Journal of Psychopharmacology最新文献

{"title":"Antipsychotic polypharmacy and high-dose antipsychotic therapy compared to antipsychotic monotherapy at standard doses in schizophrenia - a systematic review.","authors":"Christopher Lawrence, Chloe Roberts, Chloe Galides, Samuel R Chamberlain, Ruihua Hou","doi":"10.1177/02698811241303652","DOIUrl":"10.1177/02698811241303652","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia is considered to have a lifetime prevalence of around 1%. Up to 30% of patients diagnosed with schizophrenia are subsequently categorised as treatment resistant. Current guidelines advise against the use of antipsychotic polypharmacy (APP) or high-dose antipsychotic therapy (HDAT) in the treatment of schizophrenia; however, these treatment approaches continue to be used in up to 25% of cases.</p><p><strong>Aims: </strong>This review was to evaluate the evidence for the efficacy and tolerability of APP and HDAT as an alternative to antipsychotic monotherapy at standard doses in the treatment of schizophrenia.</p><p><strong>Methods: </strong>This is a systematic review. We searched PubMed, EMBASE and PsycINFO, for eligible trials published prior to 24 March 2023. The protocol was registered on PROSPERO (CRD42023408785). Quality assessment was conducted using the Revised Cochrane risk-of-bias tool for randomised trials.</p><p><strong>Results: </strong>A total of 14 studies were included in this review. Two studies demonstrated clinically significant improvement with APP compared to standard treatment. There was no clear evidence that APP or HDAT is definitively less tolerable than antipsychotic monotherapy at a standard dose.</p><p><strong>Conclusions: </strong>This review found limited evidence for the efficacy of APP and HDAT in the treatment of schizophrenia over the use of antipsychotic monotherapy at a standard dose. The relative tolerability was unclear. Management of treatment-resistant schizophrenia remains a prominent clinical issue and further research, including high-quality large-scale Randomised Controlled Trials (RCTs) of APP and HDAT in patients who have been unresponsive to clozapine, would be of significant benefit to the field of psychiatry.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"132-140"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The efficacy of vortioxetine in the acute treatment of major depressive disorder: A systematic review and meta-analysis.","authors":"Isabella Berardelli, Elena Rogante, Federico Formica, Riccardo Iannazzo, Attilio Valerio Mammoliti, Raffaele Riccioni, Skender Veizi, Roger S McIntyre, Maurizio Pompili","doi":"10.1177/02698811241309612","DOIUrl":"10.1177/02698811241309612","url":null,"abstract":"<p><strong>Background: </strong>Among the available pharmacological treatments for acute major depressive disorder (MDD), vortioxetine, a serotonin transporter inhibitor (SERT), has been widely used for its multimodal action on serotonin neurotransmission, which produces essential changes also on glutamate, gamma amino butyric acid (GABA), norepinephrine, acetylcholine, and dopamine.</p><p><strong>Aim: </strong>This systematic review and meta-analysis aimed to evaluate the acute efficacy of vortioxetine across multiple dosing and to evaluate whether there is a dose-response effect and as well there is a dose-response issue with respect to side effects in acute depression.</p><p><strong>Methods: </strong>According to PRISMA guidelines, we systematically searched three major electronic databases (PubMed/MEDLINE, PsycINFO, and Cochrane Central Register of Controlled Trials) for Randomized Controlled Trial (RCT) studies published between January 2013 and April 2024. Twenty-four studies were included in the review and two meta-analyses were conducted to determine whether the mean Montgomery-Asberg Depression Rating Scale (MADRS) scale values in the placebo groups differ significantly from the mean MADRS scale values in the group receiving vortioxetine 10 mg or vortioxetine 20 mg.</p><p><strong>Results: </strong>Vortioxetine significantly improved acute depression severity, anxiety symptoms, and cognitive function, with high response and remission rates in acute MDD. It was also well tolerated with a relatively low occurrence of severe or serious treatment-emergent adverse events (TEAEs). Observing the results of the meta-analysis, the effect was significant for both vortioxetine 10 and 20 mg, with a greater effect size for vortioxetine 20 mg.</p><p><strong>Conclusion: </strong>Vortioxetine should be considered efficacious as a first- and second-line therapy.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"92-105"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study).","authors":"R Hamish McAllister-Williams, Nicola Goudie, Lumbini Azim, Victoria Bartle, Michael Berger, Chrissie Butcher, Thomas Chadwick, Emily Clare, Paul Courtney, Lyndsey Dixon, Nichola Duffelen, Tony Fouweather, William Gann, John Geddes, Sumeet Gupta, Beth Hall, Timea Helter, Paul Hindmarch, Eva-Maria Holstein, Ward Lawrence, Phil Mawson, Iain McKinnon, Adam Milne, Aisling Molloy, Abigail Moore, Richard Morriss, Anisha Nakulan, Judit Simon, Daniel Smith, Bryony Stokes-Crossley, Paul Ra Stokes, Andrew Swain, Adeola Taiwo, Zoë Walmsley, Christopher Weetman, Allan H Young, Stuart Watson","doi":"10.1177/02698811241309622","DOIUrl":"10.1177/02698811241309622","url":null,"abstract":"<p><strong>Background: </strong>Options for 'treatment-resistant bipolar depression' (TRBD) are limited. Two small, short-term, trials of pramipexole suggest it might be an option.</p><p><strong>Aims: </strong>To evaluate the clinical effectiveness and safety of pramipexole in the management of TRBD.</p><p><strong>Methods: </strong>A multi-centre randomised, double-blind controlled trial including participants ⩾18 years old with TRBD (failure to respond, tolerate or clinical contraindication/patient refusal of ⩾2 of quetiapine, olanzapine, lamotrigine or lurasidone) randomised 1:1 to pramipexole (max 2.5 mg/day salt weight) or placebo added to ongoing mood stabiliser (<i>n</i> = 39). Primary outcome: Quick Inventory of Depressive Symptoms, Self-rated (QIDS-SR) at 12 weeks. Up to 48 weeks follow-up.</p><p><strong>Results: </strong>Pramipexole (<i>n</i> = 18) was associated with a greater reduction in QIDS-SR score at 12 weeks versus placebo (<i>n</i> = 21, 4.4 (4.8) vs 2.1 (5.1)): a medium sized (<i>d</i> = -0.72) but not statistically significant difference (95% CI: -0.4 to 6.3, <i>p</i> = 0.087). Similarly, there was a non-significant approximate 2-point (<i>d</i> = -0.76) improvement in pleasure at 6 weeks (95% CI: -0.11 to 4.20). Significant advantages of pramipexole on QIDS-SR score (6.28 points: 95% CI: 1.85-10.71) and psychosocial function (5.36 points: 95% CI: 0.38-10.35) were seen at 36 weeks post-randomisation, and on the response (46% vs 6%; <i>p</i> = 0.026) and remission (31% vs 0%; <i>p</i> = 0.030) rates at trial exit (48 weeks or last available data after 16 weeks for those affected by the early study closure). Hypomania ratings were significantly higher at 12 weeks. Otherwise, pramipexole was well tolerated.</p><p><strong>Conclusions: </strong>Clinically large, but statistically non-significant, effects of pramipexole on depression at 12 weeks, with significant longer-term benefits on mood and function were observed. Pramipexole use was complicated by dose titration and increased hypomanic symptoms. The small sample size limits interpretation. Furthermore, larger randomised placebo-controlled trials are warranted.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"106-120"},"PeriodicalIF":4.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketamine: Therapeutic potential versus recreational misuse.","authors":"Mario F Juruena, Allan H Young","doi":"10.1177/02698811241308935","DOIUrl":"https://doi.org/10.1177/02698811241308935","url":null,"abstract":"","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":"39 1","pages":"3-4"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketamine for refractory depression: Save the best for last?","authors":"Kabir Nigam, Franklin King, Fernando Espi Forcen","doi":"10.1177/02698811241282646","DOIUrl":"10.1177/02698811241282646","url":null,"abstract":"<p><p>Ketamine has recently been shown to be non-inferior to electroconvulsive therapy (ECT), one of psychiatry's most effective treatments for depression. Given the novelty of ketamine as well as its interventional nature, ketamine is currently viewed as an alternative to ECT and as such, considered a third-line agent for treatment-refractory depression. However, available data suggest that ketamine carries a low side-effect burden and is better tolerated than many second-line augmentation strategies for depression. With this combination of higher efficacy and lower side-effect burden in conjunction with what is known about treatment outcomes in relation to the duration of untreated illness, it is in the best interest of patients for the field of psychiatry to evaluate ketamine as a second-line augmentation strategy for refractory depression.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"5-7"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm.","authors":"Henry A MacConnel, Mitch Earleywine, Steven Radowitz","doi":"10.1177/02698811241286726","DOIUrl":"10.1177/02698811241286726","url":null,"abstract":"<p><strong>Background: </strong>Traditional treatments for post-traumatic stress disorder (PTSD) often show limited success with high dropout. Ketamine, an <i>N</i>-methyl-D-aspartate antagonist known for rapid antidepressant effects, has decreased PTSD symptoms in some studies but not in others. Administering ketamine in ways that parallel psychedelic-assisted treatments-including preparatory, integration, sensory immersion, and psychotherapy sessions-could decrease PTSD symptoms meaningfully.</p><p><strong>Methods: </strong>A retrospective sample of 117 screened outpatients with elevated PTSD Checklist for DSM-5 (PCL-5) scores received intravenous ketamine in supportive environments. The protocol included preparation, intention-setting, and integration sessions accompanying at least six administrations. Administration sessions included eye shades and evocative music paralleling typical psychedelic therapy trials.</p><p><strong>Results: </strong>Mean PCL scores decreased from 52.54 (SD = 12.01) to 28.78 (SD = 16.61), <i>d</i> = 1.64. Patients tolerated treatment well, with no serious adverse events. Covariates, including age, gender, days between PCL assessments, number of psychiatric medications, and suicidal ideation were not significant moderators; concomitant psychotherapy did reach significance, <i>d</i> = 0.51. Of the 117 patients' final PCL scores, 88 (75.21%) measures suggested clinically meaningful improvement and 72 (61.54%) suggested remission of PTSD symptoms.</p><p><strong>Conclusion: </strong>Intravenous ketamine in supportive environments, with hallmarks of psychedelic therapy, preceded large reductions in PTSD symptoms. These results highlight ketamine's potential when delivered in this manner, suggesting environmental factors might account for some variation seen in previous work. Given the molecule's cost, minimal interaction with other psychiatric medications, and legal status, intravenous ketamine in a psychedelic paradigm may be a promising option for PTSD unresponsive to other treatments.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"29-37"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combining bioinformatics, network pharmacology and artificial intelligence to predict the target genes of S-ketamine for treating major depressive disorder.","authors":"Zhou Xianjin, Shen Fuyi, Yang Ti, Li Shan, Zhao Kang, Wang Ying, Deng Shengqiong","doi":"10.1177/02698811241268884","DOIUrl":"10.1177/02698811241268884","url":null,"abstract":"<p><strong>Background: </strong>Ketamine has received attention owing to its rapid and long-lasting antidepressant effects; however, its clinical application is restricted by its addictiveness and adverse effects. S-ketamine, which is the S-enantiomer of ketamine, is considered safer and better tolerated by patients than ketamine.</p><p><strong>Aims: </strong>This study aimed to identify the key gene targets and potential signalling pathways associated with the mechanism of S-ketamine in major depressive disorder (MDD) treatment.</p><p><strong>Methods: </strong>The GSE98793 dataset was extracted from the Gene Expression Omnibus database, and differentially expressed genes were identified in blood samples from patients with MDD and healthy individuals. The hub genes among the differentially expressed genes were identified and enrichment analysis was performed. The therapeutic targets and related signalling pathways of S-ketamine in MDD treatment were analysed. The 3D structures of the target proteins were predicted using AlphaFold2, and molecular docking was performed to verify whether S-ketamine could be successfully docked to the predicted targets. A quantitative polymerase chain reaction was performed to determine the effect of ketamine on the screened targets. Among 228 target genes annotated using pharmacophore target gene analysis, 3 genes were identified and 2 therapeutic signalling pathways were discovered.</p><p><strong>Results: </strong>S-ketamine exerts downregulatory effects on TGM2 and HSP90AB1 expression but exerts an up-regulatory effect on ADORA3 expression. The protein structures of the therapeutic targets were successfully predicted using AlphaFold2.</p><p><strong>Conclusions: </strong>S-ketamine may alleviate depression by targeting specific genes, including <i>TGM2</i>, <i>HSP90AB1</i> and <i>ADORA3</i>, as well as signalling pathways, including the gonadotropin-releasing hormone and relaxin signalling pathways.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"66-75"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is there a risk of addiction to ketamine during the treatment of depression? A systematic review of available literature.","authors":"Gianmarco Ingrosso, Anthony J Cleare, Mario F Juruena","doi":"10.1177/02698811241303597","DOIUrl":"10.1177/02698811241303597","url":null,"abstract":"<p><strong>Background: </strong>Ketamine has demonstrated both rapid and sustained efficacy in treating depression, especially in treatment-resistant cases. However, concerns regarding the addictive potential of ketamine during long-term depression treatment persist among clinicians.</p><p><strong>Aim: </strong>This review aimed to summarise the evidence on addiction phenomena associated with ketamine treatment of depression.</p><p><strong>Methods: </strong>A comprehensive search was conducted in MEDLINE, Embase, PsycInfo and Global Health databases, with additional relevant studies identified through reference lists. Sixteen studies were included, comprising six randomised controlled trials, three single-arm open-label studies, one retrospective study, three case series and three case reports, for a total of 2174 patients.</p><p><strong>Results: </strong>The studies employed various routes of administration, including intravenous, intramuscular, intranasal, oral and sublingual. Ketamine was administered in the racemic form, except for the studies that utilised intranasal esketamine. Among the included population, four patients were reported to exhibit clear signs of tolerance to the antidepressant effect of ketamine or dependence on the drug, while the majority did not. Cases of addiction phenomena reported in studies that did not meet the inclusion criteria are also discussed.</p><p><strong>Conclusions: </strong>Despite the heterogeneity in study designs and outcome assessment methods, the review underscores the relative safety of ketamine treatment for adult patients with depression, emphasising the importance of medically supervised administration, vigilant monitoring and judicious dosing. Future long-term studies employing quantitative scales to assess dependence phenomena could contribute to strengthening the evidence for the safe and effective use of ketamine in the treatment of depression.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"49-65"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ketamine use in a large global sample: Characteristics, patterns of use and emergency medical treatment.","authors":"Karen P Barrios, Dean J Connolly, Jason A Ferris, Larissa J Maier, Monica J Barratt, Adam R Winstock, Cheneal Puljević, Gail Gilchrist","doi":"10.1177/02698811241273850","DOIUrl":"10.1177/02698811241273850","url":null,"abstract":"<p><strong>Background: </strong>Ketamine's popularity has surged globally in the past decade, especially among young men. Emergency department visits due to its toxicity remain relatively rare, often linked to co-occurring use of other substances.</p><p><strong>Aims: </strong>Using data from the Global Drug Survey (GDS) 2018, this study explored the correlates associated with lifetime and past-year ketamine use, and estimated the socio-demographic characteristics, usage patterns and experiences of respondents seeking emergency medical treatment (EMT) after ketamine use.</p><p><strong>Methods: </strong>Secondary analysis of GDS 2018, an online cross-sectional survey on drug use patterns conducted between November 2017 and January 2018.</p><p><strong>Results: </strong>The survey received 130,761 valid responses, with 5.93% reporting lifetime ketamine use, of which 57.70% used ketamine within the past year. Predominantly, respondents were from Germany, England and Denmark. Within the past year, 8.55% met the criteria for ketamine dependence. Respondents who used ketamine in their lifetime tended to be young (mean (x̄) = 27.37 years), men, heterosexual and of white ethnicity. Younger age (x̄ = 24.84 years), gay sexual orientation, student status, past-year use of other drugs and no lifetime mental health diagnosis were associated with past-year ketamine use. Among 4477 respondents reporting past-year ketamine use, 120 adverse events were reported, with less than 0.10% prompting EMT seeking.</p><p><strong>Conclusion: </strong>The study reveals frequent ketamine use but low harm occurrence, underscoring the complex interplay between ketamine use, substance use and dependence, and related factors. This underscores the need to reassess EMT priorities, implement tailored harm reduction strategies and incorporate comprehensive screening for addressing ketamine and substance dependence challenges.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"8-22"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Compassionate use of esketamine intranasal in patients with severe major depressive disorder resistant to the treatment.","authors":"Luis Gutiérrez-Rojas, Julia Vendrell-Serres, J Antoni Ramos-Quiroga, Jon Iñaki Etxeandia-Pradera, Eduardo Aguilar, Ana Isabel De Santiago-Díaz, Daniel Hernández-Huerta, Vicente Tordera, Carlos Vázquez-Ventoso, Moisés Bolívar, Asunción Abril, Rubén Catalán-Barragán, Jesús García-Jiménez","doi":"10.1177/02698811241267837","DOIUrl":"10.1177/02698811241267837","url":null,"abstract":"<p><strong>Background: </strong>Treatment-resistant depression (TRD) is defined as the failure of at least two antidepressants in adequate doses and timing during a major depressive episode. Esketamine intranasal (ESK-IN) has been approved by the Food and Drug Administration and the European Medicines Agency for the treatment of TRD in combination with other antidepressants.</p><p><strong>Aims: </strong>To assess the effectiveness and tolerability of a sample of TRD patients who received treatment with ESK-IN as part of the compassionate use program.</p><p><strong>Methods: </strong>A retrospective, observational study was carried out on patients with a diagnosis of TRD enrolled in the early access program of ESK-IN in nine centers. Effectiveness was assessed with the Montgomery-Asberg depression rating scale (MADRS) at four time points: baseline, 28, 90, and 180 days of treatment.</p><p><strong>Results: </strong>The sample included 71 patients (70% women) with a mean baseline MADRS score of 38.27 ± 5.9 and total or partial work disability rates of 85%. ESK-IN treatment was associated with a statistically and clinically significant reduction in the severity of depressive symptoms at all time points assessed. The presence of side effects was common but the majority were mild in severity and resolved after the observation period. Those patients who received psychotherapy in combination with ESK-IN showed a significantly lower MADRS score at 90 and 180 days than those patients who did not undergo psychotherapy.</p><p><strong>Conclusion: </strong>ESK-IN has proven to be effective and safe in a clinical sample of patients with severe TRD. To optimize clinical outcomes, the pharmacological treatment for TRD should always be integrated into a comprehensive therapeutic plan that encompasses strategies such as psychotherapy, social support, and family interventions.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"38-48"},"PeriodicalIF":4.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}