The standard medication levodopa does not always work against tremors in Parkinson’s disease, especially in stressful situations. Propranolol, however, does work during stress, providing insight into the role of the stress system in tremors. MRI scans reveal that propranolol directly inhibits activity in the brain circuit that controls tremors. Doctors may consider this medication when levodopa is ineffective.
People with Parkinson’s disease report that tremors worsen during stressful situations. ‘Tremors act as a sort of barometer for stress; you see this in all people with Parkinson’s’, says neurologist Rick Helmich from Radboud university medical center. The commonly used drug levodopa usually helps with tremors, but it tends to be less effective during stress, when tremors are often at their worst. Helmich and his team wanted to investigate whether a medication targeting the stress system could help and how this effect of stress on tremors works in the brain.
Mathematical calculations
The medication in question, 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.
Amplifier
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. Helmich explains: ‘We know that abnormalities in systems like the dopamine system cause tremors. 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 researchers that propranolol also worked to reduce tremors at rest. ‘Apparently, our stress system is occasionally active, even at rest’, says researcher Anouk van der Heide. ‘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.’
Mindfulness
Helmich already prescribes propranolol for some Parkinson’s patients. ‘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 explains. ‘However, in about forty percent 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’s team is also exploring lifestyle changes that could help with Parkinson’s. ‘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.’
