Per Damkier

Background Serotonin syndrome is a potentially life‐threatening syndrome with manifestations spanning from mild adverse effects to life‐threatening toxicity. The syndrome is caused by overstimulation of serotonin receptors by serotonergic drugs. Since the use of serotonergic drugs is increasing, primarily due to the widespread use of selective serotonin reuptake inhibitors, cases of serotonin syndrome have likely seen a parallel increase. The true incidence of serotonin syndrome remains unknown due to its diffuse clinical presentation. Objectives This review aims to provide a clinically focused overview of serotonin syndrome, covering its pathophysiology, epidemiology, clinical manifestations, diagnostic criteria, differential diagnosis and treatment, as well as classifying serotonergic drugs and their mechanism of action. The pharmacological context is emphasized, as it is crucial for the detection and management of serotonin syndrome. Methods Focused review based on a literature search using the PubMed database. Findings and conclusion Serotonin syndrome can occur through therapeutic use or overdose of a single serotonergic drug or as a drug interaction between two or more serotonergic drugs. Central clinical features consist of neuromuscular excitation, autonomic dysfunction and altered mental status, occurring in a patient undergoing new or altered serotonergic therapy. Early clinical recognition and treatment are crucial to prevent significant morbidity.

Gabapentin and pregabalin have been associated with an increased risk of fragility fractures. Due to differences in pharmacokinetics, we aimed to assess the fracture‐risk difference between the two medicines. We performed a Danish nationwide new user, high‐dimensional propensity score‐matched cohort study to assess the 90‐day risk of fragility fractures among adults, from January 1996 to December 2018. We applied a high‐dimensional propensity score to match new users of gabapentin with new users of pregabalin in a 1:1 intention‐to‐treat approach. Hazard ratios (HRs), incidence rates (IRs) and incidence rate difference (IRD) were obtained. We identified 388 236 eligible patients of which 294 223 and 98 869 initiated gabapentin and pregabalin, respectively. We included 48 272 matched pairs for further analysis. The mean age was 56 (IQR 44–69) years, and the average follow‐up was approximately 11 500 person‐years (PY). The IRs of fragility fractures were 23.7 (95%CI 21.0–26.7) and 23.2 (95%CI 20.5–26.2) per 1000 PY for gabapentin and pregabalin‐exposed patients, respectively. This yielded an HR of 1.02 (95%CI 0.86–1.21) when using gabapentin as the intervention drug and pregabalin as the reference drug. The IRD was estimated to 0.5 PY (95%CI −3.5–4.5). In conclusion, short‐term risk of fragility fractures among gabapentin initiators was not different compared to those initiating pregabalin.