Ravi Anand, Alessio Turolla, Giovanni Chinellato, Arjun Roy, Richard D Hartman
{"title":"Therapeutic Effect of Evenamide, a Glutamate Inhibitor, in Patients With Treatment-Resistant Schizophrenia (TRS): Final, 1-Year Results From a Phase 2, Open-Label, Rater-Blinded, Randomized, International Clinical Trial.","authors":"Ravi Anand, Alessio Turolla, Giovanni Chinellato, Arjun Roy, Richard D Hartman","doi":"10.1093/ijnp/pyae061","DOIUrl":"10.1093/ijnp/pyae061","url":null,"abstract":"<p><p>The results from a pilot, 1-year, randomized, open-label, add-on treatment study in treatment-resistant schizophrenia (TRS) with evenamide, a glutamate modulator, were not associated with any safety abnormalities at all doses (7.5-30 mg bid), with a high retention rate even at 6-month (~85%), and 1-year (~75%), and the absence of psychotic relapses during the 1-year treatment period. Overall, treatment with evenamide showed a gradual, sustained, and clinically important improvement up to 1 year in all efficacy measures (eg, PANSS mean change ~ -20%; CGI-S mean change ~ -1.0). In addition, compared to the results at Week 6, the responder rates generally more than doubled at 1-year (PANSS \"≥20% improvement from baseline\" = ~45%; CGI-S \"2-category of improvement\" = ~25%; CGI-C \"much improved\" = ~40%). These results, rarely replicated in other trials in TRS, support the use of evenamide as an add-on treatment in patients who are not benefiting from their current first- or second-generation antipsychotic medication.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael J Mueller, Helena D Aicher, Dario A Dornbierer, Laurenz Marten, Dila Suay, Daniel Meling, Claudius Elsner, Ilhui A Wicki, Jovin Müller, Sandra N Poetzsch, Luzia Caflisch, Alexandra Hempe, Camilla P Steinhart, Maxim Puchkov, Jonas Kost, Hans-Peter Landolt, Erich Seifritz, Boris B Quednow, Milan Scheidegger
{"title":"Pharmacokinetics and pharmacodynamics of an innovative psychedelic N,N-dimethyltryptamine/harmine formulation in healthy participants: a randomized controlled trial.","authors":"Michael J Mueller, Helena D Aicher, Dario A Dornbierer, Laurenz Marten, Dila Suay, Daniel Meling, Claudius Elsner, Ilhui A Wicki, Jovin Müller, Sandra N Poetzsch, Luzia Caflisch, Alexandra Hempe, Camilla P Steinhart, Maxim Puchkov, Jonas Kost, Hans-Peter Landolt, Erich Seifritz, Boris B Quednow, Milan Scheidegger","doi":"10.1093/ijnp/pyaf001","DOIUrl":"10.1093/ijnp/pyaf001","url":null,"abstract":"<p><strong>Background: </strong>Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects in various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) and β-carboline alkaloids such as harmine. However, its use is often accompanied by distressing effects like nausea, vomiting, and intense hallucinations, possibly due to complex pharmacokinetic/pharmacodynamic (PK-PD) interactions and lack of dose standardization.</p><p><strong>Methods: </strong>This study addresses these limitations by testing a novel pharmaceutical formulation containing pure forms of DMT and harmine in a double-blind, randomized, placebo-controlled trial with 31 healthy male volunteers. We evaluated PK-PD by monitoring drug and metabolite plasma levels, subjective effects, adverse events, and cardiovascular parameters. Each participant received 3 randomized treatments: (1) 100 mg buccal harmine with 100 mg intranasal DMT, (2) 100 mg buccal harmine with intranasal placebo, and (3) full placebo, using a repeated-intermittent dosing scheme, such that 10 mg of DMT (or placebo) was administered every 15 minutes.</p><p><strong>Results: </strong>N,N-dimethyltryptamine produced consistent PK profiles with Cmax values of 22.1 ng/mL and acute drug effects resembling the psychological effects of ayahuasca with a duration of 2-3 hours. Likewise, buccal harmine produced sustained-release PK profiles with Cmax values of 32.5 ng/mL but lacked distinguishable subjective effects compared to placebo. All drug conditions were safe and well tolerated, indicating the formulation's suitability for clinical applications.</p><p><strong>Conclusions: </strong>This study underscores the potential of a patient-oriented pharmaceutical formulation of DMT and harmine to reduce risks and improve therapeutic outcomes in treating mental health disorders.</p><p><strong>Clinical trial registration number: </strong>Neurodynamics of prosocial emotional processing following serotonergic stimulation with N,N-dimethyltryptamine (DMT) and harmine in healthy subjects (NCT04716335) https://clinicaltrials.gov/ct2/show/NCT04716335.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Erika Kertes, László Péczely, Tamás Ollmann, Kristóf László, Beáta Berta, Veronika Kállai, Olga Zagorácz, Anita Kovács, Ádám Szabó, Zoltán Karádi, László Lénárd
{"title":"The role of pallidal substance P and neurokinin receptors in the consolidation of spatial memory of rats.","authors":"Erika Kertes, László Péczely, Tamás Ollmann, Kristóf László, Beáta Berta, Veronika Kállai, Olga Zagorácz, Anita Kovács, Ádám Szabó, Zoltán Karádi, László Lénárd","doi":"10.1093/ijnp/pyaf002","DOIUrl":"10.1093/ijnp/pyaf002","url":null,"abstract":"<p><strong>Background: </strong>The tachykinin substance P (SP) facilitates learning and memory processes after its central administration. Activation of its different receptive sites, neurokinin-1 receptors (NK1Rs), as well as NK2Rs and NK3Rs, was shown to influence learning and memory. The basal ganglia have been confirmed to play an important role in the control of memory processes and spatial learning mechanisms, and as part of the basal ganglia, the globus pallidus (GP) may also be involved in this regulation. SP-immunoreactive fibers and terminals, as well as NK1Rs and NK3Rs, were shown to be present in the GP.</p><p><strong>Methods: </strong>The present study aimed to examine whether the SP administered into the GP can influence spatial memory consolidation in the Morris water maze (MWM). Therefore, male Wistar rats received a post-trial microinjection of 0.4 µLf 10 ng SP, 100 ng SP, or vehicle solution. The possible involvement of pallidal NK1Rs and NK3Rs in the SP effects was also studied by applying WIN51708 for NK1R antagonism and SR142801 as a selective NK3R antagonist.</p><p><strong>Results: </strong>Our results showed that the lower dose of SP significantly decreased escape latency on the second day compared to control animals, while the higher dose was ineffective. Prior treatment with the NK1R antagonist WIN51708 could not block, while the NK3R antagonist SR142801 inhibited the effects of SP on memory consolidation in the MWM.</p><p><strong>Conclusions: </strong>Our results are the first to demonstrate that SP improves consolidation of spatial memory in the GP, and this effect is mediated through NK3Rs but not NK1Rs.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ahmad Shamabadi, Elham-Sadat Rafiei-Tabatabaei, Kimia Kazemzadeh, Kimia Farahmand, Bita Fallahpour, Mohammad-Reza Khodaei Ardakani, Shahin Akhondzadeh
{"title":"Pentoxifylline adjunct to risperidone for negative symptoms of stable schizophrenia: a randomized, double-blind, placebo-controlled trial.","authors":"Ahmad Shamabadi, Elham-Sadat Rafiei-Tabatabaei, Kimia Kazemzadeh, Kimia Farahmand, Bita Fallahpour, Mohammad-Reza Khodaei Ardakani, Shahin Akhondzadeh","doi":"10.1093/ijnp/pyae051","DOIUrl":"10.1093/ijnp/pyae051","url":null,"abstract":"<p><strong>Background: </strong>Negative symptoms of schizophrenia represent an unmet therapeutic need for many patients in whom pentoxifylline may be effective in terms of its dopaminergic, anti-inflammatory, and cerebral blood flow-increasing properties. This study aimed to evaluate pentoxifylline as a therapeutic agent for improving negative symptoms of schizophrenia.</p><p><strong>Methods: </strong>Chronic schizophrenia outpatients experiencing significant negative symptoms were randomly allocated to receive pentoxifylline 400 mg or matched placebo every 12 hours for 8 weeks. All patients were clinically stable as they had received risperidone for at least 2 months, which was continued. The participants were assessed using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, Extrapyramidal Symptom Rating Scale, and side effect checklist.</p><p><strong>Results: </strong>The patients' baseline characteristics were comparable between the groups. There was a significant time-treatment interaction effect on PANSS negative subscale scores (ηP2=0.075), with the pentoxifylline group showing significantly greater reductions until weeks 4 (Cohen d = 0.512) and 8 (Cohen d = 0.622). Also, this group showed a significantly better response by week 8. Other PANSS scores, Hamilton Depression Rating Scale scores, Extrapyramidal Symptom Rating Scale scores, and side effect frequencies were comparable between the groups. Pentoxifylline showed a nonsignificant higher remission of 37.1% compared with 14.7% in the placebo group.</p><p><strong>Conclusions: </strong>Pentoxifylline was safely and tolerably beneficial for the primary negative symptoms of chronic schizophrenia.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haiting Zhao, Haoyu Li, Li Meng, Peng Du, Xin Mo, Mengqi Gong, Jiaxin Chen, Yiwei Liao
{"title":"Disrupting heroin-associated memory reconsolidation through actin polymerization inhibition in the nucleus accumbens core.","authors":"Haiting Zhao, Haoyu Li, Li Meng, Peng Du, Xin Mo, Mengqi Gong, Jiaxin Chen, Yiwei Liao","doi":"10.1093/ijnp/pyae065","DOIUrl":"10.1093/ijnp/pyae065","url":null,"abstract":"<p><strong>Background: </strong>Understanding drug addiction as a disorder of maladaptive learning, where drug-associated or environmental cues trigger drug cravings and seeking, is crucial for developing effective treatments. Actin polymerization, a biochemical process, plays a crucial role in drug-related memory formation, particularly evident in conditioned place preference paradigms involving drugs like morphine and methamphetamine. However, the role of actin polymerization in the reconsolidation of heroin-associated memories remains understudied.</p><p><strong>Methods: </strong>This study employed a rodent model of self-administered heroin to investigate the involvement of actin polymerization in the reconsolidation of heroin-associated memories. Rats underwent ten days of intravenous heroin self-administration paired with conditioned cues. Subsequently, a 10-day extinction phase aimed to reduce heroin-seeking behaviors. Following this, rats participated in a 15-minute retrieval trial with or without cues. Immediately post-retrieval, rats received bilateral injections of the actin polymerization inhibitor Latrunculin A (Lat A) into the nucleus accumbens core (NACc), a critical brain region for memory reconsolidation.</p><p><strong>Results: </strong>Immediate administration of Lat A into the NACc post-retrieval significantly reduced cue-induced and heroin-primed reinstatement of heroin-seeking behavior for at least 28 days. However, administering Lat A 6-hour post-retrieval or without a retrieval trial, as well as administering Jasplakionlide prior to memory reactivation did not affect heroin-seeking behaviors.</p><p><strong>Conclusions: </strong>Inhibiting actin polymerization during the reconsolidation window disrupts heroin-associated memory reconsolidation, leading to decreased heroin-seeking behavior and prevention of relapse. These effects are contingent upon the presence of a retrieval trial and exhibit temporal specificity, shedding light on addiction mechanisms and potential therapeutic interventions.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ryan T Terry-Lorenzo, Reuben H Fan, Ni A Khin, Jaskaran B Singh
{"title":"Therapeutic potential of D-amino acid oxidase inhibitors for cognitive impairment associated with schizophrenia: learnings from luvadaxistat.","authors":"Ryan T Terry-Lorenzo, Reuben H Fan, Ni A Khin, Jaskaran B Singh","doi":"10.1093/ijnp/pyae066","DOIUrl":"10.1093/ijnp/pyae066","url":null,"abstract":"<p><p>Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has been proposed to underlie the pathophysiology of schizophrenia, suggesting that promoting NMDAR activity may alleviate the negative or cognitive symptoms associated with schizophrenia. To circumvent excitotoxicity that may accompany direct agonism of the glutamate binding site on the NMDAR, therapeutic trials have focused on targeting the glycine binding site on the NMDAR. Direct administration of either glycine or D-serine, both of which are endogenous coagonists at the NMDAR glycine site, has yielded mixed outcomes across an array of clinical trials investigating different doses or patient populations. Furthermore, directly administering D-serine and glycine is challenging, and thus attention has turned to alternative, indirect methods that increase endogenous D-serine and glycine levels in the brain, such as D-amino acid oxidase (DAAO) inhibitors and glycine transporter 1 inhibitors, respectively. In this review, we provide an overview of the evidence supporting the potential of NMDAR modulators in general, and DAAO inhibitors in particular, as potential adjunctive treatments for schizophrenia. We also discuss the preclinical and clinical data related to luvadaxistat, an investigational highly selective and potent DAAO inhibitor that was under development for the treatment of the cognitive impairment associated with schizophrenia.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mary R Lee, Ehsan Shokri Kojori, William Dieckmann, Erick Singley, Julie A Mattison, Peter Herscovitch, Lorenzo Leggio
{"title":"Oxytocin Reduces Methylphenidate-Induced Dorsal Striatal Dopamine Release in Male Rhesus Macaques.","authors":"Mary R Lee, Ehsan Shokri Kojori, William Dieckmann, Erick Singley, Julie A Mattison, Peter Herscovitch, Lorenzo Leggio","doi":"10.1093/ijnp/pyae056","DOIUrl":"10.1093/ijnp/pyae056","url":null,"abstract":"<p><strong>Background: </strong>Oxytocin is being evaluated as a potential treatment for psychostimulant use disorders. It is unknown what effect oxytocin has on dopamine signaling in response to psychostimulants in brain regions such as the striatum where oxytocin and dopamine interact to process natural rewards. We investigated the effect of oxytocin on striatal dopamine release stimulated by methylphenidate whose mechanism of action is analogous to that of cocaine.</p><p><strong>Methods: </strong>We conducted an [11C] raclopride positron emission tomography study to assess striatal dopamine release in male rhesus macaques treated with oxytocin (80 IU) (administered via the intranasal [N = 5] and intravenous [N = 6] routes) followed by methylphenidate/[11C] raclopride.</p><p><strong>Results: </strong>Oxytocin delivered by both routes significantly reduced methylphenidate-stimulated dopamine release in the dorsal striatum (caudate/putamen). These effects were, in part, evidenced by a reduction in dorsal striatal [11C] raclopride binding potential (increased dopamine release) following oxytocin administration.</p><p><strong>Conclusions: </strong>The results provide translational and mechanistic evidence for the potential role of oxytocin as a treatment for psychostimulant use disorders.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matan Dahan, Joseph Zohar, Doron Todder, Aleksander A Mathé, Hagit Cohen
{"title":"Exploring the Anxiolytic Potential of NPY by a Dipeptidyl Peptidase-IV Inhibitor in an Animal Model of PTSD.","authors":"Matan Dahan, Joseph Zohar, Doron Todder, Aleksander A Mathé, Hagit Cohen","doi":"10.1093/ijnp/pyae062","DOIUrl":"10.1093/ijnp/pyae062","url":null,"abstract":"<p><strong>Background: </strong>The regulatory neuropeptide Y (NPY) is implicated in anxiety and post-traumatic stress disorder (PTSD)-related behaviors. NPY exerts its effects through 5 receptor subtypes, with Y1 and Y2 receptors being predominantly expressed in the rat brain. Activation of Y1 by full-length NPY1-36 induces anxiolytic effects, whereas Y2 binds truncated peptides, eliciting region-specific anxiogenic responses. Dipeptidyl peptidase-IV (DPP-IV) cleaves NPY, thereby modulating its functionality. Sitagliptin, a DPP-IV inhibitor (DPP-IV-I), inhibits the degradation of various vasoactive peptides, including cerebral NPY. As such, the therapeutic potential of DPP-IV-I following a traumatic event remains inconclusive. We assessed the effects of a highly selective DPP-IV-I, administered either shortly after the stressor or intermittently over 3 days, on behavioral outcomes using the predator scent stress (PSS) model of PTSD.</p><p><strong>Methods: </strong>Rats exposed to PSS or sham-PSS received a single dose of sitagliptin (10 or 30 mg/kg) or saline 1 hour post-exposure, or repeated doses over 3 days (20 mg/kg). Behavioral outcomes were evaluated using the elevated plus maze and acoustic startle response at 7 days post-exposure. Additionally, rats exposed to PSS or sham-PSS were treated with sitagliptin (30 mg/kg) or saline, and their brains were prepared for immunofluorescence and enzyme-linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>Sitagliptin did not attenuate anxiety-related behaviors or PTSD-related behavior prevalence compared to saline. Notably, the 30 mg/kg dose increased NPY levels in several brain regions without affecting NPY-Y1 levels.</p><p><strong>Conclusions: </strong>The findings suggest that sitagliptin-induced upregulation of NPY levels shortly after PSS is insufficient to prevent the development of post-traumatic responses. The effectiveness of NPY signaling may be influenced by factors beyond peptide concentration alone, potentially limiting its therapeutic efficacy. Activation of NPY-Y1 receptors, rather than merely increasing NPY levels, appears to be crucial for modulating anti-anxiety and post-traumatic responses.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lakshmi Thangavelu, Siddig Ibrahim Abdelwahab, Abdullah Farasani, Suhas Ballal, Pooja Bansal, Deepak Nathiya, Kiranjeet Kaur, M Ravi Kumar, Aashna Sinha, Hayam A Alrasheed, Maha F Al-Subaie, Nawal A Al Kaabi, Ali Al Bshabshe, Mona A Al Fares, Hawra Albayat, Ali A Rabaan, Kumud Pant, Quazi Syed Zahiruddin, Arathi P Rao, Mahalaqua Nazli Khatib, Hassan Ahmad Alfaifi, Syam Mohan, Sanjit Sah, Prakasini Satapathy
{"title":"Risk of cognitive decline among patients with dengue virus infection: a systematic review.","authors":"Lakshmi Thangavelu, Siddig Ibrahim Abdelwahab, Abdullah Farasani, Suhas Ballal, Pooja Bansal, Deepak Nathiya, Kiranjeet Kaur, M Ravi Kumar, Aashna Sinha, Hayam A Alrasheed, Maha F Al-Subaie, Nawal A Al Kaabi, Ali Al Bshabshe, Mona A Al Fares, Hawra Albayat, Ali A Rabaan, Kumud Pant, Quazi Syed Zahiruddin, Arathi P Rao, Mahalaqua Nazli Khatib, Hassan Ahmad Alfaifi, Syam Mohan, Sanjit Sah, Prakasini Satapathy","doi":"10.1093/ijnp/pyae053","DOIUrl":"10.1093/ijnp/pyae053","url":null,"abstract":"<p><p>Dengue fever, caused by the dengue virus and transmitted through Aedes mosquitoes, is a growing public health concern, particularly in tropical and subtropical regions. Traditionally associated with febrile and hemorrhagic symptoms, recent research suggests a potential link between dengue and cognitive impairments. This systematic review assessed existing research to understand the association between dengue virus infection and cognitive impairments, including dementia, Alzheimer disease, memory loss, and confusion. This systematic review followed preferred reporting items for systematic reviews and meta-analyses guidelines. A comprehensive literature search was conducted in PubMed, EMBASE, and Web of Science up to January 18, 2024. Studies examining the prevalence and association of cognitive impairments in dengue patients were included. Data extraction and quality assessment were performed using Nested Knowledge software and the Newcastle-Ottawa Scale. Of the 1129 articles identified, 5 were included in the review, covering a total of 200 873 participants from Taiwan, Brazil, and France. Evidence from population-based cohort studies indicated short-term cognitive impairments, including confusion and memory loss, in some dengue patients. Additionally, long-term risks of dementia, including Alzheimer disease and vascular dementia, were observed, particularly among older adults. Although the findings suggest there might be an association between dengue infection and cognitive decline, the mechanisms underlying this link remain unclear. This systematic review suggests that dengue virus infection may affect cognitive function in both acute and long-term contexts. However, the current evidence is not strong enough to establish a conclusive link. Further research with larger sample sizes and longitudinal studies is essential to confirm the impact of dengue virus on cognitive health.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631092/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Real-World Safety of Esketamine Nasal Spray: A Comprehensive Analysis of Esketamine and Respiratory Depression.","authors":"Craig Chepke, Richard Shelton, Gerard Sanacora, Teodora Doherty, Palina Tsytsik, Nancy Parker","doi":"10.1093/ijnp/pyae058","DOIUrl":"10.1093/ijnp/pyae058","url":null,"abstract":"<p><strong>Background: </strong>Esketamine nasal spray (ESK) is approved, in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression in adults and for the treatment of depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. No adverse events (AEs) of respiratory depression were reported in ESK phase 3 clinical trials; however, postmarketing incidents of respiratory depression associated with ESK use have been observed.</p><p><strong>Methods: </strong>The Janssen Global Medical Safety (GMS) database was reviewed for cases meeting the criteria for respiratory depression with ESK using 47 months of postapproval data, based on the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query (SMQ) acute central respiratory depression (broad). FDA Adverse Event Reporting System (FAERS), EudraVigilance, and literature searches were performed to identify reports of respiratory depression related to ESK use.</p><p><strong>Results: </strong>Fifty cases, representing 50 patients, in the GMS database met the case definition for respiratory depression; 8 of these had a stronger association with ESK use. The MedDRA preferred term (PT) hypopnea met the threshold for disproportionality with ESK in FAERS. The MedDRA PTs asphyxia, oxygen saturation decreased, respiratory depression, and apnea met the threshold for disproportionality with ESK in EudraVigilance.</p><p><strong>Conclusion: </strong>Despite extensive soliciting of AEs for ESK with the US Risk Evaluation and Mitigation Strategy program, respiratory depression is infrequently observed with ESK treatment in the postmarketing setting (estimated incidence: 1 case per 20 000 treatment sessions). Symptoms are manageable and resolve with minor supportive measures. Monitoring for symptoms of respiratory depression, including pulse oximetry, is recommended within the postdose observation period.</p>","PeriodicalId":14134,"journal":{"name":"International Journal of Neuropsychopharmacology","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}