenase the symptoms and pathophysiology of SS, and without using validated criteria to establish diagnoses (eg, the Hunter Serotonin Toxicity Criteria [HSTC]17,20). The HSTC demonstrate unequivocally that clonus is the single most important sign required to diagnose SS, a fact that has now been established for many years, yet case reports of SS rarely, if ever, document the presence, or absence, of this sign. When such key information is lacking, little credence can be given to many reports. Case reports constitute a low grade of evidence, but they command undue attention and are repeatedly cited, even when they have been firmly rebutted (for just such an error that occurs in the FDA case reports, see24,25). The 3 classes of therapeutic drugs that, in certain combinations at usual doses, have been reliably documented to be capable of precipitating severe SS are: monoamine oxidase inhibitors (MAOIs), SRIs, and releasers.