Intranasal insulin shows promise for faster delirium recovery in older adults

Delirium affects many hospitalized older Australians, and while it can have many complications, treatments are limited. However, researchers have identified intranasal insulin as a potential new treatment that leads to a faster recovery and reduced 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. The research is published in Age and Ageing.

“Delirium is a sudden onset of confusion or drowsiness that affects up to 25% of hospitalized 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 hospitalized older adults, based on our previous laboratory research showing a defect in brain metabolism during delirium.

“Intranasal 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 recognized 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 randomized, 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 2,500-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, multin-center 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.