Clinical Neuropharmacology最新文献

{"title":"Regulating the Hyperdopaminergic Substrate in Restless Legs Syndrome With Augmentation: An Open-label Study on the Safety and Efficacy of Aripiprazole.","authors":"Celia Garcia-Malo, Raquel Martín García, Sara Boi","doi":"10.1097/WNF.0000000000000707","DOIUrl":"https://doi.org/10.1097/WNF.0000000000000707","url":null,"abstract":"<p><strong>Objectives: </strong>Dopamine agonists (DA) were the first-line therapy for restless legs syndrome (RLS) for many years, but their long-term use is limited by augmentation: a paradoxical worsening of symptoms. Managing augmentation remains a clinical challenge, as DA withdrawal often exacerbates symptoms. Aripiprazole, a third-generation antipsychotic with dopaminergic stabilizing properties, may offer a novel therapeutic approach.</p><p><strong>Methods: </strong>This open-label observational study recruited 18 adults with severe RLS and augmentation under dopaminergic therapy. Aripiprazole 5 mg daily was initiated, followed by gradual DA tapering. Efficacy was assessed with the International RLS Study Group Rating (IRLS) and Clinical Global Impression (CGI) scales. Safety, sleep outcomes, and changes in concomitant treatments were also evaluated.</p><p><strong>Results: </strong>All patients successfully discontinued DA (baseline levodopa equivalent dose: 64.66±55.71 mg). IRLS scores improved significantly (from 32.06±3.72 to 2.94±5.46; P<0.0001), as did CGI (6.89±1.75 to 1.78±1.31; P<0.0001). Subjective sleep time increased by 2.18±1.31 hours, and sleep quality improved from 3.4±1.35 to 7.03±1.23 (both P <0.0001). Mild and transient adverse events included akathisia (16.7%), fatigue (11.1%), somnolence (5.6%), and apathy (5.6%). Most side effects resolved after dose adjustments, without loss of efficacy.</p><p><strong>Conclusions: </strong>Low-dose morning aripiprazole was effective and well tolerated in patients with severe RLS and augmentation, enabling complete DA withdrawal and substantial improvement in RLS symptoms and sleep. These findings suggest that dopaminergic stabilizers could be a promising therapeutic option for RLS with augmentation. Controlled trials are warranted to confirm these results.</p>","PeriodicalId":10449,"journal":{"name":"Clinical Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Inhaled and Sublingual Apomorphine for On‑Demand Treatment of OFF Episodes in Parkinson Disease: A Systematic Review and Meta-Analysis With Exploratory Network Comparison.","authors":"Jamir Pitton Rissardo, Jorge Luis Vargas Rojas, Juan Aristizabal Marin, Ana Leticia Fornari Caprara","doi":"10.1097/WNF.0000000000000706","DOIUrl":"https://doi.org/10.1097/WNF.0000000000000706","url":null,"abstract":"<p><strong>Objectives: </strong>OFF episodes are a major source of disability in Parkinson disease (PD). Noninjectable apomorphine formulations, including inhaled (INH) and sublingual (SL) delivery systems, provide rapid dopaminergic stimulation for on-demand symptom relief. However, their efficacy and safety remain incompletely characterized.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis of randomized parallel-group and crossover trials evaluating inhaled or sublingual apomorphine for OFF episodes in PD. The primary outcome was change from baseline in MDS-UPDRS III scores at 30 and 60 minutes post-dose, pooled as mean differences (MD). Safety outcomes were summarized as risk ratios (RR). Random-effects models were applied when substantial heterogeneity was present. PROSPERO (CRD420261440116).</p><p><strong>Results: </strong>Four randomized controlled trials (n=406) were included. At 30 minutes, noninjectable apomorphine significantly improved motor function compared with control interventions (MD: -11.66 points, 95% CI: -17.56 to -5.76; I2= 92%). A similar effect was observed at 60 minutes (MD: -13.03 points, 95% CI: -20.75 to -5.31; I2=87%). Formulation type was not a significant moderator of treatment effect, although subgroup analyses suggested greater persistence of benefit with SL formulations at 60 minutes. Somnolence/fatigue (RR: 2.19, 95% CI: 1.11-4.31) and yawning (RR: 3.90, 95% CI: 1.06-14.00) were more frequent with apomorphine. Certainty of evidence for motor outcomes was moderate according to GRADE.</p><p><strong>Conclusions: </strong>INH and SL apomorphine provide clinically meaningful short-term motor improvement during OFF episodes in PD. Despite substantial heterogeneity, these findings support their use as effective on-demand therapies and highlight the need for individualized treatment strategies and further comparative-effectiveness research.</p>","PeriodicalId":10449,"journal":{"name":"Clinical Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retrograde Ejaculation Associated With Paliperidone Palmitate: A Case Report.","authors":"Hazal Yavuzlar Civan","doi":"10.1097/WNF.0000000000000704","DOIUrl":"https://doi.org/10.1097/WNF.0000000000000704","url":null,"abstract":"<p><strong>Objectives: </strong>Retrograde ejaculation is a rare but distressing adverse effect of antipsychotic treatment, primarily mediated by alpha-1 adrenergic receptor antagonism. While this complication has been widely reported with risperidone, reports associated with paliperidone palmitate are extremely limited. This report aims to present a case of paliperidone palmitate-induced retrograde ejaculation and to highlight its clinical implications.</p><p><strong>Methods: </strong>This report describes a 49-year-old male who developed retrograde ejaculation during treatment with paliperidone palmitate. Clinical evaluation, including urological assessment, was conducted to exclude organic causes. The temporal relationship between medication exposure, dose adjustment, and symptom progression was carefully assessed.</p><p><strong>Results: </strong>Retrograde ejaculation emerged under paliperidone palmitate monotherapy, persisted despite dose reduction, and resolved only after discontinuation and switch to aripiprazole. No organic etiology was identified. Partial improvement was observed during cross-titration, with complete resolution following discontinuation.</p><p><strong>Conclusions: </strong>Paliperidone palmitate can induce retrograde ejaculation despite its lower alpha-1 adrenergic affinity compared with risperidone. This adverse effect may be underrecognized in clinical practice and can contribute to treatment nonadherence. Proactive assessment and appropriate treatment modification are essential to improve clinical outcomes.</p>","PeriodicalId":10449,"journal":{"name":"Clinical Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxic Lesion of the Corpus Callosum After Hospital-Administered Intravenous Fentanyl for Trigeminal Neuralgia: A Case Report and Focused Review.","authors":"Julián Benito-León","doi":"10.1097/WNF.0000000000000698","DOIUrl":"10.1097/WNF.0000000000000698","url":null,"abstract":"<p><strong>Objectives: </strong>Fentanyl-associated neurotoxicity is increasingly recognized across illicit, inhalational, transdermal, pediatric, and delayed posthypoxic exposures, but isolated splenial CLOCC after hospital-administered intravenous fentanyl has not been well characterized.</p><p><strong>Methods: </strong>This is a single-patient case report with a focused review of fentanyl-associated neurotoxic syndromes and proposed mechanisms.</p><p><strong>Results: </strong>A 41-year-old woman with trigeminal neuralgia presented with severe facial pain. After droperidol, metoclopramide, and metamizole failed to control symptoms, intravenous fentanyl (75 μg) was administered. Soon afterward, she developed dizziness, nausea, vomiting, left-sided paresthesias, hypoesthesia, and mild weakness. Initial computed tomography was unrevealing, and cerebrospinal fluid findings were normal. Brain magnetic resonance imaging (MRI) obtained 8 days later showed a 6-mm midline splenial lesion that was hyperintense on T2-weighted and FLAIR sequences, restricted on diffusion-weighted imaging, and nonenhancing, consistent with CLOCC. Follow-up MRI showed complete radiologic resolution, but serial assessments documented persistent deficits in the left upper and lower extremities, including impaired fine motor control, dysdiadochokinesia, arm and leg weakness, foot drag, and gait imbalance; somatosensory-evoked potentials showed mild dysfunction of the left lower-extremity pathway. Review of comparable fentanyl-associated cases shows a spectrum ranging from isolated callosal injury to diffuse, cerebellar, and delayed leukoencephalopathic phenotypes.</p><p><strong>Conclusions: </strong>This case expands the neuroimaging spectrum of fentanyl-associated brain injury and supports a toxic-metabolic pathogenesis in which splenial CLOCC may represent a focal manifestation of broader opioid-related white-matter vulnerability.</p>","PeriodicalId":10449,"journal":{"name":"Clinical Neuropharmacology","volume":"49 5","pages":"192-194"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overlapping Hyperosmolar Therapy in Patients With Elevated and Refractory Intracranial Pressure.","authors":"Madelyn J Johnson, Caitlin S Brown, Alejandro A Rabinstein, Maximiliano A Hawkes, Kristin C Cole, Nicholas J Vollmer","doi":"10.1097/WNF.0000000000000687","DOIUrl":"10.1097/WNF.0000000000000687","url":null,"abstract":"<p><strong>Objectives: </strong>Elevated intracranial pressure (ICP) remains a challenge and immediate danger in patients with acute brain injury. Current literature supports the use of a single hyperosmolar agent to reduce ICP. However, the efficacy and safety of overlapping hyperosmolar agents have not been evaluated. The objectives of this study are to analyze the ICP lowering effects and evaluate the safety profile of overlapping hyperosmolar therapy.</p><p><strong>Materials and methods: </strong>This single-center, retrospective study included adults (≥18 y) admitted to the Neurosciences Intensive Care Unit between May 2018 and September 2024 with acute brain injury leading to intracranial hypertension refractory to a single hyperosmolar agent and an ICP monitor. They received overlapping doses of mannitol and hypertonic sodium approximately every 3 hours. We evaluated the impact of overlapping hyperosmolar therapy on ICP. Safety outcomes included acute kidney injury incidence, electrolyte disturbances, and volume status changes.</p><p><strong>Results: </strong>Forty-six patients were included in this study with a median (IQR) age of 46.5 (35.9, 62.4) years. Median (IQR) dose of mannitol was 40.1 (34.6, 50.0) g, while median (IQR) dose of hypertonic sodium was 120 (90, 125) mEq. About 86% of patients experienced a decrease in ICP after initiation of overlapping hyperosmolar therapy. Six acute kidney injuries occurred, and 7 patients experienced pulmonary edema. Median (IQR) peak sodium, chloride, and osmolar gap values were 149 (144, 155) mEq/L, 115 (111, 119) mEq/L, and 5.7 (0.7, 9.0) mOsm/kg.</p><p><strong>Conclusions: </strong>Overlapping hyperosmolar therapy may provide a transient ICP reduction without excessive adverse effects in patients with refractory ICP to a single hyperosmolar agent.</p>","PeriodicalId":10449,"journal":{"name":"Clinical Neuropharmacology","volume":" ","pages":"181-187"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of Medications That Reduce Neurological Deficits in Patients With Traumatic Brain Injury.","authors":"Saleh Saeed Al Jathnan Al Qahtani, Sadin Khalid Almuzaini, Kholoud Mudhi Alsheri, Raghad Abdul Aziz Alosaimi, Maysa Mousa Alarawi, Anas Saleh Alshehri, Al Habeeb Malek Abdulwahab","doi":"10.1097/WNF.0000000000000689","DOIUrl":"10.1097/WNF.0000000000000689","url":null,"abstract":"<p><strong>Background: </strong>Traumatic brain injury is a leading cause of death and disability worldwide, yet no single drug has proven effective in improving long-term neurological recovery. Understanding the pharmacological efforts made so far is essential for guiding future research and treatment strategies.</p><p><strong>Purpose: </strong>This narrative review aimed to summarize current evidence on medications that reduce neurological deficits in TBI and to highlight emerging therapeutic directions toward neural restoration.</p><p><strong>Methods: </strong>A comprehensive literature search was conducted using MEDLINE, Embase, and ClinicalTrials.gov up to May 2025. Studies in English focusing on human trials, meta-analyses, and relevant translational research were included. Articles were appraised for quality using the GRADE and Cochrane risk-of-bias tools, and findings were summarized thematically.</p><p><strong>Results: </strong>Tranexamic acid given early after injury, nimodipine for traumatic subarachnoid hemorrhage, and short-term anticonvulsants for seizure prevention showed the strongest evidence. Adjunctive drugs such as statins, β-blockers, and SSRIs demonstrated potential benefits in improving vascular, inflammatory, and cognitive outcomes. Newer agents, including minocycline, anakinra, cyclosporine A, and N-acetylcysteine, showed encouraging results in phase II studies. Advances in biomarkers, imaging, and adaptive trials are improving patient selection and precision dosing.</p><p><strong>Conclusion: </strong>Progress in TBI pharmacotherapy is shifting from symptom control toward neurorepair. Continued research integrating biomarkers, affordable therapies, and personalized approaches holds promise for reducing disability and improving recovery after TBI.</p>","PeriodicalId":10449,"journal":{"name":"Clinical Neuropharmacology","volume":" ","pages":"198-211"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clozapine Induced Myocarditis and Pericarditis: An Analysis of Two Illustrative Cases.","authors":"Mehmet Murat Kırpınar, Büşra Uçar Bostan, Christopher Deniz Polat, Kıvanç Yalın, Cana Aksoy Poyraz","doi":"10.1097/WNF.0000000000000695","DOIUrl":"10.1097/WNF.0000000000000695","url":null,"abstract":"<p><strong>Objectives: </strong>Clozapine is regarded as the gold standard pharmacotherapy agent for treatment-resistant schizophrenia patients. However, myocarditis and pericarditis, which are significant life-threatening side effects of clozapine, should be closely monitored. These side effects frequently manifest with subtle and insidious symptoms that can be easily misinterpreted as psychiatric symptoms, thereby complicating their identification. Consequently, a high level of clinical awareness and suspicion is imperative.</p><p><strong>Methods: </strong>Cases of clozapine-associated myocarditis and pericarditis are presented in this study. Following a detailed examination of the electronic records, the patient data are presented.</p><p><strong>Results: </strong>In the first case, tachycardia, hypertension, elevated C-reactive protein (CRP) and troponin T levels, and echocardiographic findings indicative of myocarditis led to a diagnosis of myocarditis. In the second patient, flu-like symptoms, electrocardiogram changes, elevated CRP levels on day 10, and the presence of effusion on echocardiography, but without troponin elevation, led to a diagnosis of pericarditis. In both cases, due to early suspicion, a cardiology consultation was requested, followed by further investigations as recommended, resulting in the diagnoses. Immediate discontinuation of clozapine resulted in rapid resolution of systemic inflammation and normalization of vital signs.</p><p><strong>Conclusions: </strong>These cases emphasize the dual necessity of clozapine monitoring: early identification and management of cardiac complications, and the judicious approach to discontinuation, avoiding premature cessation based on nonspecific findings. Timely, multidisciplinary evaluation is integral to ensuring cardiac safety and uninterrupted psychiatric treatment.</p>","PeriodicalId":10449,"journal":{"name":"Clinical Neuropharmacology","volume":" ","pages":"195-197"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benzodiazepine-Sparing Alcohol Withdrawal Protocol Pilot in Postsurgical Head and Neck Cancer Patients.","authors":"Anna P Shapiro-Krew, Andrew Coulter, Marilyn Davies, Heather Torbic, Elias Khawam, Leopoldo Pozuelo","doi":"10.1097/WNF.0000000000000702","DOIUrl":"10.1097/WNF.0000000000000702","url":null,"abstract":"<p><strong>Background: </strong>Alcohol use disorder is associated with high rates of morbidity and mortality in hospitalized patients. Patients with head and neck cancer have rates of comorbid alcohol use as high as 30% to 60%. Traditionally, withdrawal is managed by assessing symptoms with the Clinical Institute Withdrawal Assessment (CIWA) and treating with benzodiazepines. Benzodiazepines perpetuate neurotransmitter dysregulation in alcohol withdrawal, but valproic acid can correct dysregulations of glutamic and GABAergic systems.</p><p><strong>Methods: </strong>We conducted an IRB-approved retrospective chart review of patients admitted from January 2019 to February 2020 who were admitted for head or neck cancer surgery and had concurrent diagnoses of alcohol use disorder. We reviewed cases of patients who received nonbenzodiazepine withdrawal treatments (gabapentin, valproic acid) and compared them to patients who received benzodiazepine tapers.</p><p><strong>Results: </strong>In the benzodiazepine population, 60% of patients underwent active alcohol withdrawal. Of these, 66.7% were given as-needed benzodiazepines based on CIWA scores. In the benzodiazepine-sparing group, 50% received valproic acid and 50% received gabapentin. Only 1 had an elevated CIWA score above 8, and only 1 patient had a dose of lorazepam (for agitation).</p><p><strong>Discussion: </strong>This preliminary data demonstrates improvement in outcomes, increased control over withdrawal symptoms, and minimization of episodes of agitation and rates of delirium.</p><p><strong>Conclusions: </strong>In patients with significant medical comorbidities, the utilization of a benzodiazepine-sparing protocol is protective against withdrawal. We have found benefit from proactive utilization of a benzodiazepine-sparing protocol versus a traditional CIWA-based reactive treatment model for alcohol withdrawal.</p>","PeriodicalId":10449,"journal":{"name":"Clinical Neuropharmacology","volume":" ","pages":"188-191"},"PeriodicalIF":1.2,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc-associated Copper Deficiency Myelopathy: A Case Report.","authors":"Zachary Goodrich, Jennifer Schneider","doi":"10.1097/WNF.0000000000000701","DOIUrl":"https://doi.org/10.1097/WNF.0000000000000701","url":null,"abstract":"<p><strong>Objective: </strong>Copper deficiency myelopathy is an uncommon but potentially reversible neurologic disorder characterized by sensory ataxia, gait impairment, and dorsal column dysfunction. Acquired copper deficiency most commonly results from malabsorption, prior gastrointestinal surgery, or excess zinc exposure. Zinc induces intestinal metallothionein, which preferentially binds copper and reduces its systemic absorption, potentially leading to hypocupremia and neurologic dysfunction. Although zinc-containing nutritional supplements are widely used, clinically significant neurologic complications remain rare.</p><p><strong>Methods: </strong>A retrospective review of the patient's medical history was performed in addition to a comprehensive literature review.</p><p><strong>Results: </strong>A 70-year-old woman receiving long-term zinc-containing PreserVision AREDS 2 supplementation for age-related macular degeneration presented with 6 months of progressive paresthesia, gait instability, and frequent falls. Neurologic examination demonstrated bilateral sensory deficits and weakness, while magnetic resonance imaging revealed dorsal column T2 hyperintensity. Laboratory evaluation showed undetectable serum copper, mildly elevated serum zinc, normocytic anemia, hypokalemia, and concurrent thiamine deficiency. Zinc-containing supplementation was discontinued, and the patient received copper and thiamine replacement. Over the following two months, serum copper normalized, and she experienced substantial neurologic recovery with restoration of independent ambulation.</p><p><strong>Conclusions: </strong>This report describes a case of copper deficiency myelopathy in a patient receiving long-term high-dose zinc supplementation in the setting of multiple nutritional abnormalities. It highlights the importance of including copper deficiency in the differential diagnosis of patients receiving zinc-containing supplements who present with progressive myelopathy. It is intended to be hypothesis-generating and suggests that individual susceptibility and concurrent nutritional factors may contribute to the development of zinc-associated copper deficiency.</p>","PeriodicalId":10449,"journal":{"name":"Clinical Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Last of the Just: A Novel Highlighting Descriptive Relations Between Trauma-induced Episodes of Dissociation and Psychosis. Does Pathologic Disruption of NMDA Receptor-mediated Neurotransmission Underlie These Relations and Serve as a Promising Therapeutic Target?","authors":"Stephen I Deutsch, Jeffrey Elikan, David R Spiegel, Mary-Caroline Cockerham, Jessica A Burket","doi":"10.1097/WNF.0000000000000700","DOIUrl":"https://doi.org/10.1097/WNF.0000000000000700","url":null,"abstract":"<p><p>Last of the Just, a novel of historical fiction published in 16 languages and recipient of France's highest literary award, is recognized for its scholarly contribution to Holocaust education and conceptualization of the Lamid Vavnik, one of \"36 (largely anonymous) Just Men of Jewish Tradition\" responsible for sustaining humanity. The book's main character is Ernie Levy, who has clinical manifestations of dissociation, psychosis, and an anesthetized tolerance of severe pain associated with repeated traumatic exposures to emotional and physical abuse. Clinical investigation of disordered personality structures with heightened sensitivity to dissociation and psychosis; episodes of dissociation and psychosis associated with traumatic exposures; and small numbers of community-dwelling adults endorsing frequent dissociation, whose characterization includes depersonalization and derealization, associated with histories of childhood abuse have probable explanatory relevance to Ernie's presentation. Phencyclidine (PCP), an uncompetitive NMDA receptor antagonist, introduced into human medicine as a novel anesthetic agent precipitates dissociation and a schizophreniform psychosis in susceptible persons. D-Cycloserine (DCS), a partial NMDA receptor agonist, has been explored for several psychiatric indications in dosages with acceptable tolerability and safety. Adjunctive acute \"time-limited\" administration of DCS in conjunction with psychotherapy may contribute to mitigating severity and lessening duration of episodes of dissociation and psychosis associated with traumatic exposures. However, significant limitations of DCS exist and disappointing results of meta-analyses exploring effectiveness in a variety of psychiatric indications necessitate consideration of strategically targeted, single, or intermittent administration in conjunction with behavioral or cognitive-behavioral interventions. DCS may have a niche indication for a narrowly defined \"dissociative\" subtype of PTSD. More broadly, a selective review of literature suggests that insights gleaned from translational neuroscience can contribute, albeit modestly, to scholarly considerations in seemingly remote disciplines, such as history, literature, and theology.</p>","PeriodicalId":10449,"journal":{"name":"Clinical Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}