Parkinson’s UK
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Parkinson’s UK

Investigating treatments to improve mood and slow the progression of Parkinson’s

Researchers are looking for 408 people with Parkinson’s to help find a treatment to improve mood and potentially slow the progression of motor symptoms.

There are many symptoms of Parkinson’s that aren’t talked about enough. Whether that’s bladder problems or struggling with things like a lack of motivation, anxiety or low mood. These all fall into the category of non-motor symptoms of Parkinson’s. Not everyone will experience the same set of symptoms but it’s of vital importance that research helps to find new treatments to address some of these symptoms, as currently there are limited options available.

There’s a range of research looking at treatments to improve low mood, anxiety and wellbeing in Parkinson’s. From looking at the effectiveness of delivering mindfulness via online sessions, to gathering more insights about anxiety, to looking at repurposing existing medication to see if it can help in Parkinson’s.

Let’s focus on the latter, the only UK based study that is looking to find a treatment for low mood in Parkinson’s — ADepT-PD. This study is also exciting as it aims to see if a potential treatment for low mood can also slow down the progression of motor symptoms of the condition.

What’s happening in the brain to cause low mood?

It’s estimated that around 40% of people with Parkinson’s are affected by low mood or depression. However, there’s currently a lack of Parkinson’s specific options to help people manage this.

Some people may say they have depression, others may describe it as low mood. It’s important to recognise that this might be the same thing and depression in Parkinson’s can look different to depression in general. You might want to read more about this on the Parkinson’s UK website parkinsons.org.uk/information-and-support/depression.

Parkinson’s can impact mood due to changes that are happening deep within the brain. However, some people’s mood may also be impacted by the challenges and adaptations that are required when living with Parkinson’s. It is a bit of a double edged sword.

The brain uses lots of chemical messengers to orchestrate complex communications that allow us to think, feel, move, remember and much more. Dopamine is a chemical messenger involved in how we move and learn, our memory and attention, and even responsible for addictive behaviours. Levels of dopamine decrease in the brain in Parkinson’s and it’s the brain chemical that most Parkinson’s treatments focus on.

But it’s not just dopamine that’s involved. A number of other chemical signalling pathways are now also known to be affected in the condition and may be responsible for many of the symptoms that are not improved by current medication. For instance:

  • Norepinephrine (also known as noradrenaline) — is a chemical involved in controlling mood, sleep and cognition.
  • Serotonin — often thought of as the ‘happy hormone’ — helps to control circuits in the brain involved with mood and reward. Most anti-depressants work to boost serotonin levels.

Changes in these brain chemicals could provide a clue as to why people with Parkinson’s may experience changes to their mood.

What’s ADepT-PD investigating?

ADepT-PD is being led by Professor Anette Schrag at University College London alongside research teams across the UK to investigate whether two drugs currently used for treating depression in the general population could be repurposed for people who experience low mood in Parkinson’s. The researchers are comparing these medications to a placebo.

The drugs are called escitalopram and nortriptyline. The drugs work in slightly different ways. Escitalopram works by making serotonin more available to brain cells, whereas nortriptyline has more of an impact on norepinephrine levels. Both have potential for treating low mood in Parkinson’s and the researchers want to understand which one might work best.

A participant of the study shares why they believe the trial is important:
“Finding the best anti-depressant for low mood in people with Parkinson’s would stop all the self-blame, and help people to regain their enjoyment in life. This is why this trial is so important — it could really make a difference.”

Professor Anette Schrag

What’s this got to do with slowing the progression of Parkinson’s?

The researchers are particularly interested in nortriptyline to see if it can help with motor symptoms of Parkinson’s and potentially slow the progression of these symptoms. This is because there is some evidence from studies done in cell and animal models of Parkinson’s that nortriptyline can stop the build up of the troublesome protein alpha-synuclein, which is believed to be responsible for brain cell death in Parkinson’s.

Therefore, the researchers are now keen to see whether nortriptyline has this effect in people with Parkinson’s to potentially protect brain cells. So, as well as measuring changes to mood they will also measure participant’s motor symptoms at the start and the end of the trial to help understand how symptoms have progressed over time. The hypothesis is that progression of symptoms may have slowed in those on nortriptyline but not escitalopram.

Who can take part?

The researchers are looking for 408 people, between the age of 18 and 85, diagnosed with Parkinson’s and who are experiencing feelings of low mood or loss of enjoyment on most days. Unfortunately, people who are already taking anti-depressants or have a diagnosis of dementia will not be able to take part.

What’s involved?

People who are interested in the trial will be asked to attend 5 assessments, either at a specified hospital or remotely from home. The study will span 12 months:

  • At the first assessment participants will be screened to check they are eligible to take part.
  • They will then be randomly allocated to either receive one of the drugs or a placebo (dummy) medication. The medication is delivered directly to the participant’s house.
  • Participants will take the medication, or placebo, for 12 months. During this time they will complete 4 assessments including questionnaires to assess mood and motor symptoms. There is an optional opportunity to wear a watch to help measure movement.
  • There is also an option to participate in additional research to understand the influence of genetics and inflammation in response to the treatment. This would involve two blood sample collections.

What are the possible benefits of taking part?

Taking part in this trial represents an opportunity to potentially access treatments that hold genuine potential for people with Parkinson’s. If this trial is shown to be beneficial it could result in a better treatment for low mood in Parkinson’s being quickly available with no further clinical studies needed. This is because the medication is already licensed on the NHS.

However, further clinical studies may be needed if nortriptyline is shown to have an impact on progression of symptoms, before it could be used as a licensed medication to possibly slow or stop Parkinson’s.

Interested in taking part?

Go to the Parkinson’s UK website to find more information and a full list of research sites and contact details parkinsons.org. uk/ADepT–PD

This trial is likely to be recruiting people to take part until 30 April 2023.

This trial is funded by The National Institute for Health Research and Cure Parkinson’s and is led by Professor Anette Schrag at the University College London and delivered by research teams across the UK. This blog has been produced by Parkinson’s UK for information only and should not be taken as an endorsement or advice to join the trial. Anyone considering taking part in research should read the full trial information carefully and discuss this with their loved ones and health professionals.

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