A pioneering clinical trial led by Neuroscience Research Australia (NeuRA) has found that intranasal insulin could offer a promising new treatment for delirium, potentially reducing hospital stays for older patients by several days and addressing a significant gap in care.
Delirium affects more than 130,000 people each year in Australia, up to one in four older hospitalised patients, yet there are currently no effective pharmacological treatments. The randomised, double-blind, placebo-controlled trial, conducted at Prince of Wales Hospital, is the first to demonstrate that delivering insulin through the nose can safely accelerate recovery.
Geriatrician Anita Nitchingham, from NeuRA and Prince of Wales Hospital, said the results mark an essential advance in a field where treatment options have remained stagnant for centuries. “Delirium is a sudden onset of confusion or drowsiness that affects up to 25 per cent of hospitalised older people and is frightening for patients and their families, plus slows recovery,” Dr Nitchingham said. “There are no medications for the prevention or treatment of delirium on general hospital wards. Intranasal insulin resulted in a faster recovery, with patients being discharged five days earlier than those who received placebo. This is a very significant finding that transforms recovery from delirium.”
Delirium has been recognised since the time of Hippocrates, but its impact remains profound. It is associated with falls, longer hospital stays, dementia, and increased mortality. Current off-label use of antipsychotics and benzodiazepines may manage distressing symptoms, but do not improve outcomes and can cause harm.
The study enrolled 100 patients over the age of 64 who were diagnosed with delirium. Half received 20 international units of long-acting insulin intranasally twice daily, while the others received a placebo. The treatment continued until delirium resolved, the patient was discharged, or pre-specified criteria were met. “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.”
While mild nasal irritation was reported, no serious adverse events occurred. The study included real-world patients—many living with frailty and dementia—who are often excluded from clinical research. “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,” Dr Nitchingham said.
The research team, including co-investigator Gideon Caplan, now plans larger, multi-centre studies to confirm the findings and explore whether intranasal insulin could also be used to prevent delirium in high-risk patients.