Medication Taper Research Articles

Epilepsy surgery in children with operculoinsular epilepsy: Results of a large unicentric cohort.

Epilepsy surgery in the operculoinsular cortex is challenging due to the difficult delineation of the epileptogenic zone and the high risk of postoperative deficits. Pre- and postsurgical data from 30 pediatric patients who underwent operculoinsular cortex surgery at the Motol Epilepsy Center Prague from 2010 to 2022 were analyzed. Focal cortical dysplasia (FCD; n = 15, 50%) was the predominant cause of epilepsy, followed by epilepsy-associated tumors (n = 5, 17%) and tuberous sclerosis complex (n = 2, 7%). In eight patients where FCD was the most likely etiology, the histology was negative. Seven patients (23%) displayed normal magnetic resonance imaging results. Seizures exhibited diverse semiology and propagation patterns (frontal, perisylvian, and temporal). The ictal and interictal electroencephalographic (EEG) findings were mostly extensive. Multimodal imaging and advanced postprocessing were frequently used. Stereo-EEG was used for localizing the epileptogenic zone and eloquent cortex in 23 patients (77%). Oblique electrodes were used as guides for better neurosurgeon orientation. The epileptogenic zone was in the dominant hemisphere in 16 patients. At the 2-year follow-up, 22 patients (73%) were completely seizure-free, and eight (27%) experienced a seizure frequency reduction of >50% (International League Against Epilepsy class 3 and 4). Fourteen patients (47%) underwent antiseizure medication tapering; treatment was completely withdrawn in two (7%). Nineteen patients (63%) remained seizure-free following the definitive outcome assessment (median = 6 years 5 months, range = 2 years to 13 years 5 months postsurgery). Six patients (20%) experienced corona radiata or basal ganglia ischemia; four (13%) improved to mild and one (3%) to moderate hemiparesis. Two patients (7%) operated on in the anterior insula along with frontotemporal resection experienced major complications: pontine ischemia and postoperative brain edema. Epilepsy surgery in the operculoinsular cortex can lead to excellent patient outcomes. A comprehensive diagnostic approach is crucial for surgical success. Rehabilitation brings a great chance for significant recovery of postoperative deficits.

Leaving the Norwegian opioid maintenance treatment program - patient experiences

BackgroundOpioid maintenance treatment (OMT) saves lives and makes it possible to start a process of health and social rehabilitation. Previous research shows that those who leave OMT after years of a drug free life and a reasonable level of health and social rehabilitation can have a good chance of living a stable drug free life after leaving the treatment. The aim of this study was to gain more knowledge about how patients who were in the process of leaving, or who had left OMT, experienced the leaving process.MethodsThe study was based on a thematic analysis of transcripts from individual in-depth interviews with 24 patients who had experience with leaving the Norwegian OMT program. Results: The participants in this study had a strong motivation to endure a demanding substitution medication tapering process and leave the OMT program. The tapering benefited strongly from adaptive routines based on ongoing dialog between patients and service providers throughout the process, based on individualized goals and patient experiences each step on the way. The participants had varied experiences regarding the quality and relevance of the support and meeting the need for further treatment and services.ConclusionsGiven a high level of rehabilitation and good support, this study shows that some OMT program patients are in a good position to successfully leave the OMT program or continue the substitution treatment on a low dosage in a less OMT program-dominated life.

Examining what works for whom and how in mindfulness-based cognitive therapy (MBCT) for recurrent depression: moderated-mediation analysis in the PREVENT trial.

Personalised management of recurrent depression, considering individual patient characteristics, is crucial. This study evaluates the potentially different mediating role of mindfulness skills in managing recurrent depression using mindfulness-based cognitive therapy (MBCT) among people with varying depression severity. Data from the Prevention of Depressive Relapse or Recurrence (PREVENT) trial, comparing MBCT (with antidepressant medication (ADM) tapering support, MBCT-tapering support) versus maintenance-ADM, were used. The study included pre, post, 9-, 12-, 18- and 24-month follow-ups. Adults with ≥3 previous major depressive episodes, in full/partial remission (below threshold for a current episode), on ADM, were assessed for eligibility in primary care practices in the UK. People were randomised (1:1) to MBCT-tapering support or maintenance-ADM. We used the Beck Depression Inventory-II to evaluate depressive symptom changes over the six time points. Pre-post treatment, we employed the Five Facets of Mindfulness Questionnaire to gauge mindfulness skills. Baseline symptom and history variables were used to identify individuals with varying severity profiles. We conducted Latent Profile Moderated-Mediation Growth Mixture Models. A total of 424 people (mean (s.d.) age = 49.44 (12.31) years; with 325 (76.7%) self-identified as female) were included. A mediating effect of mindfulness skills, between trial arm allocation and the linear rate of depressive symptoms change over 24 months, moderated by depression severity, was observed (moderated-mediation index = -0.27, 95% CI = -0.66, -0.03). Conditional indirect effects were -0.42 (95% CI = -0.78, -0.18) for higher severity (expected mean BDI-II reduction = 10 points), and -0.15 (95% CI = -0.35, -0.02) for lower severity (expected mean BDI-II reduction = 3.5 points). Mindfulness skills constitute a unique mechanism driving change in MBCT (versus maintenance-ADM). Individuals with higher depression severity may benefit most from MBCT-tapering support for residual symptoms. It is unclear if these effects apply to those with a current depressive episode. Future research should investigate individuals who are not on medication. This study provides preliminary evidence for personalised management of recurrent depression. ISRCTN26666654.

Transforming Care in SEA: Evidence and Considerations for Evolution of the Current Treatment Paradigm

This article reviews an industry symposium held on 8 September 2024 as part of the European Respiratory Society (ERS) Congress 2024 in Vienna, Austria, which brought together four experts to discuss the current treatment paradigm for severe eosinophilic asthma (SEA), including the role of biologics and background medication tapering. Katrin Milger-Kneidinger, Professor of Respiratory Medicine at the University Hospital of the Ludwig Maximilian University Munich (LMU), in Germany, and the MedUni Graz, in Austria, explored the critical role eosinophils play in SEA pathology and how biologic therapies targeting eosinophils can address key disease features, including airway remodelling, airway hyperresponsiveness (AHR), and mucus production. Felix Herth, Professor of Pulmonary and Critical Care Medicine at Thoraxklinik Heidelberg, Heidelberg University Hospital, in Germany, discussed persistent airflow obstruction (PAO) in patients with SEA, focusing on a typical patient profile to understand the clinical manifestation and opportunities for management. Stephanie Korn, Professor of Pulmonary and Respiratory Medicine at Thoraxklinik Heidelberg, Heidelberg University Hospital, in Germany, and Head of the Clinical Research Centre, Institute für Klinische Forschung (IKP) Pneumologie in Mainz, Germany, presented on remission as a clinical target in SEA, focusing on how biologics can help achieve remission in some patients. Lastly, in a discussion led by symposium chair Stefano Del Giacco, Professor of Medicine, Allergy, and Clinical Immunology, at the University of Cagliari, Sardinia, in Italy, the experts agreed that a positive practice change would be to get more patients with relevant clinical manifestations on biologics, and that background medication tapering, when appropriate, could lead to improved patient outcomes and quality of life (QoL) in SEA.

Lacosamide Boluses Decreased Seizure Burden and Were Well Tolerated in Neonates With Acute Seizures: A Single-Center Retrospective Case Series.

Introduction: Neonatal seizures are associated with worsened neurodevelopmental outcomes. Phenobarbital, the only US Food and Drug Administration (FDA)-approved treatment for neonatal seizures, can cause neuronal apoptosis and may worsen neurodevelopmental outcomes. Lacosamide may be an efficacious treatment for neonatal seizures. Methods: We assessed the impact of lacosamide boluses on seizure burden in a retrospective cohort of 15 neonates monitored with video electroencephalography (EEG). Medication bolus times and seizure start/end times on EEG tracings determined change in seizure burden. Results: Seven patients received lacosamide as first- or second-line treatment and 8 as third-line or later. Average 4-hour seizure burden decreased from 13% to 3% following lacosamide boluses (P = .002). Reduction in seizure burden greater than 30% followed 79% of boluses. Lacosamide was well tolerated; one patient experienced mild asymptomatic episodic bradycardia that medication taper resolved. Conclusions: Lacosamide significantly decreased seizure burden in this cohort. Prospective studies of lacosamide treatment for neonatal seizures are warranted.

Stability of infraslow correlation structure in time-shifted intracranial EEG signals.

It is increasingly understood that the epilepsies are characterized by network pathology that can span multiple spatial and temporal scales. Recent work indicates that infraslow (<0.2Hz) envelope correlations may form a basis for distant spatial coupling in the brain. We speculated that infraslow correlation structure may be preserved even with some time lag between signals. To this end, we studied intracranial EEG (icEEG) data collected from 22 medically refractory epilepsy patients. For each patient, we selected hour-long background, awake icEEG epochs before and after antiseizure medication (ASM) taper. For each epoch, we selected 5,000 random electrode contact pairs and estimated magnitude-squared coherence (MSC) below 0.15Hz of band power time-series in the traditional EEG frequency bands. Using these same contact pairs, we shifted one signal of the pair by random durations in 15-s increments between 0 and 300s. We aggregated these data across all patients to determine how infraslow MSC varies with duration of lag. We further examined the effect of ASM taper on infraslow correlation structure. We also used surrogate data to empirically characterize MSC estimator and to set optimal parameters for estimation specifically for the study of infraslow activity. Our empirical analysis of the MSC estimator showed that hour-long segments with MSC computed using 3-min windows with 50% overlap was sufficient to capture infraslow envelope correlations while minimizing estimator bias and variance. The mean MSC decreased monotonically with increasing time lag until 105s of lag, then plateaued between 106 and 300s. Significantly nonzero infraslow envelope MSC was preserved in all frequency bands until about 1min of time lag, both pre- and post-ASM taper. We also saw a slight, but significant increase in infraslow MSC post-ASM taper, consistent with prior work. These results provide evidence for the feasibility of examining infraslow activity via its modulation of higher-frequency activity in the absence of DC-coupled recordings. The use of surrogate data also provides a general methodology for benchmarking measures used in network neuroscience studies. Finally, our study points to the clinical relevance of infraslow activity in assessing seizure risk.

Pain medication tapering for patients with Persistent Spinal Pain Syndrome Type II, treated with Spinal Cord Stimulation: A RCT-study protocol of the PIANISSIMO study.

Spinal Cord Stimulation (SCS) may provide pain relief in patients with therapy-refractory Persistent Spinal Pain Syndrome Type II (PSPS-T2). Despite the evidence that SCS can reduce disability and reduce pain medication usage, only 25% of the patients is able to completely omit pain medication usage after 12 months of SCS. To tackle the high burden of patients who consume a lot of pain medication, tapering programs could be initiated before starting a trajectory with SCS. The current objective is to examine whether a pain medication tapering program before SCS alters disability in PSPS-T2 patients compared to no tapering program. A three-arm, parallel-group multicenter randomized controlled trial will be conducted including 195 patients who will be randomized (1:1:1) to either (a) a standardized pain medication tapering program, (b) a personalized pain medication tapering program, or (c) no tapering program before SCS implantation, all with a follow-up period until 12 months after implantation. The primary outcome is disability. The secondary outcomes are pain intensity, health-related quality of life, participation, domains affected by substance use, anxiety and depression, medication usage, psychological constructs, sleep, symptoms of central sensitization, and healthcare expenditure. Within the PIANISSIMO project we propose a way to reduce the risks of adverse events, medication-induced hyperalgesia, tolerance, and dependence by providing pain medication tapering before SCS. Due to the lack of a commonly accepted in-hospital tapering approach, two different tapering programs will be evaluated in this study. If pain medication tapering programs are deemed to be more effective than no tapering on disability, this would add to the evidence towards an improved patient-centered care model in this patient group and set a clear path to advocate for pain medication tapering before SCS as the new standard treatment guideline for these patients. ClinicalTrials.gov NCT05861609. Registered on May 17, 2023.

Antipsychotic Medication Continuation vs Taper and Discontinuation in Patients With Schizophrenia and Other Nonaffective Psychotic Disorders.

Schizophrenia is a major mental illness that is managed with long-term antipsychotic medication as a standard of care. Antipsychotic medications, however, are associated with many subjective and objective adverse effects. These adverse effects have driven the study of risk-mitigation strategies such as targeted intermittent therapy and dose reduction and drug discontinuation. Randomized controlled trials (RCTs) of these strategies have been synthesized in meta-analysis; both strategies have been associated with no functional benefits and with an increased risk of relapse. The RCTs, however, have been criticized because, in many, patients were abruptly switched to the target dose or too rapidly tapered, thereby predisposing the RCT to failure of the intervention. Two important RCTs examined gradual individualized dose reduction and discontinuation. One, conducted in first-episode psychosis patients who were free from positive symptoms for 6 months, found that, at 18-month follow-up, dose reduction was associated with a higher risk of relapse (number needed to harm [NNH] = 5) and with no functional benefits. However, after return to routine clinical care, at a 7-year follow-up, the dose reduction group had better functional outcomes and similar clinical outcomes relative to the maintenance treatment group. The other RCT, conducted in patients with relapsing psychosis, found that, at a 2-year follow-up, dose reduction was associated with a higher risk of relapse (NNH = 5) and with no improvements in social, cognitive, quality of life, satisfaction, and other domains. Many large nationwide observational studies have found that antipsychotic discontinuation by patients with first-episode psychosis and schizophrenia is associated with increased relapse, rehospitalization, suicide mortality, cardiovascular mortality, and all-cause mortality. There is also the ethical matter that attempts to identify the few who may benefit from antipsychotic dose reduction and discontinuation may compromise the health and stability of the many who require long-term maintenance treatment.

Clinical experiences of guided tapering of antipsychotics for patients with schizophrenia– a case series

Background80% of patients value information on treatment options as an important part of recovery, further patients with a history of psychotic episodes feel excluded from decision making about their antipsychotic treatment, and on top of that, mental health staff is prone to be reluctant to support shared decision making and medication tapering for patients with schizophrenia. This case series aims to demonstrate the tapering of antipsychotic medication and how guided tapering affects the patient’s feeling of autonomy and psychiatric rehabilitation.Case presentationWe present six patients diagnosed with schizophrenia (International Classification of Mental and Behavioral Disorders– 10th Edition codes F20.0–5, F20.7–9) who underwent professionally guided tapering in our clinic. The clinic aims to guide the patients to identify the lowest possible dose of antipsychotic medication in a safe setting to minimise the risk of severe relapse. Two patients completely discontinued their antipsychotic medication, two suffered a relapse during tapering, one chose to stop the tapering at a low dose, and one patient with treatment resistant schizophrenia, which is still tapering down.ConclusionsReducing the antipsychotic dose increased emotional awareness in some patients (n = 4) helping them to develop better strategies to handle stress and increased feelings of recovery. Patients felt a greater sense of autonomy and empowerment during the tapering process, even when discontinuation was not possible. Increased awareness in patients and early intervention during relapse may prevent severe relapse.Impact and implicationsSome patients with schizophrenia might be over medicated, leading to unwanted side effects and the wish to reduce their medication. The patients in our study illustrate how guided tapering of antipsychotic medication done jointly with the patient can lead to improved emotional awareness and the development of effective symptom management strategies. This may in turn lead to a greater sense of empowerment and identity and give life more meaning, supporting the experience of personal recovery.

An age-friendly approach to primary care in an academic health system.

Age-friendly care, addressing what matters most, medications, mentation, and mobility, is a successful model for improving older adult care. We describe the initial outcomes of age-friendly care implementation in five primary care clinics in an academic health system. In partnership with a regional quality improvement (QI) organization, we used practice facilitation to implement age-friendly care from July 2020 to June 2023. Clinic workflows and electronic health record (EHR) templates were modified to capture six QI measures for patients ≥65 years: Documenting what matters most to patients Advance care planning (ACP) Annual cognitive screening Caregiver referral to dementia community resources Fall-risk screening Co-prescription of opioid and sedative-hypnotic drugs Providers were alerted if patients had positive screens and given support tools for clinical decision-making. QI measures from January-June 2023 were compared to the year prior to implementation. Providers and staff were interviewed about implementation barriers and facilitators. All six measures improved in Geriatrics and and other clinics showed improvement in ACP and cognitive screening. All clinics had high fall-risk screening rates (≥85%). The least improved measure was co-prescription of opioids and sedative-hypnotics with co-prescription rates ranging from 7% to 39%. Implementation hinged on leadership prioritization, practice facilitator guidance, clinical team buy-in, EHR functionality, and clinical performance review. Three clinics received Age-Friendly Health System recognition. A QI approach using practice facilitation and EHR templates improved some but not all age-friendly care measures. Future interventions will focus on training in high-risk medication tapering and elicitation of health goals.

Evaluation of medication withdrawal in patients with non-systemic juvenile idiopathic arthritis in Japan using a web-based survey.

Although treatments for juvenile idiopathic arthritis (JIA) have seen considerable advancements, there remains a lack of clear guidelines on withdrawing medications. This study aimed to investigate the current strategies for discontinuing non-systemic JIA treatment. A web-based questionnaire was distributed to members of the Pediatric Rheumatology Association of Japan. According to 126 responses, the most significant factors influencing JIA treatment tapering were the duration of clinically inactive disease, medication toxicity, and a history of arthritis flares. Respondents were often cautious about discontinuing medication if symptoms, e.g. 'morning stiffness' or 'intermittent joint pain', persisted. Among subtypes, oligoarticular JIA was more amenable to treatment tapering, whereas rheumatoid factor-positive polyarticular JIA proved less amenable. Most respondents started medication tapering after a continuous clinical inactive duration exceeding 12 months, and >50% of them required >6 months to achieve treatment discontinuation. Additionally, 40% of the respondents consistently underwent imaging before treatment tapering. The relative risks of treatment continuation and withdrawal should be considered, and decisions should be made accordingly. To obtain improved understanding of and more robust evidence for the optimal strategies for safely discontinuing JIA treatment, it is crucial to continue investigations including long-term outcomes.

Treatment of axial spondyloarthritis patients with biologic disease-modifying anti-rheumatic drugs in 2022 - data from the Romanian Registry of Rheumatic Diseases

Objective. The objective of this cross-sectional study was to analyze data available in the Romanian Registry of Rheumatic Diseases (RRBR) in 2022 for axial spondyloarthritis (axSpA) patients treated with biologic disease modifying anti-rheumatic drugs (bDMARDs). Methods. From the RRBR electronic database were collected multiple variables, including patient’s demographic and clinical characteristics, treatment characteristics, patterns of treatment use (initiations, continuations, switching, tapering), and treatment efficacy data of axSpA patients, from 1 January 2022 to 31 December 2022. Results. In 2022, a total of 4315 axSpA patients were registered in the RRBR database: 70% were men, 48.4 years mean age, 13.3 years mean disease duration, 90% with radiographic axSpA, with high prevalence of extra-musculoskeletal manifestations and cardiovascular comorbidities. Most patients (88%) were treated with a tumor necrosis factor inhibitor (TNFi), usually in monotherapy. The most frequently prescribed bDMARDs were adalimumab (36%), etanercept (32%) and secukinumab (12%). The uptake of biosimilars reached one third of patients from molecules with available biosimilars in 2022. Most patients had a good clinical response, irrespective of clinical form, disease duration, type of medication or line of treatment. Medication switching was needed in 10% of patients, the main reason for switching was secondary loss of efficacy. Medication tapering was implemented in 11% of patients, and it was successful in 90% of cases. Conclusion. Data from RRBR provide a valuable real-world view of clinical practice at the national level regarding biologic treatment of axSpA patients.

Ruxolitinib add-on therapy in steroid-refractory graft-vs-host disease following hematopoietic cell transplantation: A single institutional experience

Steroid-refractory graft-vs-host disease (SR-GVHD) remains a significant cause of mortality after allogeneic hematopoietic cell transplantation (HCT), and the trajectory of treatment response for that vary. In our case series, we introduced six cases experiencing SR-GVHD who achieved better disease control after applying ruxolitinib (RUX). Of the six cases, five of them achieved symptoms-free while one of them, unfortunately, died of invasive fungal infection. Three alive cases were weaned off the RUX treatment successfully, while the remaining were on a medication tapering program. We demonstrated mixed efficacy in patients with SR-GVHD, suggesting that the RUX add-on may be a useful therapeutic adjunct in combination with other immunosuppressants.

A real-world 2-year prospective study of medication tapering in patients with well-controlled rheumatoid arthritis within the rheumatoid arthritis medication tapering (RHEUMTAP) cohort.

This study had two aims: (i) to investigate outcomes of medication tapering in stable RA patients on biologic or targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs/tsDMARDs) and conventional synthetic DMARDs (csDMARDs) in a real-world prospective cohort; and (ii) to evaluate possible predictors of flare with medication taper. A prospective cohort of patients with RA in sustained remission or low disease activity while on stable bDMARD/tsDMARDs +/- csDMARDs for at least 6 months underwent medication tapering/stopping and was tracked for 2 years. Patients were evaluated for flares in four groups: no taper, only bDMARD/tsDMARD taper, only csDMARD taper and both csDMARD and bDMARD/tsDMARD taper. The RHEUMTAP cohort included 131 patients that met eligibility criteria, of which 52 patients underwent a medication taper. Flare was experienced by 15 patients in the taper and twoin the no-taper groups. Patients undergoing any taper/stop overall were 10 times more likely to experience a flare compared with those not tapered (HR 10.43, 95% CI 2.98-36.53, P = 0.0002). The group tapering bDMARD/tsDMARD had 31 times higher risk of flare (HR 31.43, 95% CI 6.35-155.55, P<0.0001) than the no-taper group. Patients tapering both csDMARDs and bDMARD/tsDMARDs had 18 times higher risk of flare than the no-taper group (HR 18.45, 95% CI 2.55-133.37, P = 0.0039). The only csDMARD taper group had a 91% lower risk of flare than the bDMARD/tsDMARD taper group (HR 0.09, 95% CI 0.01-0.69, P = 0.0213). In our real-world prospective RHEUMTAP cohort study on the outcomes of different medication tapering groups in well-controlled RA, patients who tapered or stopped bDMARDs/tsDMARDs with or without background therapy were more likely to experience a flare than patients that did not taper any medications and those that tapered only csDMARDs.

Medication tapering in stable rheumatoid arthritis: where do we stand and what work needs to be done?

Medication tapering in stable rheumatoid arthritis: where do we stand and what work needs to be done?

Descent into Mania: A Case of Tacrolimus-Induced Psychosis

Background: Tacrolimus has historically been used as an effective immunosuppressant in solid organ transplants. Although it is standard care in most organ transplants, it is accompanied by a vast number of side effects, including headache, fatigue, and even psychosis. The neurotoxic side effects that accompany tacrolimus are usually apparent at supratherapeutic doses and resolve after dose adjustment or discontinuation. Case Presentation: We present a case of a 68-year-old male who sustained tacrolimus-induced mania post- transplant, refractory to both medication tapering and removal. He ultimately required the use of prolonged antipsychotic therapy. Conclusion: This study highlights the necessity for thorough psychiatric evaluations in patients undergoing organ transplantation as well as the continued need for further research and interventions in patients undergoing prolonged immunosuppressive therapy. This report may signify a novel mechanism of dose-independent neurotoxicity secondary to tacrolimus.

Single-Dose Psilocybin Treatment for Major Depressive Disorder

Psilocybin shows promise as a treatment for major depressive disorder (MDD). To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. ClinicalTrials.gov Identifier: NCT03866174.

Xenografts Show Signs of Concentric Hypertrophy and Dynamic Left Ventricular Outflow Tract Obstruction After Orthotopic Pig-to-baboon Heart Transplantation.

Orthotopic cardiac xenotransplantation has seen substantial advancement in the last years and the initiation of a clinical pilot study is close. However, donor organ overgrowth has been a major hurdle for preclinical experiments, resulting in loss of function and the decease of the recipient. A better understanding of the pathogenesis of organ overgrowth after xenotransplantation is necessary before clinical application. Hearts from genetically modified ( GGTA1-KO , hCD46/hTBM transgenic) juvenile pigs were orthotopically transplanted into male baboons. Group I (control, n = 3) received immunosuppression based on costimulation blockade, group II (growth inhibition, n = 9) was additionally treated with mechanistic target of rapamycin inhibitor, antihypertensive medication, and fast corticoid tapering. Thyroid hormones and insulin-like growth factor 1 were measured before transplantation and before euthanasia, left ventricular (LV) growth was assessed by echocardiography, and hemodynamic data were recorded via a wireless implant. Insulin-like growth factor 1 was higher in baboons than in donor piglets but dropped to porcine levels at the end of the experiments in group I. LV mass increase was 10-fold faster in group I than in group II. This increase was caused by nonphysiological LV wall enlargement. Additionally, pressure gradients between LV and the ascending aorta developed, and signs of dynamic left ventricular outflow tract (LVOT) obstruction appeared. After orthotopic xenotransplantation in baboon recipients, untreated porcine hearts showed rapidly progressing concentric hypertrophy with dynamic LVOT obstruction, mimicking hypertrophic obstructive cardiomyopathy in humans. Antihypertensive and antiproliferative drugs reduced growth rate and inhibited LVOT obstruction, thereby preventing loss of function.

Safety and efficacy of rapid withdrawal of anti-seizure medication during long-term video-EEG monitoring.

Anti-seizure medications (ASMs) are often withdrawn during long-term video-EEG monitoring (LTM) to allow pre-surgical evaluation. Herein, we evaluated the safety and efficacy of ultra-rapid withdrawal (URW) and rapid withdrawal (RW) of ASMs in an epilepsy monitoring unit (EMU). This retrospective study examined all consecutive patients admitted to our EMU between May 2021 and October 2022. Patients were classified into the URW and RW groups according to the way ASMs were withdrawn. We compared the efficacy and safety of the procedures used in the groups in terms of duration of LTM, latency to the first seizure, and incidence of focal to bilateral tonic-clonic seizures (FBTCS), seizure clusters (SC), and status epilepticus (SE). Overall, 110 patients (38 women) were included. The mean age of patients at the time of LTM was 29 years. All medications were stopped on admission for monitoring in the URW group (n = 75), while in the RW group (n = 35) ASMs were withdrawn within 1 day. In both groups, the duration of LTM was approximately 3 days: URW group (2.9 ± 0.5 days) and RW group (3.1 ± 0.8 days). The latency to the first seizure was significantly different between the two groups; however, there were no differences between the two groups in terms of the distribution of FBTCS, SC, or SE, number of seizures, and the requirement for intravenous rescue medication was low. The rapid withdrawal of ASMs to provoke seizures during monitoring for pre-surgical evaluation following the URW protocol was as effective and safe as with RW. Ultra-rapid ASM withdrawal has the benefits of reducing LTM duration and shortening the time to first seizure compared to rapid medication tapering.

Change In Fall Risk-Increasing Drug Use Among Individuals with Parkinson Disease Before and After a Serious Injury (P2-5.032)

<h3>Objective:</h3> To describe fall risk-increasing drug (FRID) use before and after an unintentional traumatic injury or fall-related fracture and examine the extent to which hospital encounters affect medication prescribing in individuals with Parkinson disease (PD). <h3>Background:</h3> Individuals with PD are at increased risk of falls and fractures. FRIDs represent a major modifiable factor that can potentially reduce the risk of subsequent events. <h3>Design/Methods:</h3> We identified persons with PD hospitalized for injury or fracture and matched each person to up to 4 individuals with PD who were hospitalized for other reasons using 2013–2017 U.S. Medicare data. A difference-in-difference design was used to compare FRID dispensing before and after hospitalization between the two groups. We examined the changes in standardized daily doses of FRIDs in the two groups upon hospital admission and at 3-, 6-, and 12-months post-discharge, adjusting for covariates. Exploratory analyses were performed to evaluate potential medication discontinuation and tapering following discharge. <h3>Results:</h3> We identified 9,437 persons with PD who had a qualifying hospitalization for injury or fracture and 32,487 matched individuals. While both groups experienced reductions in standardized daily doses of FRIDs, the differences in dose reductions were minimal (−1.94, 95% CI [−2.05, −1.82] in the injury group vs. −1.91, 95% CI [−1.97, −1.84] in the non-injury group; p=0.66 at 12 months). Over 40% of subjects discontinued FRIDs at 3 months in both groups, and ~2/3 to 3/4 of these sustained discontinuations through one year. <h3>Conclusions:</h3> There were no clinically significant differences in FRID dose reductions pre- to post-hospitalization between PD individuals with injury or fracture versus those without. More efforts are needed to enhance deprescribing practices during transition of care, especially after a sentinel event, to prevent subsequent unintentional injuries or fractures. <b>Disclosure:</b> The institution of Dr. Pham Nguyen has received research support from National Institute of Health. The institution of Dr. Pham Nguyen has received research support from National Institute of Health. Dr. Gray has nothing to disclose. Mr. Newcomb has nothing to disclose. Miss Liu has nothing to disclose. The institution of Dr. Hamedani has received research support from Michael J. Fox Foundation. The institution of Dr. Hamedani has received research support from NIH. The institution of Dr. Hamedani has received research support from Biogen. The institution of Dr. Hamedani has received research support from Biohaven. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intercept Pharmaceuticals. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medullary Thyroid Cancer Consortium. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Provention Bio, Inc. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bluebird bio, Inc. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx Pharmaceuticals. Dr. Hennessy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen Bioscence Inc.. The institution of Dr. Hennessy has received research support from US Food and Drug Administration. The institution of Dr. Hennessy has received research support from US National Institutes of Health. The institution of Dr. Hennessy has received research support from US Centers for Disease Control and Prevention. Dr. Wright Willis has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Pharmacoepidemiology and Drug Safety. The institution of Dr. Wright Willis has received research support from NIH. The institution of Dr. Wright Willis has received research support from NIA. The institution of Dr. Wright Willis has received research support from Biogen. The institution of Dr. Wright Willis has received research support from Parkinson Foundation. The institution of Dr. Wright Willis has received research support from Arcadia.