Study links semaglutide and suicidal ideation risk

International research has raised concerns about a disproportionately high risk of suicidal ideation among people with anxiety or depression who take semaglutide.
 
The study, which is based on analysis of adverse reactions within the World Health Organization’s global database, found reports of suicidal thoughts were slightly higher than expected for semaglutide, even when compared to other diabetes drugs.
 
It identified semaglutide-associated suicidal ideation ‘remained significant’ when compared with dapagliflozin and metformin, and in the sub-group of patients with ‘co-reported use of antidepressants and benzodiazepines’.
 
‘People with anxiety and depressive disorders may be at higher probability of reporting suicidal ideation when medicated with semaglutide,’ it states.
 
The study says its findings ‘warrants urgent clarification’.
 
Reports of patients experiencing suicidal thoughts while using semaglutide were only small, with researchers finding just 107 reported cases.
 
However, this represented a 45% higher risk of suicidal ideation than for those using other medications on the database.
 
Semaglutide products, such as Ozempic and Wegovy, have been in short supply in Australia due to demand – with the TGA issuing advice last year not to initiate new patients on the drug unless there is a compelling clinical reason to do so.
 
The demand quickly prompted a surge in compounded replica drugs, which were banned by the Government earlier this year after several concerns were raised.
 
The University of Melbourne’s Dr Trevor Steward says the study raises questions about whether additional precautions are needed and if warnings about suicidal ideation should be included on the medication’s labels.
 
‘The findings also suggest that people with diabetes or obesity who don’t have mental health conditions might not be at high risk of experiencing suicidal thoughts while taking semaglutide, but more studies are needed to confirm this,’ he said.
 
Chair of RACGP Specific Interests Obesity Management, GP and dietitian Dr Terri-Lynne South says this is not the first time issues around semaglutide and mental health have been raised, but the studies can be conflicting.
 
However, she says there are still several things GPs can take from these findings.
 
‘It’s important for GPs to be aware of some of these concerns, but to try and put it into context,’ she told newsGP.
 
‘I take both the negative … and positive things with a grain of salt as well, and make sure that patients know that semaglutide is still a relatively new medication.’
 
She also posed questions about whether the researchers had looked at any variables between dosages from Ozempic and Wegovy.
 
‘It raises a number of questions that we need better evidence for,’ she said.
 
RACGP Expert Committee – Quality Care member, Associate Professor Magda Simonis, is sceptical of the results.
 
‘I don’t think there is sufficient evidence to support their statement that suicidality risk is increased due to pharmacological effects of semaglutide,’ she told newsGP.
 
‘For now, there is no strong evidence that prescribing semaglutide needs to change in our practice.’
 
Associate Professor Simonis says all patients on weight-lowering medications should still be reviewed monthly regarding their response and that ‘is an opportunity to discuss other issues’.
 
The researchers did outline several of the study’s limitations, stating ‘additional adjustments for potential confounders, such as alcohol or substance misuse, were limited by the relatively small number of reports found’.
 
‘In the absence of more details about off-label prescribing, we were not able to further qualify the extent to which prescribing was off-label and its impact on the results,’ it reads.
 
Dr Steward said the rise in off-label prescribing is concerning but the results here should still be enough to ring alarm bells.
 
‘There is an urgent need for larger studies to understand any potential risks related to both the patient and the medication itself,’ he said.
 
‘Major factors to consider include the patient’s specific motivations for using the medication, any history of mental health issues, and sociodemographic issues.
 
‘Given that these medications have become so popular, this study should be seen as a wake-up call on the importance of supporting larger studies that aim to understand how these medications may impact the brain, who they are safe for, and who might be at risk.’
 
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