Readable Research

A lay summary by Harry McDonough, reviewed by Ian Coldicot and by an MND lay panel.

Background

Motor neurone disease (MND) is a progressive and disabling condition of the nervous system with no current cure. Faced with this diagnosis and outlook, it might be expected that the mood and emotional wellbeing of people living with MND could be affected.

Whilst each individual will process and respond to their MND diagnosis in their own way, some may have more persistent psychological difficulty. Depression is a condition in which there is a persistent change in mood, where individuals may feel sad, anxious, worthless, or lose interest in things previously enjoyed.

Why is the study important?

It is currently uncertain how common depression is in MND. This would be useful and important information for:

• MND sufferers and their loved ones – to be aware of the signs of depression and discuss with healthcare professionals as needed

• Healthcare professionals – to know whether to routinely assess for depression and, if required, offer treatment

• Planning clinical services – to ensure psychological services are available and accessible for people with MND

What did the authors do and how did they do it?

This study aimed to determine how common depression is in MND. The study was part of a wider national study called TONiC (Trajectories of Outcome in Neurological Conditions). TONiC looks at the factors that influence quality of life for people with neurological conditions, including MND.

People living with MND were recruited to the TONiC study. To best determine how common depression was in the group studied, the authors identified cases of depression in multiple ways:

• Modified-Hospital Anxiety Depression scale (M-HADS-D): a questionnaire commonly used to assess individuals for depression

• Medications taken by people with MND: was the individual already prescribed an antidepressant medication?

• Questionnaire of past medical history: this asked individuals if they had already been diagnosed with depression in the past

The researchers also looked at how depression symptoms changed over a period of 2.5 years in the group recruited to the study. To do this, they used computer modelling techniques to identify groups of individuals that followed similar trajectories of depressive symptoms over time.

What are the results?

Depression was found in 23% of the 1120 people living with MND recruited into the study. On average, those with depression were more likely to be younger and have more advanced MND than those without depression. Females were more likely to have depression than males and those with depression reported a worse level of quality of life in comparison to those without depression. The presence of depression did not, however, seem related to how long an individual had had MND.

Depression was more common in people with MND if they

• Were young

• Were female

• Had more advanced MND

The authors looked at when people were diagnosed with depression in relation to their MND diagnosis. They found 23% were diagnosed with depression at the time of or following their MND diagnosis. 5% reported their depression began more than 3 years prior to their MND diagnosis, with the remaining 72% being affected in the 3 years leading up to their MND diagnosis.

The authors studied whether those identified as having depression were on antidepressant medication. They found that 82% of people with MND with depression were on antidepressant medication. Those not on medication were much more likely to be male and at an advanced stage of MND.

The study aimed to categorise people with MND into groups based on their trajectories of depressive symptoms over time. Doing this, the authors found that people fell into 3 different groups. As they studied the groups over time throughout the study, they saw that the level of depressive symptoms stayed stable in each group. The table above describes that depression was more common in people with MND if they were female, young, or had advanced MND.

What do the findings mean going forward for people with the disease?

The study estimates that 23% of people living with MND have depression. Given how common depression would appear to be, the authors suggest MND clinics should routinely and proactively assess people for depression, exploring treatment options, including ready access to psychology services.

Nearly three-quarters of depression cases in people with MND start less than 3 years before MND diagnosis. With this in mind, the authors suggest that depression may be an early feature of MND before the more widely recognised symptoms start. Indeed, depression has been recognised as an early symptom in other neurological conditions, such as multiple sclerosis. It is, however, worth remembering that more than 75% of people with MND in this study did not have depression. Therefore, if depression is an early symptom of MND, it does not appear to be the case for everyone.

Looking to areas for future research, the authors suggest it is important to consider undertaking a trial of treatments of depression symptoms in MND. This study shows that depression is common in people with MND, affects quality of life, yet the effects of treatments for depression in MND are not yet known.

This study can be found at:
https://www.tandfonline.com/doi/pdf/10.1080/21678421.2022.2096410?casa_token=SfHRxtDNXmQAAAAA:PyXfSYlAsuV8oe0Xghl4bTOrq5935CLRxIqwVQTrHKDc9TVzBpo-oaiEjqjr38ZFAI23ReHDOS582Q

Paper title
Prevalence of depression in amyotrophic lateral sclerosis / motor neuron disease: multi-attribute ascertainment and trajectories over 30 months

Author list
C. A. Young, J. Ealing, C. J. McDermott, T. L. Williams, A. Al-Chalabi, T. Majeed, K. Talbot, T. Harrower, C. Faull, A. Malaspina, J. Annadale, R. J. Mills, A. Tennant & On Behalf Of The Tonic Study Group

Publication details including date of publication

Journal: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
Year: 2023

How common is depression in motor neurone disease? - Readable Research 

Lay summary by Louise Heywood, reviewed by Dr Tom Payne, and by a Parkinson’s Disease Lay Panel.

Background

Mitochondria act as the batteries of the cell, producing high amounts of energy for cells to function properly. In Parkinson’s, these batteries produce less energy, resulting in brain cells starving and dying. Therefore, one hope to slow down the progression of Parkinson’s is to use medication to keep mitochondria healthy. Ursodeoxycholic acid (UDCA) is commonly used as a treatment for liver disease, making it an ideal candidate for drug repurposing – using existing drugs to treat different conditions. This study was a Phase II clinical trial, where patients were randomly assigned to either UDCA treatment or a placebo drug, with neither participants nor doctors knowing which participants were taking UDCA. The study took place across two centres, one at Sheffield Teaching Hospitals (STH) and one at University College London (UCL) Hospitals. All participants had been diagnosed with Parkinson’s for less than three years.

Why is the study important?

There are currently no approved treatments for Parkinson’s that can prevent the loss of affected brain cells nor alter the progression of the condition – the available treatments can help reduce symptoms, but not the underlying causes. UDCA is a potential ‘neuroprotective’ drug that is hoped can prevent further loss of brain cells, and as such, represents an important step forward in the treatment of Parkinson’s. The first step to getting a new treatment to patients is to assess its safety and efficacy in clinical trials.

What did the authors do and how did they do it?

The trial consisted of 31 total participants randomly assigned to either UDCA treatment or placebo group with 20 taking UDCA and 10 taking a placebo. Participants remained on the treatments for 48 weeks, followed by an 8-week ‘wash-out’ period where treatment was stopped, to assess the longevity of UDCAs effects.

The main assessments were regarding safety and tolerability, but the study also looked at the effects of UDCA on the brain, and on Parkinson’s movement symptoms. To confirm that UDCA was having an effect on the brain a type of brain scan known as phosphorus-31 magnetic resonance spectroscopy was used. This is a specific brain scan that can measure the changes in levels of energy in the brain. Changes in movement symptoms were assessed using the standard clinical rating scale (MDP-UPDRS-III) and a digital, wearable, sensor-based system (Sheffield cohort only).

What are the results?

One participant completely withdrew from the study, due to problems swallowing, the high number of capsules, and was subsequently replaced. Another two participants stopped taking their tablets early, but still completed the study. This was due to the burden of taking so many capsules in addition to their existing medication. There were two serious adverse events during the trial, both of which affected the same patient in the placebo group, and in total 24 adverse reactions in 14/31 participants, affecting 10 UDCA participants and 4 placebo participants. The most frequently reported side effects of UDCA were mild diarrhoea and mild nausea, which required no treatment and was of short (24-72 hr) duration, therefore the authors felt that the 30 mg/kg dose of UDCA daily was well-tolerated and safe.

The brain scans of participants taking UDCA showed that there was a potentially increased efficiency of energy breakdown in the brains of UDCA participants, suggesting that UDCA is having a positive effect on Parkinson’s. The sensor-based movement analysis showed that participants taking UDCA had an increase in steps per minute when walking, and a reduction in time taken to make a full stride, and the time stood on both feet while walking when compared to those taking placebo. All of this would tentatively suggest an improvement in walking ability in the UDCA group, however the small number of participants means that the results must be approached with caution. However, the MDP-UPDRS-III clinical rating scale showed that both those taking UDCA and placebo experienced an improvement in their Parkinson’s symptoms during the study.

The study also looked at effects of UDCA on non-motor symptoms, such as depression; on a depression rating scale (MADRS), scores showed a small but important increase in the UDCA group, compared to the placebo group, though scores were overall still far below the cut off that indicates depression.

What do the findings mean going forward for people with the disease?

The study shows an improvement, or comparatively slower decline, in walking ability in the UDCA group, in addition to a slower progression of movement symptoms on the standard rating scale, suggesting UDCA has potential as a new Parkinson’s drug. Though the results of this study seem promising for the safety of UDCA, which was its primary aim, the study is limited by its small number of participants, and therefore a larger trial is needed to confirm whether UDCA can slow down the progression of Parkinson’s.

This study can be found at
Wiley Online Library DOI: 10.1002/mds.29450

Paper title
A Double-Blind, Randomised, Placebo-Controlled Trial of Ursodeoxycholic Acid (UDCA) in Parkinson’s Disease

Author list
Payne, T., Appleby, M., Buckley, E., van Gelder, L. M. A., Mullish, B. H., Sassani, M., Dunning, M. J., Hernandez, D., Scholz, S. W., McNeill, A., Libri, V., Moll, S., Marchesi, J. R., Taylor, R., Su, L., Mazza, C., Jenkins, T. M., Foltynie, T. and Bandmann, O.

Publication details including date of publication.
Movement Disorders, Published May 2023

Clinical trial results for UDCA as a new drug for Parkinson’s Disease - Readable Research