Fabrizio Turiaco, Federico Arnone, Antonio Drago, Maria Rosaria Anna Muscatello, Antonio Bruno, Fiammetta Iannuzzo
{"title":"Escitalopram and functional connectivity in major depressive disorder: A systematic review.","authors":"Fabrizio Turiaco, Federico Arnone, Antonio Drago, Maria Rosaria Anna Muscatello, Antonio Bruno, Fiammetta Iannuzzo","doi":"10.1177/02698811251370998","DOIUrl":"https://doi.org/10.1177/02698811251370998","url":null,"abstract":"<p><p>Functional connectivity (FC) plays a critical role in understanding major depressive disorder (MDD) and treatment mechanisms. Altered FC patterns, particularly within the default mode network (DMN), have been associated with MDD symptoms and therapeutic outcomes. This study systematically reviews the literature on Escitalopram, a selective serotonin reuptake inhibitor (SSRI) with a particular receptor profile, in relation to FC in MDD. A systematic review was conducted using three databases: PubMed, Scopus, and Web of Science. Eleven articles meeting the inclusion criteria were categorized into two groups: treatment effects (six studies) and treatment response prediction (five studies). The six treatment effect studies included 198 patients with MDD and 219 control participants: 205 healthy controls and 14 placebo-treated patients. These studies highlighted Escitalopram's ability to normalize baseline FC disruptions (hypo- or hyperconnectivity), particularly in DMN subsystems. The five treatment prediction studies examined 159 MDD patients, 97 healthy controls, 22 placebo-treated individuals, and 56 non-responders. Poor treatment efficacy was linked to baseline hypoconnectivity in the dorsolateral prefrontal cortex and altered connectivity between the DMN and the frontoparietal network. Overall, Escitalopram treatment appears to restore FC by normalizing both hyperconnectivity and hypoconnectivity patterns associated with MDD, suggesting a rebalancing of network dynamics underlying symptom improvement. Normalization of altered FC patterns after treatment and associations between baseline FC and treatment response suggest FC's potential as a biomarker for understanding and predicting SSRI efficacy.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251370998"},"PeriodicalIF":5.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191814","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}
Jade Pullen, John M Corkery, Rebecca McKnight, Caroline S Copeland
{"title":"Deaths following illicit ketamine use in England, Wales and Northern Ireland 1999-2024: An update report to inform the reclassification debate.","authors":"Jade Pullen, John M Corkery, Rebecca McKnight, Caroline S Copeland","doi":"10.1177/02698811251373058","DOIUrl":"https://doi.org/10.1177/02698811251373058","url":null,"abstract":"<p><strong>Background: </strong>Ketamine is increasingly used in the United Kingdom in non-clinical settings for its psychoactive effects, with rising reports of harms including hospital admissions, dependence and deaths. In light of current debates surrounding the reclassification of ketamine under the Misuse of Drugs Act 1971, up-to-date surveillance of associated mortality is warranted.</p><p><strong>Aims: </strong>We aimed to quantify trends in deaths following illicit ketamine use in England, Wales and Northern Ireland, and to examine changes in demographic and contextual characteristics since the last national analysis which comprised illicit ketamine deaths up to 2019.</p><p><strong>Methods: </strong>Cases where illicit ketamine was detected at post-mortem were extracted from the National Programme on Substance Use Mortality and analysed.</p><p><strong>Results: </strong>There were 696 deaths identified with illicit ketamine between 1999 and 2024. Annual deaths increased over 10-fold from 2014 (15 deaths) to 2024 (197 projected deaths). Whilst absolute deaths implicating illicit ketamine rose (2014: 6 deaths; 2023: 123 projected deaths), the proportion of deaths where illicit ketamine was implicated in causing death declined (2014: 60.0% of cases; 2024: 42.6% of cases). Concurrently, polydrug use increased (median number of co-administered substances 1999-2004: 3; 2005-2009: 3, 2010-2014: 4, 2015-2019: 6; 2020-2024: 6), and the demographic profile of decedents shifted towards greater deprivation and dependence-related contexts.</p><p><strong>Discussion and conclusions: </strong>There has been an acceleration in deaths following illicit ketamine in recent years, which are increasingly featuring complex patterns of polydrug use and socio-economic vulnerability. Policy responses must extend beyond single-substance legislative controls to encompass harm reduction, treatment integration, and social support strategies.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251373058"},"PeriodicalIF":5.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191865","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}
Rubina Fray Gogolu, Alexander Tobias Ysbæk-Nielsen, Jon Lansner
{"title":"The effects of antenatal depression and SSRI exposure on children: A systematic review.","authors":"Rubina Fray Gogolu, Alexander Tobias Ysbæk-Nielsen, Jon Lansner","doi":"10.1177/02698811251370973","DOIUrl":"https://doi.org/10.1177/02698811251370973","url":null,"abstract":"<p><strong>Introduction: </strong>Antenatal depression (AD) affects 7%-13% of pregnant women, with adverse implications for mother and child. Treatment often requires pharmacological intervention, typically with selective serotonin reuptake inhibitors (SSRIs). However, it remains unclear whether SSRIs introduce developmental consequences in children distinct from those associated with AD alone. This systematic review aims to elucidate the behavioral and neurological consequences of AD and prenatal SSRI exposure on child development.</p><p><strong>Methods: </strong>A systematic review of databases PubMed, PsycInfo, Web of Science, and Scopus was conducted using the PICO framework. Studies were eligible if they included at least two comparison groups: children with exposure to only AD (AD-only) and those exposed to both AD and in utero SSRIs (AD + SSRI). A total of 14 articles were included.</p><p><strong>Results: </strong>Studies report effects of both AD + SSRI and AD-only exposure on several measures. When compared to controls (CON), both AD + SSRI and AD-only displayed alterations in the corticolimbic system, abnormal language development, and increases in internalizing and externalizing problems. Specific to AD + SSRI were alterations in the corticothalamic system and impairment of psychomotor functioning. Specific to AD-only were steeper white matter volume increases across childhood and lower arousal scores as infants. No significant differences between AD + SSRI, AD-only, and CON were reported on attention and interference suppression. Notably, inconsistencies were found on several measurements, for example, IQ, cortical, and subcortical volume.</p><p><strong>Conclusion: </strong>We present an updated review of the potential implications of AD and SSRIs on child development. Ultimately, a preponderance of observational studies and numerous confounding factors make their effects difficult to disentangle, underscoring the need for further research.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251370973"},"PeriodicalIF":5.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137800","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}
You-Ran Dai, Yan-Kun Wu, Lin-Lin Zhu, Qian Yu, Ke Li, Ya-Wei Zeng, Ji-Tao Li, Yun-Ai Su, Ming-Rui Xia, Tian-Mei Si
{"title":"Eight-week antidepressant treatment effects on connectome gradient in first-episode drug-naïve patients with major depressive disorder.","authors":"You-Ran Dai, Yan-Kun Wu, Lin-Lin Zhu, Qian Yu, Ke Li, Ya-Wei Zeng, Ji-Tao Li, Yun-Ai Su, Ming-Rui Xia, Tian-Mei Si","doi":"10.1177/02698811251370981","DOIUrl":"https://doi.org/10.1177/02698811251370981","url":null,"abstract":"<p><strong>Background: </strong>Given the limited understanding of the pathogenesis underlying depression and the specific targets of antidepressant medications, treatment of depression predominantly relies on empirical methodologies. Previous magnetic resonance imaging studies utilizing connectome gradient methods have revealed disruptions of the principal gradient in major depressive disorder (MDD) patients. However, the semiological meaning of the brain gradient and the effect of antidepressants are unknown.</p><p><strong>Methods: </strong>We recruited MDD patients and healthy controls to investigate baseline alterations in the principal connectome gradient. Changes in gradient scores were further analyzed within the responder group post-treatment, and repeated measures ANOVA was used to assess the gradient score changes across time (within-subject) and antidepressant types (between-subject).</p><p><strong>Results: </strong>Compared to controls, MDD patients exhibited gradient score alterations in default and visual networks. After antidepressant treatment, the gradient scores for the left ventromedial prefrontal cortex (VMPFC) increased in patients who responded to therapy. The gradient scores for left VMPFC had an interaction effect between time and antidepressant types and correlated negatively with the core factor scores of HRSD<sub>17</sub> at baseline.</p><p><strong>Conclusion: </strong>These results highlight the single-target antidepressants' effects on gradient scores for left VMPFC and provide evidence for future treatment targets and neurobiological underpinnings of antidepressant therapy.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251370981"},"PeriodicalIF":5.5,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131236","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":"High dose of psilocybin induces acute behavioral changes without inducing conditioned place preference in Sprague-Dawley rats.","authors":"Vitor Bruno, Martha López-Canul, Brandon Richardson, Rosana Camarini, Tania Marcourakis, Gabriella Gobbi","doi":"10.1177/02698811251368361","DOIUrl":"https://doi.org/10.1177/02698811251368361","url":null,"abstract":"<p><strong>Background: </strong>In recent years, there has been a resurgence of scientific interest in psychedelics, including psilocybin, for their potential in treating neuropsychiatric disorders. However, the reward-related effects of psilocybin and its impact on behavior remain underexplored.</p><p><strong>Aims: </strong>We aimed to evaluate the potential rewarding effects of high doses of psilocybin and its effects on rat behavior.</p><p><strong>Methods: </strong>Sprague-Dawley rats were exposed to the conditioned place preference (CPP) paradigm. Over an 8-day period, rats were administered either psilocybin (10 mg/kg, i.p.) or vehicle (0.9% saline, i.p.) on odd conditioning days, while receiving vehicle (0.9% saline, i.p.) on even conditioning days. The potential rewarding effect induced by psilocybin was assessed 48 hours after the last psilocybin injection. Behavioral assessments, including head twitch, body shaking, grooming, body licking, defecation pellets, and rearing, were conducted during the CPP exposure.</p><p><strong>Results: </strong>Psilocybin did not induce CPP in rats, highlighting its lack of reinforcing effects under these conditions. However, this regimen of administration led to modifications in the behavioral profile during CPP test by increasing head twitching, wet-wet-dog shaking, and defecation pellets and decreasing grooming, body licking, and rearing compared to the vehicle group. Importantly, 48 hours after the final psilocybin injection, no behavioral differences were observed between psilocybin and vehicle groups.</p><p><strong>Conclusion: </strong>Psilocybin at this regimen (10 mg/kg, every other day) does not induce CPP, but induces changes in behavior, which disappear 48 hours after the last injection. More research is needed to better evaluate the addiction liability of psychedelics using different paradigms, doses, and protocols.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251368361"},"PeriodicalIF":5.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145125035","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":"Meta-analysis of clozapine and somnolence in schizophrenia.","authors":"Matthew R Hopkins, Brian J Miller","doi":"10.1177/02698811251364385","DOIUrl":"https://doi.org/10.1177/02698811251364385","url":null,"abstract":"<p><strong>Background: </strong>Clozapine has anti-suicidal properties and significant effects on sleep. Sleep disturbances are associated with suicide risk. Daytime somnolence and sedation are commonly reported adverse effects of clozapine treatment.</p><p><strong>Aims: </strong>Systematic review and meta-analysis of somnolence in randomized controlled trials (RCTs) of patients with schizophrenia treated with clozapine.</p><p><strong>Methods: </strong>We systematically searched PubMed, PsycINFO, and Web of Science databases. We included RCTs, in English, with data on somnolence in patients with schizophrenia treated with clozapine versus other antipsychotics. Data were pooled using a random effects model.</p><p><strong>Results: </strong>Twenty-two RCTs (2991 patients: 1404 on clozapine and 1587 on other antipsychotics) met inclusion criteria. Patients treated with clozapine had a significantly increased odds of somnolence compared to other antipsychotics (36.3% vs 21.9%, OR = 2.06, 95% CI: 1.65-2.57, <i>p</i> < 0.01). Clozapine was also associated with significantly increased odds of somnolence compared to olanzapine and risperidone. In meta-regression analyses, clozapine dose, age, sex, race, and publication year were unrelated to the association.</p><p><strong>Conclusions: </strong>Clozapine is associated with significantly more somnolence, compared to other antipsychotics. A greater mechanistic understanding of associations between sleep changes and suicide risk in patients treated with clozapine is needed.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251364385"},"PeriodicalIF":5.5,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080861","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}
Joel L Young, Richard N Powell, Anna Powell, Lisa L M Welling, Lauren Granata, Jaime Saal
{"title":"Solriamfetol improves daily fatigue symptoms in adults with myalgic encephalomyelitis/chronic fatigue syndrome after 8 weeks of treatment.","authors":"Joel L Young, Richard N Powell, Anna Powell, Lisa L M Welling, Lauren Granata, Jaime Saal","doi":"10.1177/02698811251368371","DOIUrl":"https://doi.org/10.1177/02698811251368371","url":null,"abstract":"<p><strong>Background: </strong>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a long-term illness with no treatment options that address the disease directly. Solriamfetol is a selective dual norepinephrine-dopamine reuptake inhibitor that promotes wakefulness in obstructive sleep apnea and narcolepsy.</p><p><strong>Aims: </strong>This study evaluated the efficacy and safety of solriamfetol for fatigue symptoms in adults with ME/CFS over 8 weeks of treatment.</p><p><strong>Methods: </strong>This was a phase 4, double-blind, randomized, placebo-controlled trial of solriamfetol in adults with ME/CFS. Eligible participants (<i>N</i> = 38) were randomly assigned to receive 75 mg (titrated to 150 mg as needed) solriamfetol or placebo. Participants completed a battery of assessments at weekly visits. The primary outcome was Fatigue Symptom Inventory (FSI) scores, and the secondary outcome measure was Behavioral Rating Inventory of Executive Function for Adults (BRIEF-A), at Weeks 6 and 8. T-tests assessed the differences in mean change from baseline between solriamfetol and placebo. Adverse events were monitored throughout the study.</p><p><strong>Results: </strong>At Week 8 (<i>p</i> = 0.039), but not Week 6 (<i>p</i> = 0.270), solriamfetol improved FSI severity compared to placebo. On the BRIEF-A global executive composite, solriamfetol improved more than placebo at Week 8 (<i>p</i> = 0.012), driven by improved metacognition index (<i>p</i> = 0.004), but not behavioral regulation index (<i>p</i> = 0.574). Solriamfetol was well tolerated, with most common AEs being sleep loss and headaches.</p><p><strong>Conclusions: </strong>Solriamfetol demonstrated good safety and efficacy in improving fatigue and executive functioning in patients with ME/CFS. As a dual norepinephrine-dopamine reuptake inhibitor and wakefulness-promoting factors, solriamfetol has the potential to improve fatigue symptoms of ME/CFS.</p><p><strong>Clinical trial number: </strong>NCT04622293.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251368371"},"PeriodicalIF":5.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075524","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}
Ramona L Martinez, Nina Radošić, Hanna Molla, Harriet de Wit, Sonja Lyubomirsky
{"title":"The empathogen 3,4-methylenedioxymethamphetamine, but not methamphetamine, increases feelings of global trust.","authors":"Ramona L Martinez, Nina Radošić, Hanna Molla, Harriet de Wit, Sonja Lyubomirsky","doi":"10.1177/02698811251370999","DOIUrl":"https://doi.org/10.1177/02698811251370999","url":null,"abstract":"<p><strong>Background: </strong>The empathogen and psychostimulant 3,4-methylenedioxymethamphetamine (MDMA) is thought to boost both subjective well-being and social connection. Although MDMA is considered to enhance social connection to a greater extent than other stimulant drugs, few studies have compared MDMA to other stimulants. In addition, previous studies have focused on social positivity effects (e.g., increased trust) for specific in-lab interaction partners without considering more generalized social positivity effects (e.g., trust in one's community).</p><p><strong>Aims: </strong>We tested the effects of MDMA on subjective ratings of well-being and global social connection, including feelings of trust toward one's community and society. The effects of MDMA were compared to a prototypic stimulant, methamphetamine (MA).</p><p><strong>Methods: </strong>Across two studies, we examined differences in subjective well-being and global social well-being 90 minutes after a conversation on MDMA (study 1; <i>N</i> = 15; 100 mg) and after a conversation on MA (study 2; <i>N</i> = 20; 20 mg) compared to a placebo.</p><p><strong>Results: </strong>After MDMA, participants reported significantly higher global trust, <i>t</i>(14) = -2.583, <i>p</i> = 0.022, and marginally higher self-worth, <i>t</i>(14) = -2.000, <i>p</i> = 0.065, compared with after the placebo. Furthermore, MA did not alter scores of subjective well-being and social connection.</p><p><strong>Conclusions: </strong>Our findings extend previous research by demonstrating that MDMA increases feelings of trust in the social world beyond lab-specific interaction partners. These findings are consistent with user reports of generalized social well-being effects and support the idea that MDMA may have clinical value from a social psychological perspective.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251370999"},"PeriodicalIF":5.5,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075553","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":"Loss of responsiveness on reinstatement of antidepressants after treatment interruption - A systematic review.","authors":"Ninoslav Majkic, David Taylor","doi":"10.1177/02698811251364388","DOIUrl":"https://doi.org/10.1177/02698811251364388","url":null,"abstract":"<p><strong>Background: </strong>The societal burden of depression continues to increase despite the greater use of antidepressants. It is not clear why wider antidepressant prescribing has not reduced the impact of depression at a population level. One possible explanation is that intermittent use of antidepressants at an individual level might reduce responsiveness to antidepressants.</p><p><strong>Methods: </strong>We searched EMBASE and PubMed from the beginning of records to June 2024 for articles describing loss of response to antidepressants (in any psychiatric condition) occurring as a result of interruption in treatment. We did not restrict our search with respect to language or date.</p><p><strong>Results: </strong>We found 6869 articles of potential interest, of which 5360 were excluded after initial screening by title, and 1453 were excluded as duplicates. We ultimately included 12 studies that provided data on 594 participants. Non-response was reported in 4%-57% of people who stopped and restarted antidepressant treatment that was previously effective.</p><p><strong>Conclusion: </strong>Non-continuous consumption of antidepressants leads to a loss of responsiveness in an important proportion of people. Intermittent adherence to antidepressants may lessen their effectiveness and explain the relationship between wider antidepressant use and increased societal burden of depression.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251364388"},"PeriodicalIF":5.5,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145053826","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}
Stephan C Tap, Kelan Thomas, Tomáš Páleníček, Dea S Stenbæk, Albino J Oliveira-Maia, Jens van Dalfsen, Robert Schoevers
{"title":"Concomitant use of antidepressants and classic psychedelics: A scoping review.","authors":"Stephan C Tap, Kelan Thomas, Tomáš Páleníček, Dea S Stenbæk, Albino J Oliveira-Maia, Jens van Dalfsen, Robert Schoevers","doi":"10.1177/02698811251368360","DOIUrl":"https://doi.org/10.1177/02698811251368360","url":null,"abstract":"<p><p>Classic psychedelics are increasingly studied as potential treatments for different psychiatric disorders. Current research protocols often require patients to discontinue antidepressants (ADs) for at least 2 weeks before psychedelic administration to decrease the risk of serotonin syndrome and limit their effect on efficacy and the acute subjective effects of psychedelics. Moreover, the discontinuation of ADs represents a significant burden to patients that could also worsen their depression status and increase suicidal ideation. Together, this suggests that the general recommendation for AD discontinuation might be unnecessary and even detrimental to the therapeutic efficacy of psychedelics. In this scoping review, we summarise the existing literature on the concomitant use of conventional ADs with classic psychedelics in humans with the aims to assess safety, tolerability, efficacy, and subjective effects. Following PRISMA-ScR guidelines, we searched MEDLINE, Embase, and Scopus databases to retrieve relevant literature from inception to March 3, 2025. Data were systematically charted from included studies. We included 18 studies and found that the concomitant use of ADs and classic psychedelics is generally safe and tolerable, with no increased risk of serotonin syndrome, particularly for psilocybin. Some studies reported significant improvements in depression and other mental health symptoms. While some evidence indicates a potential attenuation of acute subjective psychedelic effects, this was not observed in all studies. Accordingly, we conclude that the use of ADs can be maintained to enhance patient access to psychedelic treatments and avoid the risk of AD discontinuation syndrome. Finally, this review highlights limitations and several knowledge gaps in the current literature that need to be addressed in future randomized double-blind, placebo-controlled trials.</p>","PeriodicalId":16892,"journal":{"name":"Journal of Psychopharmacology","volume":" ","pages":"2698811251368360"},"PeriodicalIF":5.5,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040488","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}