Over the years, a number of small studies have suggested that a class of antidepressants called tricyclics may be more effective than others at treating depression in people with Parkinson’s. These are not always first-line treatments because they can have side effects, but depression is very common in people with Parkinson’s, and many take antidepressants to help.

There are lots of different antidepressants on the market, and their effectiveness varies between individuals. Now, a large trial is underway to more robustly test if tricyclics outperform other antidepressants, and to carefully assess their side-effects. We hope the evidence will help clinicians and people with Parkinson’s to work out which type of antidepressant might be best for them.

But that’s only part of the story, because tricyclic antidepressants also hold promise for Parkinson’s beyond their impact on mental health. Evidence is mounting that they could actually protect dopamine neurons in the brain; the crucial cells that are damaged and lost in Parkinson’s.

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

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 International Linked Clinical Trials (iLCT) committee prioritised nortriptyline for further research. Since then, further alpha-synuclein evidence has strengthened the case even further.

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 depression in people with Parkinson’s. It’s called the ADepT-PD trial and it begins recruiting participants in 2021.

The trial will involve 400 people with Parkinson’s and depression from all across the UK. Its primary goal is to assess how effective the different medicines are at treating depression in Parkinson’s, and how the side effects compare.

This is a very important trial that could lead to big improvements in the way depression is treated. However, at Cure Parkinson’s we’re searching for ways to slow, halt and reverse Parkinson’s itself. That’s why we’re funding a substudy of the main trial, to investigate the critical question of whether nortriptyline could alter the course of the disease. The substudy 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 hopefully 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 our ear to the ground for medicines that could have similar potential with fewer side effects, as well as ways that the side effects of tricyclics might be mitigated.