Despite the prominent loss of motor skills, artistic capacities remain preserved in Parkinson’s disease (PD). Furthermore, artistic creativity may emerge in art-naïve PD patients treated with levodopa and dopamine agonists. The present review discusses reported PD patients who developed enhanced artistic skills under anti-Parkinsonian therapy and the course of this phenomenon in the clinical context. It is unclear whether creative drive is related to dopamine dysregulation, and the mechanisms remain speculative. The delineation of the particular constellation that enables this emergence in PD patients may shed light on the comprehension of the concept of creativity in general. (PsycINFO Database Record © 2013 APA, all rights reserved).
Motor complications in Parkinson’s disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine.
Inhaled drugs offer advantages, such as rapid onset of action, but require formulations and delivery systems that reproducibly and conveniently administer the drug. CVT-301 is a powder formulation of levodopa delivered by a breath-actuated inhaler that has been developed for treating OFF episodes (motor fluctuations between doses of standard oral levodopa) in patients with Parkinson’s disease (PD). We present preclinical, phase 1, and phase 2 results for CVT-301. In dogs insufflated with a levodopa powder, plasma levodopa peaked in all animals 2.5 min after administration; in contrast, in dogs dosed orally with levodopa plus carbidopa, plasma levodopa was not detected until 30 min after administration. In 18 healthy persons, comparisons between inhaled CVT-301 and oral carbidopa/levodopa showed analogous differences in pharmacokinetics. Among 24 PD patients inhaling CVT-301 as a single 50-mg dose during an OFF episode, 77% showed an increase in plasma levodopa (>400 ng/ml) within 10 min versus 27% for oral dosing with carbidopa/levodopa at a 25-mg/100-mg dose. Improvements in timed finger tapping and overall motor function (Part III of the Unified Parkinson’s Disease Rating Scale) were seen 5 and 15 min after administration, the earliest assessment time points. For average and best change, the improvements were statistically significant compared to placebo. The most common adverse event was cough; all cough events were mild to moderate, occurred at the time of inhalation, resolved rapidly, and became less frequent after initial dosing. These results support further development of CVT-301 for better management of PD.
Whether initial treatment for Parkinson’s disease should consist of levodopa, dopamine agonists, or monoamine oxidase type B inhibitors (MAOBI) is uncertain. We aimed to establish which of these three classes of drug, as initial treatment, provides the most effective long-term control of symptoms and best quality of life for people with early Parkinson’s disease.
Our previous randomized double-blind study showed that drinking hydrogen (H2) water for 48 weeks significantly improved the total Unified Parkinson’s Disease Rating Scale (UPDRS) score of Parkinson’s disease (PD) patients treated with levodopa. We aim to confirm this result using a randomized double-blind placebo-controlled multi-center trial.
Intermittent oral delivery of levodopa is a major contributing factor for motor complications in Parkinson’s disease (PD). Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) into the jejunum using a portable pump via percutaneous endoscopic gastrostomy (PEG) improves motor complications and quality of life (QoL).
Adequate treatment of Parkinson’s patients in off periods with orally administered levodopa is hindered by a poor bioavailability and a slow onset of action. Hence, there is a need for a fast and reliable alternative as for instance via pulmonary administration of the drug. We developed a levodopa containing powder formulation for pulmonary delivery by a recently presented high dose dry powder inhaler (Cyclops). The objective was to produce the drug formulation by means of simple techniques such as micronisation, either as pure active substance or with a minimum amount of excipients. After an initial screening on dispersion behaviour, the most promising formulation in the Cyclops was characterised in vitro over a range of pressure drops (2 - 6 kPa) and doses (20, 30 and 40 mg), representative of those to be expected in practice. A co-micronised levodopa formulation with 2% l-leucine appeared to yield the best aerosol properties for inhalation and highest delivered dose reproducibility. The combination of this particular formulation and the Cyclops inhaler seems to meet the basic requirements for satisfactory deposition in the airways. This formulation is therefore expected to be a promising candidate for the treatment of Parkinson’s patients in an off period.
Dopamine replacement therapy by its precursor, L-3.4-Dihydroxyphenylalanine (L-DOPA), has been the treatment of choice for Parkinson’s disease. However, the possible contributory effect of L-DOPA therapy on the progression of Parkinson’s disease mediated by the L-DOPA-induced toxic metabolites remains elusive.
Levodopa is the most effective therapy for Parkinson’s disease, but chronic treatment is associated with the development of potentially disabling motor complications. Experimental studies suggest that motor complications are due to non-physiological, intermittent administration of the drug, and can be reduced with continuous delivery. We aimed to assess efficacy and safety of levodopa-carbidopa intestinal gel delivered continuously through an intrajejunal percutaneous tube.
IPX066 is an oral, extended-release, capsule formulation of carbidopa-levodopa. We aimed to assess this extended-release formulation versus immediate-release carbidopa-levodopa in patients with Parkinson’s disease and motor fluctuations.