The European Medicines Agency's strategies to meet the challenges of Alzheimer disease

Regulatory agencies have a key role in facilitating the development of new drugs for Alzheimer disease, particularly given the challenges associated with early intervention. Here, we highlight the strategies of the European Medicines Agency to help address such challenges

Current and Emerging Technologies to Address the Placebo Response Challenge in CNS Clinical Trials: Promise, Pitfalls, and Pathways Forward

Excessive placebo response rates have long been a major challenge for central nervous system (CNS) drug discovery. As CNS trials progressively shift toward digitalization, decentralization, and novel remote assessment approaches, questions are emerging about whether innovative technologies can help mitigate the placebo response. This article begins with a conceptual framework for understanding placebo response. We then critically evaluate the potential of a range of innovative technologies and associated research designs that might help mitigate the placebo response and enhance detection of treatment signals. These include technologies developed to directly address placebo response; technology-based approaches focused on recruitment, retention, and data collection with potential relevance to placebo response; and novel remote digital phenotyping technologies. Finally, we describe key scientific and regulatory considerations when evaluating and selecting innovative strategies to mitigate placebo response. While a range of technological innovations shows potential for helping to address the placebo response in CNS trials, much work remains to carefully evaluate their risks and benefits

The new European Medicines Agency guideline on antidepressants: a guide for researchers and drug developers

According to the World Health Organization (WHO), depressive disorders are currently considered as one of the most disabling medical conditions in the world with one of the highest disability-adjusted life years [1] and this situation has apparently been further worsened during the COVID-19 pandemic [2]. Up to two thirds of patients with major depressive disorders (MDD) do not achieve full remission following an adequate first line standard of care and/or experience residual symptoms such as anxiety, impaired cognition, fatigue, sleep disturbance, or anhedonia [3]. Several attempts are often needed to find the most suitable treatment [4]. Thus, there is a need for medicinal products with better efficacy (e.g., faster onset of action, higher rates of response and remission), improved safety and/or more personalised profiles [5]

Severe insomnia is associated with hypertriglyceridemia in women with major depression treated in psychiatry settings

International audienceBACKGROUND:Hypertriglyceridemia (HTG) is a cardiovascular risk factor. In the general population, elevated fasting triglyceridemia (TG) is associated with insomnia. Since insomnia is a core symptom of Major Depressive Episodes (MDE), we studied the association of severe insomnia with HTG in major depression.METHODS:We used the baseline data of the METADAP cohort, comprising 624 patients with a current MDE in a context of Major Depressive Disorder treated in psychiatry settings, without current alcohol use disorders. Patients were screened for severe insomnia, defined by a score of four or more on the three Hamilton Depression Rating Scale (HDRS) sleep items, and for HTG characterised by TG≥200mg/dL.RESULTS:Severe insomnia was observed in 335(54%) patients with a current MDE, of whom 234(70%) were women; 49(8%) patients had HTG, of whom 25(51%) were women. 69(11%) patients were treated with lipid-lowering drugs. Severe insomnia was associated with a higher frequency of HTG in the whole sample (9.9% vs 5.6%, p=0.046) and in the subgroup of women (9.0% vs 2.0%, p=0.002). Multivariate logistic regression analyses adjusted for age, education levels, BMI and total HDRS scores confirmed the association between severe insomnia and HTG in the whole sample (OR=2.02, 95%CI [1.00-4.08], p=0.05) as well as in the subgroup of women (OR=4.82, 95%CI [1.5-15.5], p=0.008). No association was shown in men.PERSPECTIVES:HTG should be systematically investigated in depressed patients with severe insomnia and particularly in women. Further studies are needed to explain the association we observed between severe insomnia and HTG

Comparison of burnout, anxiety and depressive syndromes in hospital psychiatrists and other physicians: Results from the ESTEM study

International audienceAims: To compare prevalence and risk factors for burnout, anxiety and depression among hospital psychiatrists and non-psychiatrists.Method: Regional online survey of psychiatric and non-psychiatric hospital physicians was performed including: a job-stress scale, the Hospital Anxiety and Depression Scale (HADS), the Copenhagen Burnout Inventory (CBI), a stressful work relationships list and a six items scale about work-related psychosocial risk factors (PRFs). The client-related burnout scale of the CBI has been changed to an interpersonal burnout scale. Cases were defined by a score of 8+ for the HADS-A/HADS-D and 50+ for the three CBI subscales.Results: 285 psychiatrists and 326 non-psychiatrists participated. The prevalence of depression, personal burnout and work-related burnout did not differ between physicians. Anxiety was lower in psychiatrists and interpersonal burnout was higher in senior psychiatrists. Multivariate analysis showed two main PRFs, common to both groups of physicians: "work intensity and time" was associated with four of the five syndromes and "emotional demands" with the three burnout syndromes. Interpersonal burnout was associated with stressful relationships with leaders, but not with patients.Conclusion: Reducing the workload, improving the management of emotions and increasing managerial skills are important approaches for prevention

Methods for Neuroscience Drug Development: Guidance on Standardization of the Process for Defining Clinical Outcome Strategies in Clinical Trials

Neurosciences clinical trials continue to have notoriously high failure rates. Appropriate outcomes selection in early clinical trials is key to maximizing the likelihood of identifying new treatments in psychiatry and neurology. The field lacks good standards for designing outcome strategies, therefore The Outcomes Research Group was formed to develop and promote good practices in outcome selection. This article describes the first published guidance on the standardization of the process for clinical outcomes in neuroscience. A minimal step process is defined starting as early as possible, covering key activities for evidence generation in support of content validity, patient-centricity, validity requirements and considerations for regulatory acceptance. Feedback from expert members is provided, regarding the risks of shortening the process and examples supporting the recommended process are summarized. This methodology is now available to researchers in industry, academia or clinics aiming to implement consensus-based standard practices for clinical outcome selection, contributing to maximizing the efficiency of clinical research