Expert interview on the identification and treatment of end-of-dose phenomenon in Parkinson's disease

The end-of-dose phenomenon is a common complication in the treatment of Parkinson's disease patients.
Early identification and timely measures can be effectively improved and improve the quality of life of patients
.
Regarding the diagnosis and treatment of the end-of-dose phenomenon, the reporter had the honor to interview Professor Zhu Hongcan from the Department of Neurology, the First Affiliated Hospital of Zhengzhou University

01

Principles of clinical medication for Parkinson's disease

In the early stage of Parkinson's disease, usually dopaminergic drugs with a moderate dose or less can significantly improve the symptoms of patients, so that the patients' work and activities of daily living are basically not affected, but the "honeymoon period" of drug treatment is only about 3 to 5 years
.
How to ensure the quality of life of patients, and at the same time extend the "honeymoon period" as much as possible, and delay the progression of the disease, combined with the recommendations of domestic and foreign Parkinson's disease treatment guidelines, clinical medication should follow several principles

(1) Promote early diagnosis and early treatment
.
(2) Adhere to the principle of “dose titration” and strive to achieve the principle of “satisfying clinical effects with as small a dose as possible”

02

Diagnosis of end-of-dose phenomenon

After a period of "honeymoon period" of drug therapy in Parkinson's disease patients, the efficacy of drug therapy gradually decreases, the effective time of each medication is shortened, and the alleviation and aggravation of symptoms fluctuate regularly with the blood drug concentration, which is called the end-of-dose phenomenon
.
The end-of-dose phenomenon refers to a recurrence of motor or non-motor symptoms that is usually foreseeable.

03

Treatment method of end-of-dose phenomenon

(1) To avoid the influence of diet on the absorption of levodopa and its passage through the blood-brain barrier, it is necessary to take compound levodopa 0.

(2) On the premise that it can still effectively improve motor symptoms, do not increase the total daily dose of compound levodopa, appropriately increase the number of daily doses, and reduce the dose per dose
.
If necessary, the total dose of levodopa can also be increased

(3) The replacement of compound levodopa from a regular-release agent with a sustained-release tablet can prolong the action time.
It is more suitable for the early deterioration of the dosage, especially at night, which is a better choice, but the bioavailability is low and the dosage needs to be increased.
20%~30%
.

(4) Add a long half-life dopamine receptor agonist that produces continuous dopaminergic stimulation to the striatum
.
The regular-release and sustained-release tablets of pramipexole and ropinirole, rotigotine patch and intermittent subcutaneous infusion of apomorphine are all effective in the treatment of symptom fluctuations

(5) Add catechol that can stimulate the striatum to produce dopamine? O? Methyltransferase inhibitor
.
In the US guidelines, entacapone is grade A evidence, and tocapone is grade B evidence

(6) Add selective monoamine oxidase B inhibitor
.
In the US guidelines, rasagiline is grade A evidence, and selegiline is grade C evidence
.
Rasagiline, safinamide, and zonisamide are evaluated as effective and clinically useful in the treatment of symptom fluctuations
.

(7) The adenosine A2 receptor antagonist istrafylline is evaluated as possibly effective in the treatment of symptom fluctuations and may be clinically useful
.

If the patient's end-of-dose phenomenon is serious and the improvement is not clear after the above adjustments, anticholinergic drugs (for young patients) or amantadine can be added, which may be effective for some patients
.
Most PD patients ultimately need a combination of multiple drugs, because a single treatment method is difficult to adequately improve exercise fluctuations
.