Ketanserin Reverses the Acute Response to LSD in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Participants.

BACKGROUND: Lysergic acid diethylamide (LSD) is currently being investigated in psychedelic-assisted therapy. LSD has a long duration of acute action of 8-11 hours. It produces its acute psychedelic effects via stimulation of the serotonin 5-hydroxytryptamine-2A (HT2A) receptor. Administration of the 5-HT2A antagonist ketanserin before LSD almost fully blocks the acute subjective response to LSD. However, unclear is whether ketanserin can also reverse the effects of LSD when administered after LSD. METHODS: We used a double-blind, randomized, placebo-controlled, crossover design in 24 healthy participants who underwent two 14-hour sessions and received ketanserin (40 mg p.o.) or placebo 1 hour after LSD (100 µg p.o.). Outcome measures included subjective effects, autonomic effects, acute adverse effects, plasma brain-derived neurotrophic factor levels, and pharmacokinetics up to 12 hours. RESULTS: Ketanserin reversed the acute response to LSD, thereby significantly reducing the duration of subjective effects from 8.5 hours with placebo to 3.5 hours. Ketanserin also reversed LSD-induced alterations of mind, including visual and acoustic alterations and ego dissolution. Ketanserin reduced adverse cardiovascular effects and mydriasis that were associated with LSD but had no effects on elevations of brain-derived neurotrophic factor levels. Ketanserin did not alter the pharmacokinetics of LSD. CONCLUSIONS: These findings are consistent with an interaction between ketanserin and LSD and the view that LSD produces its psychedelic effects only when occupying 5-HT2A receptors. Ketanserin can effectively be used as a planned or rescue option to shorten and attenuate the LSD experience in humans in research and LSD-assisted therapy. TRIAL REGISTRY: ClinicalTrials.gov (NCT04558294).

Immune thrombocytopenia associated with COVID-19 mRNA vaccine tozinameran - a clinical case and global pharmacovigilance data.

We report the occurrence of immune thrombocytopenia (ITP) in a 77-year-old man a few days after receiving the first dose of the COVID-19 mRNA vaccine tozinameran (Comirnaty®). The patient was treated with systemic corticosteroids, intravenous immunoglobulins and eltrombopag. He elected to proceed with the second dose of tozinameran 14 weeks after the first and his platelet count remained stable under a tapered eltrombopag dose. To our knowledge, this is the first case in which a second tozinameran dose has been administered to a patient who developed presumed secondary ITP after the first vaccination. We also report global pharmacovigilance data for the occurrence of ITP after vaccination with tozinameran.

Myocarditis and pericarditis in association with COVID-19 mRNA-vaccination: cases from a regional pharmacovigilance centre.

In this article we summarize suspected adverse events following immunization (AEFI) of pericarditis, myocarditis and perimyocarditis that were reported by our regional pharmacovigilance centre after COVID-19 mRNA-vaccination and discuss their association with these vaccines. Seventeen cases were reported between March and July 2021. Of these, nine had perimyocarditis, five myocarditis and three pericarditis. Twelve patients were male (71%). The median age was 38 years (range 17-88). The most commonly observed presenting symptom was acute chest pain (65%). While 47% of the patients were previously healthy, 53% had at least one pre-existing comorbidity, with hypertension being the most prevalent (24%). The European Society of Cardiology diagnostic criteria for the reported AEFIs were fulfilled in twelve cases (71%). The AEFIs occurred after the first vaccine dose in six cases (35%), after the second vaccine dose in ten cases (59%) and after both doses in one case (6%). The median latency of all AEFIs taken together was 14 days (range 1-28) after the first vaccination and 3 days (range 1-17) after the second one. All patients except one were hospitalized (94%) with a median length of stay of 7.5 days (range 3-13). The majority of patients (n = 11, 65%) did not experience any complications, and 13 (77%) of the patients had recovered or were recovering at the time of discharge. In 16 of the 17 cases (94%), the association between the AEFI and mRNA-vaccination was considered possible by the pharmacovigilance centre.

Cardiovascular adverse effects of lopinavir/ritonavir and hydroxychloroquine in COVID-19 patients: Cases from a single pharmacovigilance centre.

In this article we summarize the cardiovascular adverse events that were observed in three patients during their treatment for COVID-19 and discuss their association with lopinavir/ ritonavir (LPV/r) and hydroxychloroquine (HCQ). The cases were reported to our regional pharmacovigilance centre in April 2020. All three patients were above 75 years in age, male and multimorbid, and had been hospitalized for treatment of COVID-19. As part of their treatment, all of them received a very strictly monitored off-label therapy with LPV/r and HCQ, for which they had given their prior, written, informed consent. In one patient, erythromycin was also administered. All three patients developed a significant QTc time prolongation during or shortly after therapy with the above drugs. On account of this, the treatment had to be discontinued early in each case and QTc time recovered in all three patients.

Development and Implementation of an e-Trigger Tool for Adverse Drug Events in a Swiss University Hospital.

PURPOSE: The purpose of the study was to develop and implement an institution-specific trigger tool based on the Institute for Healthcare Improvement medication module trigger tool (IHI MMTT) in order to detect and monitor ADEs. METHODS: We performed an investigator-driven, single-center study using retrospective and prospective patient data to develop ("development phase") and implement ("implementation phase") an efficient, institution-specific trigger tool based on the IHI MMTT. Complete medical data from 1008 patients hospitalized in 2018 were used in the development phase. ADEs were identified by chart review. The performance of two versions of the tool was assessed by comparing their sensitivities and specificities. Tool A employed only digitally extracted triggers ("e-trigger-tool") while Tool B employed an additional manually extracted trigger. The superior tool - taking efficiency into account - was applied prospectively to 19-22 randomly chosen charts per month for 26 months during the implementation phase. RESULTS: In the development phase, 189 (19%) patients had ≥1 ADE (total 277 ADEs). The time needed to identify these ADEs was 15 minutes/chart. A total of 203 patients had ≥1 trigger (total 273 triggers - Tool B). The sensitivities and specificities of Tools A and B were 0.41 and 0.86, and 0.43 and 0.86, respectively. Tool A was more time-efficient than Tool B (4 vs 9 minutes/chart) and was therefore used in the implementation phase. During the 26-month implementation phase, 22 patients experienced trigger-identified ADEs and 529 did not. The median number of ADEs per 1000 patient days was 6 (range 0-13). Patients with at least one ADE had a mean hospital stay of 22.3 ± 19.7 days, compared to 8.0 ± 7.6 days for those without an ADE (p = 2.7×10-14). CONCLUSION: We developed and implemented an e-trigger tool that was specific and moderately sensitive, gave consistent results and required minimal resources.