JAMA PsychiatryPub Date : 2025-03-19DOI: 10.1001/jamapsychiatry.2025.0054
Beth Han, Christopher M. Jones, Nora D. Volkow, S. Michaela Rikard, Deborah Dowell, Emily B. Einstein, Gery P. Guy, Naomi Tomoyasu, Jean Ko, Grant Baldwin, Yngvild Olsen, Wilson M. Compton
{"title":"Prescription Stimulant Use, Misuse, and Use Disorder Among US Adults Aged 18 to 64 Years","authors":"Beth Han, Christopher M. Jones, Nora D. Volkow, S. Michaela Rikard, Deborah Dowell, Emily B. Einstein, Gery P. Guy, Naomi Tomoyasu, Jean Ko, Grant Baldwin, Yngvild Olsen, Wilson M. Compton","doi":"10.1001/jamapsychiatry.2025.0054","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.0054","url":null,"abstract":"ImportanceStimulants are increasingly prescribed for US adults. Whether such prescribing is associated with misuse and prescription stimulant use disorder (PSUD) is less understood.ObjectivesTo examine (1) sex- and age-specific trends in the number of persons dispensed stimulants and trends in dispensed prescription stimulants by prescriber specialty in 2019 through 2022; (2) prevalence of misuse and PSUD by use of prescription amphetamine-type stimulants (hereafter referred to as <jats:italic>amphetamines</jats:italic>) and methylphenidate; and (3) PSUD prevalence and sociodemographic and behavioral health correlates among persons using prescription stimulants with and without prescription stimulant misuse.Design, Setting, and ParticipantsThis cross-sectional survey study used the 2019-2022 IQVIA Total Patient Tracker and National Prescription Audit New to Brand databases and the 2021-2022 National Surveys on Drug Use and Health (NSDUH) (community-dwelling 18- to 64-year-old individuals). Data analysis was performed from March to April 2024.ExposurePast-year use of prescription stimulants.Main Outcomes and MeasuresPSUD using <jats:italic>DSM-5</jats:italic> criteria.ResultsOf the sampled 83 762 adults aged 18 to 64 years, 33.8% (unweighted) were aged 18 to 25 years, 53.0% (unweighted) were aged 26 to 49 years, and 56.0% (unweighted) were women. Among those using prescription stimulants, 25.3% (95% CI, 23.8%-26.8%) reported misuse, and 9.0% (95% CI, 8.0%-10.0%) had PSUD. Among those with PSUD, 72.9% (95% CI, 68.3%-77.6%) solely used their own prescribed stimulants, 87.1% (95% CI, 82.3%-90.8%) used amphetamines, 42.5% (95% CI, 36.6%-48.5%) reported no misuse, and 63.6% (95% CI, 56.8%-69.8%) had mild PSUD. Individuals using amphetamines, compared with those using methylphenidate, had higher prevalence ratios of misuse (3.1 [95% CI, 2.2-4.3]) and PSUD (2.2 [95% CI, 1.3-3.8]). The largest increase in the number of individuals dispensed prescription stimulants was among women aged 35 to 64 years, from 1.2 million in quarter 1 of 2019 to 1.7 million in quarter 4 of 2022 (average quarterly percentage change, 2.6% [95% CI, 2.1%-3.1%]). The prevalence of prescription stimulant misuse was lower among women aged 35 to 64 years using these medications (13.7% [95% CI, 11.1%-16.8%]) than other sex- and age-specific subgroups (ranging from 22.0% [95% CI, 17.9%-26.7%] for men aged 35-64 years to 36.8% [95% CI, 32.6%-41.2%] for women aged 18-25 years).Conclusions and RelevanceHigh prevalence of prescription stimulant misuse and PSUD (regardless of misuse status) suggests the importance of ensuring clinically appropriate use and of screening for and treating PSUD among all adults prescribed stimulants, especially those using amphetamines. Findings may suggest potential progress in addressing the mental health care gap for middle-aged women and the need for evidence-based clinical guidance and training on benefits and risks of prescription stimulants for adults.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"36 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA PsychiatryPub Date : 2025-03-19DOI: 10.1001/jamapsychiatry.2025.0091
Pouya Ebrahimi, Juan Carlos Batlle, Aryan Ayati, M. Haisum Maqsood, Clarine Long, Constantine Tarabanis, Natalie McGowan, David T. Liebers, Gregory Laynor, Kaveh Hosseini, Sean P. Heffron
{"title":"Suicide and Self-Harm Events With GLP-1 Receptor Agonists in Adults With Diabetes or Obesity","authors":"Pouya Ebrahimi, Juan Carlos Batlle, Aryan Ayati, M. Haisum Maqsood, Clarine Long, Constantine Tarabanis, Natalie McGowan, David T. Liebers, Gregory Laynor, Kaveh Hosseini, Sean P. Heffron","doi":"10.1001/jamapsychiatry.2025.0091","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.0091","url":null,"abstract":"ImportanceBariatric surgery, once the criterion standard in obesity treatment, has a small but concerning association with increased suicidality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed to treat diabetes, now provide substantial efficacy in the treatment of obesity. However, concerns of risk of suicidality with these medicines have been raised.ObjectiveTo evaluate the risk of suicidality and self-harm in randomized, placebo-controlled trials of GLP-1 RAs in adults with diabetes or obesity.Data SourcesMEDLINE, Embase, ClinicalTrials.gov, and Cochrane databases were systematically searched from inception to August 29, 2023.Study SelectionReports of randomized clinical trials (RCTs) lasting 6 or more months comparing GLP-1 RAs with placebo for the treatment of diabetes or obesity published in peer-reviewed journals were identified. Two independent reviewers screened all search-identified studies for inclusion. Records of outcomes were queried from primary papers, ClinicalTrials.gov entries, and corresponding authors.Data Extraction and SynthesisTwo independent researchers abstracted data and assessed data quality and validity using PRISMA guidelines. Data were pooled using random-effects models.Main Outcomes and MeasuresPooled incidence of completed or attempted suicide, occurrences of suicidal ideation, or self-harm.ResultsA total of 27 of 144 RCTs meeting inclusion criteria systematically recorded suicide and/or self-harm-related events and included 32 357 individuals receiving GLP-1 RAs and 27 046 treated with placebo, over 74 740 and 68 095 person-years of follow-up, respectively. Event incidence was very low in the GLP-1 RA (0.044 per 100 person-years) and placebo (0.040 per 100 person-years) groups, with no statistically significant difference (rate ratio [RR], 0.76; 95% CI, 0.48-1.21; <jats:italic>P</jats:italic> = .24). Subgroup analyses did not suggest differences in outcomes based on diabetes status or GLP-1 RA used. Five studies were considered at risk of bias due to the loss of more than 5% of participants to follow-up. Otherwise, studies were not found to be heterogeneous nor at high risk of bias.Conclusions and RelevanceThere is unlikely to be an increase in the very low incidence of suicide-related adverse events among individuals receiving GLP-1 RAs within the context of RCTs. While these findings may further ease concerns about these adverse effects, continued monitoring is warranted to identify particular patients who may be at risk as extended use of GLP-1 RAs expands.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"22 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA PsychiatryPub Date : 2025-03-19DOI: 10.1001/jamapsychiatry.2025.0044
Lorenz Mueller, Joyce Santos de Jesus, Yasmin Schmid, Felix Müller, Anna Becker, Aaron Klaiber, Isabelle Straumann, Dino Luethi, Eline C. H. M. Haijen, Petra P. M. Hurks, Kim P. C. Kuypers, Matthias E. Liechti
{"title":"Safety and Efficacy of Repeated Low-Dose LSD for ADHD Treatment in Adults","authors":"Lorenz Mueller, Joyce Santos de Jesus, Yasmin Schmid, Felix Müller, Anna Becker, Aaron Klaiber, Isabelle Straumann, Dino Luethi, Eline C. H. M. Haijen, Petra P. M. Hurks, Kim P. C. Kuypers, Matthias E. Liechti","doi":"10.1001/jamapsychiatry.2025.0044","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.0044","url":null,"abstract":"ImportanceMicrodosing psychedelics, including lysergic acid diethylamide (LSD), has gained attention for its potential benefits in several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). However, LSD’s efficacy in reducing ADHD symptoms remains unknown.ObjectiveTo determine the safety and efficacy of repeated low doses of LSD in reducing ADHD symptoms compared with placebo.Design, Setting, and ParticipantsThis was a 6-week, multicenter, double-blind, placebo-controlled, parallel-group phase 2A randomized clinical trial conducted between December 17, 2021, and December 4, 2023. Data were analyzed from March 22, 2024, to August 19, 2024. Outpatient treatment was provided at 2 centers: University Hospital in Basel, Switzerland, and Maastricht University in the Netherlands. Adults aged 18 to 65 years with a prior ADHD diagnosis who presented with moderate to severe symptoms (Adult Investigator Symptom Rating Scale [AISRS] score ≥26 and Clinical Global Impression Severity score ≥4) were eligible for inclusion. Key exclusion criteria included selected current major psychiatric or somatic disorders and the use of potentially interacting medications.InterventionParticipants received either LSD (20 μg) or placebo twice weekly for 6 weeks (total of 12 doses).Main Outcome and MeasuresThe primary outcome was the change in ADHD symptoms from baseline to week 6, assessed by the AISRS and analyzed with a mixed-effects model for repeated measures.ResultsA total of 53 participants were randomized to LSD (n = 27) or placebo (n = 26). Mean (SD) participant age was 37 (12) years, and 22 participants (42%) were female. The LSD group presented a mean AISRS improvement of −7.1 points (95% CI, −10.1 to −4.0). The placebo group presented a mean AISRS improvement of −8.9 points (95% CI, −12.0 to −5.8), with no difference between groups. LSD was physically safe and psychologically well tolerated overall.Conclusions and RelevanceIn this randomized clinical trial, repeated low-dose LSD administration was safe in an outpatient setting, but it was not more efficacious than placebo in reducing ADHD symptoms.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://www.clinicaltrials.gov/study/NCT05200936?term=NCT05200936&amp;amp;rank=1\">NCT05200936</jats:ext-link>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"46 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA PsychiatryPub Date : 2025-03-19DOI: 10.1001/jamapsychiatry.2025.0161
Dost Öngür
{"title":"JAMA Psychiatry-The Year in Review 2024.","authors":"Dost Öngür","doi":"10.1001/jamapsychiatry.2025.0161","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.0161","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA PsychiatryPub Date : 2025-03-12DOI: 10.1001/jamapsychiatry.2025.0122
Tingting Wang, Parisa Mohammadzadeh, Jens Richardt Møllegaard Jepsen, Jonathan Thorsen, Julie Bøjstrup Rosenberg, Cecilie Koldbæk Lemvigh, Nicklas Brustad, Liang Chen, Mina Ali, Rebecca Vinding, Casper-Emil Tingskov Pedersen, María Hernández-Lorca, Birgitte Fagerlund, Birte Y. Glenthøj, Niels Bilenberg, Jakob Stokholm, Klaus Bønnelykke, Bo Chawes, Bjørn H. Ebdrup
{"title":"Maternal Inflammatory Proteins in Pregnancy and Neurodevelopmental Disorders at Age 10 Years","authors":"Tingting Wang, Parisa Mohammadzadeh, Jens Richardt Møllegaard Jepsen, Jonathan Thorsen, Julie Bøjstrup Rosenberg, Cecilie Koldbæk Lemvigh, Nicklas Brustad, Liang Chen, Mina Ali, Rebecca Vinding, Casper-Emil Tingskov Pedersen, María Hernández-Lorca, Birgitte Fagerlund, Birte Y. Glenthøj, Niels Bilenberg, Jakob Stokholm, Klaus Bønnelykke, Bo Chawes, Bjørn H. Ebdrup","doi":"10.1001/jamapsychiatry.2025.0122","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.0122","url":null,"abstract":"IMPORTANCEMaternal inflammation during pregnancy has been associated with an increased risk of neurodevelopmental disorders (NDDs), such as attention-deficit/hyperactivity disorder (ADHD) and autism, and cognitive deficits in early childhood. However, little is known about the contributions of a wider range of inflammatory proteins to this risk.OBJECTIVETo determine whether maternal inflammatory proteins during pregnancy are associated with the risk of NDDs and executive functions (EF) in middle childhood and to identify protein patterns associated with NDDs and EF.DESIGN, SETTING, AND PARTICIPANTSThis was a 10-year follow-up cohort study of the Danish Copenhagen Prospective Studies on Asthma 2010 mother-child birth cohort, using plasma samples collected at week 24 in pregnancy, where 92 inflammatory proteins were assessed. NDDs and EF were assessed in the offspring at age 10 years, between January 2019 and December 2021. Mother-offspring dyads with available maternal prenatal inflammatory proteins during pregnancy and offspring NDD psychopathology data at follow-up were included. Data analyses took place between December 2023 and August 2024.EXPOSURESLevels of 92 inflammatory proteins from panel collected at week 24 during pregnancy.MAIN OUTCOMES AND MEASURESCategorical and dimensional psychopathology of NDDs (primary outcome) and EF (secondary outcome).RESULTSA total of 555 mothers (mean [SD] age, 32.4 [4.3] years) and their children (285 male [51%]) were included. The principal component analysis showed that higher levels of maternal inflammatory proteins depicted in principal component 1 were associated with a higher risk of any NDD (OR, 1.49; 95% CI, 1.15-1.94; <jats:italic>P</jats:italic> = .003), particularly autism (OR, 2.76; 95% CI, 1.45-5.63; <jats:italic>P</jats:italic> = .003) and ADHD with predominantly inattentive presentation (OR, 1.57; 95% CI, 1.05-2.39; <jats:italic>P</jats:italic> = .03). The single protein analysis showed that 18 of 92 proteins reached false discovery rate (FDR) 5% significance after adjustment. Vascular endothelial growth factor A, C-C motif chemokine ligand, CD5, interleukin 12B, fibroblast growth factor-23, and monocyte chemoattractant protein-1 emerged as top proteins associated with risk of NDDs. The sparse partial least squares approach identified 34 proteins associated with any NDD, and 39 with ADHD with predominantly inattentive presentation. There were no associations with EF after FDR correction.CONCLUSIONS AND RELEVANCEThe maternal inflammatory proteome during pregnancy was associated with NDDs risks in offspring at age 10 years. Further research is warranted to elucidate the specific pathways involving these proteins during pregnancy that could be targeted with prevention strategies to reduce risk of NDDs in children.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"68 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA PsychiatryPub Date : 2025-03-12DOI: 10.1001/jamapsychiatry.2025.0030
Olivia Metcalf, David Forbes
{"title":"Addressing the Double Bind of Women's Anger After Trauma.","authors":"Olivia Metcalf, David Forbes","doi":"10.1001/jamapsychiatry.2025.0030","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.0030","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA PsychiatryPub Date : 2025-03-12DOI: 10.1001/jamapsychiatry.2025.0033
Upasana Bhattacharyya, Jibin John, Max Lam, Jonah Fisher, Benjamin Sun, Denis Baird, Stephen Burgess, Chia-Yen Chen, Todd Lencz
{"title":"Circulating Blood-Based Proteins in Psychopathology and Cognition","authors":"Upasana Bhattacharyya, Jibin John, Max Lam, Jonah Fisher, Benjamin Sun, Denis Baird, Stephen Burgess, Chia-Yen Chen, Todd Lencz","doi":"10.1001/jamapsychiatry.2025.0033","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.0033","url":null,"abstract":"ImportancePeripheral (blood-based) biomarkers for psychiatric illness could benefit diagnosis and treatment, but research to date has typically been low throughput, and traditional case-control studies are subject to potential confounds of treatment and other exposures. Large-scale 2-sample mendelian randomization (MR) can examine the potentially causal impact of circulating proteins on neuropsychiatric phenotypes without these confounds.ObjectiveTo identify circulating proteins associated with risk for schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) as well as cognitive task performance (CTP).Design, Setting, and ParticipantsIn a 2-sample MR design, significant proteomic quantitative trait loci were used as candidate instruments, obtained from 2 large-scale plasma proteomics datasets: the UK Biobank Pharma Proteomics Project (2923 proteins per 34 557 UK individuals) and deCODE Genetics (4719 proteins per 35 559 Icelandic individuals). Data analysis was performed from November 2023 to November 2024.ExposureGenetic influence on circulating levels of proteins in plasma.Main Outcomes and MeasuresOutcome measures were summary statistics drawn from recent large-scale genome-wide association studies for SCZ (67 323 cases and 93 456 controls), BD (40 463 cases and 313 436 controls), MDD (166 773 cases and 507 679 controls), and CTP (215 333 individuals). MR was carried out for each phenotype, and proteins that showed statistically significant (Bonferroni-corrected <jats:italic>P</jats:italic> &amp;lt; .05) associations from MR analysis were used for pathway, protein-protein interaction, drug target enrichment, and potential druggability analysis for each outcome phenotype separately.ResultsMR analysis revealed 113 Bonferroni-corrected associations (46 novel) involving 91 proteins across the 4 outcome phenotypes. Immune-related proteins, such as interleukins and complement factors, showed pleiotropic effects across multiple outcome phenotypes. Drug target enrichment analysis provided support for repurposing of anti-inflammatory agents for SCZ, amantadine for BD, retinoic acid for MDD, and duloxetine for CTP.Conclusions and RelevanceIdentifying potentially causal effects of circulating proteins on neuropsychiatric phenotypes suggests potential biomarkers and offers insights for the development of innovative therapeutic strategies. The study also reveals pleiotropic effects of many proteins across different phenotypes, indicating shared etiology among serious psychiatric conditions and cognition.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"56 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
JAMA PsychiatryPub Date : 2025-03-12DOI: 10.1001/jamapsychiatry.2025.0085
Nathan T. M. Huneke, Guilherme Fusetto Veronesi, Matthew Garner, David S. Baldwin, Samuele Cortese
{"title":"Expectancy Effects, Failure of Blinding Integrity, and Placebo Response in Trials of Treatments for Psychiatric Disorders","authors":"Nathan T. M. Huneke, Guilherme Fusetto Veronesi, Matthew Garner, David S. Baldwin, Samuele Cortese","doi":"10.1001/jamapsychiatry.2025.0085","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.0085","url":null,"abstract":"ImportanceExpectancy effects are significant confounding factors in psychiatric randomized clinical trials (RCTs), potentially affecting the interpretation of study results. This narrative review is the first, to our knowledge, to explore the relationship between expectancy effects, compromised blinding integrity, and the effects of active treatment/placebo in psychiatric RCTs. Additionally, we present statistical and experimental approaches that may help mitigate the confounding impact of expectancy effects. The review concludes with recommendations to enhance the reliability of RCTs in psychiatry.ObservationsThe placebo response comprises both specific and nonspecific elements, with expectation being a key specific component. Evidence from experimental and clinical studies suggests that expectancy can influence treatment responses in RCTs. Blinding integrity may be compromised by perceived treatment efficacy and adverse effects, introducing bias into outcome assessments. Treatment expectations can lead to unblinding during RCTs, and meta-analytic data from studies in the fields of psychedelics and anxiety disorders indicate that this can influence effect sizes. Therefore, controlling for expectancy effects is essential when interpreting RCT results. Novel statistical methods, though still in need of further validation, offer strategies to address this issue. Another approach may involve experimental medicine models, which aim to develop objective improvement markers (readouts) less affected by expectancy effects.Conclusions and RelevanceExpectancy effects represent a significant confound in psychiatric RCTs. We recommend collecting data on treatment expectations alongside monitoring blinding integrity to more accurately interpret study results. Additionally, developing objective readouts that are less confounded by expectancy effects offers another promising avenue for mitigating these confounding influences in psychiatric RCTs.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"4 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143599448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}