What Are the Best Therapeutic Options for Parkinson’s Disease?

New and Investigational Treatments

Deep brain stimulation (DBS) techniques are advancing, said Dr. Nirenberg. With DBS, a device implanted in the chest sends electrical pulses to electrodes inserted into targeted areas of the brain. “Recent studies are looking at closed-loop systems that provide direct feedback from the brain to the pacemaker so that stimulation is adjusted in real time.”

Continuous enteral infusion of carbidopa–levodopa intestinal gel over 16 hours via percutaneous endoscopic gastrojejunostomy is an option for people for whom DBS is being considered, but who have contraindications such as cognitive impairment or psychosis. “This [treatment] should only be prescribed to someone who has a good caregiver, because the pump has to be flushed often, removed before bathing, and checked to make sure there are no hardware problems or infections associated with its use.”

Droxidopa, a synthetic amino acid precursor of noradrenaline, received orphan-product designation for treatment of neurogenic orthostatic hypotension. Its effectiveness was shown in two two-week clinical trials. “It is expensive, costing tens of thousands of dollars per year. Although it is well tolerated, there is evidence of tachyphylaxis, and it may not work for longer than two weeks.”

Pimavanserin, a first-in-class drug approved in 2016 to treat hallucinations and delusions associated with Parkinson’s disease psychosis, is an atypical antipsychotic with a serotonergic mechanism of action. While the prospect of having such a treatment option initially generated excitement in the medical community, there have been recent concerns about adverse events in patients taking pimavanserin, including deaths, falls, insomnia, and nausea, in addition to continued hallucinations.

Focused ultrasound is approved for essential tremor and is investigational for Parkinson’s disease, Dr. Nirenberg noted. During the procedure, which can be performed on an outpatient basis, focused beams of ultrasonic energy are trained on targets deep in the brain to destroy diseased tissue without damaging surrounding normal tissue. Because of the lack of long-term follow-up of these patients, neurologists “do not know where this ultimately will fit in with Parkinson’s disease management,” said Dr. Nirenberg. Focused ultrasound is mainly being investigated as unilateral treatment because of concerns about the safety of bilateral ablative therapy.

To date, research on oral cannabinoids has not shown evidence of benefit for Parkinson’s disease, said Dr. Nirenberg. Neurologists have concerns about potential drug interactions and side effects such as imbalance, falls, cognitive impairment, and psychosis, which are of particular concern in people with Parkinson’s disease.

—Adriene Marshall

Suggested Reading

Cilia R, Akpalu A, Sarfo FS, et al. The modern pre-levodopa era of Parkinson’s disease: insights into motor complications from sub-Saharan Africa. Brain. 2014;137(Pt 10):2731-2742.

Tetrud J, Nausieda P, Kreitzman D, et al. Conversion to carbidopa and levodopa extended-release (IPX066) followed by its extended use in patients previously taking controlled-release carbidopa-levodopa for advanced Parkinson’s disease. J Neurol Sci. 2017;373:116-123.