The medicines regulator has added two new safety warnings about mental health and contraception for people taking high-profile diabetes and weight loss drugs.
While there is no proof of a causal association, experts say the risks are significant enough that awareness is important as part of a precautionary approach.
The Therapeutic Goods Administration (TGA) says that because suicidal behaviour and ideation have been reported with these relatively new GLP-1 receptor agonists, doctors should “monitor patients for the emergence or worsening of depression, suicidal thoughts or behaviours, and/or any unusual changes in mood or behaviour”.
The warning of the potential risk of suicidal thoughts applies across the GLP-1 RA class of medicines (often called semaglutides), including Ozempic, Wegovy, Saxenda, Trulicity and Mounjaro.
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A 2024 study analysed the World Health Organization’s global database of adverse reactions and found reports of suicidal thoughts were slightly higher than expected for semaglutide, even when compared to other diabetes drugs.
Following this international signal (an adverse event that is potentially caused by a medicine that warrants further investigation), the TGA asked its Advisory Committee on Medicines for independent expert advice.
They found there was not enough evidence for causality, but noted there was a complex interplay between mental illness and chronic endocrine disorders for which GLP-1 RAs may be used for treatment.
A search of the TGA’s database of adverse event notifications for the GLP-1 RA class up to September found there were 72 reports for suicidal ideation, six reports for depressional suicide, four reports of suicide attempt, two reports of completed suicide and one report of self-injurious ideation.
Data on semaglutide prescriptions on the pharmaceutical benefits scheme show there were more than two million in 2023-24, but there would be even more users whose use wasn’t subsidised.
Dr Terri-Lynne South, the chair of the Royal Australian College of General Practitioners’ specific interest group for obesity management, said: “We do think there might be a subgroup of patients who may be more vulnerable to a worsening of their mental health.
“At the moment, that seems to be people who might already have a past or current history of depression or anxiety or on a antidepressant type medication.”
Studies of patients who have undergone bariatric surgery have also shown that significant or rapid weight loss can be a “real triggering event from a mental health point of view,” South said.
The TGA has also issued a separate warning around Mounjaro and contraception.
After investigating the potential reduced effectiveness of oral contraception when first taking or increasing the dose of Mounjaro, the TGA said it could not rule out an association.
As a precautionary measure, it has updated the product warnings for Mounjaro to include further advice for patients using oral contraceptives to switch to a non-oral contraceptive or add a barrier method of contraception for four weeks after first taking the medicine and for four weeks after each increase in the dose.
It added that none of the GLP-1 RA class of medicine should be used during pregnancy.
South said since Mounjaro had been available in Australia, the product information had mentioned potential concerns around the delay in gastric emptying.
“What that means is [the drug] delays the food and everything else that you eat actually coming through the digestive system, and therefore having an impact on the absorption of the oral contraceptive pill, and therefore possibly the effectiveness of the oral contraceptive pill,” she said.
South said the warnings were part of normal post-market surveillance, which meant due to the smaller numbers of people involved in initial drug trials, some associations can’t be seen until tens of thousands of people take them when they are let out to market.
• In Australia, the crisis support service Lifeline is 13 11 14. In the UK and Ireland, Samaritans can be contacted on freephone 116 123, or email jo@samaritans.org or jo@samaritans.ie. In the US, you can call or text the 988 Suicide & Crisis Lifeline at 988 or chat at 988lifeline.org. Other international helplines can be found at befrienders.org
