In neurodegenerative cerebellar ataxias, not only ataxia but also extra-cerebellar signs have a significant impact on patients’ health related to quality of life (HRQoL). The aim of this study was to evaluate the various aspects of HRQoL and predictors of QoL in patients with neurodegenerative cerebellar ataxias. We included a total of 107 patients with cerebellar degenerative ataxia. Patients filled out the validated Serbian version of the SF-36 used for the assessment of HRQoL. All patients were clinically evaluated using SARA, INAS, and neuropsychological tests to assess their global cognitive status and different psychiatric scales. The most frequent types of neurodegenerative cerebellar ataxias were autosomal dominant ataxias (38.3%) and sporadic ataxias (32.7%). Mean age at diagnosis was 35.3 ± 16.23 years, and disease duration was on average 12.1 ± 9.91 years. Mean total SF-36 score was 50.63 ± 20.50. Hierarchical regression analysis showed that in the case of the PHC score, the most significant predictors are the patient’s actual age, severity of ataxia, and ACE total score. For MHC, the Hamilton depression score was the most important predictor. Our study has shown that HRQoL measured by SF-36 in patients with neurodegenerative cerebellar disorders is strongly influenced by impaired mobility and depression.

Sage, in collaboration with Biogen, submitted a new drug approval for zuranolone for postpartum depression (PPD) and major depressive disorder (MDD) in December 2022. In August 2023, the US Food and Drug Administration granted approval for PPD but denied approval for MDD. The approval process took only 7 months because it was given priority review and granted ‘fast‐track’ designation, which is intended for drugs that fill unmet needs. This designation allows pharmaceutical companies to submit a smaller number of trials and limits evaluation to surrogate rather than clinically relevant outcomes. Indeed, policy shifts aiming to improve innovation and efficiency have lowered the threshold for evidence of benefit. In turn, this may skew the potential benefits versus potential harms for newly approved medicines in ways that are not in the public's best interest. We examine the clinical trial data submitted by the manufacturer for zuranolone and discuss how regulatory bodies may be failing in their role as gatekeepers. The approval of zuranolone for PPD can thus be seen as a case study for recent developments in drug regulatory sciences.

Background/Objectives: Degenerative cerebellar ataxias (DCA) present a group of complex neurological disorders primarily affecting the cerebellum and its pathways. Classic manifestations include motor symptoms of cerebellar ataxia. However, emerging evidence suggests that the cerebellum also plays a crucial role in various cognitive and emotional processes. The objective was to assess the psychiatric profile of a heterogeneous group of patients with degenerative cerebellar ataxia. Methods: Our sample comprised 107 participants diagnosed with cerebellar degenerative ataxia. All patients were clinically evaluated using SARA, INAS, and different neuropsychiatric scales (ACE-R, HAMA, HAMD, AS, and GAF). Results: The majority of patients had autosomal dominant ataxia (38.3%) followed by sporadic ataxia (32.7%) with an average age at the moment of diagnosis of 35.3 ± 16.23 years, while the mean duration of disease at the study beginning was 12.1 ± 9.9 years. Psychiatric disorders were present in 40 patients (37.4%), with dysthymia (14.2%), major depressive disorder (9.4%), and MDD with melancholic features (7.6%). The presence of MDD with melancholic features was statistically significantly correlated with a lower ACE-R total score (r = −0.223; p = 0.022), while dysthymia was statistically significantly associated with a shorter duration of the disease (r = −0.226; p = 0.020) and older age (r = 0.197; p = 0.043). Statistically significant differences were observed between MSA-C patients and those with sporadic ataxia (HDRS p < 0.001, HARS p < 0.001, Apathy Scale p = 0.003, and GAF p = 0.004). Conclusions: Based on our findings, we can conclude that the degree of motor deficit has a significant impact on the development of psychiatric disorders, including depression, anxiety, and apathy. However, it is not the only factor, and the impact also depends on the type of DCA.

This case report presents a patient with no history of suicidal crisis who experienced 2 suicidal crises within 6 months, each directly following rapid discontinuation of venlafaxine.