A Swedish registry study suggests semaglutide may offer the strongest mental health benefit.
Semaglutide may help protect people with depression or anxiety from serious mental health deterioration, according to a large Swedish registry study published in The Lancet Psychiatry.
Researchers analysing national health data from 95,490 people with depression, anxiety or both found semaglutide use was associated with a 42% lower risk of serious psychiatric worsening, including hospitalisation, extended sick leave for mental illness, hospital-treated self-harm or suicide.
The study tracked people in Sweden who used antidiabetic medicines between 2009 and 2022. Compared with periods when individuals were not using GLP-1 receptor agonists, semaglutide was linked to a 44% lower risk of worsening depression, a 38% lower risk of worsening anxiety and a 47% lower risk of worsening substance use disorder.
Liraglutide was also associated with a reduced risk of worsening depression, although other GLP-1 drugs studied, including exenatide and dulaglutide, did not show similar associations.
Overall, GLP-1 receptor agonists were linked to a lower risk of self-harm, fuelling interest in whether the drugs may have neuropsychiatric effects beyond glucose control and weight loss.
The authors said the findings could be particularly relevant given people with diabetes already faced a higher risk of depression, anxiety and suicide than the general population, and mental illness was a major driver of disability and sick leave.
However, they cautioned that the observational study could not prove the drugs directly improved mental health. The analysis also lacked detailed clinical data such as changes in weight, HbA1c or BMI.
The researchers said randomised trials were needed to determine whether GLP-1 medicines could play a dual role in treating metabolic disease while stabilising mental health.
Codeine–breastfeeding case under fresh scrutiny
A widely cited case report that helped drive global warnings against codeine use while breastfeeding is under renewed scrutiny after allegations of falsified data and authorship issues triggered a fresh investigation into the study.
The 2006 report in The Lancet described the death of a 12-day-old infant from opioid toxicity while the mother was taking codeine for postpartum pain.
The authors proposed that some women rapidly convert codeine into morphine, potentially exposing breastfed infants to dangerously high morphine levels through breast milk.
The paper has been cited more than 800 times and influenced guidance advising against codeine use in breastfeeding women.
But the journal has now issued an expression of concern and referred the case to the Research Integrity Office at Toronto’s Hospital for Sick Children (SickKids), where the research was conducted, after new allegations surfaced in January 2026, according to a report in The BMJ.
The complaint came from Parvaz Madadi, a former member of the research team and first author on related publications, who told investigators she discovered discrepancies while reviewing archived materials and said she had not written a rebuttal letter to the journal that carried her name.
Independent experts have also questioned the pharmacological plausibility of the study’s interpretation. Toxicologists argue that the morphine concentrations reported in the infant were far higher than could reasonably be explained by genetic variations affecting codeine metabolism.
They also pointed to previously unreported findings of codeine in the baby’s stomach, which could indicate direct ingestion rather than exposure through breast milk alone.
The study’s senior author, pharmacologist Gideon Koren, has previously been at the centre of major scientific controversy and was dismissed from SickKids in 2015 after investigations found his laboratory produced flawed drug testing results used in child protection cases.
Critics said the original case report had far-reaching consequences for clinical practice and infant death investigations, potentially shaping an entire line of paediatric pharmacology based on what they now argue may have been a misinterpreted single case.
SickKids said it was reviewing the complaint and would determine next steps through its research integrity processes.
Read the full report here.
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Fat-linked approach advances oral neurosteroid antidepressant
A drug delivery strategy that hijacks the body’s fat absorption pathway could allow an antidepressant neurosteroid previously limited to intravenous infusion to be taken orally, with early human trials showing the approach can blunt physiological stress responses.
Researchers from Monash University and Seaport Therapeutics report that chemically linking the neurosteroid allopregnanolone to a lipid enables the compound to bypass first-pass liver metabolism and reach therapeutically relevant blood levels after oral dosing.
The approach, reported in Science Translational Medicine, uses a lipid-modified prodrug of allopregnanolone called GlyphAllo, designed to mimic dietary fat.
When absorbed in the gut, the modified molecule is routed through the intestinal lymphatic system rather than the portal vein, allowing it to avoid rapid breakdown by the liver and enter the bloodstream directly.
Allopregnanolone is a naturally occurring neurosteroid with established antidepressant, anxiolytic and sleep-promoting effects, but its clinical use has been constrained by the need for a prolonged 60-hour IV infusion to achieve therapeutic exposure.
In phase 1 studies, oral GlyphAllo produced dose-dependent plasma levels of allopregnanolone following single and multiple doses ranging from 70–1000mg, with the treatment generally well tolerated in healthy volunteers.
An initial phase 2a proof-of-concept trial found that a single 375mg oral dose significantly reduced salivary cortisol levels compared with placebo, suggesting the drug can dampen the acute physiological stress response in humans.
Investigators say the findings represent the first clinical evidence that attaching drugs to dietary fat molecules can redirect absorption pathways in humans to enable oral delivery of compounds previously limited by pharmacokinetic barriers.
The candidate is now being evaluated in a global randomised phase 2b trial, BUOY-1, assessing GlyphAllo in adults with major depressive disorder, with or without anxious distress.
Researchers suggest the lipid-linking platform could potentially be applied to other small molecules with poor oral bioavailability, with possible future applications across neuropsychiatry, oncology, immunology and metabolic disease.
