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Antipsychotic Drugs and Cognitive Function: A Systematic Review and Pairwise Network Meta-Analysis. 抗精神病药物与认知功能:系统回顾与配对网络元分析》(A Systematic Review and Pairwise Network Meta-Analysis)。
IF 25.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-16 DOI: 10.1001/jamapsychiatry.2024.2890
Lena Feber,Natalie L Peter,Virginia Chiocchia,Johannes Schneider-Thoma,Spyridon Siafis,Irene Bighelli,Wulf-Peter Hansen,Xiao Lin,Daniel Prates-Baldez,Georgia Salanti,Richard S E Keefe,Rolf R Engel,Stefan Leucht
ImportanceCognitive deficits are a substantial part of the symptoms of schizophrenia spectrum disorders (SSDs) and contribute heavily to the burden of disease. Antipsychotic drugs are not cognitive enhancers, but due to their different receptor-binding profiles, they could differ in their effects on cognition. No previous network meta-analysis compared antipsychotics to placebo, which is important to determine whether use of these drugs is associated with cognitive performance in SSDs at all.ObjectiveTo determine the association of treatment with various antipsychotics and cognition in patients with SSDs.Data SourcesCochrane Schizophrenia Trials Register through June 25, 2023.Study SelectionRandomized clinical trials examining the effects on cognition of antipsychotic drugs or placebo in participants with SSD.Data Extraction and SynthesisA systematic review and random-effects frequentist network meta-analysis was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses-Network Meta-analysis reporting guideline.Main Outcomes and MeasuresThe primary outcome was change in overall cognition score calculated for each study. Secondary outcomes included cognitive domains, quality of life, and functioning.ResultsThis study included 68 studies involving 9525 participants (mean [SD] age, 35.1 [8.9] years; 5878 male [70%] and 2890 [30%] female; some studies did not provide this information). There were few clear differences between antipsychotics, but first-generation dopamine antagonists haloperidol (standardized mean difference [SMD], 0.04; 95% CI, -0.25 to 0.33) and fluphenazine (SMD, 0.15; 95% CI, -0.39 to 0.69) as well as clozapine (SMD, 0.12; 95% CI, -0.23 to 0.48) ranked low. No individual antipsychotic was associated with a clearly better outcome than placebo, but antipsychotics as a group were, with small effect sizes (mean SMDs: adrenergic/low dopamine, 0.21; serotonergic/dopaminergic, 0.26; muscarinic, 0.28; dopaminergic, 0.40).Conclusion and RelevanceAlthough data are relatively sparse, those reviewed in this study suggest that first-generation dopamine antagonists and clozapine should be avoided when cognitive deficits are a concern. Antipsychotics are not procognitive drugs. The overall small superior outcomes compared to placebo may be explained by less disordered thought patterns associated with fewer positive symptoms rather than cognitive deficits in the proper sense. The findings also suggest that harmonizing measurement of cognitive function in randomized clinical trials would be beneficial.
重要性认知障碍是精神分裂症谱系障碍(SSD)症状的重要组成部分,也是造成疾病负担的重要原因。抗精神病药物不是认知增强剂,但由于其受体结合特征不同,它们对认知的影响也可能不同。此前没有任何网络荟萃分析将抗精神病药物与安慰剂进行比较,而这对于确定这些药物的使用是否与SSD患者的认知能力有关联非常重要。研究选择考察抗精神病药物或安慰剂对 SSD 参与者认知能力影响的随机临床试验。数据提取和合成根据《系统综述和元分析首选报告项目--网络元分析报告指南》进行了系统综述和随机效应频数网络元分析。主要结果和测量指标主要结果是每项研究计算的总体认知能力评分变化。结果本研究共纳入 68 项研究,涉及 9525 名参与者(平均 [SD] 年龄为 35.1 [8.9] 岁;5878 名男性 [70%] 和 2890 名女性 [30%];部分研究未提供相关信息)。抗精神病药物之间几乎没有明显差异,但第一代多巴胺拮抗剂氟哌啶醇(标准化平均差 [SMD],0.04;95% CI,-0.25 至 0.33)和氟奋乃静(SMD,0.15;95% CI,-0.39 至 0.69)以及氯氮平(SMD,0.12;95% CI,-0.23 至 0.48)的差异较小。没有一种抗精神病药物的疗效明显优于安慰剂,但抗精神病药物作为一个群体,其效应大小较小(平均 SMD:肾上腺素能/低多巴胺能,0.21;5-羟色胺能/多巴胺能,0.26;毒蕈碱能,0.结论和相关性虽然数据相对稀少,但本研究中回顾的数据表明,当认知障碍是一个问题时,应避免使用第一代多巴胺拮抗剂和氯氮平。抗精神病药物并不是促认知药物。与安慰剂相比,总体疗效略胜一筹的原因可能是与较少的阳性症状相关的思维模式紊乱较少,而非正常意义上的认知障碍。研究结果还表明,在随机临床试验中统一认知功能的测量方法将是有益的。
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引用次数: 0
Toward Equitable Interventions in Public Mental Health: A Review. 实现公共心理健康的公平干预:回顾。
IF 25.8 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-16 DOI: 10.1001/jamapsychiatry.2024.3206
Ulrich Reininghaus,Annika S Reinhold,Stefan Priebe,Christian Rauschenberg,Leonie Fleck,Anita Schick,Frederike Schirmbeck,Inez Myin-Germeys,Craig Morgan,Jessica A Hartmann
ImportanceThe field of public mental health is evolving to tackle the profound impact of global challenges such as climate change, migration, and health crises. These issues accentuate health and social inequities, necessitating a focus on how to achieve interventions that are equitable and enhance mental health across all societal strata.ObservationsPopulation-based interventions can inadvertently exacerbate mental health inequities if they are primarily assessed by, and beneficial to, the most advantaged. Dimensional approaches such as the Hierarchical Taxonomy of Psychopathology offer a more nuanced understanding of mental health, capturing the whole spectrum of symptom severity in a culturally sensitive and less stigmatizing way. In addition, adopting intersectional, participatory, and settings-based approaches can help tailor interventions to the unique needs of marginalized groups.Conclusions and RelevanceIn moving toward more equitable interventions in public mental health, it is imperative to adopt an approach that integrates multiple frameworks to address the complexity of mental health inequities. At the core of this integrated approach is the recognition that mental health exists on a continuum. Intersectionality theory can help to identify the root (fundamental) causes of mental health while participatory and settings-based approaches ensure that interventions are relevant, culturally sensitive, and accessible to all. By adopting these approaches, interventions that are not only effective in "shifting the curve" toward better mental health, but are also equitable in their reach and impact, can be developed.
重要性公共心理健康领域正在不断发展,以应对气候变化、移民和健康危机等全球挑战的深远影响。这些问题加剧了健康和社会的不平等,因此有必要关注如何在社会各阶层实现公平的干预措施,并提高心理健康水平。意见基于人群的干预措施如果主要由最有优势的人群来评估并使其受益,则可能会无意中加剧心理健康的不平等。精神病理学层次分类法等维度方法提供了对心理健康更细致入微的理解,以文化敏感性和较少污名化的方式捕捉了症状严重程度的整个范围。此外,采用交叉性、参与性和基于环境的方法可以帮助定制干预措施,以满足边缘化群体的独特需求。结论与相关性在公共心理健康领域采取更公平的干预措施时,当务之急是采用一种整合多种框架的方法来应对心理健康不公平的复杂性。这种综合方法的核心是认识到心理健康是一个连续体。交叉性理论可以帮助确定心理健康的根本(根本)原因,而参与式方法和基于环境的方法则可以确保干预措施具有相关性、文化敏感性,并为所有人所接受。通过采用这些方法,可以制定出不仅能有效地 "改变曲线 "以改善心理健康,而且在覆盖范围和影响方面也是公平的干预措施。
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引用次数: 0
Deconstructing Cognitive Impairment in Psychosis With a Machine Learning Approach. 用机器学习方法解构精神病患者的认知障碍
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-09 DOI: 10.1001/jamapsychiatry.2024.3062
Robert A McCutcheon, Richard S E Keefe, Philip M McGuire, Andre Marquand
<p><strong>Importance: </strong>Cognitive functioning is associated with various factors, such as age, sex, education, and childhood adversity, and is impaired in people with psychosis. In addition to specific effects of the disorder, cognitive impairments may reflect a greater exposure to general risk factors for poor cognition.</p><p><strong>Objective: </strong>To determine the extent that impairments in cognition in psychosis reflect risk factor exposures.</p><p><strong>Design, setting, and participants: </strong>This cross-sectional study examined the relationship between exposures and cognitive function using data from the Bipolar-Schizophrenia Network on Intermediate Phenotypes studies 1 and 2 across 6 sites. Participants included healthy controls; patients with schizophrenia, schizoaffective disorder, or bipolar I disorder with psychosis; and relatives of patients. Predictive modeling was performed using extreme gradient boosting regression to train a composite cognitive score prediction model with nested cross-validation. Shapley additive explanations values were used to examine the relationship between exposures and cognitive function.</p><p><strong>Exposure: </strong>Exposures were chosen based on associations with cognition previously identified: age, sex, race and ethnicity, childhood adversity, education, parental education, parental socioeconomic status, parental age at birth, substance use, antipsychotic dose, and diagnosis.</p><p><strong>Main outcomes and measures: </strong>Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia.</p><p><strong>Results: </strong>A total of 3370 participants were included: 840 healthy controls, 709 patients with schizophrenia, 541 with schizoaffective disorder, 457 with bipolar I disorder with psychosis, and 823 relatives of patients. The mean (SD) age was 37.9 (13.3) years; 1887 were female (56%) and 1483 male (44%). The model predicted cognitive scores with high accuracy: out-of-sample Pearson correlation between predicted and observed cognitive composite score was r = 0.72 (SD = 0.03). Individuals with schizophrenia (z = -1.4), schizoaffective disorder (z = -1.2), and bipolar I disorder with psychosis (z = -0.5) all had significantly worse cognitive composite scores than controls. Factors other than diagnosis and medication accounted for much of this impairment (schizophrenia z = -0.73, schizoaffective disorder z = -0.64, bipolar I disorder with psychosis z = -0.13). Diagnosis accounted for a lesser proportion of this deficit (schizophrenia z = -0.29, schizoaffective disorder z = -0.15, bipolar I disorder with psychosis z = -0.13), and antipsychotic use accounted for a similar deficit across diagnostic groups (schizophrenia z = -0.37, schizoaffective disorder z = -0.33, bipolar I disorder with psychosis z = -0.26).</p><p><strong>Conclusions and relevance: </strong>This study found that transdiagnostic factors accounted for a meaningful share of the variance in cognitive fu
重要性:认知功能与年龄、性别、教育程度和童年逆境等多种因素有关,精神病患者的认知功能也会受损。除了精神障碍的特殊影响外,认知功能障碍还可能反映出患者更多地暴露于导致认知功能低下的一般风险因素:目的:确定精神病患者的认知障碍在多大程度上反映了所暴露的风险因素:这项横断面研究利用双相情感障碍-精神分裂症中间表型网络研究 1 和研究 2 在 6 个地点获得的数据,研究了暴露因素与认知功能之间的关系。参与者包括健康对照组;精神分裂症、分裂情感障碍或伴有精神病的双相情感障碍 I 型患者;以及患者亲属。预测建模采用极端梯度提升回归法,通过嵌套交叉验证训练综合认知分数预测模型。沙普利加法解释值用于检验暴露与认知功能之间的关系。暴露:暴露的选择基于之前确定的与认知相关的因素:年龄、性别、种族和民族、童年逆境、教育、父母教育、父母的社会经济地位、父母的出生年龄、药物使用、抗精神病药物剂量和诊断:认知能力采用精神分裂症认知能力简要评估进行评估:结果:共纳入 3370 名参与者:结果:共纳入了 3370 名参与者:840 名健康对照者、709 名精神分裂症患者、541 名分裂情感障碍患者、457 名躁狂 I 型精神障碍患者以及 823 名患者亲属。平均(标清)年龄为 37.9 (13.3) 岁;1887 名女性(占 56%),1483 名男性(占 44%)。该模型预测认知分数的准确性很高:预测认知综合分数与观察认知综合分数之间的样本外皮尔逊相关性为 r = 0.72(标度 = 0.03)。精神分裂症(z =-1.4)、分裂情感障碍(z =-1.2)和伴有精神病的双相情感障碍 I(z =-0.5)患者的认知综合评分均明显低于对照组。除诊断和药物治疗外,其他因素也是造成认知障碍的主要原因(精神分裂症 z = -0.73,分裂情感障碍 z = -0.64,伴有精神病的双相 I 型障碍 z = -0.13)。诊断在这一缺陷中所占比例较小(精神分裂症 z = -0.29,分裂情感性障碍 z = -0.15,Ⅰ型双相情感障碍伴有精神病 z =-0.13),而抗精神病药物的使用在各诊断组中造成的缺陷相似(精神分裂症 z = -0.37,分裂情感性障碍 z = -0.33,Ⅰ型双相情感障碍伴有精神病 z =-0.26):本研究发现,跨诊断因素在精神病认知功能的变异中占了相当大的比例。很大一部分精神病患者的认知功能障碍可能反映了与普通人群认知功能相关的因素。因此,在考虑干预措施时,以诊断为导向、以症状为目标的方法可能是合适的。
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引用次数: 0
An Architecture for Transformation in Child Mental Health. 儿童精神健康转型架构。
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-09 DOI: 10.1001/jamapsychiatry.2024.3072
John N Constantino, Laura J Dilly
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引用次数: 0
A Group Parenting Intervention for Male Postpartum Depression: A Cluster Randomized Clinical Trial. 针对男性产后抑郁症的集体育儿干预:集群随机临床试验。
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-02 DOI: 10.1001/jamapsychiatry.2024.2752
M Ishrat Husain, Tayyeba Kiran, Rabia Sattar, Ameer B Khoso, Ming Wai Wan, Daisy R Singla, Madeha Umer, Rabdino Mangrio, Paul Bassett, Imran B Chaudhry, Shehla N Zafar, Farhat A Jafri, Nasim Chaudhry, Nusrat Husain
<p><strong>Importance: </strong>Male postpartum depression is prevalent across populations; however, there is limited evidence on strategies to address it, particularly in low-income settings.</p><p><strong>Objective: </strong>To evaluate the effectiveness of Learning Through Play Plus Dads (LTP + Dads), a nonspecialist-delivered psychosocial intervention, in improving symptoms of male postpartum depression compared to treatment as usual.</p><p><strong>Design, setting, and participants: </strong>This cluster randomized clinical trial was conducted in Karachi, Pakistan, between June 2018 and November 2019. Assessors were blind to treatment allocation. Participants were recruited from 2 large towns in the city of Karachi via basic health units. Fathers aged 18 years and older with a DSM-5 diagnosis of major depressive episode and a child younger than 30 months were recruited. Of 1582 fathers approached, 1527 were screened and 357 were randomized in a 1:1 ratio to either the intervention or treatment as usual; 328 were included in the final analysis. Data were analyzed from April to June 2022.</p><p><strong>Interventions: </strong>LTP + Dads is a manualized intervention combining parenting skills training, play therapy, and cognitive behavior therapy. The intervention was delivered by community health workers via 12 group sessions over 4 months.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was change in 17-item Hamilton Depression Rating Scale score at 4 months. Secondary outcomes included anxiety symptoms; parenting stress; intimate partner violence; functioning; quality of life; and child social, emotional, and physical health outcomes. Assessments were completed at baseline and 4 and 6 months postrandomization.</p><p><strong>Results: </strong>Of the 357 fathers included (mean [SD] age, 31.44 [7.24] years), 171 were randomized to the intervention and 186 to treatment as usual. Participants randomized to the intervention demonstrated significantly greater improvements in depression (group difference ratio [GDR], 0.66; 95% CI, 0.47 to 0.91; P < .001), anxiety (GDR, 0.62; 95% CI, 0.48 to 0.81; P < .001), parenting stress (GDR, -12.5; 95% CI, -19.1 to -6.0; P < .001), intimate partner violence (GDR, 0.89; 95% CI, 0.80 to 1.00; P = .05), disability (GDR, 0.77; 95% CI, 0.61 to 0.97; P = .03), and health-related quality of life (GDR, 12.7; 95% CI, 0.17 to 0.34; P < .001) at 4 months. The difference in depression and parenting stress was sustained at 6 months. Children of fathers randomized to the parenting intervention had significantly greater improvements in social-emotional development scores (mean difference, -20.8; 95% CI, -28.8 to -12.9; P < .001) at 6 months.</p><p><strong>Conclusions and relevance: </strong>The psychosocial parenting intervention in this study has the potential to improve paternal mental health and child development in Pakistan. Further studies in other populations and with longer follow-up are warranted
重要性:男性产后抑郁症在不同人群中普遍存在;然而,有关解决这一问题的策略的证据却很有限,尤其是在低收入环境中:目的:评估 "通过游戏学习+爸爸"(LTP + Dads)这种非专家提供的社会心理干预与常规治疗相比在改善男性产后抑郁症状方面的有效性:这项分组随机临床试验于 2018 年 6 月至 2019 年 11 月在巴基斯坦卡拉奇进行。评估者对治疗分配持盲态度。参与者通过基层医疗单位从卡拉奇市的两个大镇招募。被招募的父亲年龄在 18 岁及以上,DSM-5 诊断为重度抑郁发作,孩子小于 30 个月。在接触的 1582 名父亲中,1527 名接受了筛查,357 名按 1:1 的比例随机接受了干预或常规治疗;328 名被纳入最终分析。数据分析时间为 2022 年 4 月至 6 月:LTP + 爸爸 "是一项结合了育儿技能培训、游戏疗法和认知行为疗法的手册化干预措施。干预措施由社区卫生工作者在 4 个月内通过 12 节小组课程实施:主要结果和测量方法:主要结果是 4 个月后 17 项汉密尔顿抑郁量表得分的变化。次要结果包括焦虑症状、养育压力、亲密伴侣暴力、功能、生活质量以及儿童社会、情感和身体健康结果。评估在基线和随机化后的 4 个月和 6 个月完成:在 357 名父亲(平均 [SD] 年龄为 31.44 [7.24] 岁)中,171 名被随机纳入干预方案,186 名被随机纳入常规治疗方案。随机接受干预的参与者在抑郁方面的改善幅度明显更大(组间差异比 [GDR],0.66;95% CI,0.47 至 0.91;P 结论及意义:本研究中的社会心理养育干预有可能改善巴基斯坦父亲的心理健康和儿童发展。有必要在其他人群中开展进一步研究,并进行更长时间的随访:试验注册:ClinicalTrials.gov Identifier:NCT03564847.
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引用次数: 0
Bright Light Therapy for Nonseasonal Depressive Disorders: A Systematic Review and Meta-Analysis. 治疗非季节性抑郁障碍的亮光疗法:系统回顾与元分析》。
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-02 DOI: 10.1001/jamapsychiatry.2024.2871
Artur Menegaz de Almeida, Francisco Cezar Aquino de Moraes, Maria Eduarda Cavalcanti Souza, Jorge Henrique Cavalcanti Orestes Cardoso, Fernanda Tamashiro, Celso Miranda, Lilianne Fernandes, Michele Kreuz, Francinny Alves Kelly

Importance: Seasonal humor disorders are prone to have a link with daylight exposure. However, the effect of external light on nonseasonal disorders remains unclear. Evidence is lacking for the validity of bright light therapy (BLT) as an adjunctive treatment for these patients.

Objective: To assess BLT effectiveness as an adjunctive treatment for nonseasonal depressive disorders.

Data sources: In March 2024, a comprehensive search was performed of publications in the MEDLINE, Embase, and Cochrane databases for randomized clinical trials (RCTs) evaluating BLT effects in patients with nonseasonal depression.

Study selection: RCTs published since 2000 were eligible. Comparisons between BLT and dim red light or antidepressant monotherapy alone were considered for inclusion.

Data extraction and synthesis: Using the systematic review approach on RCTs published from January 1, 2000, through March 25, 2024, differences between patients treated with and without BLT were estimated using the Mantel-Haenszel method; heterogeneity was assessed using I2 statistics.

Main outcomes and measures: Remission of symptoms, response to treatment rates, and depression scales were assessed.

Results: In this systematic review and meta-analysis of 11 unique trials with data from 858 patients (649 female [75.6%]), statistically significant better remission and response rates were found in the BLT group (remission: 40.7% vs 23.5%; odds ratio [OR], 2.42; 95% CI, 1.50-3.91; P <.001; I2 = 21%; response: 60.4% vs 38.6%; OR, 2.34; 95% CI, 1.46-3.75; P <.001; I2 = 41%). With BLT, subgroup analysis based on follow-up times also showed better remission (<4 weeks: 27.4% vs 9.2%; OR, 3.59; 95% CI, 1.45-8.88; P = .005; I2 = 0% and >4 weeks: 46.6% vs 29.1%; OR, 2.18; 95% CI, 1.19-4.00; P = .01; I2 = 47%) and response (<4 weeks: 55.6% vs 27.4%; OR, 3.65; 95% CI, 1.81-7.33; P <.001; I2 = 35% and >4 weeks: 63.0% vs 44.9%; OR, 1.79; 95% CI, 1.01-3.17; P = .04; I2 = 32%) rates.

Conclusions and relevance: Results of this systematic review and meta-analysis reveal that BLT was an effective adjunctive treatment for nonseasonal depressive disorders. Additionally, results suggest that BLT may improve the response time to the initial treatment.

重要性:季节性情绪失调容易与日光照射有关。然而,外部光线对非季节性失调症的影响仍不明确。亮光疗法(BLT)作为这些患者的辅助治疗方法是否有效尚缺乏证据:评估亮光疗法作为非季节性抑郁障碍的辅助治疗方法的有效性:2024年3月,对MEDLINE、Embase和Cochrane数据库中评估BLT对非季节性抑郁症患者疗效的随机临床试验(RCT)的出版物进行了全面检索:研究选择:2000 年以来发表的 RCT 符合条件。数据提取与综合:对2000年1月1日至2024年3月25日期间发表的RCT采用系统综述方法,使用曼特尔-海恩泽尔法估算接受BLT治疗和未接受BLT治疗的患者之间的差异;使用I2统计量评估异质性:对症状缓解、治疗反应率和抑郁量表进行了评估:本系统综述和荟萃分析包括11项独特的试验,共收集了858名患者(649名女性[75.6%])的数据,发现BLT组的缓解率和应答率在统计学上有显著提高(缓解率:40.7% vs 23.5%):40.7% vs 23.5%;几率比 [OR],2.42;95% CI,1.50-3.91;P 4 周:46.6%对29.1%;OR,2.18;95% CI,1.19-4.00;P = .01;I2 = 47%)和反应率(4周:63.0%对44.9%;OR,1.79;95% CI,1.01-3.17;P = .04;I2 = 32%):本系统综述和荟萃分析的结果表明,BLT 是治疗非季节性抑郁障碍的有效辅助疗法。此外,研究结果表明,BLT 可缩短初始治疗的反应时间。
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引用次数: 0
Mental Health Diagnoses in People Experiencing Homelessness. 无家可归者的心理健康诊断。
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-01 DOI: 10.1001/jamapsychiatry.2024.2315
Kevin Y Xu, Sonya E Gabrielian, Tashalee R Brown
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引用次数: 0
Smoking Cessation as a Priority for Psychiatrists. 戒烟是精神科医生的当务之急。
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-01 DOI: 10.1001/jamapsychiatry.2024.2162
Robert A Kleinman, Brian S Barnett
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引用次数: 0
JAMA Psychiatry. 美国医学会精神病学杂志》。
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-01 DOI: 10.1001/jamapsychiatry.2023.3944
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引用次数: 0
Pneumonia Risk, Antipsychotic Dosing, and Anticholinergic Burden in Schizophrenia. 精神分裂症患者的肺炎风险、抗精神病药物剂量和抗胆碱能药物负担。
IF 22.5 1区 医学 Q1 PSYCHIATRY Pub Date : 2024-10-01 DOI: 10.1001/jamapsychiatry.2024.1441
Jurjen J Luykx, Christoph U Correll, Peter Manu, Antti Tanskanen, Alkomiet Hasan, Jari Tiihonen, Heidi Taipale
<p><strong>Importance: </strong>Antipsychotic drugs (particularly clozapine) have been associated with pneumonia in observational studies. Despite studies of the associations between antipsychotic use and incident pneumonia, it remains unclear to what degree antipsychotic use is associated with increased risk of pneumonia, whether dose-response associations exist, and what agents are specifically associated with incident pneumonia.</p><p><strong>Objective: </strong>To estimate pneumonia risk associated with specific antipsychotics and examine whether polytherapy, dosing, and receptor binding properties are associated with pneumonia in patients with schizophrenia.</p><p><strong>Design, setting, and participants: </strong>This cohort study identified patients with schizophrenia or schizoaffective disorder (hereafter, schizophrenia) aged 16 years or older from nationwide Finnish registers from 1972 to 2014. Data on diagnoses, inpatient care, and specialized outpatient care were obtained from the Hospital Discharge Register. Information on outpatient medication dispensing was obtained from the Prescription Register. Study follow-up was from 1996 to 2017. Data were analyzed from November 4, 2022, to December 5, 2023.</p><p><strong>Exposures: </strong>Use of specific antipsychotic monotherapies; antipsychotics modeled by dosage as low (<0.6 of the World Health Organization defined daily dose [DDD] per day), medium (0.6 to <1.1 DDDs per day), or high dose (≥1.1 DDDs per day); antipsychotic polypharmacy; and antipsychotics categorized according to their anticholinergic burden as low, medium, and high.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was hospitalization for incident pneumonia. Pneumonia risk was analyzed using adjusted, within-individual Cox proportional hazards regression models, with no antipsychotic use as the reference.</p><p><strong>Results: </strong>The study included 61 889 persons with schizophrenia (mean [SD] age, 46.2 [16.0] years; 31 104 men [50.3%]). During 22 years of follow-up, 8917 patients (14.4%) had 1 or more hospitalizations for pneumonia and 1137 (12.8%) died within 30 days of admission. Compared with no antipsychotic use, any antipsychotic use overall was not associated with pneumonia (adjusted hazard ratio [AHR], 1.12; 95% CI, 0.99-1.26). Monotherapy use was associated with increased pneumonia risk compared with no antipsychotic use (AHR, 1.15 [95% CI, 1.02-1.30]; P = .03) in a dose-dependent manner, but polytherapy use was not. When categorized by anticholinergic burden, only the use of antipsychotics with a high anticholinergic burden was associated with pneumonia (AHR, 1.26 [95% CI, 1.10-1.45]; P < .001). Of specific drugs, high-dose quetiapine (AHR, 1.78 [95% CI, 1.22-2.60]; P = .003), high- and medium-dose clozapine (AHR, 1.44 [95% CI, 1.22-1.71]; P < .001 and AHR, 1.43 [95% CI, 1.18-1.74]; P < .001, respectively), and high-dose olanzapine (AHR, 1.29 [95% CI, 1.05-1.58]; P = .02) were assoc
重要性:在观察性研究中,抗精神病药物(尤其是氯氮平)与肺炎有关。尽管对抗精神病药物的使用与肺炎事件之间的关联进行了研究,但目前仍不清楚抗精神病药物的使用与肺炎风险增加的关联程度、是否存在剂量-反应关联以及哪些药物与肺炎事件特别相关:估计与特定抗精神病药物相关的肺炎风险,并研究精神分裂症患者的多药治疗、剂量和受体结合特性是否与肺炎有关:这项队列研究从 1972 年至 2014 年期间芬兰全国范围的登记资料中确定了 16 岁或以上的精神分裂症或情感分裂症(以下简称精神分裂症)患者。有关诊断、住院治疗和专科门诊治疗的数据来自出院登记册。门诊配药信息来自处方登记册。研究随访期为 1996 年至 2017 年。数据分析时间为 2022 年 11 月 4 日至 2023 年 12 月 5 日:使用特定的抗精神病药物单一疗法;抗精神病药物按剂量模型为低剂量(主要结果和测量指标:主要结果是因肺炎住院。肺炎风险采用调整后的个体内 Cox 比例危险回归模型进行分析,以不使用抗精神病药物为参照:研究纳入了 61 889 名精神分裂症患者(平均 [SD] 年龄 46.2 [16.0] 岁;男性 31 104 [50.3%])。在22年的随访中,8917名患者(14.4%)曾因肺炎住院1次或1次以上,1137名患者(12.8%)在入院30天内死亡。与不使用抗精神病药物相比,使用任何抗精神病药物总体上与肺炎无关(调整后危险比 [AHR],1.12;95% CI,0.99-1.26)。与不使用抗精神病药物相比,单药治疗与肺炎风险增加有关(AHR,1.15 [95% CI,1.02-1.30];P = .03),且呈剂量依赖性,但多药治疗与肺炎风险增加无关。按抗胆碱能负荷分类时,只有使用抗胆碱能负荷高的抗精神病药物才与肺炎相关(AHR,1.26 [95% CI,1.10-1.45];P 结论及意义:这项队列研究的结果表明,在精神分裂症患者中,与肺炎相关的抗精神病药物不仅包括氯氮平(剂量≥180毫克/天),还包括喹硫平(≥440毫克/天)和奥氮平(≥11毫克/天)。此外,单药抗精神病药物和抗胆碱能负荷较高的抗精神病药物与肺炎风险的增加呈剂量依赖关系。这些发现要求针对需要高风险抗精神病药物的精神分裂症患者制定预防策略。
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JAMA Psychiatry
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