Innovations in clinical neuroscience最新文献

Stimulants are the first-line pharmacological treatment for attention deficit hyperactivity disorder (ADHD). We present the unique case of a patient who developed a chewing compulsion when taking mixed amphetamine salts (MAS). A 32-year-old female patient with a past medical history of gastroesophageal reflux disease (GERD), gastroparesis, and migraines was seen for initial psychiatric assessment due to concerns for irritability. She was diagnosed with post-traumatic stress disorder (PTSD); generalized anxiety disorder; ADHD, inattentive type; and unspecified bipolar disorder. Lamotrigine was started and titrated to 25mg twice per day, with improved mood stability. MAS immediate-release (IR) was started at 2.5mg and titrated to 5mg daily for ADHD. She then experienced an uncontrollable urge to chew, finding relief when chewing on a child's teething necklace, which provided satisfaction and a reduction in anxiety. She denied jaw tightness or teeth grinding. The dose of MAS IR was reduced to 2.5mg daily with improvement in symptoms and later increased again to 5mg daily, which she was then able to tolerate. Stereotyped biting behaviors have been observed in rats with the use of amphetamines, and the onset of compulsive behavior has emerged in children with the use of dextroamphetamine. However, this is the first known case of compulsive chewing or biting movements reported in humans with MAS use. This case highlights the need to assess patients for adverse events, such as compulsive biting and chewing movements or other oral facial stereotypies, after commencement of stimulants, including MAS.

Artificial intelligence (AI) encompasses computer systems that mimic human cognitive functions, performing tasks such as learning, reasoning, problem solving, and decision-making. Neurorehabilitation is a specialized healthcare field aiding individuals with neurological injuries, employing various therapies to restore motor skills and cognitive function, enhancing their quality of life. The integration of AI in neurorehabilitation holds great promise, but it is crucial to approach this technology with a clear understanding of its capabilities and limitations. AI can enhance assessment, diagnosis, and personalized treatment plans, but it should complement, rather than replace, human healthcare providers. Additionally, ethical considerations must be at the forefront of AI implementation in the field of neurorehabilitation to ensure that patient wellbeing is prioritized.

This ongoing column is dedicated to providing information to our readers on managing legal risks associated with medical practice. We invite questions from our readers. The answers are provided by PRMS (www.prms.com), a manager of medical professional liability insurance programs with services that include risk management consultation and other resources offered to health care providers to help improve patient outcomes and reduce professional liability risk. The answers published in this column represent those of only one risk management consulting company. Other risk management consulting companies or insurance carriers might provide different advice, and readers should take this into consideration. The information in this column does not constitute legal advice. For legal advice, contact your personal attorney. Note: The information and recommendations in this article are applicable to physicians and other health care professionals so "clinician" is used to indicate all treatment team members.

In our case report, a 29-year-old male patient with a known history of schizophrenia presented with altered mental status and catatonia and was found to have an enlarged (21mm) cavum septum pellucidum (CSP) on magnetic resonance imaging (MRI). He was subsequently treated with escitalopram, olanzapine, methylphenidate, lorazepam, and eight electroconvulsive therapy (ECT) treatments during his hospital course, after which his catatonia improved. We compared this to other cases in which a large CSP was identified and discussed the possibility of increased susceptibility to psychosis, specifically catatonia, which might be associated with this developmental anomaly.

Objective: This study aimed to examine the impact of the COVID-19 pandemic on patients with serious mental illness (SMI), specifically relating to psychiatric morbidity, pandemic-induced stress, and ability to cope with pandemic-related precautionary measures, restrictions, and disruptions to daily life.

Design: A cross-sectional survey study of 277 clinical trial patients was conducted. This sample included nonpsychiatric controls (n=139) and patients with a diagnosis of bipolar disorder, major depressive disorder (MDD), or schizophrenia (n=138) located at five clinical trial sites across the United States. A univariate analysis was performed to obtain general frequencies of the sample. Unpaired t-tests were used in comparing the groups on numerical variables, and analysis of variance (ANOVA) was performed to identify differences when comparing three or more categories.

Results: Patients with SMI were more likely to report wearing face masks, avoiding large gatherings, and endorsing the use of precautionary measures, despite receiving a COVID-19 vaccine (p<0.001). A total of 70.3 percent (n=97) of all patients with SMI reported experiencing at least one episode of symptom worsening, 48 percent reported experiencing suicidal ideation, and 66 percent reported a need for increased mental healthcare due to COVID-19-related distress. Patients with SMI reported higher levels of stress, compared to controls, with patients with MDD having the highest levels of stress (p<0.001).

Conclusion: These findings demonstrate an increased vulnerability to symptom worsening in patients with SMI during a pandemic and suggest the need to account for pandemic-induced psychological stress in clinical trial design, subject selection, and symptoms ratings.

Moral injury is a relatively new concept with varying definitions that attempts to define a profound and lasting insult to one's conscience caused by perpetration of or directly witnessing harm to another person in a high-pressure situation. This entity is separate from posttraumatic stress disorder (PTSD), but it can coexist with PTSD. This article provides psychotherapeutic examples of the diagnosis of moral injury from a psychodynamic perspective, focusing on morally challenging situations related to warfare and the healthcare system.

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.

Background: Clinical practice guidelines support efforts to improve functioning in patients with schizophrenia. Discrepancies in the perception of cognitive status between clinicians, patients with schizophrenia, and their caregivers have been associated with impaired functional abilities in patients; medication side effects might worsen both cognition and daily functioning. We assessed daily/social functioning and cognition in stable patients with schizophrenia who switched to the long-acting injectable (LAI) antipsychotic aripiprazole lauroxil (AL).

Methods: Clinically stable adults with residual symptoms of schizophrenia or intolerance following three or more doses of paliperidone palmitate or risperidone LAI were switched to flexibly dosed open-label AL treatment (441mg, 662mg, or 882mg every 4 weeks or 882mg every 6 weeks) for six months (ClinicalTrials.gov identifier: NCT02634320). Daily/social functioning was assessed using the Personal and Social Performance Scale (PSP); total and subscale scores were summarized using descriptive statistics. The cognitive status of patients was assessed using the New York Assessment of Adverse Cognitive Effects of Neuropsychiatric Treatment (NY-AACENT) at baseline and Month 6 or early termination, providing patient, caregiver, and clinician perspectives. A post hoc analysis assessed level of agreement in ratings of cognitive status among respondents, evaluated at baseline and last assessment, using weighted kappa coefficients (0.01-0.20, slight agreement; 0.21-0.40, fair agreement; 0.41-0.60, moderate agreement; 0.61-0.80, substantial agreement.).

Results: All 51 enrolled patients received one or more AL doses; 35 completed the study, and 45 contributed data at last assessment. Mean age was 40.6 years; 72.5 percent of patients were male. Based on PSP total score, functioning was maintained from baseline (mean [standard deviation (SD)]: 55.1 [10.5]) through six months of AL treatment (mean [SD]: 57.7 [13.2]). Proportions of patients rating personal and social functioning issues as "not present" or "mild" remained stable between baseline and Month 6 for each PSP subscale. At baseline (n=50), cognitive difficulties were most commonly rated "not present" or "mild" in all NY-AACENT domains by patients (58-86% across domains), clinicians (62-94%), and caregivers (50-92%), and these rates were maintained or increased at last assessment for all reporters. Weighted kappa coefficients indicated fair-to-substantial agreement between patients and clinicians across domains at last assessment (0.32-0.64; baseline: 0.14-0.55); patient-caregiver agreement ranged from 0.07 to 0.50 at last assessment (baseline: 0.25-0.60).

Conclusion: In clinically stable patients with schizophrenia who initiated AL, self-reported functioning was maintained over six months of treatment. Clinician-, caregiver-, and patient-reported cognitive func

The 1983 Orphan Drug Act in the United States (US) changed the landscape for development of therapeutics for rare or orphan diseases, which collectively affect approximately 300 million people worldwide, half of whom are children. The act has undoubtedly accelerated drug development for orphan diseases, with over 6,400 orphan drug applications submitted to the US Food and Drug Administration (FDA) from 1983 to 2023, including 350 drugs approved for over 420 indications. Drug development in this population is a global and collaborative endeavor. This position paper of the International Society for Central Nervous System Clinical Trials and Methodology (ISCTM) describes some potential best practices for the involvement of key stakeholder feedback in the drug development process. Stakeholders include advocacy groups, patients and caregivers with lived experience, public and private research institutions (including academia and pharmaceutical companies), treating clinicians, and funders (including the government and independent foundations). The authors articulate the challenges of drug development in orphan diseases and propose methods to address them. Challenges range from the poor understanding of disease history to development of endpoints, targets, and clinical trials designs, to finding solutions to competing research priorities by involved parties.