Thought disorders among non-demented outpatients with Parkinson's disease: prevalence and associated factors.

The objectives of the study are to evaluate the prevalence and the associated factors of thought disorders in a large cross-sectional population of non-demented out patients with Parkinson's disease (PD). Four-hundred and nineteen consecutive non-demented PD patients were studied through the DoPaMiP cross-sectional study. Demographic and clinical variables were recorded, including motor and cognitive status, dependency, depressive and anxious symptoms, dysautonomia and sleep disorders. The presence of thought disorders over the past 15 days was assessed by the Unified Parkinson's Disease Rating Scale part I. Patients with and without thought disorders were compared using parametric tests. Logistic regression was applied to significant data. Thought disorders were present in 105 patients (25%) including vivid dreams in 83 (19.8%), benign hallucinations in 17 (4.1%), and hallucinations without insight in 5 (1.2%). No patient had delusion. Patients with thought disorders were more dependent than the others. Thought disorders were associated with longer PD duration, greater UPDRS scores and the presence of motor complications. Conversely, UPDRS tremor sub-score was lower in patients without thought disorders. Thought disorders were also associated with dysautonomia, lower MMSE score, depression and sleep disorders. Logistic regression identified PD duration, lower MMSE score, depressive and dysautonomic signs as independent risk factors. In conclusion, mild thought disorders were present in 25% of non-demented outpatients with PD, but hallucinations were present in 5% only. Thought disorders were associated with PD duration, depressive and dysautonomic symptoms and lower MMSE score.

Tesofensine (NS 2330), a monoamine reuptake inhibitor, in patients with advanced Parkinson disease and motor fluctuations: the ADVANS Study.

OBJECTIVE: To assess the safety and efficacy of tesofensine, a triple monoamine reuptake inhibitor, in patients with advanced Parkinson disease (PD). DESIGN: A pilot phase 2, randomized, double-blind, placebo-controlled, parallel-group trial. The study occurred in hospital-based outpatient clinics and in clinical trial units. Patients with advanced PD and levodopa-related motor fluctuations were enrolled. Tesofensine (0.125, 0.25, 0.5, or 1 mg) or placebo tablets were administered once daily for 14 weeks. MAIN OUTCOME MEASURES: Coprimary end points were the changes from baseline in Unified Parkinson Disease Rating Scale (UPDRS) subscale II (activities of daily living) plus subscale III (motor function) total score and in percentage of waking hours spent in "off" time noted in self-scoring diaries. Secondary end points were safety, pharmacokinetics, responder analysis (> or =20% reduction in UPDRS score and in off time), and changes in percentage of waking hours spent in "on" time with and without troublesome dyskinesia. RESULTS: The adjusted mean differences (relative to placebo) were -4.7 points in UPDRS subscale II plus subscale III total score (P =.005) with tesofensine, 0.5 mg, and -7.1% in off time (-68 minutes, P =.02) with tesofensine, 0.25 mg. Other dosages did not induce statistically significant effects. The plasma concentration increased with the dosage, but no clear dose-response relationship was observed. Gastrointestinal tract and neuropsychiatric adverse events were more frequent with tesofensine than with placebo, especially at the higher dosages. CONCLUSIONS: Patients with PD in advanced stages showed modest improvements in UPDRS subscale II plus subscale III total score and in off time when treated with tesofensine, but a dose-response relationship could not be established for efficacy, while adverse drug reactions tended to be more frequent at higher dosages. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00148512.