Daily Levodopa Dose Research Articles

Risk factors for hallucinations in Parkinson's disease: Results from a large prospective cohort study

The aim of this study was to identify risk factors for the development of hallucinations in patients with Parkinson's disease (PD). A broad range of motor and nonmotor features was assessed at baseline and during the following 5 years in 386 PD patients. Cross-sectional analyses of baseline data and longitudinal analyses of follow-up data were performed to identify risk factors for hallucinations in PD. Twenty-one percent of the patients had hallucinations at baseline, whereas 46% of the patients without hallucinations at baseline developed this feature during follow-up. Univariate survival analysis showed that older age, female sex, less education, higher age at onset, and more severe motor and cognitive impairment, depression, daytimes sleepiness, autonomic dysfunction, and motor fluctuations and dyskinesias, as well as higher daily levodopa dose, were associated with the risk of developing hallucinations. This largely corresponds with the features that were associated with the presence of hallucinations at baseline. In a stepwise regression model, older age at onset, female sex, excessive daytime sleepiness, autonomic dysfunction, and dyskinesias emerged as independent risk factors for developing hallucinations. Female sex, autonomic dysfunction, motor fluctuations, and dyskinesias have not been reported as risk factors in previous studies. These findings lend support to the notion that hallucinations in PD are caused by a combination of risk factors that are associated with (the interaction between) older age and more advanced disease. The identification of female sex as a risk factor for developing of hallucinations in PD is a new finding and should be verified in future studies.

Morning Akinesia and the Potential Role of Gastroparesis – Managing Delayed Onset of First Daily Dose of Oral Levodopa in Patients with Parkinson’s Disease

In patients with Parkinson’s disease (PD), motor and non-motor symptoms are frequent during OFF periods, especially when the next levodopa dose has a delayed onset of action (delayed ON). Delayed ON of the first daily dose of levodopa is known as morning akinesia, which can significantly affect quality of life and impair daily activities. Morning akinesia can occur due to a delay in gastric emptying, impaired intestinal absorption, pharmacodynamic effects or other mechanisms. Gastroparesis is common in patients with PD and can cause gastrointestinal symptoms, delayed ON and morning akinesia. Alternative delivery of dopaminergic therapy by a non-oral route may be useful in patients with PD and gastroparesis. Subcutaneous apomorphine injection is used by patients with PD in the OFF state to decrease time-to-ON. An ongoing study is investigating its use for morning akinesia, as well as the frequency of delayed gastric emptying in these patients.

The catechol-O-methyltransferase and monoamine oxidase B polymorphisms and levodopa therapy in the Iranian patients with sporadic Parkinson's disease.

Parkinson's disease (PD) patients vary widely in their response to levodopa treatment, and this may be partially genetic in origin. Recent studies suggest that catechol-O-methyltransferase (COMT), G1947A and monoamine oxidase B (MAOB), A644G polymorphisms might influence the risk and treatment of PD. Herein, we aimed to test the possible influence of MAOB and COMT genetic polymorphisms on the effective daily dose of levodopa administered in the fifth year of treatment. We also examined the effect of COMT and MAOB haplotypes on levodopa therapy outcome. There were 31 females and 72 males of Iranian origin diagnosed with sporadic PD included into the study. The patients were divided into two groups. Group 1: patients received daily doses of levodopa below 500 mg in the fifth year of treatment. Group 2: those patients receiving daily doses exceeding 500 mg in the fifth year of treatment. MAOB and COMT polymorphism genotyping was performed by using PCR-based restriction fragment length polymorphism (RFLP) analyses. Our data show that the first group suffered less frequently from dyskinesia than patients from the second group. No statistically significant differences were found in allele frequencies and genotype distributions of the studied genes between two groups. In addition, the incidence of the specific haplotypes between the two groups did not show any difference. The present data suggest that pharmacokinetic or pharmacodynamic factors other than the investigated genetic variants of the MAOB and COMT enzymes seem to determine the response to levodopa in the Iranian PD patients.

Age, drugs, or disease: What alters the macrostructure of sleep in Parkinson’s disease?

To describe the alterations in the macrostructure of sleep in a large cohort of sleep-disturbed patients with Parkinson's disease (PD) and investigate influencing factors. A cohort of sleep-disturbed but otherwise unselected PD patients (n=351) was investigated with video-supported polysomnography. We analyzed the influence of age, disease duration, disease severity, and dopaminergic medication on subjective sleep perception, sleep efficiency, the amount of slow wave sleep, awakenings, periodic leg movements in sleep (PLMS), and REM sleep behavior disorder (RBD). Sleep efficiency and slow wave sleep decreased with age (p=0.003 and p=0.041, respectively). The number of awakenings and the frequency of RBD increased with age (p=0.028 and p=0.006, respectively). Higher Hoehn & Yahr stages were associated with more PLMS (p=0.017). A higher daily dose of levodopa corresponded to more RBD (p<0.001). Neither disease duration nor levodopa dosage had any influence on sleep efficiency, slow wave sleep, awakenings, or PLMS. Dopamine agonists increased awakenings (p<0.001) and lowered PLMS (p<0.001). Subjective sleep perception was not influenced by any of the factors analyzed. The only path model that could be replicated identified disease severity and dopamine agonists as interdependent factors influencing awakenings and PLMS. Age leads to less sleep and a higher risk for RBD, and disease severity increases motor phenomena such as PLMS; dopamine agonists reduce PLMS but increase awakenings. No single factor analyzed influenced subjective sleep perception in this cohort of sleep disturbed PD patients.

A Systematic Review of Catechol-O-Methyltransferase Inhibitors

Catechol-O-methyltransferase (COMT) inhibitors are drugs commonly used in the management of patients with Parkinson disease complicated by motor fluctuations. Among them, entacapone is the most commonly used. Tolcapone has been reintroduced in patients where entacapone has proved to be ineffective after being withdrawn from the market because of sporadic cases of hepatotoxicity. The last COMT inhibitor is nebicapone, which use in clinical practice is still under study. The objectives of this study were to analyze the clinical efficacy in reducing motor complications and to evaluate their use in clinical practice and the adverse events reported in the literature. Scientific articles of the main previously mentioned drugs have been reviewed. All these 3 drugs have proved to be effective in improving wearing-off and significantly reduce the daily dose of levodopa at the number of daily intakes. Tolcapone is undoubtedly the most effective drug, although in clinical practice sporadic cases of hepatotoxicity have limited its use in patients unresponsive to entacapone. Nebicapone is effective, and its safety is still under evaluation. Entacapone is generally well tolerated, and no significant adverse events are reported. To manage motor fluctuations, the use of COMT inhibitors is now consolidated in the common clinical practice. Tolcapone is used as a second choice in patients with severe motor fluctuations not responsive to entacapone.

Effect of Bilateral Deep Brain Stimulation of the Subthalamic Nucleus on Freezing of Gait in Parkinson's Disease

A prospective cohort study to evaluate the efficacy of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on freezing of gait (FOG) in patients with advanced Parkinson's disease. Patients (n = 10) with advanced Parkinson's disease were surgically implanted with microelectrodes to facilitate STN-DBS. Evaluations of FOG, motor function, activities of daily living and neuropsychological function were carried out in on-medication and off-medication states (with and without levodopa treatment), before surgery and at 6 and 12 months postoperatively. STN-DBS was associated with significant improvement in FOG score and neuropsychological function at both 6 and 12 months postoperatively, compared with preoperatively. Significant postoperative improvements were also observed in motor function and activities of daily living. Daily levodopa dosage was significantly lower at both 6 and 12 months postoperatively. STN-DBS improved FOG in patients with advanced Parkinson's disease. The significant reduction in levodopa dosage and improvement in neuropsychological function may be the reason for the therapeutic effect seen with STN-DBS.

Experiencia con la infusión continua de levodopa intraduodenal (Duodopa ®) en pacientes con enfermedad de Parkinson avanzada en un hospital de segundo nivel asistencial

Introduction Continuous levodopa delivery by enteral infusion (Duodopa ®) is an alternative to deep brain stimulation and subcutaneous apomorphine to control motor fluctuations and dyskinesias in advanced Parkinson's disease (PD). We report our experience with Duodopa ® therapy in 11 patients with advanced PD. Methods We retrospectively assessed clinical and quality of life changes in all patients with PD with severe motor fluctuations and dyskinesias who started continuous daily levodopa duodenal infusion through percutaneous endoscopic gastrostomy from September 2006 (Duodopa ® was approved for advanced PD treatment in Spain at that date) until April 2010 at the A. Marcide Hospital of Spain. Results Nine patients received Duodopa ® [62.7 ± 10.6 (44-74) years, 63.6% male)]. Pre-Duodopa ® clinical characteristics of patients were: disease duration 14.5 ± 8.9 (3-34) years, oral levodopa dose 918.2 ± 277.7 (450-1300) mg/day, and Hoehn and Yahr staging 3.7 ± 0.5 (3-4). Nine patients are still receiving Duodopa ®. Patients improved motor fluctuations (72.7% significant improvement), dyskinesia (55.5% significant improvement), daily off-time (90.9%) and daily duration dyskinesia (66.6%) after total infusion time of 170.5 months (3-31). The improvement in Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39) and Schwab&England Capacity for Daily Living Scale were 38.5 ± 19.8 and 24 ± 12.5 respectively ( P < 0.05). Equivalent daily dose of levodopa (April 2010) was 1683.4 ± 295.8 (1234-2216) mg/day. Conclusions Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease.

Characteristics and influencing factors of non-motor symptoms in Parkinson's disease

To assess the characteristics and influencing factors of non-motor symptoms (NMS) in patients with Parkinson's disease (PD). A total of 111 patients with PD and 46 healthy controls (HC) matched with age, gender, education status and occupation were investigated by NMS questionnaire. They were all outpatients of Beijing hospital. The distribution of NMS items was analyzed between two groups. And their clinical characteristics were also collected to assess the dominant influencing factors for the prevalence of NMS. There was significant difference in the prevalence of NMS between two groups (P < 0.01). Each PD patient had an average of 12 NMS throughout the disease stages and the number of NMS was increasing with the degree of disease severity. UPDRS-III (united Parkinson's disease rating scale), daily dose of levodopa and age showed a positive correlation with NMS-T (NMS Total) and they accounted for 26.9% of the variance of NMS-T. Daily dose of levodopa, Hoehn-Yahr stage, UPDRS-III and NMS-T showed a positive correlation with UPDRS-II and they accounted for 70.3% variance of UPDRS-II. NMS are more commonly seen in PD patients than in controls. NMS is present throughout every stages of PD and its number increases with the degree of disease severity and age. The quality of life is impaired significantly by NMS in PD patients.

Large differences in levodopa dose requirement in Parkinson’s disease: men use higher doses than women

The characteristics of levodopa dosing are not well described in the literature. The aims were to investigate the use of levodopa in a nationwide Swedish survey and to study the characteristics of low-dose and high-dose patients with Parkinson's disease (PD) in a university hospital. Patients with >or= 1 and >or= 2 purchases of levodopa during 2007 were selected from the prescribed drug register. Daily levodopa doses were estimated. Records of 504 patients with PD who visited the neurology clinic at Uppsala University Hospital during 2006-2007 were examined to select a low-dose group (< or = 400 mg levodopa daily, n = 21) and a high-dose group (>or= 1200 mg daily, n = 26) with at least 5 years of PD duration. In total, 33 534 levodopa users with > or = 1 levodopa purchase were found. Daily levodopa dose range was large; median daily dose was 465 mg for men and 395 mg for women (P < 0.0001). Almost half (46%) of the patients used < 400 mg levodopa daily. Significantly, more men were treated with doses >or= 1200 mg daily. Dose and age correlated negatively (P < 0.0001). Patients with high dose at 5 years PD duration continuously increased their dosage the following years, whereas low-dose patients did not. The occurrence of dyskinesias was about the same in both groups despite the large difference in levodopa dose. We conclude that the levodopa requirement in PD ranges considerably, and that men use higher levodopa dose than women. Levodopa requirement is constant during the progression of the disease in low-dose patients but increases in high-dose patients.

Circadian Rhythmicity in Levodopa Pharmacokinetics in Patients With Parkinson Disease

The purpose of this study was to compare daytime and nighttime plasma pharmacokinetics (PK) of levodopa in patients with Parkinson disease. Four-hour plasma profiles of levodopa were captured in 8 patients with Parkinson disease after the second daily levodopa dose and after the identical dose at bedtime. Patients were fasting 2 hours before and 2 hours after dose intakes, except standardized amounts of tap water. Body position was upright during daytime testing and supine during nighttime testing. Four patients were additionally tested at daytime in supine position. The absorption rate was significantly delayed at nighttime dosing. The time at which the maximum peaks occurred was delayed from 25 (15-240) to 105 (20-240) minutes, respectively. Maximum concentrations were significantly lower at night, but the plasma exposure (area under the curve, 0-4 hours) was unaffected. Supine daytime plasma PK was in between day and night results. There is a slower absorption rate of levodopa during nighttime, probably related to delayed gastric emptying. However, the extent of absorption and bioavailability were unaffected. As the effect of posture on plasma PK was less than the effect of nighttime, this study suggests that the circadian rhythm has a pronounced effect on gastric emptying and absorption rate. Nevertheless, body position may also be an important factor, and it can be recommended that levodopa tablets be taken in upright position that probably should be sustained for at least 30 minutes.

Experience with continuous levodopa enteral infusion (Duodopa ®)in patients with advanced Parkinson's disease in a secondary level hospital

Introduction Continuous levodopa delivery by enteral infusion (Duodopa ®) is an alternative to deep brain stimulation and subcutaneous apomorphine to control motor fluctuations and dyskinesias in advanced Parkinson's disease (PD). We report our experience with Duodopa ® therapy in 11 patients with advanced PD. Methods We retrospectively assessed clinical and quality of life changes in all patients with PD with severe motor fluctuations and dyskinesias who started continuous daily levodopa duodenal infusion through percutaneous endoscopic gastrostomy from September 2006 (Duodopa ® was approved for advanced PD treatment in Spain at that date) until April 2010 at the A. Marcide Hospital of Spain. Results Nine patients received Duodopa ® [62.7±10.6 (44–74) years, 63.6% male)]. Pre- Duodopa ® clinical characteristics of patients were: disease duration 14.5±8.9 (3–34) years, oral levodopa dose 918.2±277.7 (450–1300) mg/day, and Hoehn and Yahr staging 3.7±0.5 (3–4). Nine patients are still receiving Duodopa ®. Patients improved motor fluctuations (72.7% significant improvement), dyskinesia (55.5% significant improvement), daily off-time (90.9%) and daily duration dyskinesia (66.6%) after total infusion time of 170.5 months (3–31). The improvement in Parkinson's Disease Quality of Life Questionnaire-39 (PDQ-39) and Schwab&England Capacity for Daily Living Scale were 38.5±19.8 and 24±12.5 respectively (P<0.05). Equivalent daily dose of levodopa (April 2010) was 1683.4±295.8 (1234–2216) mg/day. Conclusions Intraduodenal infusion of levodopa offers an important alternative in treating patients with advanced Parkinson disease

Bilateral subthalamic nucleus stimulation in the treatment of advanced Parkinson's disease. Five years' personal experience

Background and purposeThe objective of the study was to assess bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) for patients with advanced Parkinson disease (PD). Material and methodsThe study population included 5 patients with bilateral STN DBS who completed a 5-year postoperative follow-up period. In all patients electrodes (Model 3387 or 3389) were stereotactically bilaterally inserted into the STN using a Leksell stereotactic G frame. The clinical rating tests included Unified Parkinson's Disease Rating Scale (UPDRS) and two motor-timed tests derived from CAPIT (rapid movements between two points and stand-walk-sit test). All patients were assessed in off and on condition before implantation and 1, 3 and 5 years in medication on and off condition and stimulation on condition and stimulation off condition. To compare preoperative to postoperative UPDRS scores, only mean values and standard deviations are presented because of the small study population. ResultsThe stimulation effect was noted in the off state, resulting in a 59% improvement in motor scores of UPDRS at 5-year follow-up, when compared to preoperative scores. In the on state the stimulation improved motor scores by 17%. At 5-year follow-up, reduction of daily levodopa dose was 50%. ConclusionsBilateral STN DBS is an effective and safe treatment for patients with advanced PD. Bilateral STN DBS contributes to improvement of parkinsonian symptoms in the off state and levodopa-induced dyskinesia. This can be correlated with a 50% reduction of daily levodopa dose 5 years postoperatively.

Dopaminergic treatment is associated with decreased body weight in patients with Parkinson’s disease and dyskinesias

Several studies suggested that patients with advanced Parkinson's disease (PD) showed a too low body weight when compared with age-matched, healthy subjects. We aimed to investigate whether PD patients with dyskinesias display body weight alterations and to observe any correlations between medication and other putative determinants. Charts of 166 PD patients with fluctuations and dyskinesias, admitted within 6 months to a German movement disorders clinic, were investigated for body mass index (BMI), age at onset, disease duration, Unified Parkinson's Disease Rating Scale motor score, eating coordination and medication. Analysis showed that 4.2% of PD patients were underweight (BMI < 18.5 kg/m(2)), 46.4% were normal (BMI > 18.5-25 kg/m(2)), 33.7% were overweight (BMI > 25-30 kg/m(2)), 15.7% were obese (BMI > 30 kg/m(2)). Daily levodopa dosage per kg and total dopaminergic dosage per kg body weight were negatively correlated with BMI. Overall, patients' BMI had not significantly changed within 2 years of follow-up. In sum, advanced PD patients showed a reduced BMI when compared with a control population obtained from an age-matched group taken from a survey of the German Federal Office for Statistics. Our findings indicate that patients with a lower BMI received a higher cumulative levodopa dosage and that levodopa may be responsible for weight loss in PD.

Health related quality of life in early Parkinson's disease: Impact of motor and non-motor symptoms, results from Chinese levodopa exposed cohort

Objective To identify the motor and non-motor factors that are associated with health related quality of life (HR-QOL) in a subgroup of Parkinson's disease (PD) patients with Levodopa therapy in early clinical stages. Methods 391 Levodopa exposed patients were evaluated during the baseline assessment of a clinical trial in China. HR-QOL was measured by the Short Form 36 (SF-36). Motor and non-motor variables were determined during a structured interview and by clinical examination by movement disorder specialists. Multiple regression analyses were used to determine which variables were associated with low levels of HR-QOL. Results Even if excluding non-motor variables from the regression model, motor factors, particularly motor deficits (measured by motor score of UPDRS), rigidity (measured by item 22 of UPDRS), and disease severity (measured by Hoehn&Yahr scale), explained only 18.9% of the variance of total SF-36 score. Whereas, when non-motor variables were included in the model, especially depression (measured by CES-D), sleep disturbances (measured by PSQ-I), and fatigue (measured by FSS), 61.7% of the variance of SF-36 score could be explained. Two motor variables, UPDRS motor score and Hoehn&Yahr score, were also contributed to the model, however, the 95% confidence intervals (CIs) of these two motor factors were wide and included the null value (CIs −0.282, 0.019 for UPDRS motor score, and CIs −4.043, 0.856 for Hoehn&Yahr score). Neither, did higher daily levodopa dose contribute significantly to both models predicting SF-36 score. Conclusions In our sample patients with levodopa therapy, motor disability and severity of parkinsonism contributed to a lesser extent to patients’ self-report distress, within the first 5 years of disease onset. The clinical factors that showed the highest predictive value for worsen HR-QOL were non-motor symptoms, such as depression, sleep disorders, and fatigue. Great effort should be made to recognize and treat those conditions, thus improving all aspects of PD and giving these patients as a good HR-QOL as possible.

Noradrenergic modulation of the motor response induced by long-term levodopa administration in Parkinsonian rats

A decrease in noradrenergic activity in Parkinson's disease might play a critical role in long-term motor complications associated with chronic dopaminergic replacement. Using the rat model of parkinsonism with an additional noradrenergic degeneration induced by the N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) toxin we evaluated whether the circling motor activity and dose-failure episodes induced by levodopa (L-DOPA) differ between single (6-OHDA) and double (6-OHDA + DSP-4) denervated animals challenged with a single daily dose of L-DOPA. While single-lesioned animals showed a sensitization-desensitization turning response with a significant increase on day 15 and a decrease on day 22, in double-lesioned animals, the turning activity was maximal from day 1 and did not decay on day 22. Double-lesioned rats exhibited significantly higher number of turns on days 15 and 22 and a significantly lower percentage of dose-failure episodes during treatment. Noradrenergic denervation appears to be associated with prolonged long-term dopaminergic sensitization. This type of response appears to be comparable to that in the clinical setting with intermittent L-DOPA administration where no desensitization occurs once the abnormal response is established.

Levodopa use and sleep in patients with dementia with Lewy bodies

Sleep disturbance and excessive daytime somnolence (EDS) are features of Parkinson's disease (PD) and dementia with Lewy bodies (DLB) that may be influenced by dopamine replacement therapy. The effect of levodopa on sleep and EDS in DLB is unknown and unclear in PD. The aim of this study is to determine if levodopa treatment alters sleep symptoms and EDS in DLB. Dopamine naïve patients with DLB (n = 15; mean mini mental state examination (MMSE) score 17.7(4.6)) and PD (n = 9; mean MMSE 25.5(2.2)) were assessed using the Epworth sleep scale, Parkinson's disease sleep scale, and the neuropsychiatric inventory prior to initiating treatment with levodopa. All measures were repeated after 3 and 6 months of levodopa therapy. The median final daily levodopa dose was 300 mg in both groups. Baseline sleep measures were comparable between groups. Levodopa treatment did not affect sleep or lead to increased EDS in DLB patients. The use of levodopa does not appear to adversely affect subjective sleep measures or increase EDS in DLB patients.

Effect of a slow release preparation of levodopa on Parkinson's disease in combination with a peripheral decarboxylase inhibitor

Plasma concentrations of levodopa were determined after therapeutic oral levodopa-carbidopa doses. The wide fluctuations observed in plasma levodopa levels could be considerably reduced by the addition of a slow release levodopa preparation. This kind of combination medication was given to 15 parkinsonian patients, whose earlier therapy had proved inadequate. With the combination medication, levodopa-carbidopa, on an average 420 mg/42 mg combined with 950 mg of levodopa in slow release form, a statistically significant improvement in parkinsonian signs could be achieved without any worsening of the side effects. The results suggest that parkinsonian patients may tolerate much higher daily levodopa doses if the fluctuations in plasma levels of the drug can be diminished.

Intérêts de la stimulation dopaminergique continue par Duodopa ® dans la maladie de Parkinson évoluée : efficacité et tolérance

Introduction When advanced Parkinson's disease (PD) patients experience motor complications (fluctuations and dyskinesias) despite standard oral treatment, two treatment options are available: deep brain stimulation and subcutaneous apomorphine infusion with respects of indications for each strategy. Continuous intraduodenal infusion of levodopa (Duodopa ®) via a gastrojejunal tube may be proposed at this stage of the disease and the study of indications and clinical results with Duodopa ® may develop this new therapeutic alternative. Patients and methods Seven patients with advanced PD (dementia for all and psychiatric disorders for some of them, axial signs) were treated with Duodopa ®. We evaluated neuropsychological functions, all UPDRS scales, gait and quality-of-life just before Duodopa ® onset and six months after treatment end. Moreover, we described all adverse events (early and late) and studied daily levodopa doses before and 6 months after treatment. Results We demonstrated an improvement in motor UPDRS (44%), in axial signs (40% for UPDRS part III axial subscore and 12% for gait) and a reduction of fluctuations (37.5%) and in UPDRS part IV dyskinesia (20%). These significant results are observed without any change in the quality-of-life. Adverse events were due to PEG positioning for four patients, the equipment (pump, connection, inner tube) for all patients and levodopa for four patients. Daily levodopa dose had to be increased 13.5%. Conclusion Duodopa ® can be considered as a new treatment strategy providing significant improvements in motor fluctuations, dyskinesia and severe axial signs. These results were demonstrated in very advanced PD patients, who had been excluded from previous studies, with cognitive disorders and for some of them dopaminergic psychosis well controlled by medications.

Is There a Difference between Levodopa/ Dopa-Decarboxylase Inhibitor and Entacapone and Levodopa/Dopa-Decarboxylase Inhibitor Dose Fractionation Strategies in Parkinson’s Disease Patients Experiencing Symptom Re-Emergence due to Wearing-Off?

Two strategies to manage symptom re-emergence due to wearing-off with conventional levodopa/dopa-decarboxylase inhibitor (DDCI) therapy were compared in patients with Parkinson’s disease (PD) in this randomized, open-label trial. PD patients receiving 3 daily doses of levodopa/DDCI were randomized to either levodopa/DDCI and entacapone or an increased dose frequency of levodopa/DDCI with or without an increased total daily dose (dose fractionation). After 1 month of treatment, patients were followed up for 1 year. A greater proportion of levodopa/DDCI and entacapone-treated patients had treatment success compared with dose-fractionated patients, according to investigator Clinical Global Impression of Change scores at 1 month (68 vs. 59%, respectively) and 1 year (60 vs. 51%, respectively). Mean ‘off’ time (time with symptoms) was improved in both groups at 1 month and 1 year, despite a reduction in the mean daily levodopa dose in the levodopa/DDCI and entacapone group at 1 month. The mean daily levodopa dose was increased in the dose fractionation group. At 1 month, there was a 4% reduction in patients experiencing dyskinesia with levodopa/DDCI and entacapone and a 3% increase with dose fractionation. These data suggest that levodopa/DDCI and entacapone reduces time with symptoms, the rate of motor complications and the daily levodopa dose compared with dose fractionation. However, as the observed differences were not statistically significant, further studies are required to confirm these results.

Naturalistic evaluation of entacapone in patients with signs and symptoms of L-dopa wearing-off

ABSTRACTObjective: To evaluate the effectiveness of entacapone in the management of levodopa wearing-off in Parkinson's disease (PD) in a naturalistic, real-life setting.Research design and methods: This prospective, open-label, observational study included patients with idiopathic PD. Patients were eligible for inclusion if they had been taking 3–5 doses of levodopa per day for ≥2 months and had shown signs of levodopa wearing-off for ≥1 month. Subjects received entacapone (recommended dose: 1 × 200 mg tablet with each levodopa dose) for 28 days. Patients were asked to complete a wearing-off questionnaire and the eight-question Parkinson's Disease Questionnaire Quality of Life assessment (PDQ-8). Activities of daily living (both in the on and off states) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) part II. Clinical Global Impression (CGI) of severity of PD-related symptoms was assessed using a modified CGI tool.Patient global assessment of severity of PD symptoms was also obtained.Results: A total of 341 patients were enrolled by 68 physicians across Canada. At Day 28, 56.9% of the subjects indicated improvement compared to baseline on the modified CGI of change (CGI-C); 21.4% reported no change. Improvements were also observed on the UPDRS II and the PDQ-8. Benefit from entacapone appeared to be relatively uniform across subgroups (e.g., number of daily levodopa doses, use of other anti-PD medications).Study limitations: The results of this study may be biased due to factors inherent in open-label, community-based trials (e.g., compliance). This is, however, reflective of everyday clinical practice.Conclusions: In this naturalistic, real-life study, the addition of entacapone to levodopa therapy provided benefits in quality of life and activities of daily living for a substantial proportion of PD patients experiencing wearing-off.