The standard medication, levodopa, does not always work against tremors in Parkinson’s disease, especially in stressful situations. Propranolol, however, works during stress, providing insight into the role of the stress system in tremors. MRIs reveal that propranolol directly inhibits activity in the brain circuit that controls tremors. Doctors may consider this medication when levodopa is not effective.
People with Parkinson’s disease report that tremors worsen during stressful situations. «The tremors act as a kind of stress barometer; “This is seen in all people with Parkinson’s,” says neurologist Rick Helmich of Radboud University Medical Center. The commonly used drug levodopa often helps with tremors, but tends to be less effective during stress, when tremors typically occur. be worse. Helmich and his team wanted to investigate whether a drug targeting the stress system could help and how this effect of stress on tremors in the brain works.
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 cardiac 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 could reduce tremors in Parkinson’s, but until now, no comprehensive 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 in his hands measured the intensity of his tremors, while an MRI 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, the tremors worsened during stress.
Amplifier
The study showed that propranolol reduced tremors both at rest and during stress. MRIs revealed how this works: after taking the drug, the brain circuit responsible for tremors showed less activity. Helmich explains: ‘We know that abnormalities in systems such as the dopamine system cause tremors. Based on our study, we now think that the stress hormone norepinephrine acts as an amplifier that increases tremor intensity in the movement area of the brain. Propranolol inhibits this amplifying effect and therefore reduces symptoms.
Surprising the researchers, propranolol also worked to reduce resting tremors. “It seems that our stress system is activated occasionally, even at rest,” says researcher Anouk van der Heide. “This changes a person’s level of alertness and causes spontaneous fluctuations in tremors. We previously thought that the stress hormone system was only active under stress, but apparently that is too simplistic. It also plays a role at rest.’
Consciousness
Helmich already prescribes propranolol to 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 let’s start with that,” explains Helmich. «However, in around 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 careful about side effects, such as low blood pressure.’
In addition to drug 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 that makes people shake more. Even something as simple as asking yourself: Did I lock the front door? you can activate it. We are currently investigating whether mindfulness can positively influence the stress system.’