Researchers at St. Joseph’s Healthcare Hamilton and McMaster University, including Dr. Benicio Frey, are researching innovative ways to administer lithium medication that circumvent the negative side effects of lithium as a treatment for bipolar disorder (BD).
Bipolar disorder is a highly disabling mental illness characterized by periods of mania and depression. Since the 1960s, lithium has been a mainstream treatment for BD; however, long-term use of lithium has been associated with a risk of negative health repercussions.
Bipolar Disorder & Lithium Treatment
Bipolar disorder (BD) is a severe mood disorder that involves recurrent episodes of depression as well as mania, in the case of bipolar I disorder, or hypomania, which occurs in bipolar II disorder. BD I and II are also related to bipolar spectrum disorder (BSD); in total, approximately 2.4 per cent of the population is affected by one of these mental illnesses.
BD is one of the most disabling illnesses worldwide – considering not only mental illnesses but physical illnesses as well. Researchers estimate that between 25-60 per cent of people diagnosed with BD attempt suicide at least once in their lifetime.
Approximately one third of people with BD respond very positively to lithium treatment, which is considered a “gold standard” for treatment of BD due to how effective it can be. As BD can be so debilitating, practitioners typically recommend that those who improve while taking lithium continue to take it for the rest of their lives. While this medication can dramatically improve quality of life, its side effects can include additional physical problems, especially with long-term use.
Common side effects of lithium treatment include weight gain, drowsiness, an upset stomach, and more. People who take lithium for a long time may develop more problematic health issues, most notably chronic kidney disease.
“I’ve seen many patients who have been taking lithium for decades and now are facing significant kidney disease,” said Dr. Benicio Frey, Director of the Centre for Clinical Neurosciences at St. Joe’s and McMaster. “Some of them would like to stop this treatment, but unfortunately a medication switch later in life can be very challenging in some cases.”
Dr. Frey and other researchers are working to develop a novel way of taking lithium that effectively manages symptoms of BD with lower lithium concentration in the bloodstream, offering a potential solution to prevent harmful side effects of this medication.
A Novel Solution to Lithium Side Effects
Through researching intranasal delivery of psychiatric medications, Dr. Frey and his team are changing the landscape of psychiatry research. In a study published in collaboration with Dr. Todd Hoare and Dr. Ram Mishra, they demonstrated that taking lithium via an intranasal hydrogel effectively decreased hyperlocomotion (one of the symptoms of bipolar mania) in rats and resulted in about half of the lithium concentration in the bloodstream. By lowering the amount of lithium present in the bloodstream, this delivery of lithium might result in fewer side effects.
Their research, “Nose-to-brain delivery of lithium via a sprayable in situ-forming hydrogel composed of chelating starch nanoparticles,” was published in the Journal of Controlled Release in February 2025. It isthe first of its kind to examine intranasal delivery of lithium.
While this study presented very promising results, it’s important to note that this research was conducted in rodents, and further research is needed to see how effective this treatment may be in humans.
“The next step in our research is to examine the safety and tolerability of this intranasal lithium treatment in humans,” Dr. Frey said. “From there, we will be able to examine how effective this drug administration may be in managing symptoms of BD, as well as how it impacts lithium concentration in the bloodstream its potential side effects.”