Current Neuropharmacology最新文献

{"title":"Metabotropic Glutamate Receptor 5: A Potential Target for Neuropathic Pain Treatment.","authors":"Chalton Manengu, Chun-Hao Zhu, Guo-Dong Zhang, Miao-Miao Tian, Xiao-Bing Lan, Li-Jun Tao, Lin Ma, Yue Liu, Jian-Qiang Yu, Ning Liu","doi":"10.2174/1570159X23666241011163035","DOIUrl":"10.2174/1570159X23666241011163035","url":null,"abstract":"<p><p>Neuropathic pain, a multifaceted and incapacitating disorder, impacts a significant number of individuals globally. Despite thorough investigation, the development of efficacious remedies for neuropathic pain continues to be a formidable task. Recent research has revealed the potential of metabotropic glutamate receptor 5 (mGlu5) as a target for managing neuropathic pain. mGlu5 is a receptor present in the central nervous system that has a vital function in regulating synaptic transmission and the excitability of neurons. This article seeks to investigate the importance of mGlu5 in neuropathic pain pathways, analyze the pharmacological approach of targeting mGlu5 for neuropathic pain treatment, and review the negative allosteric mGlu5 modulators used to target mGlu5. By comprehending the role of mGlu5 in neuropathic pain, we can discover innovative treatment approaches to ease the distress endured by persons afflicted with this incapacitating ailment.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"276-294"},"PeriodicalIF":4.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808587/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459940","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":"Comparison of the Antianhedonic Effects of Repeated-dose Intravenous Ketamine in Older and Younger Adults with Major Depressive Episode.","authors":"Wei Zheng, Limei Gu, Jianqiang Tan, Yanling Zhou, Chengyu Wang, Xiaofeng Lan, Bin Zhang, Zezhi Li, Yuping Ning","doi":"10.2174/1570159X23666240923112548","DOIUrl":"10.2174/1570159X23666240923112548","url":null,"abstract":"<p><strong>Objectives: </strong>Growing evidence suggests that repeated-dose intravenous ketamine in patients with depression had rapid antianhedonic effects. However, a comparison of the antianhedonic effects of repeated-dose intravenous ketamine between younger adults and older depressed patients has not been examined.</p><p><strong>Methods: </strong>To the best of my knowledge, this study with a total of 135 patients with major depressive episodes (MDE) is the first to compare the antianhedonic effects between younger adult (n = 116) and older (n = 19) depressed patients receiving six ketamine infusions (0.5 mg/kg over 40 min). Montgomery- Åsberg Depression Rating Scale (MADRS) was applied in this study to evaluate the clinical symptoms, and MADRS anhedonia item scoring was used to evaluate anhedonia symptoms.</p><p><strong>Results: </strong>Patients received six open-label intravenous infusions of ketamine for 12 days. MADRS anhedonia subscale scores decreased in both younger (3.3, 95% CI = 2.5-4.1, p < 0.05) and older (2.8, 95% CI = 1.1-4.6, p < 0.05) MDE patients at 4h after the first infusion compared to baseline scores and the reduction was maintained over the subsequent infusion period in both groups (all Ps < 0.05). Younger MDE patients had lower MADRS anhedonia subscale scores on day 26 compared with older patients (P = 0.02). Compared with younger adult MDE patients, older patients had a lower antianhedonic response (51.7% [95% CI = 42.5%-61.0%] versus 31.6% [95% CI = 8.6%-54.6%)] and remission (24.1% [95% CI = 16.2%-32.0%] versus 0%).</p><p><strong>Conclusion: </strong>This study indicates that repeated-dose intravenous ketamine administration induces rapid and robust antianhedonic effects in older MDE patients. However, older MDE patients displayed less response to ketamine than younger adult MDE patients.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"232-239"},"PeriodicalIF":4.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343317","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":"Esketamine Treatment Trajectory of Patients with Treatment-Resistant Depression in the Mid and Long-Term Run: Data from REAL-ESK Study Group.","authors":"Gianluca Rosso, Giacomo d'Andrea, Stefano Barlati, Marco Di Nicola, Ileana Andriola, Matteo Marcatili, Vassilis Martiadis, Miriam Olivola, Stefania Di Mauro, Gabriele Di Salvo, Pasquale De Fazio, Massimo Clerici, Bernardo Maria Dell'Osso, Antonio Vita, Giorgio Di Lorenzo, Mauro Pettorruso, Giovanni Martinotti, Giuseppe Maina","doi":"10.2174/011570159X337670241029062524","DOIUrl":"https://doi.org/10.2174/011570159X337670241029062524","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Data on long-term treatment with Esketamine Nasal Spray (ESKNS) in real-world patients with treatment resistant depression (TRD) is scarce. The primary aim of the study is to evaluate the effectiveness and tolerability of ESK-NS treatment at 6 and 12-month follow-ups.</p><p><strong>Methods: </strong>This is part of an observational, retrospective, multicentric Italian study (REAL-ESK study). Subjects for the present study underwent psychiatric assessments after 6 and 12 months from the start of ESK-NS treatment. Repeated measures analysis of variance (ANOVA) was used to assess changes in continuous variables, such as scores on psychometric scales from baseline to follow-up time points.</p><p><strong>Results: </strong>Of 63 patients who maintained ESK-NS treatment for at least 6 months, 48 were responders or remitters (76.2%). Among 15 non-responders at 6 months, 4 significantly improved at 12-month follow-up. At least one side effect was reported by 71.8% of subjects with a 6-month follow-up assessment. An overall reduction of side effects was noticed as treatment progressed (42% of patients who continued the treatment reported side effects at 12 months). The most common side effects were sedation (31.7%) and dissociation (28.6%) during ESK-NS sessions. Only 2 patients discontinued ESK-NS for tolerability reasons.</p><p><strong>Conclusion: </strong>The results support the effectiveness and safety of esketamine in the mid and long-term treatment of TRD patients. The late clinical response of a subgroup of patients represents a novel finding. Data needs to be confirmed in larger samples and longer observation periods.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":"23 5","pages":"e1570159X337670"},"PeriodicalIF":4.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982709","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}

{"title":"MiRNA Dysregulation in Brain Injury: An <i>In Silico</i> Study to Clarify the Role of a MiRNA Set.","authors":"Francesco Sessa, Cristoforo Pomara, Flavia Schembari, Massimiliano Esposito, Emanuele Capasso, Mauro Pesaresi, Eduardo Osuna, Efehan Ulas, Christian Zammit, Monica Salerno","doi":"10.2174/1570159X22666240808124427","DOIUrl":"10.2174/1570159X22666240808124427","url":null,"abstract":"<p><strong>Background: </strong>The identification of specific circulating miRNAs has been proposed as a valuable tool for elucidating the pathophysiology of brain damage or injury and predicting patient outcomes.</p><p><strong>Objective: </strong>This study aims to apply several bioinformatic tools in order to clarify miRNA interactions with potential genes involved in brain injury, emphasizing the need of using a computational approach to determine the most likely correlations between miRNAs and target genes. Specifically, this study centers on elucidating the roles of miR-34b, miR-34c, miR-135a, miR-200c, and miR-451a.</p><p><strong>Methods: </strong>After a careful evaluation of different software available (analyzing the strengths and limitations), we applied three tools, one to perform an analysis of the validated targets (miRTarBase), and two to evaluate functional annotations (miRBase and TAM 2.0).</p><p><strong>Results: </strong>Research findings indicate elevated levels of miR-135a and miR-34b in patients with traumatic brain injury (TBI) within the first day post-injury, while miR-200c and miR-34c were found to be upregulated after 7 days. Moreover, miR-451a and miR-135a were found overexpressed in the serum, while miRNAs 34b, 34c, and 200c, had lower serum levels at baseline post brain injury.</p><p><strong>Conclusion: </strong>This study emphasizes the use of computational methods in determining the most likely relationships between miRNAs and target genes by investigating several bioinformatic techniques to elucidate miRNA interactions with potential genes. Specifically, this study focuses on the functions of miR-34b, miR-34c, miR-135a, miR-200c, and miR-451a, providing an up-to-date overview and suggesting future research directions for identifying theranomiRNAs related to brain injury, both at the tissue and serum levels.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"209-231"},"PeriodicalIF":4.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916308","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":"A New Augmentation Strategy against Depression Combining SSRIs and the N-terminal Fragment of Galanin (1-15).","authors":"Antonio Flores-Burgess, Carmelo Millon, Noelia Cantero-Garcia, Juan Pedro Pineda-Gomez, Marta Flores-Gomez, Zaida Diaz-Cabiale","doi":"10.2174/1570159X23666241003125019","DOIUrl":"10.2174/1570159X23666241003125019","url":null,"abstract":"<p><p>Depression is one of the most disabling mental disorders, with the second highest social burden; its prevalence has grown by more than 27% in recent years, affecting 246 million in 2021. Despite the wide range of antidepressants available, more than 50% of patients show treatment-resistant depression. In this review, we summarized the progress in developing a new augmentation strategy based on combining the N-terminal fragment of Galanin (1-15) and SSRI-type antidepressants in animal models.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"295-309"},"PeriodicalIF":4.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557362","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":"Vortioxetine <i>versus</i> SSRI/SNRI with Pregabalin Augmentation in Treatment-Resistant Burning Mouth Syndrome: A Prospective Clinical Trial.","authors":"Daniela Adamo, Federica Canfora, Giuseppe Pecoraro, Stefania Leuci, Noemi Coppola, Gaetano Marenzi, Giulia Ottaviani, Katia Rupel, Luca Pellegrini, Massimo Aria, Luca D'Aniello, Michele Davide Mignogna, Umberto Albert","doi":"10.2174/1570159X22999240729103717","DOIUrl":"https://doi.org/10.2174/1570159X22999240729103717","url":null,"abstract":"<p><strong>Objectives: </strong>The treatment of Burning Mouth Syndrome (BMS) represents a challenge in tailoring appropriate medication for individual patients. The augmentation of pregabalin to conventional treatment has shown promising outcomes in relieving pain and improving the quality of life in chronic pain conditions. This study aimed to compare the efficacy of vortioxetine with other antidepressants (SSRIs/SNRIs) in combination with pregabalin in a cohort of unresponsive BMS patients and to predict treatment response by using clinical data.</p><p><strong>Methods: </strong>A 52-week randomized, open-label, comparative clinical study was conducted, enrolling 203 BMS patients previously treated with one antidepressant for 12 weeks and non-responders to the treatment (clinical trial registration: NCT06025474). The study sample included two groups: Group A (136) received vortioxetine, while Group B (67) received SSRIs/SNRIs. Pregabalin (75 mg/day) was added to both groups, with a potential dosage increase to 150 mg/day for inadequate responders after 12 weeks. Treatment response was assessed with VAS and SF-MPQ, HAM-A, and HAM-D scores at 12, 24, 36, and 52 weeks. Stepwise logistic regression analysis was used to predict treatment response.</p><p><strong>Results: </strong>A total of 84 (61.8%) BMS patients in Group A and 39 (58.2%) in Group B showed treatment response. Group A reported a faster onset of action compared to Group B (44.8% versus 22.4% at time 1; p:0.002**) and lower adverse event rates (8.8% versus 20.8%; p:0.001).</p><p><strong>Conclusion: </strong>The addition of pregabalin to vortioxetine may be considered a potential treatment option for BMS. Further research is required to corroborate these findings and optimize personalized treatment approaches for BMS patients.</p><p><strong>Clinical trial registration number: </strong>ClinicalTrials.gov (NCT06025474).</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":"23 7","pages":"e290724232360"},"PeriodicalIF":4.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522862","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}

{"title":"Early Enteral Feeding Restores Neurofilament Light Chain Serum Levels in Preterm Newborns.","authors":"Maria Di Chiara, Gianluca Terrin, Marco Fiore, Maria Chiara De Nardo, Gianluigi Laccetta, Flavia Gloria, Antonio Minni, Christian Barbato, Carla Petrella","doi":"10.2174/1570159X23666240920165612","DOIUrl":"10.2174/1570159X23666240920165612","url":null,"abstract":"<p><strong>Background: </strong>Positive effects of early nutritional strategies on neurological outcomes have been observed when nutrients were administered by the enteral route, especially during the first week of life. Evidence reports that serum neurofilament light chain (NfL), a structural protein of neurons, is a specific and reliable biomarker of neuronal damage.</p><p><strong>Objective: </strong>The present study aimed to investigate the effect of early enteral nutrition (EN) in minimizing neuroaxonal damage and assessing NfL serum levels in preterm neonates.</p><p><strong>Methods: </strong>Fifty-four preterm neonates without severe brain impairment and 20 full-term babies as controls were enrolled from the Neonatal Intensive Care Unit at the Policlinico Umberto I in Rome. We performed blood sampling at birth (day of life 0 - DoL 0) in 20 full-term newborns and in 19 pre-term infants. Furthermore, we executed blood sampling at DoL 28 in other 22 pre-term newborns who received early enteral nutrition (EN) within the third DoL (Early-EN) and in 13 other pre-term newborns who received EN after the third DoL (Late-EN).</p><p><strong>Results: </strong>Serum levels of NfL were higher in preterm babies when compared to full-term neonates, at DoL 0 (48.81 ± 9.4 vs. 11.67 ± 1.4 pg/ml; p = 0.007). Interestingly, at DoL 28, serum NfL was significantly decreased in the Early-EN newborns compared to the Late-EN groups (15.22 ± 2.0 vs. 50.05 ± 17.9 pg/ml; p = 0.03).</p><p><strong>Conclusion: </strong>It was shown that early enteral feeding, within the first week of life, could be a useful tool for limiting neurological impairment in pre-term neonates by restoring NfL.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"349-357"},"PeriodicalIF":4.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603600","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":"An Association of Framingham Risk Score with Patient Determined Disease Steps in a Cohort of Relapsing-Remitting Multiple Sclerosis Patients: An Italian Real-World Monocentric Experience.","authors":"Aurora Zanghi, Paola Sofia Di Filippo, Carlo Avolio, Emanuele D'Amico","doi":"10.2174/1570159X22666240815120018","DOIUrl":"10.2174/1570159X22666240815120018","url":null,"abstract":"<p><strong>Background: </strong>The associations between Multiple Sclerosis (MS) and cardiovascular diseases, drawn from epidemiological studies, have attracted much attention in recent years.</p><p><strong>Materials and methods: </strong>The present study employed a monocentric, observational, retrospective cohort design. The primary objective of the study was to describe the Framingham Risk Score (FRS) rate in a cross-sectional analysis of our cohort of relapsing-remitting MS patients who are regularly followed up and, if applicable, to identify any association with the patient's Patient Determined Disease Steps (PDDS). Cardiovascular risk was classified as follows: low if the FRS is less than 10%, moderate if it is 10% to 19%, and high if it is 20% or higher.</p><p><strong>Results: </strong>A total cohort of 229 patients was enrolled. The sample consists of 163 women (71.2%). FRS categories were distributed as follows: 97 (42.3%) patients had low FRS, 84 (36.7%) patients had moderate FRS, and 48 (21%) patients had high FRS. In the univariable ordinal regression analysis, one one-point increase in the PDDS scale was associated with a 24% risk of high FRS (vs. low) (proportional odds ratio [OR] =2.426, 95% confidence interval [CI] 1.660-3.545; p <.0001). The results were also confirmed by the EDSS score, with a point increase in the EDSS score associated with a 19% risk of high FRS (vs. low) (proportional OR =1.953, 95% CI 1.429-2.669-1.04; p <.0001).</p><p><strong>Conclusion: </strong>The FRS demonstrated an association with the patient's \"perception of the disease\" as indicated by the PDDS. Further studies with larger cohorts are needed to adequately address cardiovascular risk in life-threatening conditions, such as MS.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"310-316"},"PeriodicalIF":4.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141987514","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":"The Role of Alpha-7 Nicotinic Acetylcholine Receptors in Pain: Potential Therapeutic Implications.","authors":"Yu Tao, Yufang Sun, Xinghong Jiang, Jin Tao, Yuan Zhang","doi":"10.2174/1570159X22666240528161117","DOIUrl":"10.2174/1570159X22666240528161117","url":null,"abstract":"<p><p>Chronic pain represents a prevalent and costly medical challenge globally. Nicotinic acetylcholine receptors (nAChRs), one type of ligand-gated ion channels found extensively in both the central and peripheral nervous systems, have emerged as promising therapeutic targets for chronic pain. Although there are currently no FDA-approved analgesics specifically targeting nAChRs, accumulating preclinical and clinical evidence suggest that selective ligands for alpha 7 (α7) nAChRs show potential for treating chronic pain, boasting a reduced incidence of side effects compared with other nicotinic receptor types. The recent structural resolution of human α7 nAChRs has confirmed their negative association with heightened pain, providing a valuable foundation for the development of targeted medications. This review presents a comprehensive overview, encompassing insights into the roles of α7 nAChRs derived from structural and functional studies, recent advancements in pharmacology, and investigations into their involvement in the pathophysiology of chronic pain. Moreover, the review addresses the variability in analgesic effects based on the type of receptor agonist and highlights the current research limitations. As such, this review offers potential therapeutic approaches for the development of innovative strategies for chronic pain management.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"129-144"},"PeriodicalIF":4.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11793049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160755","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":"Major Depression in Comorbidity with Substance use Disorders: Patients' Features and Clinical-Neurobiological Rationale of Antidepressant Treatments.","authors":"Sergio De Filippis, Giovanni Martinotti, Ferdinando Nicoletti, Andrea Mastrostefano, Giada Trovini, Anna Pugliese, Marco Di Nicola","doi":"10.2174/1570159X22666240827165327","DOIUrl":"10.2174/1570159X22666240827165327","url":null,"abstract":"<p><p>The frequent co-occurrence of major depressive disorder (MDD) and substance use disorders (SUDs) entails significant clinical challenges. Compared to patients with MDD alone, patients with MDD and SUD often show increased anhedonia, emotional blunting, and impaired cognitive function. These symptoms lead to an inability to control cravings, more substance use, increased relapse rates, and poor adherence to the treatment. This fosters a detrimental cycle leading to more severe depressive symptoms, functional impairment, and chronicity, culminating in heightened morbidity, mortality, and healthcare resource utilization. Data on antidepressant treatment of MDD-SUD patients are inconclusive and often conflicting because of a number of confounding factors in clinical trials or difficulty in dissecting the specific contributions of pharmacological versus psychological interventions in real-world studies. The patient's unique clinical features and specific SUD and MDD subtypes must be considered when choosing treatments. Ideally, drug treatment for MDD-SUD should act on both conditions and address core symptoms such as anhedonia, craving, and cognitive dysfunction while ensuring minimal emotional blunting, absence of drug interactions, and no addictive potential. This approach aims to address unmet needs and optimize the outcomes in a clinical population often underrepresented in treatment paradigms.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"256-275"},"PeriodicalIF":4.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105210","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}