The Neuropsychiatric Safety Profile of Lasmiditan: A Comparative Disproportionality Analysis with Triptans

International audienceMigraine constitutes the world's second-leading cause of disability. Triptans, as serotonin 5-HT1B/1D receptor agonists, remain the first-line treatment, despite discouraged use in individuals at high cardiovascular risk. Lasmiditan, a selective lipophilic 5-HT1F agonist without vasoconstrictive effects, is an emerging option. We aimed to investigate the safety profile of lasmiditan in the WHO pharmacovigilance database (VigiBase®) using a comparative disproportionality analysis with triptans. VigiBase® was queried for all reports involving lasmiditan and triptans. Disproportionality analyses relied on the calculation of the information component (IC), for which 95% confidence interval (CI) lower bound positivity was required for signal detection. We obtained 826 reports involving lasmiditan. Overall, 10 adverse drug reaction classes were disproportionately reported with triptans, while only neurological (IC 1.6; 95% CI 1.5-1.7) and psychiatric (IC 1.5; 95% CI 1.3-1.7) disorders were disproportionately reported with lasmiditan. Sedation, serotonin syndrome, euphoric mood, and autoscopy had the strongest signals. When compared with triptans, 19 out of 22 neuropsychiatric signals persisted. The results of our analysis provide a more precise semiology of the neuropsychiatric effects of lasmiditan, with symptoms such as autoscopy and panic attacks. The cardiovascular adverse drug reaction risk with triptans was confirmed. In contrast, caution is warranted with lasmiditan use in patients with neurological or psychiatric comorbidities or serotonin syndrome risk. Our study was hindered by pharmacovigilance flaws, and further studies should help in validating these results. Our findings suggest that lasmiditan is a safe alternative for migraine treatment, especially when the neuropsychiatric risk is outweighed by the cardiovascular burden

Drug-Associated Parosmia: New Perspectives from the WHO Safety Database

Parosmia is a qualitative distortion of smell perception. Resulting from central causes, sinonasal diseases, and infections, parosmia has also been associated with medications. Therefore, we aimed to investigate potential signals for drugs associated with parosmia. VigiBase® (the WHO pharmacovigilance database) was queried for all reports of “Parosmia” (MedDRA Preferred Term), registered up to 23 January 2022. Disproportionality analysis relied on the reporting odds ratio and the information component. A signal is detected when the lower end of the 95% confidence interval of the information component is positive. We found 14,032 reports of parosmia, with a median patient age of 53 years. Most reported drugs were antiinfectives, among which COVID-19 vaccines accounted for 27.1% of reports. Antibiotics and corticosteroids were involved in 6.8% and 4.6% of reports. Significant disproportionate reporting was detected for corticosteroids, antibiotics, drugs used in nicotine dependence, COVID-19 and HPV vaccines, serotonin–norepinephrine reuptake inhibitors (SNRI), and incretin mimetics. We suggest potential safety signals involving nicotine replacement therapies and vaccines. We also highlight the potential role of less suspected classes, such as SNRIs and incretin mimetics. An iatrogenic etiology should be evoked when parosmia occurs, especially in the elderly

Spontaneous reporting of adverse-drug reactions as an outlet for patient dismay? The case of Levothyrox(R) change of excipients

Following minor changes of excipients of Levothyrox®, the French Pharmacovigilance Database was overwhelmed by patients' spontaneous reports of adverse drug reactions associated with the new formula. After noticing that most of these reports differed from those related to other drugs, we aimed to characterize their features and compared them with spontaneous reports associated with other chronic treatments as comparators. We randomly sampled patient reports associated with either Levothyrox® new formula (n=200) or with comparator drugs (n=200) from March 2017 till March 2018 from the national pharmacovigilance database. We evaluated the number of incriminated drugs and adverse drug reactions per report, and verified whether they were "expected" or not according to the Summary of Product Characteristics. Levothyrox® associated reports included, on average, more adverse drug reactions (8±4) than comparators (2±2, p0.05), but female predominated in Levothyrox® group (94.5%) as compared with comparators (60.8%, p<0.001). A mere third of the Levothyrox® associated adverse drug reactions were deemed "expected", versus two-third for comparators (p<0.001). The pattern of spontaneous reports associated with Levothyrox®, whether fueled by media or influenced by social networks, appears atypical, as compared with that of comparators. Such reports, by their abundance may impair the automatic detection of relevant concomitant signals

Medications as a Trigger of Sleep-Related Eating Disorder: A Disproportionality Analysis

Sleep-related eating disorder (SRED) is a parasomnia with recurrent, involuntary, amnestic eating episodes during sleep. There is growing evidence of the association between SRED and medications. Therefore, we aimed to rank drugs showing the strongest association. VigiBase&reg; (WHO pharmacovigilance database) was queried for all reports of &ldquo;Sleep-related eating disorder&rdquo;. Disproportionality analysis relied on the Reporting Odds Ratio, with its 95% Confidence Interval (CI), and the Information Component. Our VigiBase&reg; query yielded 676 cases of drug-associated SRED. Reports mostly involved zolpidem (243, 35.9%), sodium oxybate (185, 27.4%), and quetiapine (97, 14.3%). Significant disproportionality was found for 35 medications, including zolpidem (387.6; 95%CI 331.2&ndash;453.7), sodium oxybate (204.2; 95%CI 172.4&ndash;241.8), suvorexant (67.3; 95%CI 38.0&ndash;119.2), quetiapine (53.3; 95%CI 43.0&ndash;66.1), and several psychostimulants and serotonin-norepinephrine reuptake inhibitors (SNRIs). Patients treated with nonbenzodiazepines or SNRIs were significantly older (mean age: 49.0 vs. 37.5; p &lt; 0.001) and their SRED were more likely to be serious (62.6% vs. 51.4%; p = 0.014) than patients treated with sodium oxybate or psychostimulants. Psychotropic drugs are involved in almost all reports. In patients with SRED, an iatrogenic trigger should be searched for

Inhomogeneous Magnetization Transfer (ihMT) in normal-appearing tissue correlates with clinical EDSS score of MS patients.

International audienceThe present study was aimed at evaluating the potential of ihMT (inhomogeneous Magnetization transfer) contrast in characterizing the severity of MS disease, and investigating possible correlations between ihMT and the clinical disability score

Inhomogeneous Magnetization Transfer (ihMT) in normal-appearing tissue correlates with clinical EDSS score of MS patients.

International audienceThe present study was aimed at evaluating the potential of ihMT (inhomogeneous Magnetization transfer) contrast in characterizing the severity of MS disease, and investigating possible correlations between ihMT and the clinical disability score