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Advanced Neurology Piribedil for Parkinson’s disease

piribedil dosage advised is 150 – 300 mg/day, usually taken piribedil (up to 150 mg/day) and levodopa may improve
3 times daily . Studies have demonstrated piribedil motor symptoms, such as tremor, with good tolerance.
[29]
efficacy as monotherapy and in combination therapy. In this Moreover, piribedil reduces the dose of levodopa
section, the results of clinical trials of piribedil on motor and prolongs the duration of its effect and may help
symptoms are reviewed. Table 2 summarizes the evidence to decrease the risk for levodopa-induced motor
for the improvement of motor symptoms by piribedil [34-42] . complications, and prolong the “ON” time [36] . Due to the
limitations of the design in this study, the results need to
3.1.1. Monotherapy for early patients with PD be cautiously interpreted.

Piribedil monotherapy may improve motor symptoms,
such as tremor, rigidity, and bradykinesia, in patients with 3.2. Non-motor symptoms
early PD, and delay the need for levodopa [30,40] . Studies on patients with early PD showed that piribedil

A 7-month, randomized, double-blind, placebo- monotherapy or as an adjunct to levodopa both resulted
controlled trial (REGAIN study) showed that the in some improvement in patient’s non-motor symptoms,
piribedil monotherapy (150 – 300 mg/day) could achieve including mental state, depression, and sleep disorders.
comprehensive control over motor symptoms, with The early combination of piribedil may improve patients’
[29]
proportion of both responders and patients remaining on quality of life . Table 3 summarizes the evidence
monotherapy significantly higher than that of the placebo for the improvement of non-motor symptoms by
[35,38,40,43-47]
group. Researchers presumed that the treatment effect piribedil.
of piribedil monotherapy (effect size of 7.26 points for 3.2.1. Apathy
UPDRS III score) may be higher than or comparable with
other dopaminergic agonists, including ropinirole (effect Apathy is a common feature in end-stage PD that affects
size of about 5 points), pramipexole (effect size of about up to 42% of patients with PD. Apathy is associated with
[48]
6 points), pergolide (effect size of about 5 points), and cognitive impairment and depression . Many studies
rotigotine (effect size of about 4 points) . have shown that they are two different but commonly
[39]
co-occurring syndromes, and depression can occur
3.1.2. Patients with early PD insufficiently controlled by simultaneously with or after apathy [12,49] .
levodopa
A 12-week, randomized, double-blind, and placebo-
A 6-month, open-label, multicenter trial showed that controlled trial showed that (n=37) treatment of piribedil
piribedil (150 mg/day) in early combination with levodopa (maximum dose 300 mg/day) may effectively reverse
and then a switch to piribedil monotherapy may improve postoperative apathy symptoms (Starkstein Apathy Scale
[41]
motor symptoms and was well tolerated . A 6-month score: -34.6% vs. -3.2%, P = 0.015, Robert Inventor score:
RCT showed that piribedil (150 mg/day) as adjunct to improved by 46.6% vs. worsened by 2.3%, P = 0.005) after
levodopa may significantly improve motor symptoms, deep brain stimulation of the subthalamic nucleus. The
[42]
with a good safety and tolerance profile . A 12-month remission rate of clinical symptoms was also higher than
multicenter RCT showed that the early combination of the control group (47.4% vs. 16.7%), and the treatment
piribedil (150 mg/day) or bromocriptine (25 mg/day) and response was usually achieved in the first 6 weeks after
levodopa resulted in a similarly significant improvement treatment. It was suggested that piribedil should be
of all motor symptoms in patients with PD; however, less initiated quickly in patients with postoperative apathy.
dose of levodopa is required when piribedil is used, as Moreover, the piribedil group presented a trend towards
[38]
compared to bromocriptine . improvement in symptoms of anhedonia .
[47]
3.1.3. Patients with moderate and advanced PD 3.2.2. Cognitive and executive functions
A previous review on piribedil indicates that the PD In a 12-month, multicenter, randomized, double-blind,
treatment generally requires long-term medication, and Phase IV trial, and 425 patients with incomplete levodopa
the long-term use of piribedil may not aggravate motor response were enrolled, and a subgroup analysis (n = 178)
complications, with low incidence of dyskinesia . Due to showed that only the combination of piribedil (150 mg/day)
[30]
the restrictions of the number of cited papers, these results and levodopa may significantly improve the scores of
may be not comprehensive. Wisconsin Card Sorting Test (WCST) rather than other
scales in patients with PD compared with bromocriptine
3.1.4. Patients with advanced PD treated with levodopa (25 mg/day) and levodopa. The cognitive and executive
An Asian phase IV, open-label, clinical study showed functions were tested by the widely used WCST, which
that an 8-week short-term combination therapy of requires the participation of all cognitive processes needed

Volume 2 Issue 1 (2023) 4 https://doi.org/10.36922/an.290