No abstract

Background: Pain, a frequent non-motor symptom in Parkinson’s Disease (PD), significantly impacts on quality of life. Safinamide is a new drug with dopaminergic and non-dopaminergic properties, approved in Europe as adjunct therapy to levodopa for the treatment of fluctuating PD patients. Results from two 24-month, double-blind, placebo-controlled studies demonstrated that safinamide has positive effects on both motor functions and quality of life in PD patients.Objective: To investigate the effects of safinamide on pain management in PD patients with motor fluctuations using pooled data from studies 016 and SETTLE.Methods: This post-hoc analysis evaluated the reduction of concomitant pain treatments and the changes in the scores of the items related to pain of the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39). A path analysis was performed in order to examine direct and indirect associations between safinamide and PDQ-39 pain-related items assessed after 6-months of treatment.Results: The percentage of patients with no pain treatments at the end of the trials was significantly lower in the safinamide group compared to the placebo group. Safinamide 100 mg/day significantly reduced on average the individual use of pain treatments by ≈24% and significantly improved two out of three PDQ-39 pain-related items of the “Bodily discomfort” domain.Path analysis showed that the direct effect of safinamide on pain accounted for about 80% of the total effect.Conclusions: These results suggest that safinamide may have a positive effect on pain, one of the most underestimated non-motor symptoms. Prospective studies are warranted to investigate this potential benefit.

A median safinamide (SAF) dose of 70 mg/day (range 40 to 90 mg/day) increased the percentage of parkinsonian patients improving their motor scores by > or =30% from baseline (responders) after 3 months from 21.4% (placebo) to 37.5% (p < 0.05, calculated by logistic regression analysis). In a subgroup of 101 patients under stable treatment with a single dopamine agonist, addition of SAF magnified the response (47.1% responders, mean 4.7-point motor score decrease; p > or = 0.05). These results suggest that doses of SAF exerting ion channel block and glutamate release inhibition add to its symptomatic effect and warrant exploration of higher doses.

This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Background: Safinamide is a novel α-aminoamide with dopaminergic and non-dopaminergic properties developed as adjunctive therapy for patients with PD. Results from a 24-month double-blind controlled study suggested that as add-on to levodopa (and other PD medications) the benefits of safinamide on dyskinesia may be related to severity of dyskinesia at baseline. Objective: This post-hoc analysis further characterized the effects of safinamide on dyskinesia in mid- to late-stage PD patients. Methods: Patients were stratified by the presence or absence of dyskinesia at baseline, and by whether or not the dose of levodopa had been changed during the 24-month treatment period. Differences between safinamide and placebo were evaluated using the Wilcoxon rank-sum test. Results: For the overall treated population (with or without baseline dyskinesia), safinamide 100 mg/day significantly improved the dyskinesia rating scale score, compared with placebo, in the subgroup of patients with no change in levodopa dose (p = 0.0488). For patients with baseline dyskinesia, improvements over placebo were also significant (p = 0.0153) in patients with or without changes in levodopa dose, and nearly significant (p = 0.0546) in patients with no change in levodopa dose, suggesting that these improvements were not due to levodopa dose reductions. Conclusions: While no statistically significant difference in mean DRS scores was seen between safinamide and placebo in the original study population, the present post-hoc analysis helps to provide a meaningful interpretation of the long-term effects of safinamide on dyskinesia. These results may be related to safinamide state- and use-dependent inhibition of sodium channels and stimulated glutamate release, and are unlikely due to reduced dopaminergic stimulation.