On and off states in Parkinson’s: ask the expert

We speak with Dr Bruce Fernie about dealing with the emotional stress that experiencing off states in Parkinson’s can bring.

Lynn Duffy
Jul 1, 2019 · 6 min read

Drugs like levodopa can be extremely helpful in managing movement symptoms. But over time, their effects become less constant. Dealing with off states in Parkinson’s can be highly distressing, with people experiencing motor fluctuations reporting higher levels of depression and anxiety.

We speak with psychologist, Dr Bruce Fernie, about his work to help people cope with these periods. But first, a bit of background…

Photographer: Amit Lennon

What do we mean by on and off states?

Parkinson’s drugs like levodopa work by boosting the levels of dopamine in the brain, leading to big improvements in symptoms. In the early stage of Parkinson’s, people typically only need to “top-up” their dopamine levels by taking levodopa 2 or 3 times a day.

But over time, as Parkinson’s progresses, you may find the effects of the medication “wears off” faster, leading to movement difficulties throughout the day. If you go from having good control of your movement symptoms to having less control, it’s called a motor fluctuation.

Clinicians use the terms “on” and “off” to describe the different stages of the motor fluctuation. An “on” state is when a person’s symptoms are controlled and when they feel at their most capable. Being ‘off’ is when Parkinson’s symptoms come back and affect them the most. And it’s not just motor symptoms that are affected. Symptoms such as fatigue, pain, cognitive difficulties and low mood can also get worse.

There are typically 4 reasons why people experience off periods (see table below). These can be predictable — such as ‘wearing off’ when it gets near the time for the next tablet — or unpredictable, for example, if the medication stops working. Some people can experience fluctuations between on periods and off periods several times a day, describing it like a light switch being turned on and off.

Adapted from a presentation by Stuart Isaacson at WPC 2019

What causes off states in Parkinson’s?

There are several factors that can result in motor fluctuations in Parkinson’s — all relating to the levels of dopamine in the brain. As the condition progresses:

  • more dopamine-producing nerve cells are lost in the brain

These factors mean the brain becomes increasingly dependent on higher doses of levodopa medication to keep symptoms at bay. When the medication wears off, which will happen more frequently, the off states will become more apparent.

A distressing experience

Feelings of depression and anxiety are common symptoms in Parkinson’s. Nearly half of all people with Parkinson’s have experienced one of these issues. And research has shown that experiencing off periods can make feelings of distress even worse.

Some people can find these fluctuations, and particularly the off periods, distressing. ‘Distress’ can be unpleasant feelings of low mood, worry, tension, and discomfort. It is often associated with unhelpful and repetitive thinking patterns that can make the emotional distress worse and last longer.

However, the relationship between motor fluctuations and feelings of distress is not universal. It’s been noted that not everyone in an off state experiences these feelings of distress.

Researchers are interested in understanding why this is. Uncovering why some people experience emotional distress and some don’t could open up new avenues of treatment to cope better with motor fluctuations.

Dr Bruce Fernie

Psychologist Dr Bruce Fernie, from Kings College London, spoke to us about his research looking at emotional distress in off states, and how specialist therapy could help.

Hi Bruce, what made you decide to research emotional distress in Parkinson’s?

The feelings of distress that some people feel when experiencing off periods can be severe. The current way to deal with these feelings is to be given anti-depressants or anti-anxiety medications. But these are typically not effective — so there’s a huge unmet need for people with Parkinson’s when they’re trying to cope with their off periods.

Tell us about your research

We wanted to find out why some people become distressed during off periods and others don’t. So we recruited people with Parkinson’s with motor fluctuations and asked them to complete a 1-minute survey up to four times a day, over a period of a week. The survey asked how they were feeling, what they were thinking about, and their symptoms at the time.

As expected, people reported feeling more distressed when they were off than when they were on. And interestingly, they felt increased levels of distress when they had taken their medication and were waiting to enter an on period, compared with when they were wearing off. This may be because of the added anxiety of waiting to see if the medication would work.

The study also found that people who reported worrying about, or dwelling on their symptoms, asking questions, such as “why is this happening to me”, were more distressed than those who didn’t. The types of thoughts people had also played a role in the levels of distress experienced. For example, those who had thoughts such as “once I focus on my symptoms, I find it impossible to think about anything else” experienced higher levels of distress than those who focused on other things.

What could these results mean for people living with Parkinson’s?

The results we saw suggest that people’s thought patterns on their symptoms can affect their levels of distress. So the next question we had was: can we do anything to help with this?

There’s a new type of psychological therapy called metacognitive therapy that we think has the potential to help. It aims to increase the control people have over how they think and their attention. This can allow them to move away from unhelpful thinking styles that can drive distress.

Research has shown that metacognitive therapy is helpful to reduce symptoms of depression and anxiety, but it has not yet been tested on people with Parkinson’s.

So what’s next?

Based on our previous research, we’re now conducting a small trial of metacognitive therapy for people with Parkinson’s who experience distressing motor fluctuations. We hope this will give us an answer about whether this type of therapy could be helpful for people with Parkinson’s who are experiencing distress during off periods. If successful, we’d then hope to test the therapy in a larger clinical trial.

Recruitment for this study is still open — you can read more about it on our website:

Looking for a different study to take part in?

Find out about opportunities to take part in local research with the Take Part Hub. From at-home questionnaires to trialling new treatments — whatever you’re ready for, you can make a difference.

Parkinson’s UK

Get the latest research news, discover more about Parkinson’s and read about how others are getting involved. For information and support, visit www.parkinsons.org.uk

Thanks to Dr Beckie Port

Lynn Duffy

Written by

Scientific copy writer @ParkinsonsUK. Lover of tea. Views are my own

Parkinson’s UK

Get the latest research news, discover more about Parkinson’s and read about how others are getting involved. For information and support, visit www.parkinsons.org.uk

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