Now, a large trial is underway to more robustly test if tricyclics outperform other antidepressants.

The trial

At Cure Parkinson’s we’ve kept a very close eye on the tricyclics story. In 2016 – after seeing proof that tricyclics had protective effects in parts of the brain affected in Parkinson’s – our iLCT committee prioritised the tricyclic medicine nortriptyline for further research. Since then, further alpha-synuclein evidence has strengthened the case.

Now we’re driving discovery forward, by collaborating with a large clinical trial comparing nortriptyline with escitalopram (an SSRI class of antidepressant) for the treatment of low mood and depressive symptoms in people with Parkinson’s. It’s called the ADepT-PD trial and it is now underway.

The trial involves 400 people with Parkinson’s with symptoms of low mood from all across the UK. Its primary goal is to determine how effective the different medicines are at treating depression in Parkinson’s, and assess their disease – modifying potential.

This is a very important trial that could lead to big improvements in the way low mood and depression are treated. However, at Cure Parkinson’s we’re searching for ways to slow, halt and reverse Parkinson’s itself and we’re funding a sub-study of the main trial, to investigate the critical question of whether nortriptyline could alter the course of the disease. The sub-study will employ wearable technology, as well as standard methods of clinical evaluation, to assess whether a year’s course of nortriptyline has any effect on movement symptoms in people with Parkinson’s.

The results of the sub-study will, it is anticipated, be available in 2023. In the meantime, we’ll be strongly advocating for further research into the potential Parkinson’s-modifying effects of tricyclic antidepressants. We’ll also be keeping a keen eye on medicines that could have similar potential with fewer side effects, as well as ways to mitigate the side-effects of tricyclics.

Why tricyclics?

Studying cells in the lab, researchers have shown that various types of antidepressants boost the release of ‘neurotrophic factors’ in the brain. These are molecules that help neurons to grow, survive and work as they should. Although lots of antidepressants have this neuroprotective effect, the Parkinson’s community is particularly interested in tricyclics due to research published in 2012*. In the study of over 2,000 people with Parkinson’s, researchers found that taking tricyclic antidepressants appeared to slow the progression of the disease.

*Read more on this important study

Please note:

Professor Schrag is also running another research study, alongside the ADepT-PD trial, exploring anxiety in Parkinson’s.

The study is called ANxiety (with or without depressive features) in Parkinson’s Disease (the AND-PD study) and is expected to commence shortly.

This is an observational and imaging study where people at the different stages of Parkinson’s will be assessed and followed for one year. The study is looking to recruit around 200 participants:

  • 150 with Parkinson’s (at least 50 of whom will have significant anxiety).
  • 50 age-matched controls without Parkinson’s (25 with anxiety).
    Note: 50 participants from the total sample will also have an optional MRI scan.


  • Approximately 40% of people with Parkinson’s experience significant anxiety.
  • Little is known about how anxiety develops in Parkinson’s, and why some people with Parkinson’s are more prone to anxiety than others.
  • Anxiety and depression in Parkinson’s have been reported to cause greater functional impairment and lower quality of life, but it is poorly understood at present.
  • There is currently little information on effective treatments for anxiety in Parkinson’s.

Participants will answer questions about their anxiety, have an assessment of their movements and memory and undertake a series of computer tasks, which could be done remotely or in person. An optional MRI scan will be performed in some of the participants. This aims to determine the aspects of emotional processing that are impacted in Parkinson’s and underlie anxiety in Parkinson’s.