Safinamide improves executive functions in fluctuating Parkinson's disease patients: an exploratory study.

Safinamide is a monoamine-oxidase-B inhibitor with peculiar features. At the dose of 100 mg/day, safinamide stimulates dopaminergic transmission and reduces glutamatergic transmission. Here, we investigated the effects of safinamide 100 mg on executive functions at the end of levodopa dose in fluctuating Parkinson's disease (PD) patients. Thirty-two fluctuating PD patients were submitted at baseline (V1) to the UPDRS-III, the Frontal Assessment Battery (FAB) and the Stroop-Word-Color-Test (SWCT) at the end of levodopa dose. Safinamide was then added to the original therapy. After 12 weeks of treatment, patients underwent the final visit (V2), including the UPDRS-III, the FAB and the SWCT with the same daily time schedule as V1. Treatment with safinamide was associated with significant increases of the total FAB score, SWCT-interference time score and UPDRS-III score. Within FAB subdomains, add-on with safinamide significantly increased motor programming and increased mental flexibility and inhibitory control scores. The results of this exploratory study show that add-on with safinamide improves executive functions at the end of levodopa dose in fluctuating PD patients. In particular, attention and inhibition of cognitive interference were significantly ameliorated by add-on with safinamide, suggesting increased modulatory performances of prefrontal cortical pathways. If confirmed by future research on larger cohorts and under controlled conditions, the present results may represent the basis for a novel indication for the use of safinamide in fluctuating PD patients.

Drug Choices and Advancements for Managing Depression in Parkinson's Disease.

Depression is a frequent non-motor symptom of Parkinson's disease (PD), and may even precede the onset of motor symptoms of parkinsonism. Beyond its negative influence on mood, depression in PD is frequently associated with other neuropsychiatric symptoms and with late-stage complications such as dementia. Despite its profound impact on the quality of life and cognitive functioning in PD, depression in PD is often under-recognized and poorly treated. Pathophysiological studies demonstrated that depression in PD is associated with global dysfunction of interactions between discrete brain areas rather than focal structural or functional abnormalities, and that it is sustained by pathological changes of several neurotransmitter/receptor complexes. In general, all traditional antidepressants and some dopamine agonists have been found to be safe and well-tolerated to treat depressive symptoms in PD, despite initial warning on worsening of parkinsonism. Available data suggest that the time-course of response differs among antidepressants. Efficacy results from clinical trials with antidepressant in PD are, however, rather uncertain, although pooled analysis suggests a moderate benefit. Several issues may critically impact the results of clinical trials with antidepressants in PD, including the correct psychiatric diagnosis, the overlap of symptoms between depression and PD, and the selection of appropriate end-points and rating scales.

Alexithymia and anhedonia in early Richardson's syndrome and progressive supranuclear palsy with predominant parkinsonism.

INTRODUCTION: Phenotypic variants of progressive supranuclear palsy (PSP) are all characterized by the combination of motor symptoms of parkinsonism with a number of neuropsychiatric and cognitive disorders. Despite the strong effort in characterizing these features in PSP, alexithymia and anhedonia have not been investigated at present. Here, we aimed at investigating the qualitative and quantitative differences of alexithymia and anhedonia in the two more frequent variants of PSP, Richardson's syndrome (PSP-RS) and PSP with predominant parkinsonism (PSP-P) compared to Parkinson's disease (PD) patients recruited within 24 months after the onset of motor symptoms. METHODS: One hundred fifty-five PD, 11 PSP-P, and 14 PSP-RS patients underwent clinical, neuropsychiatric, and neuropsychological evaluations. Alexithymia was assessed using the Toronto Alexithymia Scale-20 item (TAS-20), and hedonic tone was measured by the Snaith-Hamilton Pleasure Scale (SHAPS). RESULTS: In PSP-P and PSP-RS patients, the frequency of alexithymia diagnosis was higher than in PD. On the TAS-20 scores, PSP-RS performed worse in the total score and in F2 sub-scale when compared to PD. Among patients with diagnosis of depression, PSP-RS showed higher scores in TAS-20 total and TAS-20 F2 than PD. No significant differences in TAS-20 scores were found in nondepressed patients. Finally, we did not find significant differences among PD, PSP-P, and PSP-RS groups in the SHAPS scores. CONCLUSIONS: Alexithymia is identifiable very early in PSP-P and PSP-RS patients. Alexithymic symptoms differentiate PSP-RS group from PD group but not between the two subtypes of PSP. Further, alexithymia in PSP seems to be predicted by the presence of depression. Altered emotional capability could be related to specific neurophysiological dysfunction occurring precociously in PSP; therefore, its identification could orient the diagnosis toward PSP cases.

Psychiatric profile of motor subtypes of de novo drug-naïve Parkinson's disease patients.

BACKGROUND: Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder. It is well established that different motor subtypes of PD evolve with different clinical courses and prognoses. The complete psychiatric profile underlying these different phenotypes since the very early stage of the disease is debated. AIMS OF THE STUDY: We aimed at investigating the psychiatric profile of the three motor subtypes of PD (akinetic-rigid, tremor-dominant, and mixed) in de novo drug-naïve patients with PD. METHODS: Sixty-eight patients with PD, divided into 39 akinetic-rigid (AR), seven mixed (MIX), and 22 tremor-dominant (TD) patients underwent a complete assessment of psychiatric, cognitive, and motor symptoms. RESULTS: No significant differences were found among groups. CONCLUSIONS: Our results suggest that a differentiation of the psychiatric symptoms associated with specific motor subtypes of PD is not detectable in de novo drug-naïve patients. Previous evidence that emerges later along the disease progression may be a consequence of the dopaminergic and nondopaminergic damage increase.