Bipolar disorder is one of the top 10 global causes of disability with significant morbidity and mortality and has the highest suicide risk and completion rates of all mental illnesses. Depression remains the major driver of disability in bipolar disorder, with individuals spending almost half of their lives depressed. While there are existing treatments, not all people respond to them.
We need to discover and test new interventions. And a blood pressure medication could be the unexpected key to improving the lives of many Australians living with depression and bipolar depression.
This finding arose from stem cell work conducted by Professor Ken Walder, who discovered that the blood pressure medication candesartan is the closest match in terms of net biological effects to the known treatments for the disorder.
Professor Michael Berk from the IMPACT Mental Health and Neuroscience team secured the funding to examine the use of candesartan in unipolar and bipolar depression. The trial is called CADET-UD (Candesartan Adjunctive bipolar DEpression Trial—Unipolar Depression) and targets the unmet need for effective treatments for bipolar depression and major depressive disorder (MDD). The CADET-BD (Candesartan Adjunctive bipolar DEpression Trial) specifically targets bipolar depression.
CADET-UD has been funded by a Medical Research Future Fund (MRFF) five-year grant of $2,428,397.10. CADET-BD secured funding from the National Health and Medical Council Research (NHRMC) Clinical Trials and Cohort Studies Scheme.
If successful, these studies will provide high-quality evidence of the efficacy of this new treatment for bipolar depression and MDD—a treatment that is both safe and affordable as an off-patent drug.
Project manager Dr Melanie Ashton and lead investigator Prof Berk say the CADET approach is based on previous trials repurposing adjunctive therapies that successfully showed that targeting oxidative stress, inflammation and neurogenesis can be efficacious in treating bipolar and unipolar depression. Some of these trials started as early as 2011.
Candesartan is a well-tolerated category of medications known as angiotensin II receptor 1 blockers, commonly used to treat high blood pressure and congestive heart failure. It buffers the body’s response to stress and can influence processes in the brain such as inflammation, oxidative stress and nerve growth and survival. These are all biological processes that may be important in people with bipolar depression.
Some data out of the trial is also suggesting that it may have potential in other disorders such as schizophrenia. It could have additional health benefits as there is greater risk of cardiovascular events in mental disorder populations compared to the general population.
The findings have been an accumulation of years of research and work by leaders from research fields in novel therapy development, clinical trials, study methodology and biostatistics.
Prof Berk and Dr Ashton say despite experiencing significant disruptions in their research plan due to the ongoing COVID-19 pandemic, they have overcome these difficulties and are now commencing recruitment for both CADET-UD and CADET-BD clinical trials. They will continue to “ramp up” recruitment throughout 2021.