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Advanced Neurology Piribedil for Parkinson’s disease

Table 3. (Continued)
Study, year Region Trial design Patients Treatment Primary Main results Evidence
outcome levela
Eggert et al., Germany Prospective, White men and Piribedil (213.2 Median reaction After 11 weeks of study, I
2014 [44] multicenter, women aged 35 mg/day), time during the piribedil reduced daytime
randomized, – 80 years with a pramipexole second half of the sleepiness with lower
active-controlled, diagnosis of PD in (2.7 mg/day) or subtest “vigilance,” Epworth Sleepiness
rater-blinded phase Hoehn and Yahr ropinirole test condition Scale scores at the end of
III study stages 1 – 4 (10.9 mg/day) “moving bar” of treatment compared with
(n = 80) the test battery the comparator
for attention (−4 vs. −2 points;
performances P = 0.01)
at the end of
treatment
a The evidence levels were made with reference to the 2004 EFNS Guideline
MMSE: Mini-mental state examination; NA, N = Not available; PD: Parkinson’s disease; UPDRS: Unified Parkinson’s disease rating scale

up to 35% , which may impact patients’ quality of life the incidence of dyskinesia on piribedil is different from
[52]
and may lead to suicide. Piribedil produced significant that of other DRA.
antidepressant effects in multiple behavior models of
depression, and its antidepressant effects are comparable 3.4. Recommendations for dosage of piribedil
with or better than those of multiple antidepressant drugs Piribedil is used in clinical practice since 1969 as 50 mg
(e.g., imipramine, tricyclic antidepressant drugs, and tablets. However, because of the limitations such as very
selective serotonin reuptake inhibitors) . low (< 10%) oral bioavailability due to extensive first pass
[30]
A few open clinical studies have shown that piribedil metabolism and short biological half-life, piribedil is
may significantly relieve depression symptoms in an prescribed in high dosing frequencies with 3 – 5 tablets/
[54]
effective dose for motor symptoms control; however, day . The dosage of sustained release formulation
these studies have no placebo control group [40,45] . More is 50 mg per tablet and the therapeutic effect will be
randomized, placebo-controlled, and double-blind studies lasting for 20 h. It is recommended to start with 50 mg
are needed to verify these results. once daily and an addition of 50 mg/week. Generally,
the average effective dose is 150 – 200 mg/day, and the
3.2.4. Somnolence maximum dose is 250 mg. In combination therapy, the
A few studies revealed that piribedil may improve the daily recommended maintenance dose of piribedil is 50
[55]
somnolence in patients with PD. A RCT showed that – 150 mg/day .
switching from pramipexole or ropinirole to piribedil 4. Management of adverse events caused
could decrease daytime sleepiness to a clinically relevant by piribedil
degree in PD patients with excessive daytime sleepiness .
[44]
Piribedil is generally safe and well tolerated. Most
3.3. Dyskinesia adverse reactions of piribedil overlap with those of all
The REGAIN study demonstrated that the incidence DRAs. The most commonly reported adverse reactions
of dyskinesia in piribedil is comparable with placebo were gastrointestinal and cardiovascular responses.
(8% vs. 7.5%) . A RCT showed that the incidences of Neuropsychiatric disorder or daytime somnolence was also
[17]
dyskinesia in piribedil and bromocriptine were 2.9% and reported [29,30] . Thirteen percent of patients have to change
4.7%, respectively . An animal-model study revealed the medication due to adverse effects. Suggesting the
[38]
[12]
that switching from levodopa to piribedil decreased the management of adverse reactions is highly important .
dyskinesia intensity without changing the improvement
in motor deficits; however, switching from piribedil to 4.1. Gastrointestinal tract reactions
levodopa resulted in a rapid increase in dyskinesia . Gastrointestinal tract reactions, including nausea, vomiting,
[53]
Animal models also demonstrated that α2-adrenoreceptor anorexia, and constipation, are the most common adverse
antagonists counter the dyskinesia induced by acute and reactions during treatment. The incidence ranges from 0%
chronic treatment of D2/D3 receptors agonists, such as to 33%, but most of those are not severe . During the
[12]
piribedil, and while retaining or strengthening restoration 12-month follow-up, the gastrointestinal adverse reaction
of motor function [17,35] . No data are available to show that rate of piribedil was similar to that of bromocriptine, but

Volume 2 Issue 1 (2023) 8 https://doi.org/10.36922/an.290