New research shows Parkinson’s off episodes go beyond movement issues

Review identifies 132 areas of impact, including quality of life and fatigue

Written by Andrea Lobo |

In this illustration of fatigue, a person walks using a cane, with a phantom-like figure in black hanging on to their shoulders and impeding their progress.
  • Parkinson's off episodes cause 132 impacts, a review found, including non-motor symptoms.
  • These episodes significantly impair quality of life, extending beyond visible movement problems.
  • Inbrija offers rapid motor improvement for off episodes, with good tolerability, data show.

A comprehensive review of the scientific literature identified more than 100 distinct ways in which off episodes affect people with Parkinson’s disease, highlighting a multifaceted burden that extends beyond movement symptoms to include cognitive, emotional, and quality-of-life impacts.

The research was presented by Merz Therapeutics, the company that markets Inbrija (levodopa inhalation powder), at the World Parkinson Congress 2026, held last month in Phoenix.

The findings showed that often overlooked nonmotor symptoms such as fatigue, memory difficulties, and anxiety can be as disruptive as physical symptoms during off episodes — periods when symptoms return in between medication doses — underscoring the need for treatment approaches that address the full patient experience.

The company also presented additional analysis from three Phase 3 trials confirming the safety and efficacy of Inbrija (levodopa inhalation powder) in providing consistent and rapid motor improvement for patients experiencing off episodes.

“For too long, the conversation around ‘off’ episodes has focused primarily on visible motor symptoms. Our research highlights what we’ve been hearing from people with Parkinson’s: the burden of an ‘off’ episode is far broader and more disruptive than what can be seen,” Stefan Albrecht, MD, PhD, Merz’s chief scientific and medical officer, said in a company press release. “It is a call to action for the entire Parkinson’s community to recognize and address the significant impact of ‘off’ episodes.”

Recommended Reading
An oversized red pen ticks boxes labeled

Parkinson’s therapy mirivadelgat selected for multi-drug clinical trial

Data shows Inbrija provides rapid motor benefit during off episodes

Parkinson’s is caused by the progressive loss of dopaminergic neurons, the nerve cells that produce dopamine, a signaling molecule involved in motor control. This leads to both motor symptoms, such as tremors, rigidity, and slowed movements, and nonmotor symptoms, including cognitive and emotional changes, mental issues, and sleeping problems.

Levodopa, a molecule that can be converted into dopamine, is the mainstay treatment for easing the disease’s motor symptoms. However, its long-term use may cause off episodes, which are more frequent and severe as the disease progresses. These episodes can be unpredictable and impact a person’s ability to perform daily activities.

Inbrija is an inhaled levodopa formulation approved to ease Parkinson’s symptoms during off episodes. It delivers a precise dose directly to the lungs, where it can rapidly enter the bloodstream and reach the brain to stabilize symptoms.

Researchers found that off episodes can affect patients in 132 different ways, encompassing not only movement-related difficulties but also fatigue, anxiety, memory problems, and other factors that can impair quality of life.

Additionally, data pooled from three Phase 3 trials involving 437 people with Parkinson’s disease confirmed that Inbrija provides rapid motor benefit during off episodes. Patients treated with Inbrija experienced a significant improvement in Unified Parkinson’s Disease Rating Scale Part 3 scores, reflecting reduced motor symptom severity.

In particular, patients who had been experiencing off episodes for less than two years before starting Inbrija saw a mean reduction of 14.3 points, while those with a longer history of off episodes (two years or more) experienced a similar 14.8-point decrease.

Safety analyses also confirmed Inbrija’s favorable tolerability profile, with predominantly mild treatment-emergent adverse events, most commonly cough and throat irritation. The estimated probability of remaining free of treatment-related cough after more than a year was 84.7%.

joginder p kundra avatar

joginder p kundra

I read the articles whenever i get the time. However i read it for my partner who has parkinsons disease.

Reply
Maureen mcpartland avatar

Maureen mcpartland

15 years into this PD. Inbrija for the past 2-3 years. Currently on duopa pump with occ inbrija. I know our pump dosage needs to be increased now as we have added inbrija at least 4 times a week for increasing off times. Fatigue, increased need to urinate, confusion increase, decreased spirits, and definite decrease in ability to move.
I know it’s hard and studies need controls, but so much can be gained if neurologists/staff had time to listen to patient or caregivers. PD is not a textbook condition

Reply
Ricky Morris avatar

Ricky Morris

Diagnosed just 1 yr ago and i could prob tell you every single area other than just movements that not only are impacted by my off periods (non-'medicated periods) as well as why off-periods happen. How can this be NEW Research ?

For those with significant off-periods
It IS caused from the gastric issues/delays that PD causes.
Thats why the new pumps
work, thats why this inhaled version works.
Because it Bypasses the gastric system.

I am retired health care (organ/tissue transplant) and have been trialing rectal administration. Works perfectly! And confirms the NEED for treatment to bypass the gastric system! I also am willing to bet and go on record that most of the medication induced dyskinesia is caused from the way the medication is digested and overloaded because of the need to take more bc its not getting to where its supposed to how its supposed to. Its NOT rocket science.
Just pay attention to the feedback
You get everyday from your body

You heard it Here FIRST!
TRY Rectal Admin- it works like a charm!

Reply
Darrell avatar

Darrell

Does this infer that all my levocarb intake currently oral with its own complications (nausea / type diet impacting protein intake to facilitate better pharmokinetics of oral levocarb.
My point being could all a patients levocarb intake be done outside the utility of the gastrointestinal system.
Why get a pump to by-pass the large intestine when one might be able to facilitate getting the medication via another route.
When will this drug be approved for use and will the research support a change in care that includes this option.
It seems like here on the east coast Canada PD patients take levocarb and other adjunctive therapy (mostly meds)…and suffer and wait for the gold standard DBS. The wait is painful and poorly understood as we patients seek daily relief at times not just waiting around for DBS. Thoughts…
No funded access to rTMS
No funded access to Stem Cell Therapy
No funded access without complex approval processes to use a medication off label.
Sorry done ranting and want to see RCT evidence and someone adopting evidenced based options for everyone.

Reply
Paul Kustow avatar

Paul Kustow

Those of us with Parkinson’s or who are caring for a family member with Parkinson’s have known for years that ‘off’ periods affect so much more that just movement symptoms. We have to deal with these major disruptions to life every day.
When will Inbrija be available in the UK? It sounds like it could be a significant improver of life for our Parkies and us carers.

Reply

Leave a comment

Fill in the required fields to post. Your email address will not be published.