Background Levodopa is the most effective therapy for Parkinson's disease (PD), but chronic treatment is associated with the development of potentially disabling motor complications. Experimental studies suggest that motor complications are due to non-physiologic, intermittent administration of the drug, and can be reduced with continuous delivery. Levodopa-carbidopa intestinal gel (LCIG) is a form of levodopa that can be delivered continuously through an intrajejunal percutaneous tube. Methods We performed a 12-week double-blind, double-dummy, double-titration, multi-center trial to evaluate the efficacy and safety of LCIG compared to optimized, oral, immediate-release levodopa-carbidopa (LC-IR) in advanced PD patients with motor complications. The primary endpoint was change from baseline to final visit in motor “Off” time. Motor “On” time without troublesome dyskinesia was the key secondary endpoint. Findings 71 patients with advanced PD were randomized to receive continuous LCIG infusion plus placebo LC-IR capsules (n=37) or to receive LC-IR capsules plus continuous placebo LCIG infusion (n=34). Both groups were titrated to optimal effect. 93% of subjects (n=66) completed the trial. In comparison to LC-IR, LCIG significantly reduced “Off” time by a mean (±SE) of 1·91±0·57 hours (P=0·0015) and increased “On” time without troublesome dyskinesia by a mean of 1·86±0·65 hours (P=0·006). Adverse events were primarily related to the surgical procedure and the device, and while potentially serious, were not associated with residual deficit or mortality. Interpretation In comparison to standard oral LC-IR, LCIG significantly reduced “Off” time and increased “On” time without troublesome dyskinesia in patients with advanced PD. Adverse events were largely due to the procedure and the device. Benefits are of greater magnitude than have been obtained with medical therapies to date, and represent the first demonstration of the benefit of continuous levodopa delivery in a double-blind controlled study.

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clinicaltrials.gov Identifier: NCT00497146.

In this clinical trial, duloxetine 60 mg QD and duloxetine 60 mg BID were effective and safe in the management of DPNP.

This was a 12-week, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of duloxetine, a selective serotonin and norepinephrine reuptake inhibitor, in 354 female patients with primary fibromyalgia, with or without current major depressive disorder. Patients (90% Caucasian; mean age, 49.6 years; 26% with current major depressive disorder) received duloxetine 60 mg once daily (QD) (N=118), duloxetine 60 mg twice daily (BID) (N=116), or placebo (N=120). The primary outcome was the Brief Pain Inventory average pain severity score. Response to treatment was defined as >or=30% reduction in this score. Compared with placebo, both duloxetine-treated groups improved significantly more (P<0.001) on the Brief Pain Inventory average pain severity score. A significantly higher percentage of duloxetine-treated patients had a decrease of >or=30% in this score (duloxetine 60 mg QD (55%; P<0.001); duloxetine 60 mg BID (54%; P=0.002); placebo (33%)). The treatment effect of duloxetine on pain reduction was independent of the effect on mood and the presence of major depressive disorder. Compared with patients on placebo, patients treated with duloxetine 60 mg QD or duloxetine 60 mg BID had significantly greater improvement in remaining Brief Pain Inventory pain severity and interference scores, Fibromyalgia Impact Questionnaire, Clinical Global Impression of Severity, Patient Global Impression of Improvement, and several quality-of-life measures. Both doses of duloxetine were safely administered and well tolerated. In conclusion, both duloxetine 60 mg QD and duloxetine 60 mg BID were effective and safe in the treatment of fibromyalgia in female patients with or without major depressive disorder.