Targeting the stress system reduces Parkinson's tremors

The commonly used Parkinson’s drug levodopa usually helps with tremors, but it tends to be less effective during stress, when tremors are often at their worst. Seeking to combat this, neurologist Rick Helmich and his team at Radboud University Medical Center set out to investigate whether a medication targeting the stress system could help, with their results published in Annals of Neurology.

The medication investigated, known as propranolol, is a beta blocker that inhibits the action of stress hormones. It was developed for high blood pressure and heart arrhythmias, has been around for a long time, and is already used as a standard treatment for essential tremor — a condition in which people experience tremors without other neurological symptoms. There were already indications that propranolol might reduce tremors in Parkinson’s, but until now, no thorough research has explored its potential effects.

Helmich and his team studied 27 people with Parkinson’s who experienced tremors. They were given propranolol on one day and a placebo on another day. A device on their hands measured the intensity of their tremors, while an MRI scan mapped brain activity. This was done both at rest and during a task involving stressful mathematical calculations. The stress response was measured by pupil size and heart rate, both of which increased during the calculations. As expected, without medication, tremors worsened during stress.

The study showed that propranolol reduced tremors both at rest and during stress. The MRI scans revealed how this works: after taking the medication, the brain circuit responsible for tremors showed less activity.

“We know that abnormalities in systems like the dopamine system cause tremors,” Helmich explained. “Based on our study, we now think that the stress hormone noradrenaline acts as an amplifier, which increases tremor intensity in the brain’s movement area. Propranolol inhibits this amplifying effect and thus reduces symptoms.”

It surprised the team that propranolol also worked to reduce tremors at rest, with researcher Anouk van der Heide stating, “Apparently, our stress system is occasionally active, even at rest. This changes how alert someone is and leads to spontaneous fluctuations in tremors. We previously thought that the stress hormone system was only active under stress, but apparently, that’s too simplistic. It also plays a role at rest.”

Helmich already prescribes propranolol for some Parkinson’s patients, although he still maintains that the most effective medication for Parkinson’s is levodopa.

“It not only helps with tremors but also with other symptoms, so that’s what we start with,” Helmich explained. “However, in about 40% of patients, it is not effective against tremors. In that case, we first increase the dose, but if that doesn’t work, propranolol is an option. However, we must be cautious about side effects, such as low blood pressure.”

In addition to medication studies, Helmich and his team are also exploring lifestyle changes that could help with Parkinson’s. He noted, “It doesn't take much to trigger a stress response, causing people to tremble more. Even something as simple as wondering ‘did I lock the front door?’ can set it off. We are currently investigating whether mindfulness can positively influence the stress system.”

Image credit: iStock.com/Alexey Koza