Pub Date : 2026-02-18DOI: 10.1001/jamapsychiatry.2025.4816
Howard K. Koh, Donald E. Frederick, Tracy A. Balboni, Samantha M. O’Reilly, John F. Kelly, Keith Humphreys, Michael Botticelli, Maya B. Mathur, Constantine S. Psimopoulos, Katelyn N. G. Long, Tyler J. VanderWeele
Importance This meta-analysis examines rigorous longitudinal 21st century studies on the associations of spirituality with harmful or hazardous alcohol and other drug (AOD) use. Objective To synthesize findings from independent studies about spirituality and AOD use and to produce a comprehensive estimate of the overall effect size of the associated risk reduction. Data Sources Studies previously identified in the Balboni and colleagues review on the association between spiritual exposures (including religion) and alcohol, tobacco, marijuana, or other drugs were pooled. Studies were identified through the search terms <jats:italic>spirituality</jats:italic> or <jats:italic>religion</jats:italic> or <jats:italic>spiritual*</jats:italic> or <jats:italic>religio*</jats:italic> or <jats:italic>faith</jats:italic> and also intersected with a long string of terms that captured health outcomes of interest. Study Selection From an initial retrieval of more than 20 000 articles, a total of 55 spirituality studies (as defined by Puchalski and colleagues) that were (1) published 2000-2022 in the English language, (2) used validated measures of spirituality, (3) examined longitudinal associations between spirituality and AOD use, and (4) were either prospective cohort studies with sample sizes of 1000 or more or randomized clinical trials (eg, public health interventions) with sample sizes of 100 or more, were captured. Data Extraction and Synthesis Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.equator-network.org/reporting-guidelines/prisma/">PRISMA</jats:ext-link> ) reporting guidelines were used for abstracting data and assessing quality and validity. Eligible studies were those that reported quantitative outcomes measuring AOD use in relation to spiritual exposures, provided sufficient data to calculate log-relative risks (log-RR) and associated error terms, and focused on either preventive effect (eg, delayed initiation) or recovery-related outcomes (eg, cessation). Effects extracted were transformed into log-RR based on the type of effect. Main Outcomes and Measures The primary outcome was the association between spiritual or religious involvement and AOD. Subgroup analyses examined differences by AOD use type (alcohol, tobacco, marijuana, and illicit drugs) and exposure type (spiritual or religious attendance vs broader spiritual exposures). Results Results from the 55 studies, which collectively included 540 712 participants, documented a significant protective association related to both prevention and recovery between spirituality and AOD use outcomes. Specifically, a consistent 13% risk reduction extended across the studied drugs (RR, 0.87; 95% CI, 0.84-0.91), a figure that reached 18% for individuals engaging in spiritual or religious communities (defined as &gt;weekly religious service attendance; RR, 0.82; 95% CI,
{"title":"Spirituality and Harmful or Hazardous Alcohol and Other Drug Use","authors":"Howard K. Koh, Donald E. Frederick, Tracy A. Balboni, Samantha M. O’Reilly, John F. Kelly, Keith Humphreys, Michael Botticelli, Maya B. Mathur, Constantine S. Psimopoulos, Katelyn N. G. Long, Tyler J. VanderWeele","doi":"10.1001/jamapsychiatry.2025.4816","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4816","url":null,"abstract":"Importance This meta-analysis examines rigorous longitudinal 21st century studies on the associations of spirituality with harmful or hazardous alcohol and other drug (AOD) use. Objective To synthesize findings from independent studies about spirituality and AOD use and to produce a comprehensive estimate of the overall effect size of the associated risk reduction. Data Sources Studies previously identified in the Balboni and colleagues review on the association between spiritual exposures (including religion) and alcohol, tobacco, marijuana, or other drugs were pooled. Studies were identified through the search terms <jats:italic>spirituality</jats:italic> or <jats:italic>religion</jats:italic> or <jats:italic>spiritual*</jats:italic> or <jats:italic>religio*</jats:italic> or <jats:italic>faith</jats:italic> and also intersected with a long string of terms that captured health outcomes of interest. Study Selection From an initial retrieval of more than 20 000 articles, a total of 55 spirituality studies (as defined by Puchalski and colleagues) that were (1) published 2000-2022 in the English language, (2) used validated measures of spirituality, (3) examined longitudinal associations between spirituality and AOD use, and (4) were either prospective cohort studies with sample sizes of 1000 or more or randomized clinical trials (eg, public health interventions) with sample sizes of 100 or more, were captured. Data Extraction and Synthesis Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"http://www.equator-network.org/reporting-guidelines/prisma/\">PRISMA</jats:ext-link> ) reporting guidelines were used for abstracting data and assessing quality and validity. Eligible studies were those that reported quantitative outcomes measuring AOD use in relation to spiritual exposures, provided sufficient data to calculate log-relative risks (log-RR) and associated error terms, and focused on either preventive effect (eg, delayed initiation) or recovery-related outcomes (eg, cessation). Effects extracted were transformed into log-RR based on the type of effect. Main Outcomes and Measures The primary outcome was the association between spiritual or religious involvement and AOD. Subgroup analyses examined differences by AOD use type (alcohol, tobacco, marijuana, and illicit drugs) and exposure type (spiritual or religious attendance vs broader spiritual exposures). Results Results from the 55 studies, which collectively included 540 712 participants, documented a significant protective association related to both prevention and recovery between spirituality and AOD use outcomes. Specifically, a consistent 13% risk reduction extended across the studied drugs (RR, 0.87; 95% CI, 0.84-0.91), a figure that reached 18% for individuals engaging in spiritual or religious communities (defined as &amp;gt;weekly religious service attendance; RR, 0.82; 95% CI, ","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"59 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146209978","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}
Pub Date : 2026-02-11DOI: 10.1001/jamapsychiatry.2025.4460
Benjamin Land Gorman, Katherine A. Koh, Sophie Roe, Christopher T. Lim
Importance People experiencing unsheltered homelessness face high rates of psychiatric illness and substantial barriers to care. Field-based psychiatric services built on direct outreach (known as street psychiatry ) may improve care and facilitate housing while possibly reducing total health care spending, but inadequate funding limits implementation. Observations Literature shows that street psychiatric services are currently financially supported by a variety of sources, though with outsized reliance on public and private grants and contracts. Health plan reimbursement for this care remains limited. Existing payment innovations that support street medicine and other care models illustrate the spectrum of possible reimbursement mechanisms available to payers. Payers could ensure that services are reimbursed by facilitating use of the new outreach site/street place of service code, compensating necessary activities of outreach and reimbursing activities of peer specialists and other interdisciplinary team members. To pay for services outside the scope of billable encounters, payers could develop programs to directly fund or incentivize care coordination, housing support, and other services. Sufficient fee-for-service rates and risk adjustment may encourage and support care for this population. Maintaining or expanding Medicaid eligibility and limiting administrative barriers to coverage for people experiencing homelessness are essential. Conclusions and Relevance The need for outreach-informed psychiatric care continues to grow. Payment model reforms may enable practitioners to deliver evidence-based street psychiatry at scale. Successful programs and states demonstrate that the described reforms are likely feasible and effective. Patients experiencing unsheltered homelessness, some of whom have substantial psychiatric care needs, are likely to benefit greatly from improved reimbursement for these services.
{"title":"Sustainably Funding Street Psychiatry","authors":"Benjamin Land Gorman, Katherine A. Koh, Sophie Roe, Christopher T. Lim","doi":"10.1001/jamapsychiatry.2025.4460","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4460","url":null,"abstract":"Importance People experiencing unsheltered homelessness face high rates of psychiatric illness and substantial barriers to care. Field-based psychiatric services built on direct outreach (known as <jats:italic toggle=\"yes\">street psychiatry</jats:italic> ) may improve care and facilitate housing while possibly reducing total health care spending, but inadequate funding limits implementation. Observations Literature shows that street psychiatric services are currently financially supported by a variety of sources, though with outsized reliance on public and private grants and contracts. Health plan reimbursement for this care remains limited. Existing payment innovations that support street medicine and other care models illustrate the spectrum of possible reimbursement mechanisms available to payers. Payers could ensure that services are reimbursed by facilitating use of the new outreach site/street place of service code, compensating necessary activities of outreach and reimbursing activities of peer specialists and other interdisciplinary team members. To pay for services outside the scope of billable encounters, payers could develop programs to directly fund or incentivize care coordination, housing support, and other services. Sufficient fee-for-service rates and risk adjustment may encourage and support care for this population. Maintaining or expanding Medicaid eligibility and limiting administrative barriers to coverage for people experiencing homelessness are essential. Conclusions and Relevance The need for outreach-informed psychiatric care continues to grow. Payment model reforms may enable practitioners to deliver evidence-based street psychiatry at scale. Successful programs and states demonstrate that the described reforms are likely feasible and effective. Patients experiencing unsheltered homelessness, some of whom have substantial psychiatric care needs, are likely to benefit greatly from improved reimbursement for these services.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"177 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152785","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}
Pub Date : 2026-02-11DOI: 10.1001/jamapsychiatry.2025.4453
Andre C. Tonon, Adile Nexha, Jasmyn E. A. Cunningham, Jason d’Eon, Trisha Chakrabarty, Faranak Farzan, Jane A. Foster, Kate L. Harkness, Stefanie Hassel, Keith Ho, Raymond W. Lam, Roumen Milev, Luciano Minuzzi, Daniel J. Müller, Abraham Nunes, Sagar V. Parikh, Lena C. Quilty, Susan Rotzinger, Claudio N. Soares, Valerie H. Taylor, Gustavo Turecki, Rudolf Uher, Sidney H. Kennedy, Benicio N. Frey
Importance Given its recurrent nature and burden, major depressive disorder (MDD) warrants reliable methods of relapse prediction. Objective To determine whether actigraphy-derived parameters, measured over 1 to 2 years, are associated with relapse. Design, Setting, and Participants This was an observational cohort study with data collection from July 2016 to January 2019. The setting was multicentric. A referred sample of participants from outpatient psychiatric and primary care clinics across Canada were followed up for 1 to 2 years. Participants had a diagnosis of MDD and Montgomery-Åsberg Depression Rating Scale (MADRS) score less than or equal to 14 at baseline. Exposures Actigraphy-derived parameters measured over 1 to 2 years. Main Outcome and Measures The primary outcome was relapse, defined as any of the following: MADRS score greater than or equal to 22 for 2 consecutive weeks, psychiatric hospitalization, emergence of suicidal intent or behavior, or antidepressant treatment escalation—all adjudicated by an independent panel. Continuous actigraphy data were averaged every 2 weeks. Results From a referred sample of 102 adults, 93 participants (mean [SD] age, 39.1 [12.7] years; 58 female [62%]) contributed approximately 32 000 complete actigraphy days (median, 46 weeks). In Cox models adjusted for age, sex, season, and baseline MADRS score, baseline lower sleep regularity (hazard ratio [HR], 0.46; 95% CI, 0.28-0.74; P = .002), lower relative amplitude (RA; HR, 0.45; 95% CI, 0.29-0.70; P &lt; .001), lower sleep efficiency (HR, 0.57; 95% CI, 0.38-0.85; P = .005), higher wake after sleep onset (HR, 1.77; 95% CI, 1.12-2.80; P = .01), and higher nighttime activity (HR, 1.86; 95% CI, 1.32-2.62; P &lt; .001) were associated with relapse. In time-varying models, greater composite phase deviation (HR, 1.76; 95% CI, 1.04-2.98; P = .04) and lower RA (HR, 0.45; 95% CI, 0.21-0.97; P = .046) were associated with relapse, with RA remaining significant even after adjusting for concurrent MADRS scores (HR, 0.60; 95% CI, 0.36-0.98; P = .04). Actigraphy significantly differentiated individuals experiencing relapse from those with an ultrastable (MADRS score &lt;14 throughout) and unstable (transient MADRS score, 14-22 without relapse) clinical course. Conclusions and Relevance Actigraphy measures of sleep phase variability and daily activity amplitude were associated with depressive relapse, supporting actigraphy as a potential scalable biomarker to identify high-risk individuals and enable timely, personalized relapse prevention in MDD.
鉴于其复发性和负担，重性抑郁症（MDD）需要可靠的复发预测方法。目的确定1 - 2年内测量的活动图衍生参数是否与复发有关。设计、环境和参与者这是一项观察性队列研究，数据收集时间为2016年7月至2019年1月。这个场景是多中心的。来自加拿大门诊精神科和初级保健诊所的参与者的参考样本被随访了1至2年。参与者被诊断为重度抑郁症，蒙哥马利-Åsberg抑郁评定量表（MADRS）在基线时得分小于或等于14分。在1至2年内测量的活动记录仪衍生参数。主要结局和测量主要结局是复发，定义为以下任何一项：MADRS评分连续2周大于或等于22，精神病院住院，出现自杀意图或行为，或抗抑郁治疗升级-所有这些都由独立小组裁定。连续活动记录仪数据每2周取平均值。在102名成年人的参考样本中，93名参与者（平均[SD]年龄39.1[12.7]岁，58名女性[62%]）贡献了大约32000个完整的活动记录天数（中位数，46周）。在校正了年龄、性别、季节和基线MADRS评分的Cox模型中，基线睡眠规律较低（风险比[HR]， 0.46; 95% CI, 0.28-0.74; P = 0.002），相对振幅较低（RA； HR, 0.45; 95% CI, 0.29-0.70; P <）。001)，较低的睡眠效率（HR, 0.57; 95% CI, 0.38-0.85; P = 0.005），较高的睡眠后觉醒率（HR, 1.77; 95% CI, 1.12-2.80; P = 0.01），较高的夜间活动(HR, 1.86; 95% CI, 1.32-2.62; P <；001)与复发相关。在时变模型中，较大的复合相位偏差（HR, 1.76; 95% CI, 1.04-2.98; P = 0.04）和较低的RA （HR, 0.45; 95% CI, 0.21-0.97; P = 0.046）与复发相关，即使在调整并发MADRS评分后RA仍然显著（HR, 0.60; 95% CI, 0.36-0.98; P = 0.04）。活动描记术可显著区分复发患者与临床病程超稳定（MADRS评分为14分）和不稳定（短暂MADRS评分为14-22分，无复发）患者。活动描记术测量的睡眠阶段变异性和每日活动幅度与抑郁症复发相关，支持活动描记术作为一种潜在的可扩展的生物标志物来识别高危个体，并实现及时、个性化的重度抑郁症复发预防。
{"title":"One-Year Actigraphy Study of Sleep and Rest-Activity Rhythms as Markers of Relapse in Depression","authors":"Andre C. Tonon, Adile Nexha, Jasmyn E. A. Cunningham, Jason d’Eon, Trisha Chakrabarty, Faranak Farzan, Jane A. Foster, Kate L. Harkness, Stefanie Hassel, Keith Ho, Raymond W. Lam, Roumen Milev, Luciano Minuzzi, Daniel J. Müller, Abraham Nunes, Sagar V. Parikh, Lena C. Quilty, Susan Rotzinger, Claudio N. Soares, Valerie H. Taylor, Gustavo Turecki, Rudolf Uher, Sidney H. Kennedy, Benicio N. Frey","doi":"10.1001/jamapsychiatry.2025.4453","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4453","url":null,"abstract":"Importance Given its recurrent nature and burden, major depressive disorder (MDD) warrants reliable methods of relapse prediction. Objective To determine whether actigraphy-derived parameters, measured over 1 to 2 years, are associated with relapse. Design, Setting, and Participants This was an observational cohort study with data collection from July 2016 to January 2019. The setting was multicentric. A referred sample of participants from outpatient psychiatric and primary care clinics across Canada were followed up for 1 to 2 years. Participants had a diagnosis of MDD and Montgomery-Åsberg Depression Rating Scale (MADRS) score less than or equal to 14 at baseline. Exposures Actigraphy-derived parameters measured over 1 to 2 years. Main Outcome and Measures The primary outcome was relapse, defined as any of the following: MADRS score greater than or equal to 22 for 2 consecutive weeks, psychiatric hospitalization, emergence of suicidal intent or behavior, or antidepressant treatment escalation—all adjudicated by an independent panel. Continuous actigraphy data were averaged every 2 weeks. Results From a referred sample of 102 adults, 93 participants (mean [SD] age, 39.1 [12.7] years; 58 female [62%]) contributed approximately 32 000 complete actigraphy days (median, 46 weeks). In Cox models adjusted for age, sex, season, and baseline MADRS score, baseline lower sleep regularity (hazard ratio [HR], 0.46; 95% CI, 0.28-0.74; <jats:italic toggle=\"yes\">P</jats:italic> = .002), lower relative amplitude (RA; HR, 0.45; 95% CI, 0.29-0.70; <jats:italic toggle=\"yes\">P</jats:italic> &amp;lt; .001), lower sleep efficiency (HR, 0.57; 95% CI, 0.38-0.85; <jats:italic toggle=\"yes\">P</jats:italic> = .005), higher wake after sleep onset (HR, 1.77; 95% CI, 1.12-2.80; <jats:italic toggle=\"yes\">P</jats:italic> = .01), and higher nighttime activity (HR, 1.86; 95% CI, 1.32-2.62; <jats:italic toggle=\"yes\">P</jats:italic> &amp;lt; .001) were associated with relapse. In time-varying models, greater composite phase deviation (HR, 1.76; 95% CI, 1.04-2.98; <jats:italic toggle=\"yes\">P</jats:italic> = .04) and lower RA (HR, 0.45; 95% CI, 0.21-0.97; <jats:italic toggle=\"yes\">P</jats:italic> = .046) were associated with relapse, with RA remaining significant even after adjusting for concurrent MADRS scores (HR, 0.60; 95% CI, 0.36-0.98; <jats:italic toggle=\"yes\">P</jats:italic> = .04). Actigraphy significantly differentiated individuals experiencing relapse from those with an ultrastable (MADRS score &amp;lt;14 throughout) and unstable (transient MADRS score, 14-22 without relapse) clinical course. Conclusions and Relevance Actigraphy measures of sleep phase variability and daily activity amplitude were associated with depressive relapse, supporting actigraphy as a potential scalable biomarker to identify high-risk individuals and enable timely, personalized relapse prevention in MDD.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"2 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152786","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}
Pub Date : 2026-02-11DOI: 10.1001/jamapsychiatry.2025.4738
Jonathan Cantor, Aarya Suryavanshi, Aaron Kofner, Colleen M. McCullough, Megan S. Schuler, Christopher M. Whaley, Ryan K. McBain
This cross-sectional study assesses how Medicaid’s role in financing inpatient psychiatric care has changed geographically across US states from 2014 to 2023.
{"title":"Trends in Medicaid Utilization and Financing for Hospitals With Psychiatric Beds","authors":"Jonathan Cantor, Aarya Suryavanshi, Aaron Kofner, Colleen M. McCullough, Megan S. Schuler, Christopher M. Whaley, Ryan K. McBain","doi":"10.1001/jamapsychiatry.2025.4738","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4738","url":null,"abstract":"This cross-sectional study assesses how Medicaid’s role in financing inpatient psychiatric care has changed geographically across US states from 2014 to 2023.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"4 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146152787","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}
Pub Date : 2026-02-04DOI: 10.1001/jamapsychiatry.2025.4431
Min Gao, Megan Kirk, Heather Knight, Eva Lash, Moscho Michalopoulou, Nicola Guess, Richard Stevens, Michael Browning, Scott Weich, Philip W. J. Burnet, Susan A. Jebb, Paul Aveyard
Importance Preclinical evidence and case reports suggest potential therapeutic benefits of ketogenic diets (KDs) in the treatment of depression, but evidence from well-controlled randomized clinical trials (RCTs) is lacking. Objective To assess the efficacy of a KD compared with a control diet in adults with treatment-resistant depression (TRD). Design, Setting, and Participants This RCT was conducted between February 22 and June 15, 2024. Participants aged 18 to 65 years with TRD and a score of 15 or greater on the 9-item Patient Health Questionnaire (PHQ-9) from across the UK were included. Intervention Participants were randomized 1:1 to one of two 6-week dietary interventions: (1) KD of prepared foods providing less than 30 g of carbohydrates per day with weekly individual dietetic support or (2) a control (phytochemical [phyto]) diet with vouchers to purchase 1 extra serving of vegetables or fruit and replace saturated fats with unsaturated fats, with equal dietetic support. The last follow-up was at 12 weeks. Main Outcomes and Measures The primary outcome was the between-group difference in change in PHQ-9 score from baseline to week 6. Secondary outcomes included PHQ-9 score at 12 weeks, depression remission, anxiety, anhedonia, cognitive impairment, quality of life, and functional outcomes. Results The study included 88 participants (mean [SD] age, 42.1 [13.1] years; 61 women [69%]): 44 in the KD group and 44 in the phyto diet group. Depression severity decreased markedly in both groups; the mean (SD) change in PHQ-9 score from baseline to week 6 was −10.5 (7.0) in the KD group and −8.3 (5.1) in the phyto group. The mean between-group differences in PHQ-9 score at 6 and 12 weeks were −2.18 (95% CI, −4.33 to −0.03; P = .05; Cohen d , −0.68; 95% CI −1.35 to −0.01) and −1.85 (95% CI, −4.04 to 0.33; P = .10; Cohen d , −0.58; 95% CI, −1.26 to 0.10), respectively. There were no differences in secondary outcomes between the KD and phyto groups. No serious adverse events occurred. Conclusions and Relevance In this RCT, a KD had antidepressant benefits compared with a well-matched control diet at 6 weeks. However, the clinical relevance is uncertain, as the mean effect size compared with the control was modest and not evident in secondary analyses. Trial Registration ClinicalTrials.gov Identifier: NCT06091163
{"title":"A Ketogenic Diet for Treatment-Resistant Depression","authors":"Min Gao, Megan Kirk, Heather Knight, Eva Lash, Moscho Michalopoulou, Nicola Guess, Richard Stevens, Michael Browning, Scott Weich, Philip W. J. Burnet, Susan A. Jebb, Paul Aveyard","doi":"10.1001/jamapsychiatry.2025.4431","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4431","url":null,"abstract":"Importance Preclinical evidence and case reports suggest potential therapeutic benefits of ketogenic diets (KDs) in the treatment of depression, but evidence from well-controlled randomized clinical trials (RCTs) is lacking. Objective To assess the efficacy of a KD compared with a control diet in adults with treatment-resistant depression (TRD). Design, Setting, and Participants This RCT was conducted between February 22 and June 15, 2024. Participants aged 18 to 65 years with TRD and a score of 15 or greater on the 9-item Patient Health Questionnaire (PHQ-9) from across the UK were included. Intervention Participants were randomized 1:1 to one of two 6-week dietary interventions: (1) KD of prepared foods providing less than 30 g of carbohydrates per day with weekly individual dietetic support or (2) a control (phytochemical [phyto]) diet with vouchers to purchase 1 extra serving of vegetables or fruit and replace saturated fats with unsaturated fats, with equal dietetic support. The last follow-up was at 12 weeks. Main Outcomes and Measures The primary outcome was the between-group difference in change in PHQ-9 score from baseline to week 6. Secondary outcomes included PHQ-9 score at 12 weeks, depression remission, anxiety, anhedonia, cognitive impairment, quality of life, and functional outcomes. Results The study included 88 participants (mean [SD] age, 42.1 [13.1] years; 61 women [69%]): 44 in the KD group and 44 in the phyto diet group. Depression severity decreased markedly in both groups; the mean (SD) change in PHQ-9 score from baseline to week 6 was −10.5 (7.0) in the KD group and −8.3 (5.1) in the phyto group. The mean between-group differences in PHQ-9 score at 6 and 12 weeks were −2.18 (95% CI, −4.33 to −0.03; <jats:italic>P</jats:italic> = .05; Cohen <jats:italic>d</jats:italic> , −0.68; 95% CI −1.35 to −0.01) and −1.85 (95% CI, −4.04 to 0.33; <jats:italic>P</jats:italic> = .10; Cohen <jats:italic>d</jats:italic> , −0.58; 95% CI, −1.26 to 0.10), respectively. There were no differences in secondary outcomes between the KD and phyto groups. No serious adverse events occurred. Conclusions and Relevance In this RCT, a KD had antidepressant benefits compared with a well-matched control diet at 6 weeks. However, the clinical relevance is uncertain, as the mean effect size compared with the control was modest and not evident in secondary analyses. Trial Registration ClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT06091163\">NCT06091163</jats:ext-link>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"20 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115564","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}
Pub Date : 2026-02-04DOI: 10.1001/jamapsychiatry.2025.4390
Nurul Husna Salahuddin, Emilia Herlitzius, Alexandra Schütz, Spyridon Siafis, Josef Priller, Stefan Leucht, Irene Bighelli
Importance Substance use disorder (SUD) is commonly found in individuals with schizophrenia, with a high co-occurrence rate of approximately 41.7%. Despite this high prevalence, people with both schizophrenia and SUD are frequently excluded from clinical trials and systematic reviews; this special group is particularly challenging to treat and imposes a significant economic burden on health care systems. Objective To evaluate the efficacy, acceptability, and tolerability of psychological and psychosocial interventions in patients with schizophrenia and co-occurring SUD. Data Sources The Cochrane Schizophrenia Group registry was searched up to January 13, 2025. Data analysis was performed from March to April 2025. Study Selection Randomized clinical trials (RCTs) examining psychological and psychosocial interventions compared with control groups in adults with schizophrenia and concomitant SUD were identified. No restrictions were applied regarding the type of substance used, including alcohol, cannabis, nicotine, and stimulants, such as amphetamines. Data Extraction and Synthesis A systematic review and random-effect pairwise meta-analyses were conducted to estimate standardized mean differences (SMD) with 95% confidence intervals and were reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://www.equator-network.org/reporting-guidelines/prisma/">PRISMA</jats:ext-link> ) reporting guidelines. Confidence in the estimate was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main Outcomes and Measures The primary outcomes were overall symptoms and substance use reduction measured by validated scales at posttreatment. Results A total of 35 RCTs were included (4136 participants), with 29 trials involving 3831 participants contributing to pairwise meta-analyses comparing psychological and psychosocial interventions with control conditions. Among the 3748 participants with reported sex, 951 (25.4%) were female, and mean (range) age was 37.2 (20.6-57.5) years. A very small effect favoring the intervention group was observed in reducing overall symptoms (SMD, –0.11; 95% CI, –0.27 to 0.05; 13 trials; low confidence in the estimate), mainly driven by nicotine studies. No difference was found between intervention and control groups in reducing all types of substance use (SMD, –0.01; 95% CI, –0.21 to 0.18; 8 trials; moderate confidence). When considered separately, alcohol, cannabis, amphetamines, and other stimulants showed similar no-effect results, while nicotine use indicated a small effect. Conclusion and Relevance The findings of this systematic review and meta-analysis suggest that current psychological and psychosocial interventions provide limited benefit in reducing symptoms and no effect in reducing substance use in individuals with schizophrenia and SUD compared to con
{"title":"Psychological and Psychosocial Interventions for People With Schizophrenia and Co-Occurring Substance Use Disorders","authors":"Nurul Husna Salahuddin, Emilia Herlitzius, Alexandra Schütz, Spyridon Siafis, Josef Priller, Stefan Leucht, Irene Bighelli","doi":"10.1001/jamapsychiatry.2025.4390","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4390","url":null,"abstract":"Importance Substance use disorder (SUD) is commonly found in individuals with schizophrenia, with a high co-occurrence rate of approximately 41.7%. Despite this high prevalence, people with both schizophrenia and SUD are frequently excluded from clinical trials and systematic reviews; this special group is particularly challenging to treat and imposes a significant economic burden on health care systems. Objective To evaluate the efficacy, acceptability, and tolerability of psychological and psychosocial interventions in patients with schizophrenia and co-occurring SUD. Data Sources The Cochrane Schizophrenia Group registry was searched up to January 13, 2025. Data analysis was performed from March to April 2025. Study Selection Randomized clinical trials (RCTs) examining psychological and psychosocial interventions compared with control groups in adults with schizophrenia and concomitant SUD were identified. No restrictions were applied regarding the type of substance used, including alcohol, cannabis, nicotine, and stimulants, such as amphetamines. Data Extraction and Synthesis A systematic review and random-effect pairwise meta-analyses were conducted to estimate standardized mean differences (SMD) with 95% confidence intervals and were reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses ( <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"http://www.equator-network.org/reporting-guidelines/prisma/\">PRISMA</jats:ext-link> ) reporting guidelines. Confidence in the estimate was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main Outcomes and Measures The primary outcomes were overall symptoms and substance use reduction measured by validated scales at posttreatment. Results A total of 35 RCTs were included (4136 participants), with 29 trials involving 3831 participants contributing to pairwise meta-analyses comparing psychological and psychosocial interventions with control conditions. Among the 3748 participants with reported sex, 951 (25.4%) were female, and mean (range) age was 37.2 (20.6-57.5) years. A very small effect favoring the intervention group was observed in reducing overall symptoms (SMD, –0.11; 95% CI, –0.27 to 0.05; 13 trials; low confidence in the estimate), mainly driven by nicotine studies. No difference was found between intervention and control groups in reducing all types of substance use (SMD, –0.01; 95% CI, –0.21 to 0.18; 8 trials; moderate confidence). When considered separately, alcohol, cannabis, amphetamines, and other stimulants showed similar no-effect results, while nicotine use indicated a small effect. Conclusion and Relevance The findings of this systematic review and meta-analysis suggest that current psychological and psychosocial interventions provide limited benefit in reducing symptoms and no effect in reducing substance use in individuals with schizophrenia and SUD compared to con","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"8 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115562","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}
Pub Date : 2026-02-01DOI: 10.1001/jamapsychiatry.2025.3562
Federico Cevoli, Husseini K Manji, Andrew H Miller, Brenda W J H Penninx, Martien Kas, Carmine Pariante, Livia De Picker, Pawel Swieboda, Marion Leboyer
Importance: Neuropsychiatric disorders impose a substantial burden on individuals and societies worldwide. Despite significant advances in the understanding of the brain, only a handful of mechanism-based treatments for psychiatric disorders have been discovered and validated in the past 50 years.
Observations: After discussing the reasons for poor progress in drug discovery in mental disorders, this article outlines recommendations for a paradigm shift toward precision psychiatry, emphasizing the need for biomarker discovery and suggesting a reform of clinical trial methodology. To drive this transformation, increased public and private investment must be aligned with the societal impact of mental disorders, while regulatory agencies should adopt more flexible and biomarker-informed trials, as seen in oncology and other medical fields.
Conclusion and relevance: Promoting cross-sector collaboration between academia, biotech, industry, and health care systems will be critical to support high-risk, high-reward innovations. This article reflects the broad consensus of experts from academia, industry, regulatory agencies, and patient representatives to advance the agenda for precision psychiatry.
{"title":"Implementing Precision Medicine in Psychiatry.","authors":"Federico Cevoli, Husseini K Manji, Andrew H Miller, Brenda W J H Penninx, Martien Kas, Carmine Pariante, Livia De Picker, Pawel Swieboda, Marion Leboyer","doi":"10.1001/jamapsychiatry.2025.3562","DOIUrl":"10.1001/jamapsychiatry.2025.3562","url":null,"abstract":"<p><strong>Importance: </strong>Neuropsychiatric disorders impose a substantial burden on individuals and societies worldwide. Despite significant advances in the understanding of the brain, only a handful of mechanism-based treatments for psychiatric disorders have been discovered and validated in the past 50 years.</p><p><strong>Observations: </strong>After discussing the reasons for poor progress in drug discovery in mental disorders, this article outlines recommendations for a paradigm shift toward precision psychiatry, emphasizing the need for biomarker discovery and suggesting a reform of clinical trial methodology. To drive this transformation, increased public and private investment must be aligned with the societal impact of mental disorders, while regulatory agencies should adopt more flexible and biomarker-informed trials, as seen in oncology and other medical fields.</p><p><strong>Conclusion and relevance: </strong>Promoting cross-sector collaboration between academia, biotech, industry, and health care systems will be critical to support high-risk, high-reward innovations. This article reflects the broad consensus of experts from academia, industry, regulatory agencies, and patient representatives to advance the agenda for precision psychiatry.</p>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"207-211"},"PeriodicalIF":17.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145714295","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}
Pub Date : 2026-02-01DOI: 10.1001/jamapsychiatry.2025.4225
Kerim M Munir
{"title":"Recognizing Grief in Neurodivergent Minds.","authors":"Kerim M Munir","doi":"10.1001/jamapsychiatry.2025.4225","DOIUrl":"10.1001/jamapsychiatry.2025.4225","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"116-117"},"PeriodicalIF":17.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810161","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}
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