ADepT-PD – Antidepressants And More

Introduction – Editor’s Note

In this interview about the ADepT-PD trial, Professor Anette Schrag, the Trial Lead, offers a comprehensive view of the trial objectives and what the trial entails. She responds to several questions around the challenge of recruiting participants into a trial of this nature.

If you are in or skating around a “persistent low mood”, or are the care partner, this trial merits your attention and careful consideration.

  • It is simple to take part in
  • Participation will be all but invisible to the outside world
  • It may improve your mood and maybe that of many others
  • It might confirm that an existing drug can delay progression – a big win
  • If either is the case, it may take just a few months for prescriptions to be written, not years
  • There are very few exclusions. Do not sit this one out waiting for the next trial on this topic – you may not be eligible or you may not be a target for the treatment.

Read on down here, and only then tackle the Participant’s Information Sheet!

What is it about?

The progression of Parkinson’s can affect the whole brain, not just the movement-related centres. This leads to a wide range of so-called “non-motor” symptoms, including difficulties with mood and control of emotions. Persistent low mood is one of the major non-motor symptoms affecting people with Parkinson’s.

There are several different classes of drugs that your GP can prescribe to counteract low moods. “Tricyclic” drugs are of extra interest because they have been shown to stimulate the birth of neurons, and the release of biomolecules that help the glial cells that surround and support neurons. Another class of drug, selective serotonin reuptake inhibitors (SSRIs) are also often prescribed for people with Parkinson’s; they have a more favourable side effect profile than tricyclics.

The release of dopamine by neurons is central to movement. A cardinal  biological feature of Parkinson’s is the abnormal behaviour of the alpha-synuclein protein. This protein, for reasons we do not yet fully understand, can form toxic clumps inside cells. It is believed that these clumps are directly responsible for obstructing the release of dopamine.  Researchers are looking for ways to prevent alpha-synuclein clumping, or reduce the extent to which it happens (its “gene expression”),  or encourage the clearance of it from the glial cells.

The outcomes of repairing these biological mechanisms could be a slowing down or a halt to the progression of our symptoms, or a reduction of the burden they impose. These three outcomes are increasingly referred to collectively as “disease modification”.

This is a randomised double-blind placebo-controlled trial, which means that neither you nor the Trial Unit will know who is taking what.  It is a big trial, recruiting over 400 people in many centres throughout the UK.

What is the objective?

The primary objective of the ADepT-PD trial is to examine whether Escitalopram, a SSRI, and Nortriptyline, a Tricyclic, are effective and safe for the treatment of persistent low mood in people with Parkinson’s.

The tricyclic drug nortriptyline has been shown to interfere directly with the production of alpha-synuclein, so the trial has an important subsidiary objective of finding whether this drug is effective in delaying the progressive slowing down of movement that is the hallmark  associated with Parkinson’s.

Novel features of the trial involve the use of wearable technology to allow continuous measurement of movement over a week, and the use of video motion techniques to provide accurate data about the participant’s movement at the start and end points of the trial..

Where is it?

At Home. As a result of Covid restrictions the trial protocol has been completely revised to exclude hospital visits entirely. When face to face contact is necessary the study investigators can come to you. You may visit your study centre if you prefer. (A Patient Information Sheet reference to a fixed travel fee of £10 is incorrect -you will be reimbursed according to how and how far you travel).

How long does it take?

12 months.

What does it involve?

  • A daily pill of escitalopram, nortriptyline or a placebo.
  • Video consultations. You will need to be able to conduct video-based conversations in your home. if you have the technology but not the knowledge to use it, you can ask for help.
  • Completing questionnaires on changes in symptoms of low mood.
  • Wearable technology for measurements of motor function and motion analysis by video.

Who is eligible?

Age 18 to 85 years with a diagnosis of idiopathic Parkinson’s and a clinical diagnosis of persistent low mood. Enrolment on the trial is subject to a comprehensive review including a video meeting.

How do I enrol?

  • Addresses in Mid and West Cornwall: email Charlotte Moorhouse at or call her on 01209 204020.
  • Addresses in the Plymouth area and North Cornwall:
    Jemma Inches, University Hospitals Plymouth NHS Trust, Derriford. email Jemma Inches at or call her on 01752 432845.
  • If you live elsewhere in Devon you can join the trial through the national centre. Email Laura Grover at  or call her on 020 8016 8417.
    (General email:

Participant Information Sheet

ADepT-PD Patient Information Sheet – v5.0 02.02.2021