Recent media reports commented about a possible issue of the misuse of antidiabetics related to molecules promoted as a weight-loss treatment in non-obese people. We evaluated here available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, and tirzepatide) and the phentermine–topiramate combination. To acheieve that aim, we analyzed the Food and Drug Administration’s FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AERs) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018–December 2022, a total of 31,542 AERs involving the selected molecules were submitted to FAERS; most involved dulaglutide (n = 11,858; 37.6%) and semaglutide (n = 8249; 26.1%). In comparing semaglutide vs. the remaining molecules, the respective PRR values of the AERs ‘drug abuse’, ‘drug withdrawal syndrome’, ‘prescription drug used without a prescription’, and ‘intentional product use issue’ were 4.05, 4.05, 3.60, and 1.80 (all < 0.01). The same comparisons of semaglutide vs. the phentermine–topiramate combination were not associated with any significant differences. To the best of our knowledge, this is the first study documenting the misuse/abuse potential of semaglutide in comparison with other GLP1 analogues and the phentermine–topiramate combination. The current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size. We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome. Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected. The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes. ClinicalTrials.gov identifier: NCT00927550

Data on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH. We will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events. The results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide. ClinicalTrials.gov identifier: NCT00927550

Recent media reports commented about a possible antidiabetics’ misuse issue related to molecules promoted as a weight-loss treatment in non-obese people. We here evaluated available pharmacovigilance misuse/abuse signals related to semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, in comparison to other GLP-1 receptor agonists (albiglutide; dulaglutide; exenatide; liraglutide; lixisenatide; tirzepatide) and the phentermine-topiramate combination. To that aim, we analysed the Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) dataset, performing a descriptive analysis of adverse event reports (AER) and calculating related pharmacovigilance measures, including the reporting odds ratio (ROR) and the proportional reporting ratio (PRR). During January 2018-December 2022, a total of 31,542 AER involving the selected molecules were submitted to FAERS; most involved dulaglutide (n=11,858; 37.6%) and semaglutide (n=8,249; 26.1%). In comparing semaglutide vs the remaining antidiabetics, the AER ‘drug abuse’, ‘drug withdrawal syndrome’, ‘prescription drug used without a prescription’ and ‘intentional product use issue’ respective PRR values were 4.05, 4.05, 3.60 and 1.80 (all<0.01). The same comparisons of semaglutide vs the phentermine-topiramate combination were not associated with any significant differences. To our best, this is the first study documenting the misusing/abusing potential of semaglutide in comparison with other novel antidiabetics and the phentermine-topiramate combination. Current findings will need to be confirmed by further empirical investigations to fully understand the safety profile of those molecules.

Background: Recent drug enforcement activities have possibly suggested the presence of some calcium channel blocker antihypertensives in association with cocaine. The seizure revealed the possibility that the two drugs might have been used together for some unknown reasons. Methods: Hence, this study aimed at investigating the nature and frequency of adverse drug reactions (ADRs) reported in association with the concomitant use of calcium channel blockers (CCBs) and cocaine, using data from the FDA Adverse Event Reporting System (FAERS). Results: After removing duplicate reports, a total of 67 cases involving concomitant use of cocaine and CCBs were analyzed and were stratified into three groups based on the CCB involved: verapamil (n = 19), diltiazem (n = 30), and amlodipine (n = 18). Logistic regression analysis identified “product use for unknown indication” (β = 0.33) as the strongest predictor of fatal outcomes. Age revealed a modest negative association with fatal outcome (β = −0.93, intercept = 4.07). Concomitant substance use was reported in over 84% of cases. Frequently co-used substances included opioids, benzodiazepines, antidepressants, antihistamines, and alcohol. Poly-drug use was most pronounced in the diltiazem group, which exhibited the highest burden of opioid and alcohol co-exposure. Conclusions: It is here suggested that clinicians should exercise caution when managing individuals who use cocaine, due to the potential for increased toxicity and lethality when CCBs are co-used, either as part of a prescribed treatment or if CCBs are present as adulterants in cocaine.

Recent drug enforcement activities have possibly suggested the presence of some calcium channel blocker antihypertensives in association with cocaine. The seizure revealed the possibility that the two drugs might have been used together for some unknown reasons. Hence, this study aimed at investigating the nature and frequency of adverse drug reactions (ADRs) reported in association with the concomitant use of calcium channel blockers (CCBs) and cocaine, using data from the FDA Adverse Event Reporting System (FAERS). After removing duplicate reports, a total of 67 cases involving concomitant use of cocaine and CCBs were analysed and were stratified into three groups based on the CCB involved: verapamil (n = 19), diltiazem (n = 30), and amlodipine (n = 18). Logistic regression analysis identified “completed suicide” (β = 0.35) and “product use for unknown indication” (β = 0.33) as the strongest predictors of fatal outcomes. Age revealed a modest negative association with fatal outcome (β = -0.93, intercept = 4.07). Concomitant substance use was reported in over 84% of cases. Frequently co-used substances included opioids, benzodiazepines, antidepressants, antihistamines and alcohol. Poly-drug use was most pronounced in the diltiazem group, which exhibited the highest burden of opioid and alcohol co-exposure. It is here suggested tat clinicians should exercise caution when managing individuals who use cocaine, due to the potential for increased toxicity and lethality when CCBs are co-used, either as part of a prescribed treatment or if CCBs are present as adulterants in cocaine.