Supplementary file 1_Clinical pharmacist-led interventions and their impact on outcomes in patients with bipolar I disorder: a systematic review and meta-analysis.docx

BackgroundPharmacist-led interventions have increasingly been recognized as effective strategies for improving outcomes in psychiatric care, yet their role in patients with bipolar I disorder (BD-I) remains underexplored. This systematic review and meta-analysis synthesized existing evidence on the impact of clinical pharmacist-led interventions (defined as medication education, medication review, adherence support, relapse monitoring, and collaborative care with psychiatrists) on medication adherence, relapse prevention, hospitalization, and quality of life among individuals with BD-I.
ObjectivesTo evaluate the effectiveness of pharmacist-led interventions, either alone or in collaboration with psychiatrists, on key clinical and humanistic outcomes in adults diagnosed with BD-I.
MethodsElectronic databases (PubMed/MEDLINE, Embase, PsycINFO, Scopus, Web of Science, and the Cochrane Library) were searched from January 2000 to August 2025 for randomized controlled trials and non-randomized quasi-experimental designs (prospective cohort studies and pre–post intervention studies) assessing pharmacist-led interventions in BD-I. Studies were screened and appraised independently in accordance with PRISMA 2020 guidelines, using the Cochrane RoB 2 tool for randomized controlled trials and the Newcastle–Ottawa Scale for non-randomized studies. Meta-analyses were performed using Review Manager (RevMan 5.4). Primary outcomes were medication adherence, relapse, hospitalization, and health-related quality of life (QoL). Secondary outcomes included any additional clinical or humanistic measures reported by the included studies. Effect sizes were expressed as odds ratios (ORs) for dichotomous outcomes and as mean differences (MDs) or standardized mean differences (SMDs) for continuous outcomes, each reported with 95% confidence intervals (CIs).
ResultsFive studies met the eligibility criteria, and four contributed quantitative data. Pharmacist-led interventions significantly improved medication adherence compared with usual care (MD = 1.47 [95% CI: 1.35–1.59], p < 0.00001). For relapse prevention, pooled analysis from two trials showed reduced relapse episodes (OR = 1.94 [95% CI: 1.15–3.23], p = 0.01; I2 = 38%). Improvements were also observed in quality of life (SMD = –1.89 [95% CI: –4.95–1.20], p = 0.21; I2 = 90%). Evidence for hospitalization reduction was limited but directionally favored pharmacist involvement.
ConclusionClinical pharmacist-led interventions significantly enhance medication adherence and quality of life and may reduce relapse risk among patients with BD-I. However, given the limited number of studies and small pooled sample sizes, the overall evidence remains preliminary, and the findings should be interpreted cautiously rather than as definitive conclusions. Further large-scale, multicenter studies are warranted to confirm these benefits and assess cost-effectiveness.
Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD420251123737 04/10/2025].

背景：临床药师主导的干预措施（clinical pharmacist-led interventions）作为改善精神科护理结局的有效策略已日益得到认可，但其在双相I型障碍（Bipolar I Disorder, BD-I）患者中的应用价值仍有待深入探索。本系统综述与Meta分析（systematic review and meta-analysis）整合了现有证据，旨在探讨临床药师主导的干预措施（定义为用药教育、用药审核、依从性支持、复发监测以及与精神科医师的协作诊疗）对双相I型障碍患者的用药依从性、复发预防、住院情况及生活质量的影响。
研究目的：评估临床药师主导的干预措施（单独实施或与精神科医师协作开展）对确诊为双相I型障碍的成年患者关键临床与人文结局的改善效果。
研究方法：检索2000年1月至2025年8月期间的电子数据库（PubMed/MEDLINE、Embase、PsycINFO、Scopus、Web of Science及Cochrane图书馆），筛选评估临床药师主导干预措施对双相I型障碍患者疗效的随机对照试验（randomized controlled trial）及非随机类准实验设计研究（non-randomized quasi-experimental designs，包括前瞻性队列研究（prospective cohort studies）与干预前后研究（pre–post intervention studies））。依据PRISMA 2020指南独立完成文献筛选与质量评价，其中随机对照试验采用Cochrane RoB 2工具进行偏倚风险评估，非随机研究则采用纽卡斯尔-渥太华量表（Newcastle–Ottawa Scale）评价。Meta分析采用Review Manager（RevMan 5.4）完成。本研究的主要结局指标为用药依从性、复发情况、住院事件及健康相关生活质量（health-related quality of life, QoL）；次要结局指标为纳入研究报告的其他临床或人文类测量指标。效应量指标方面，二分类结局（dichotomous outcomes）采用比值比（odds ratios, ORs）表示，连续结局采用均数差（mean differences, MDs）或标准化均数差（standardized mean differences, SMDs）表示，所有效应量均附带95%置信区间（95% confidence intervals, CIs）。
研究结果：共计5项研究符合纳入标准，其中4项提供了定量数据。与常规护理相比，临床药师主导的干预措施可显著提升患者用药依从性（均数差MD=1.47，95%置信区间CI:1.35~1.59，p<0.00001）。针对复发预防的合并分析显示，2项试验的结果表明复发事件显著减少（比值比OR=1.94，95%CI:1.15~3.23，p=0.01；I²=38%）。患者生活质量亦得到改善（标准化均数差SMD=-1.89，95%CI:-4.95~1.20，p=0.21；I²=90%）。关于降低住院率的证据较为有限，但整体方向支持临床药师参与的干预方案。
研究结论：临床药师主导的干预措施可显著提升双相I型障碍患者的用药依从性与生活质量，并可能降低其复发风险。然而，鉴于纳入研究数量有限且合并样本量较小，现有整体证据仍处于初步阶段，解读本研究结果时需谨慎，不应将其视为确定性结论。未来需开展大规模多中心研究以验证上述获益，并评估该干预方案的成本效益。
系统综述注册：[https://www.crd.york.ac.uk/prospero/]，标识符[CRD420251123737 2025年10月4日]。