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Movement disorders
Published in Henry J. Woodford, Essential Geriatrics, 2022
DAs have also been tried as supplementary therapy to levodopa in advanced PD. A study randomised 360 patients (mean age 63), with sub-optimally controlled PD plus motor fluctuations, to receive either pramipexole or placebo over a 32-week period.49 There were significant improvements in UPDRS scores with pramipexole compared to placebo for motor symptoms (25% v 12%) and reduction in ‘off' time (31% v 7%). Resting tremor, rigidity and bradykinesia were improved. Adverse effects seen more commonly with pramipexole included dyskinesia (61%), hallucinations (19%) and confusion (11%). Similar results have been found with studies of ropinirole.50 The addition of DAs to levodopa can allow a reduction in levodopa dose of up to 30%. This potential levodopa-sparing effect may reduce the occurrence of future motor fluctuations but perhaps at the cost of other adverse effects, especially in frail older people. DA can be considered as an adjunct to levodopa for people with motor fluctuations.7
Network Meta-Analysis
Published in Ding-Geng (Din) Chen, Karl E. Peace, Applied Meta-Analysis with R and Stata, 2021
After we build and validate a Bayesian network meta-analysis model, we can now summarize and report the Bayesian network meta-analysis model results. A forest plot is a commonly used approach to summarize and present the meta-analysis results, which could also be used in reporting Bayesian network meta-analysis models. The example code below is to generate a forest plot as displayed in Figure 12.11 for the objects chain. We chose placebo as the reference treatment for comparison specified in the function relative.effectso the forest plot shows four treatments as compared with placebo. It is clear that only the treatment Pramipexole is significant different in treatment effect as compared with placebo (MD = –1.8 with 95% Confidence interval (–2.9, –0.93)).
Pharmacological Management of Parkinson’s Disease
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Newman Osafo, Samuel Obeng, David D. Obiri, Oduro K. Yeboah, Leslie B. Essel
The adverse effect profile of pramipexole is associated with stimulation of peripheral and central dopamine receptors. The development of tolerance may be avoided by slow titration of pramipexole or the addition of domperidone in sensitive patients. Because the drug is a nonergoline its activity is devoid of the rare but nuisant ergot-related adverse effects associated with bromocriptine and pergolide therapy. One disturbing effect is the sudden onset of sleep which may precipitate road and other forms of accidents. Patients beginning treatment with pramipexole should be counseled on the risk and the need to exercise extreme caution when driving or operating heavy machinery (Frucht et al., 1999).
Safety review of current pharmacotherapies for levodopa-treated patients with Parkinson’s disease
Published in Expert Opinion on Drug Safety, 2023
Angela M Richmond, Kelly E Lyons, Rajesh Pahwa
The majority of patients taking adjunctive pramipexole experience AEs [34]. The most common treatment-emergent adverse events (TEAEs), reported in up to 60% of patients taking pramipexole, were dyskinesia, hallucinations, orthostatic hypotension (OH), dizziness, insomnia, nausea, vomiting, and confusion [34]. Dyskinesia, OH, dizziness, insomnia, and nausea were also common in patients taking placebo. However, dyskinesia and hallucinations were significantly more common in the pramipexole group (61.3% and 21.0%) versus placebo (40.8% and 5.6%). Confusion was not significantly different between groups [34]. Incidence of common AEs in PD patients taking adjunctive pramipexole or other adjunctive therapies relative to placebo are summarized in Table 2.
A case report of infantile parkinsonism-dystonia-2 caused by homozygous mutation in the SLC18A2 gene
Published in International Journal of Neuroscience, 2023
Hongyin Zhai, Yaofeng Zheng, Yiduo He, Yong Zhang, Zhikuan Guo, Wenzhe Cui, Li Sun
The p.Pro237His mutation of VMAT2 was also detected in two New Zealand siblings of European descent and a 7-year-old female of Iraqi, and the affected ones were all inherited from their heterozygous consanguineous parents [6, 7]. Besides, the proline-to-leucine substitution (p.Pro387Leu) in VMAT2 was described in an original Saudi Arabian family [5]. Both the p.Pro237His and p.Pro387Leu mutations are located in the fifth VMAT2 transmembrane domain and close to the tenth VMAT2 transmembrane domain, which are highly conserved in vertebrate species. The above-mentioned patients presented with a series of clinical symptoms relating to abnormal monoaminergic neurotransmission, such as truncal hypotonia, a general paucity of movement, oculogyric crises, extrapyramidal signs and cognitive delay, and then were diagnosed as brain dopamine-serotonin vesicular transport disease. Treatment with direct dopamine agonists was followed by symptomatic improvement in affected individuals, whereas treatment with levodopa was associated with deterioration of the disease. As a result, the 6-month-old infant in this report was diagnosed as PKDYS2 according to a homozygous p.Pro237His mutations and clinical symptoms (parkinsonism, dystonia). Subsequent treatment with dopamine receptor agonist pramipexole was confirmed effective.
Advancing synthetic therapies for the treatment of restless legs syndrome
Published in Expert Opinion on Pharmacotherapy, 2019
Stefano de Biase, Gaia Pellitteri, Gian Luigi Gigli, Mariarosaria Valente
Pramipexole is usually well tolerated, main side effects are nausea, headache, somnolence, dizziness, orthostatic hypotension, and hallucinations. Patients should be warned about drowsiness and even falling asleep while engaged in activities of daily living [43]. Even if lower than levodopa, significant rates of augmentation (8–56%) have been reported for pramipexole [47]. Silver et al. showed that risk of augmentation due to pramipexole persisted for up 10 years of treatment in RLS/WED patients. In particular, the authors reported an annual augmentation rate of 7% [48]. Maestri et al., in a case series of 24 patients, demonstrated that the shift from immediate-release (IR) to extended-release (ER) formulation may be an effective option to treat augmentation, sustaining the hypothesis that the half-life of the drug plays an important role in the mechanism of augmentation [49].