Investigating psychomotor response to L-DOPA challenge as a biomarker for clinical outcomes in late-life depression: A pilot feasibility trial

Major depressive disorder (depression) is a common condition affecting older adults, also called late-life depression (LLD). Depression later in life can negatively impact overall health, including increasing the risk of developing dementia. With Canada’s aging population, it is important to develop more effective ways of managing this condition.  

LLD is frequently associated with a phenomenon called psychomotor slowing, which is a decrease in the speed of both physical movements and information processing. The presence of psychomotor slowing can signify more severe illness and a risk of worse outcomes in LLD. Psychomotor slowing in LLD is related to the abnormal functioning of dopamine, a neurotransmitter that influences motivation, reward, and pleasure in the brain. This slowing may be reversible by taking a dopamine-like medication called levodopa (L-DOPA). However, we do not know whether there is a link between psychomotor slowing, reversibility by L-DOPA, and treatment outcomes in LLD. 

I am a geriatric psychiatrist at St. Paul’s Hospital and a postdoctoral research fellow at the University of British Columbia. My study, which is supported by the CANTRAIN-CTTP & Michael Smith Health Research BC Post-Doctoral Studentship Award and conducted at St. Paul’s Hospital in Vancouver BC, will invite participants to receive two weeks of treatment with a drug called Levocarb which contains L-DOPA (an L-DOPA “challenge”). We will measure participants’ walking speed, overall speed of movements, and cognitive function before and after the challenge.  

The goal of this study is to evaluate whether psychomotor slowing in LLD changes in response to changes in brain dopamine levels, and whether this change can predict improvements in depression symptoms and cognitive function following standardized antidepressant treatment. These data will improve our understanding of the biology of LLD and may enhance our ability to predict which treatments will be most helpful for older adults suffering from depression. 

End of Award Update – February 2025

Results

My pilot clinical trial has provided some of the first-ever data on the psychiatric, psychomotor, and cognitive effects of levodopa (L-DOPA) in depressed older adults. So far, we are observing significant improvements in psychomotor speed, working memory, and depressive symptoms in response to a 2-week administration of L-DOPA. 

Impact

This clinical trial has provided, to my knowledge, the first BC-based opportunity to participate in clinical interventional research for older adults living with depression. This research is providing access to a novel treatment approach which will benefit health outcomes for older adults in BC and, possibly in the future, the rest of Canada and beyond. 

Potential Influence

This clinical trial is the first in a planned sequence of studies to investigate the usefulness of L-DOPA as a challenge medication to help predict response to other medications in late-life depression. If successful, this research will lead to a practical clinical tool that enables us to provide personalized, evidence-based treatment options for older adults with depression. 

Next Steps

Early results from this study are being prepared for publication and will be presented at upcoming conferences. A follow-on study with a randomized component is currently being planned, which will build off our promising pilot data.