Be bold with metformin in mood disorder patients

Experts are calling for early metabolic testing in young people, well before the effects of psychiatric medications may be seen.

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Young people with mood disorders need to be clinically assessed early to prevent the cardiometabolic risks linked to poor mental health, Australian research suggests.  

“Our recommendations are for testing the metabolic status of kids, including their insulin status, early in the course of these illnesses because they are a high-risk group for developing early metabolic disorders,” said Professor Ian Hickie, co-director of Health and Policy at the University of Sydney’s Brain and Mind Centre.  

Professor Hickie and colleagues studied a cohort of young people with mood disorders in a Sydney mental health inpatient unit and found that only one in three were prescribed metformin, despite common signs of insulin resistance among both groups.   

The problem was that with current guidelines, young people with mood disorders were often not tested for insulin resistance unless they were already overweight, Professor Hickie said.  

And there was a widespread misperception that obesity and metabolic syndromes were simply caused by mood disorder medications, he added.  

“There’s a belief that you have to get fat first, and then you’ll develop insulin resistance in 10- or 20-years’ time. That’s not the case here. Many of these kids have insulin resistance already, some in association with being overweight, but others as a consequence of having the illness. There’s a problem in their metabolic profile.”   

Current metformin prescription practices were conservative, and management was often focused on simple lifestyle adjustments, he said.  

“As if simply focusing on diet and exercise will be okay, even though many of those kids will need psychotropic medications which might contribute to further weight gain and further risk.”   

Because medications also increased risk, clinicians needed to be proactive about managing that risk, Professor Hickie said.  

“We need a very significant focus on identifying the kids at risk very early in the course of their illness, not only so they have better mental health outcomes, but so they also have better physical health outcomes.”  

Professor Hickie and colleagues analysed patient data from 72 young people, aged 16 to 26, who were admitted to the Young Adult Mental Health Unit at St Vincent’s Private Hospital Sydney with mood or psychotic disorders.  

Data included fasting blood tests, mental health diagnoses and medication. The researchers assessed metabolic disturbance using a tool known as the homeostatic model of insulin resistance assessment (HOMA2-IR).  

Almost all of these young people were taking psychotropic medications, and more than half were taking antipsychotics. Four in five of these young people were on more than one drug, and half were overweight or obese.  

The researchers found that 18 patients were prescribed metformin for the first time during their hospital stay. Of these, 83% were overweight or obese with almost three in four having insulin resistance that classified them as prediabetic.  

In contrast, fewer than half of those not taking metformin were overweight or obese and one in four had insulin resistance.  

Queensland psychiatrist Dan Siskind said the research highlighted how cardiometabolic conditions started early and needed to be treated early to prevent chronic cardiometabolic conditions, morbidity and mortality.  

People with severe mental illness typically died 15 to 20 years earlier than the general population, largely driven by cardiometabolic disease, said Professor Siskind, who specialises in physical and mental health comorbidity, particularly cardiometabolic illness in people with severe mental illness.  

“Even from late teens, people with severe mental illness experience higher rates of cardiometabolic illness than the rest of the population.   

“Among people with psychotic illnesses, over half have metabolic syndrome, and for people on antipsychotics such as clozapine, almost half will develop diabetes.  

Professor Siskind encouraged GPs to “be assertive” in prescribing metformin to people on antipsychotics who were overweight or obese, and for antipsychotic-associated cardiometabolic disease in all ages.  

He recommended six-monthly monitoring of metabolic bloods for patients on antipsychotic medication.  

One challenge was “diagnostic overshadowing” for clinicians who have limited time to address complex issues, Professor Siskind said.   

“Mental illness takes up most of the conversation, and there is an overshadowing of the need to manage cardiometabolic disease, which may include prescribing metformin, statins, fibrates or accessing dietitian and exercise physiologist referrals through the chronic medical condition and complex care plans.” 

For Professor Hickie, the medical assessment of many young people with severe mental health problems was currently “grossly inadequate”.  

“We need much better medical assessment of many of these kids who are now entering mental health care, and GPs play a critical role in that.  

“The idea that it can all be done by psychology alone without medical assistance for many of these kids is wrong. This requires integrated medical and psychological practice.”  

Professor Hickie said there was the potential for metformin to have a “dual purpose”. As well as managing diabetes or metabolic complications, the medication was also being investigated for its effect on mood.   

“There’s a lot of interest in whether metformin is neurogenerative and whether it affects brain synaptic connection, and whether it has active mood and cognitive properties independent of its metabolic properties.”  

Australasian Psychiatry 2022, online 19 July