What are ‘off’ periods – and how can they impact people with Parkinson’s disease?

What are ‘off’ periods, what causes them – and why is raising awareness of them so important? Dr Lazzaro di Biase and advanced nurse practitioner Brian Magennis share their insights

“Management of Parkinson’s is really about symptom control,” says Brian Magennis, an advanced nurse practitioner based at Mater Misericordiae Hospital in Dublin, Ireland. His deep knowledge of Parkinson’s comes not only from his patients, but also his father, who lives with the condition.

As Brian explains, one way to control Parkinson’s symptoms is through levodopa, a dopamine replacement agent considered by many to be a “gold standard” treatment for the condition. However, as the condition progresses, moments can occur when, despite medication, it becomes more difficult to manage both motor and non-motor symptoms. These moments are known as ‘off’ periods.

Dr Lazzaro di Biase, a neurologist and head of the movement disorders service at the Campus Bio-Medico University of Rome, Italy, refers to this ‘off’ state as a “hallmark of Parkinson’s symptoms”. It can come in several forms.

Describing one such form, known as wearing ‘off’, Lazzaro says: “The ‘off’ state can kick in when levodopa is eliminated from our body – and people begin to express motor symptoms that are related to the low amount of dopamine going to the brain.”

Other types include partial ‘on’ or dose failure: “Sometimes, a dose of medication may provide incomplete relief of symptoms or fail to provide any symptom relief at all,” Lazzaro explains.

Meanwhile, unpredictable ‘off’ episodes are the moments when people transition suddenly from ‘on’ to ‘off’ with no obvious link to medicine dosage timings. “These are often the most difficult to manage,” says Lazzaro, “as they are not easily corrected by adjusting the medication schedule.”

Another type is “delayed ‘on’ – which is when it takes longer for someone’s medications to kick in”, says Brian.

Lazzaro adds that ‘off’ periods are complex and can impact a wide range of symptoms, including “tremor and stiffness, as well as non-motor symptoms such as panic attacks and depression”.

“Most people don’t just suddenly turn ‘off’ but wind down”

Brian explains that the ‘off’ period phenomenon has often been compared to an on/off light switch, but he sees it as more of a dimmer switch. “Most people don’t just suddenly ‘turn off’, but wind down, slowly switching ‘off’,” he says. This means that these states can sometimes be anticipated – and even avoided altogether.

But this might be easier said than done, according to Lazzaro – who says informing people about how to recognise an ‘off’ state is a key challenge. “This is especially the case for people in the beginning phases of Parkinson’s. ‘Off’ periods can be present, but as the symptoms are very mild, people are unlikely to recognise them.” He also notes that these periods are more noticeable in the later stages of the condition, regardless of the person’s age.

In addition to emphasising the value of being able to identify when these periods occur, the two experts stress the importance of monitoring them over time. As with many Parkinson’s symptoms and characteristics, ‘off’ periods are likely to develop in severity as the condition progresses. “That’s when you might have to adapt the current baseline treatment or look to other options,” says Brian. These other treatment options might include on-demand medication, which is designed to tackle ‘off’ periods when they occur.

He advises people with the condition to keep a diary of symptoms and medications to help identify possible ‘off’ periods. Constipation, infection and dehydration are among the factors frequently identified for triggering ‘off’ periods in such journals, he says, because they can “inhibit oral medicine absorption and limit the optimal response”.

Lazzaro adds that because levodopa is absorbed in the small intestine, delays to gastric emptying can slow the absorption of the drug. “There can also be variations in how individual people metabolise levodopa,” he adds, “which can lead to different durations of effect and levels of symptom control.”

Consistent medication intake is key. “Timing is very important to avoid ‘off’ periods,” says Lazzaro, “because it’s related to the level of fluctuation of dopamine. It may take some trial and error to find the regimen that provides the most effective symptom control.”

Brian agrees: “I always say to my patients that the more reliable they are with taking their medication, the more predictable the control of their symptoms will be.”

The importance of raising awareness

Lazzaro argues that awareness is “the most important part” of effectively managing challenges associated with ‘off’ periods. “By recognising and being aware of these symptoms, people with Parkinson’s may be able to manage parts of their own therapy,” he says.

“People often learn to recognise their own individual ‘off’ symptoms over time. It’s important for people with Parkinson’s to communicate closely with their healthcare providers about any changes in symptoms or medication response, so that the treatment plan can be adjusted as needed,” he continues.

“It’s not only for the person with the condition to understand, but also for their family or the people around them,” adds Brian. “‘Off’ periods can be very distressing for both groups when they happen.” He explains how anxiety around these states can prompt people to, for example, take risks with walking that may lead to falls. “But if people understand what ‘offs’ are, they can do something about it.”

For Brian, learning about ‘off’ periods and raising awareness of how to manage them comes back to supporting people with symptom control. “If we can get that right, then people with the condition may function better, live better, be less prone to having medical problems – and have a better quality of life.”

Lead image: Dr Lazzaro di Biase (left) and Brian Magennis (right). Brian Magennis image credit: Clinical Photography Department at the Mater Hospital, Dublin, Ireland.

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