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Intranasal insulin delivers delirium treatment hope

Neuroscience Research Australia (NeuRA)

• Intranasal insulin provides a promising new treatment option for patients with delirium, with benefits including reducing time spent in hospital.
• Delirium affects more than 130,000 people each year in Australia - up to 25% of hospitalised older people -  however there are no effective pharmacological treatments.
• Further research is needed, including larger, multi-site trials plus considering dosage and effectiveness for different demographics and delirium types.

Delirium affects many hospitalised older Australians and whilst it can have many complications, treatments are limited. However, researchers have identified intranasal insulin as a potential new treatment that lads to a faster recovery reducing time spent in hospital.

Geriatricians Dr Anita Nitchingham from Neuroscience Research Australia (NeuRA) and Professor Gideon Caplan, both from Prince of Wales Hospital said the first study of intranasal insulin for delirium treatment had found the treatment was safe and feasible.

“Delirium is a sudden onset of confusion or drowsiness that affects up to 25% of hospitalised older people and is frightening for patients and their families, plus slows recovery,” Dr Nitchingham said.

“However, there are no medications for the prevention or treatment of delirium on general hospital wards. We evaluated the use of intranasal insulin as a treatment for delirium in hospitalised older adults, based on our previous laboratory research showing a defect in brain metabolism during delirium.

“Instranasal insulin resulted in a faster recovery with patients being discharged five days earlier than those who received the placebo – this is a very significant finding that transforms recovery from delirium.”

Delirium is a distressing acute neurocognitive disorder and is associated with longer recovery times, hospital-acquired complications such as falls, longer hospital stays, dementia and death.

Current treatments

“Delirium has been recognised since Hippocrates in 500 BCE, yet despite that and the significant complications that can arise, we still have no proven treatments,” Dr Nitchingham said.

“Antipsychotics and benzodiazepines are sometimes used, off-label, to manage distressing symptoms, but studies have shown they do not improve outcomes and may cause harm. That’s why we need to look at other options to treat delirium and improve outcomes for patients.

“We selected intranasal insulin based on our research at Prince of Wales Hospital showing metabolic derangements in the brain during delirium.”

About the study

The randomised, double-blind and placebo-controlled trial was conducted at Prince of Wales Hospital with 100 participants over 64 years of age. Half the patients received 20 international units (IU) of long-acting insulin intranasally twice a day, while the other half received a placebo.  The treatment ended when delirium was resolved, patients were discharged from hospital or under pre-specified criteria.

“Our research shows altered cerebral metabolism and brain insulin resistance during delirium in older people, so we set out to assess the safety and efficacy of intranasal insulin as a treatment,” Dr Nitchingham said.

“We used intranasal insulin, as this delivers insulin directly into the nervous system, bypassing the blood-brain barrier without causing significant glucose effects at moderate doses.”

Dr Nitchingham said while some related, mild adverse events like nasal irritation were recorded during the study, no serious adverse events occurred due to the intervention.

“This was a pragmatic and inclusive trial that involved real patients living with frailty and dementia who are often excluded from research, but have the most to gain from improved health care,” she said.

“This study provides the first real step toward solving a 2500-year mystery, showing intranasal insulin is safe and feasible, and provides the evidence base we need to go to larger trials.”

What’s next

“The next step is to test intranasal insulin in larger, multi-centre trials to confirm whether it improves delirium outcomes across the health system and also to explore if it could be used to prevent delirium in high-risk patients,” Dr Nitchingham said.

The report ‘Long-Acting Intranasal Insulin for the Treatment of Delirium – A Randomised Clinical Trial’ has been published in Age and Ageing and is available here.

 

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About NeuRA
Neuroscience Research Australia (NeuRA) is an independent, not-for-profit research institute based in Sydney aiming to prevent, treat and cure brain and nervous system diseases, disorders and injuries through medical research. To learn more about NeuRA: www.neura.edu.au 

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