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Incorporation of a specialist mental health clinical pharmacist within a primary care network: patient referrals, prescribing decisions, and clinical outcomes. 在初级医疗网络中纳入专科精神健康临床药剂师:患者转诊、处方决定和临床结果。
IF 3.4 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-21 eCollection Date: 2024-01-01 DOI: 10.1177/20451253241247368
Rebecca Henry, David S Baldwin

Background: The benefit of generalist pharmacists working within primary care networks (PCNs) and with general practitioners (GPs) is established. We wished to evaluate the contributions and potential benefits of a specialist mental health care prescribing pharmacist within PCNs.

Method: We prospectively collected data, on clinical and demographic characteristics, referral sources, interventions, outcomes (objective and subjective), and patient feedback, from 466 completed patients, in one PCN by one specialist mental health pharmacist (working 0.5 whole time equivalent), over 15 months.

Results: Referrals originated from multiple sources, including GPs, other members of the PCN mental health team, and community mental health teams (CMHTs). Two-thirds of treated patients were female; the most frequent age band was 18-30 years; the most common diagnosis was mixed depression and anxiety. Patients with diagnoses of mixed anxiety with depression or personality disorder needed more appointments than those with anxiety or depression. A range of evidence-based treatments were prescribed, including non-formulary medicines, and those medicines are more typically initiated or recommended in secondary care settings. The most frequently started medications were antidepressants (principally fluoxetine and duloxetine), followed by antipsychotics (principally quetiapine and aripiprazole): the most common dosage increases were for sertraline and quetiapine. Common non-medication recommendations were for cognitive behavioral therapy, cognitive behavioral therapy for insomnia, and other psychological therapies. Patient feedback was generally positive.

Discussion: Developing and implementing a service incorporating a specialist mental health pharmacist within a PCN mental health team is potentially valuable in improving patient care quality, reducing workload for GPs and CMHTs, and enabling faster access to secondary care initiated and recommended medications. This innovative service addressed several national targets, including prevention, early intervention, and access to quality compassionate care.

背景:全科药剂师在初级医疗网络(PCN)中与全科医生(GP)合作的益处已经得到证实。我们希望评估专科精神卫生处方药剂师在 PCN 中的贡献和潜在益处:我们前瞻性地收集了一个 PCN 中 466 名患者的临床和人口特征、转诊来源、干预措施、结果(客观和主观)以及患者反馈等方面的数据,该 PCN 由一名精神健康专科药剂师(相当于 0.5 个全职药剂师)负责,历时 15 个月:转诊患者来自多个渠道,包括全科医生、PCN 精神健康团队的其他成员以及社区精神健康团队(CMHTs)。三分之二接受治疗的患者为女性;最常见的年龄段为 18-30 岁;最常见的诊断为混合型抑郁和焦虑。与焦虑症或抑郁症患者相比,被诊断为混合焦虑症和抑郁症或人格障碍的患者需要预约更多的治疗。开具了一系列循证治疗处方,包括非处方药物,这些药物通常在二级医疗机构开始使用或推荐使用。最常开始使用的药物是抗抑郁药(主要是氟西汀和度洛西汀),其次是抗精神病药(主要是喹硫平和阿立哌唑):最常增加剂量的药物是舍曲林和喹硫平。常见的非药物治疗建议包括认知行为疗法、失眠认知行为疗法和其他心理疗法。患者的反馈普遍积极:在 PCN 精神健康团队中发展和实施一项包含专业精神健康药剂师的服务,对于提高患者护理质量、减轻全科医生和社区医疗小组的工作量、更快地获得二级医疗机构发起和推荐的药物治疗具有潜在的价值。这项创新服务涉及多个国家目标,包括预防、早期干预和获得优质的体恤关怀。
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引用次数: 0
Geriatric psychiatry and brain health in old age 老年精神病学与老年人的大脑健康
IF 4.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-17 DOI: 10.1177/20451253241278557
Rajesh R. Tampi, Jordan F. Karp
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引用次数: 0
Comment on: Attentional bias modification and attention control training in PTSD: a systematic review and meta-analysis 评论创伤后应激障碍中的注意偏差修正和注意控制训练:系统回顾和荟萃分析
IF 4.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-17 DOI: 10.1177/20451253241278872
Coralie Creupelandt, Emilie Veerapa, Arnaud Bugnet, Marielle Wathelet, Alice Demesmaeker, Pierre Grandgenevre, Guillaume Vaiva, Thomas Fovet, Fabien D’Hondt
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引用次数: 0
Using in silico methods to determine optimal tapering regimens for decanoate-based long-acting injectable psychosis drugs 利用硅学方法确定癸酸盐类长效注射型精神病药物的最佳减药方案
IF 4.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-09-14 DOI: 10.1177/20451253241272790
James R. O’Neill, David M. Taylor, Mark A. Horowitz
Background:Reducing the dose of psychosis drugs in a gradual hyperbolic manner may minimise withdrawal effects and risk of relapse. There is presently limited guidance on tapering decanoate-based long-acting injectable dopamine antagonists (LIDAs).Objectives:We aimed to apply hyperbolic principles of tapering to the decanoate-based LIDAs flupentixol, zuclopenthixol and haloperidol to develop withdrawal regimens.Design:We used in silico methodology to predict plasma drug levels and D2 occupancy for different LIDA regimens.Methods:Existing pharmacokinetic and receptor occupancy data from nuclear neuroimaging studies were used to power modelling. Abrupt discontinuation was examined as a potential strategy, and dose reduction was modelled with pre-defined constraints used in similar work of 10 (fast regimens), 5 (moderate) and 2.5 (slow) percentage points of D2 occupancy change per month.Results:Abrupt discontinuation of decanoate-based LIDAs leads to excessive change in D2 occupancy which violated our pre-defined constraints, potentially resulting in withdrawal symptoms and increased risk of relapse. Reduction of LIDA dose allowed hyperbolic reduction in plasma level consistent with imposed constraints on receptor occupancy reduction rate. For equivalent per-weekly LIDA dosing, more frequent administration allowed a more gradual reduction of D2 occupancy. However, switching to oral forms is required to continue hyperbolic tapering to full discontinuation; reduction to zero using only LIDA produces too large a reduction in D2 occupancy. Guidance for reduction and cessation of LIDAs according to slow, moderate and fast criteria is provided.Conclusion:Abrupt cessation of decanoate LIDAs is not consistent with gradual hyperbolic tapering, despite their longer half-lives compared with oral formulations. Reduction to the point of full discontinuation can only be achieved by switching to oral therapy to complete the taper. These results are limited by the in silico and theoretical nature of the study, and there is a need to confirm these findings through real-world observational and interventional studies.
背景:以渐进的双曲线方式减少精神病药物的剂量,可以最大限度地减少戒断效应和复发风险。目的:我们旨在将双曲线减量原则应用于癸酸类长效注射用多巴胺拮抗剂(LIDA)氟朋噻醇、祖氯朋噻醇和氟哌啶醇,以制定停药方案。设计:我们使用硅学方法预测不同 LIDA 方案的血浆药物水平和 D2 占位率。结果:突然停用癸酸盐类 LIDA 会导致 D2 占有率的过度变化,这违反了我们预先设定的约束条件,可能会导致戒断症状并增加复发风险。减少LIDA剂量可使血浆水平呈双曲线下降,这与受体占有率下降率的限制条件相一致。在每周服用等量 LIDA 的情况下,更频繁地给药可以更渐进地降低 D2 占位率。不过,要想继续双曲线式减量直至完全停药,必须改用口服药物;仅使用 LIDA 将 D2 占位率降至零会导致 D2 占位率下降过多。结论:尽管癸酸酯类 LIDA 与口服制剂相比半衰期更长,但突然停用癸酸酯类 LIDA 与双曲线渐减并不一致。只有通过改用口服疗法来完成减量,才能达到完全停药的程度。这些结果受限于研究的硅学和理论性质,需要通过实际观察和干预研究来证实这些发现。
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引用次数: 0
Corrigendum to 'Comment on: History repeating: guidelines to address common problems in psychedelic science'. 对 "评论 "的更正:历史重演:解决迷幻剂科学常见问题的指导原则 "的评论。
IF 3.4 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-19 eCollection Date: 2024-01-01 DOI: 10.1177/20451253241263299

[This corrects the article DOI: 10.1177/20451253241243242.].

[This corrects the article DOI: 10.1177/20451253241243242.].
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引用次数: 0
Exploring psychedelic use in athletes and their attitudes toward psilocybin-assisted therapy in concussion recovery. 探索运动员使用迷幻剂的情况以及他们对迷幻剂辅助脑震荡恢复疗法的态度。
IF 3.4 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-07 eCollection Date: 2024-01-01 DOI: 10.1177/20451253241264812
Baeleigh VanderZwaag, Albert Garcia-Romeu, Mauricio A Garcia-Barrera

Background: Psychedelics are receiving growing interest among clinical researchers for their effects on mood and cognition. Psilocybin is one of the most widely studied classic psychedelics which has shown good safety and clinical benefit for major depression and substance use disorders. Athletes frequently sustain concussions and often experience myriad symptoms, including cognitive and mood issues, which can persist for weeks or months in 10%-30% of athletes. Psilocybin may be a potential symptom management option for athletes with persisting concussion symptoms.

Objectives: This study sought to summarize athlete psychedelic use, among other substances, and to examine the willingness of the sports community to engage in or support psilocybin-assisted therapy (PAT) for concussion recovery and management of persisting concussion symptoms.

Methods: In total, 175 (n = 85 athletes; n = 90 staff) respondents completed an online survey distributed in Canada and the United States which queried sport involvement and demographics, substance use, concussion history, and knowledge and willingness about psilocybin. The reporting of this study conforms to the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) statement.

Design: Substance use rates were summarized across athletes and team staff members and a path analysis was used for each sample to identify predictors of willingness to use PAT (athletes) or support PAT (staff) for concussion recovery. Participants were also asked to identify perceived barriers to the implementation of PAT for sports-related concussions, and to indicate their overall willingness.

Results: Psychedelics were the third most used substance in the past year among athletes (35.8%) while regular psychedelic use was quite low in athletes (7.5%). A path analysis conducted in RStudio found that attitudes toward psilocybin and knowledge of psilocybin were significant predictors for both athletes and staff members of their willingness to use or support PAT for concussion recovery. Athletes reported likely engaging in PAT (61.2%) and staff (71.1%) reported that they would support their athletes using PAT.

Conclusion: The results of this study suggest that the sports community may be receptive to PAT and athletes would be willing to engage in it for concussion recovery and/or the management of persisting post-concussion symptoms (PPCS). Future research should examine the effects of psilocybin for PPCS to inform whether there is any impact while addressing concerns regarding long-term effects of psilocybin use.

背景:迷幻剂对情绪和认知的影响越来越受到临床研究人员的关注。迷幻药是研究最为广泛的经典迷幻药之一,对重度抑郁症和药物使用障碍具有良好的安全性和临床疗效。运动员经常遭受脑震荡,并经常出现各种症状,包括认知和情绪问题,10%-30% 的运动员可能会持续数周或数月。对于有持续脑震荡症状的运动员来说,迷幻药可能是一种潜在的症状管理选择:本研究旨在总结运动员使用迷幻药和其他药物的情况,并考察体育界是否愿意或支持使用迷幻药辅助疗法(PAT)来促进脑震荡恢复和治疗持续性脑震荡症状:共有 175 名(n = 85 名运动员;n = 90 名工作人员)受访者完成了在加拿大和美国分发的在线调查,调查内容包括体育运动参与情况和人口统计学、药物使用情况、脑震荡病史以及对迷幻剂的了解和意愿。本研究的报告符合互联网电子调查结果报告核对表(CHERRIES)声明:对运动员和球队工作人员的药物使用率进行了总结,并对每个样本进行了路径分析,以确定使用 PAT(运动员)或支持 PAT(工作人员)进行脑震荡恢复的意愿的预测因素。此外,还要求参与者确定在运动相关脑震荡治疗中实施 "运动能力评估 "的障碍,并表明他们的总体意愿:结果:迷幻药是运动员在过去一年中使用第三多的药物(35.8%),而经常使用迷幻药的运动员却很少(7.5%)。在 RStudio 中进行的路径分析发现,对于运动员和工作人员来说,对迷幻剂的态度和对迷幻剂的了解是他们是否愿意使用或支持使用 PAT 来促进脑震荡恢复的重要预测因素。运动员表示可能会使用 PAT(61.2%),工作人员(71.1%)表示会支持运动员使用 PAT:本研究的结果表明,体育界可能会接受 "脑震荡后运动疗法",运动员也愿意使用该疗法进行脑震荡恢复和/或处理持续性脑震荡后症状(PPCS)。未来的研究应检查迷幻药对 PPCS 的影响,以了解是否有任何影响,同时解决使用迷幻药的长期影响问题。
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引用次数: 0
Long-acting antipsychotic treatments: focus on women with schizophrenia 长效抗精神病治疗:关注女性精神分裂症患者
IF 4.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-31 DOI: 10.1177/20451253241263715
Sofia Brissos, Vicent Balanzá-Martínez
Effective management of schizophrenia (SZ) requires long-term treatment with antipsychotics (APs) to prevent clinical relapse, attain remission and improve patients’ personal and social functioning, and quality of life. Although APs remain the cornerstone treatment for patients with SZ, despite their potential benefits, long-acting injectable APs (LAI-APs) remain underused, most notably in women with SZ. The efficacy and tolerability of APs differ significantly between men and women, and some of these differences are more noticeable depending on the patient’s age and the stage of the disorder. Although sex differences may influence treatment outcomes in SZ, their pertinence has been insufficiently addressed, especially regarding the use of LAI-APs. Some biological and social experiences, such as pregnancy, lactation, contraception and menopause, are specific to women, but these remain under-researched issues. Implications of this disorder in parenting are also of special pertinence regarding women; therefore, taking sex differences into account when treating SZ patients is now recommended, and improving personalized approaches has been proposed as a priority in the management of psychosis. In this narrative, critical review, we address some aspects specific to sex and their implications for the clinical management of women with SZ, with a special focus on the potential role of LAI-AP treatments.
精神分裂症(SZ)的有效治疗需要抗精神病药物(APs)的长期治疗,以防止临床复发、获得缓解并改善患者的个人和社会功能以及生活质量。尽管抗精神病药物仍是治疗 SZ 患者的基石,但尽管它们具有潜在的益处,长效注射用抗精神病药物(LAI-APs)仍未得到充分利用,尤其是在女性 SZ 患者中。APs的疗效和耐受性在男性和女性之间存在显著差异,其中一些差异因患者的年龄和疾病的阶段而更加明显。虽然性别差异可能会影响SZ的治疗效果,但其相关性尚未得到充分研究,尤其是在使用LAI-APs方面。一些生理和社会经历,如怀孕、哺乳、避孕和更年期,是女性特有的,但这些问题的研究仍然不足。这种疾病对养育子女的影响也与女性特别相关;因此,现在建议在治疗 SZ 患者时考虑到性别差异,并将改进个性化方法作为精神病治疗的优先事项。在这篇评论性综述中,我们将讨论性别的一些特殊方面及其对女性 SZ 患者临床治疗的影响,并特别关注 LAI-AP 治疗的潜在作用。
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引用次数: 0
Sublingual asenapine for agitation in malabsorptive states: three patient cases 舌下含服阿塞那平治疗吸收不良状态下的躁动:三个病例
IF 4.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-07-25 DOI: 10.1177/20451253241263714
Bradley G. Burk, Kyle Humphreys, Jim Waites, Bentley Adams, Badari Birur, Pamela E. Parker
Gastric malabsorptive conditions may prevent patients from deriving benefit from orally administered medications intended for enteric absorption. While malabsorption is an increasingly common issue, current data on alternative oral options for agitation in these patients are very sparse. Sublingual (SL) asenapine is absorbed transmucosally, bypassing gut absorption, making it a viable consideration. We report on three patients, one with short bowel syndrome, one with viral gastritis, and one with aortic dissection who were trialed on SL asenapine for agitation after failing alternative antipsychotics. Two of these patients had an extensive history of psychiatric admissions for bipolar disorder and substance-induced psychosis. All three patients had significant reductions in agitation within 1–5 days, with no reported adverse effects. However, benefit of SL asenapine was hindered in two of these patients as they began inappropriately swallowing the medication, reducing bioavailability to nil. Clinicians should consider the use of SL asenapine for medically complex agitated patients where gastric absorption is questionable. There is an urgent need for guidelines on this matter, as well as more, alternative dosage forms for various medications that may help with agitation in this population.
胃吸收不良可能导致患者无法从用于肠道吸收的口服药物中获益。虽然吸收不良是一个越来越常见的问题,但目前有关这些患者口服治疗躁动的替代方案的数据却非常稀少。舌下含服(SL)阿塞那平可经粘膜吸收,绕过肠道吸收,因此是一种可行的选择。我们报告了三名患者的情况,其中一名患有短肠综合征,一名患有病毒性胃炎,还有一名患有主动脉夹层,他们在服用其他抗精神病药物无效后,试用舌下含服阿塞那平治疗躁动。其中两名患者曾因躁郁症和药物性精神病入院治疗。这三位患者的躁动症状在 1-5 天内均有明显缓解,且无不良反应报告。然而,由于其中两名患者开始不适当地吞咽药物,导致生物利用度降至零,从而阻碍了 SL 阿塞那平的疗效。临床医生应考虑对胃部吸收有问题的病情复杂的躁动患者使用 SL 阿塞那平。目前亟需制定相关指南,并为各种药物提供更多的替代剂型,以帮助此类人群缓解躁动。
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引用次数: 0
Efficacy and safety of long-acting injectable versus oral antipsychotics in the treatment of patients with early-phase schizophrenia-spectrum disorders: a systematic review and meta-analysis. 长效注射与口服抗精神病药物治疗早期精神分裂症谱系障碍患者的疗效和安全性:系统综述和荟萃分析。
IF 4.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-06-02 eCollection Date: 2024-01-01 DOI: 10.1177/20451253241257062
Giovanni Vita, Angelantonio Tavella, Giovanni Ostuzzi, Federico Tedeschi, Michele De Prisco, Rafael Segarra, Marco Solmi, Corrado Barbui, Christoph U Correll

Background: Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with schizophrenia-spectrum disorders (SSDs), but evidence in patients with first-episode/recent-onset, that is, early-phase-SSDs is less clear.

Objectives: To assess the relative medium- and long-term efficacy and safety of LAIs versus OAPs in the maintenance treatment of patients with early-phase SSDs.

Method: We searched major electronic databases for head-to-head randomized controlled trials (RCTs) comparing LAIs and OAPs for the maintenance treatment of patients with early-phase-SSDs.

Design: Pairwise, random-effects meta-analysis. Relapse/hospitalization and acceptability (all-cause discontinuation) measured at study-endpoint were co-primary outcomes, calculating risk ratios (RRs) with their 95% confidence intervals (CIs). Subgroup analyses sought to identify factors moderating differences in efficacy or acceptability between LAIs and OAPs.

Results: Across 11 head-to-head RCTs (n = 2374, median age = 25.2 years, males = 68.4%, median illness duration = 45.8 weeks) lasting 13-104 (median = 78) weeks, no significant differences emerged between LAIs and OAPs for relapse/hospitalization prevention (RR = 0.79, 95%CI = 0.58-1.06, p = 0.13) and acceptability (RR = 0.92, 95%CI = 0.80-1.05, p = 0.20). The included trials were highly heterogeneous regarding methodology and patient populations. LAIs outperformed OAPs in preventing relapse/hospitalization in studies with stable patients (RR = 0.65, 95%CI = 0.45-0.92), pragmatic design (RR = 0.67, 95%CI = 0.54-0.82), and strict intent-to-treat approach (RR = 0.64, 95%CI = 0.52-0.80). Furthermore, LAIs were associated with better acceptability in studies with schizophrenia patients only (RR = 0.87, 95%CI = 0.79-0.95), longer illness duration (RR = 0.88, 95%CI = 0.80-0.97), unstable patients (RR = 0.89, 95%CI = 0.81-0.99) and allowed OAP supplementation of LAIs (RR = 0.90, 95%CI = 0.81-0.99).

Conclusion: LAIs and OAPs did not differ significantly regarding relapse prevention/hospitalization and acceptability. However, in nine subgroup analyses, LAIs were superior to OAPs in patients with EP-SSDs with indicators of higher quality and/or pragmatic design regarding relapse/hospitalization prevention (four subgroup analyses) and/or reduced all-cause discontinuation (five subgroup analyses), without any instance of OAP superiority versus LAIs. More high-quality pragmatic trials comparing LAIs with OAPs in EP-SSDs are needed.

Trial registration: CRD42023407120 (PROSPERO).

背景:长效注射用抗精神病药物(LAIs)与口服抗精神病药物(OAPs)相比,在预防精神分裂症谱系障碍(SSDs)慢性病患者复发和住院治疗方面具有优势,但在初发/复发,即早期SSDs患者中的证据并不明确:评估LAIs与OAPs在早期SSD患者维持治疗中的中长期疗效和安全性:我们在主要电子数据库中检索了头对头随机对照试验(RCT),比较了LAIs和OAPs在早期SSD患者维持治疗中的疗效:设计:配对随机效应荟萃分析。以研究终点衡量的复发/住院和可接受性(全因停药)为共同主要结果,计算风险比(RR)及其95%置信区间(CI)。亚组分析旨在确定调节LAIs和OAPs疗效或可接受性差异的因素:在11项头对头RCT(n = 2374,中位年龄 = 25.2岁,男性 = 68.4%,中位病程 = 45.8周)中,持续13-104周(中位 = 78周)的LAI和OAP在预防复发/住院(RR = 0.79,95%CI = 0.58-1.06,p = 0.13)和可接受性(RR = 0.92,95%CI = 0.80-1.05,p = 0.20)方面无显著差异。纳入的试验在方法和患者人群方面存在很大差异。在有稳定患者(RR = 0.65,95%CI = 0.45-0.92)、实用设计(RR = 0.67,95%CI = 0.54-0.82)和严格意向治疗方法(RR = 0.64,95%CI = 0.52-0.80)的研究中,LAIs在预防复发/住院方面优于OAPs。此外,在仅对精神分裂症患者(RR = 0.87,95%CI = 0.79-0.95)、病程较长(RR = 0.88,95%CI = 0.80-0.97)、病情不稳定的患者(RR = 0.89,95%CI = 0.81-0.99)进行的研究中,LAIs与更好的可接受性相关,并允许在LAIs中补充OAP(RR = 0.90,95%CI = 0.81-0.99):结论:LAIs和OAPs在预防复发/住院和可接受性方面没有明显差异。然而,在九个亚组分析中,在预防复发/住院(四个亚组分析)和/或减少全因停药(五个亚组分析)方面,LAIs在EP-SSD患者中优于OAPs,而OAPs在预防复发/住院(四个亚组分析)和/或减少全因停药(五个亚组分析)方面的质量指标和/或实用性设计指标均高于LAIs,但没有任何OAPs优于LAIs的实例。需要在 EP-SSDs 中开展更多比较 LAI 与 OAP 的高质量务实试验:试验注册:CRD42023407120(PROCEO)。
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引用次数: 0
Paralytic ileus in a patient on clozapine therapy showing an inverted clozapine/norclozapine ratio after switching valproic acid to carbamazepine: a case report 一名接受氯氮平治疗的患者在将丙戊酸换成卡马西平后出现氯氮平/去甲氯氮平比例倒置的麻痹性回肠症:病例报告
IF 4.2 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-05-31 DOI: 10.1177/20451253241255487
Geke van Weringh, Leonieke van Koolwijk, Lieuwe de Haan, Daan J. Touw, Mariken B. de Koning
This case report examines the possible correlation between the clozapine/norclozapine ratio and the occurrence of constipation and paralytic ileus. We present the case of a 42-year-old patient diagnosed with schizoaffective disorder undergoing clozapine therapy. Despite intensive treatment with clozapine, haloperidol, valproic acid and biweekly electroconvulsive therapy sessions for over a year, florid psychotic symptoms and fluctuating mood swings persisted. Therefore, valproic acid was replaced by carbamazepine, a potent inducer of several CYP450-enzymes. To maintain clozapine plasma levels, fluvoxamine, a CYP1A2-inhibitor, was introduced at a dose of 25 mg before this switch. After addition of carbamazepine, there was a significant decline in clozapine levels, necessitating an increase in fluvoxamine dosage to 50 mg. Five weeks later the patient was admitted to a general hospital with a diagnosis of paralytic ileus. Treatment with enemas proved effective. Drug concentration analysis revealed a 2.5-fold increase in norclozapine levels in the weeks preceding hospital admission, resulting in an inverted clozapine/norclozapine ratio. Treatment with clozapine, carbamazepine and fluvoxamine was continued as the patient demonstrated clinical improvement on carbamazepine. Concurrently, an intensive laxative regimen was initiated. Two weeks later, the patient was readmitted to the general hospital due to suspected paralytic ileus and faecal vomiting, once again displaying an inverted clozapine/norclozapine ratio. We discuss potential mechanisms contributing to the occurrence of the paralytic ileus in this patient, including the antagonism of muscarinic M3 receptors by both clozapine and norclozapine, as well as the agonism of delta-opioid receptors by norclozapine. This case highlights the potential significance of both the clozapine/norclozapine ratio and absolute norclozapine levels as risk factors for constipation and paralytic ileus in patients on clozapine therapy.
本病例报告探讨了氯氮平/去甲氯氮平比例与便秘和麻痹性回肠炎发生之间可能存在的相关性。我们介绍了一名被诊断为精神分裂症的 42 岁患者接受氯氮平治疗的病例。尽管接受了一年多的氯氮平、氟哌啶醇、丙戊酸强化治疗和每两周一次的电休克治疗,但患者的精神症状和情绪波动仍持续存在。因此,丙戊酸被卡马西平取代,卡马西平是多种 CYP450 酶的强效诱导剂。为了维持氯氮平的血浆水平,在更换药物之前,还使用了氟伏沙明(一种 CYP1A2 抑制剂),剂量为 25 毫克。在加入卡马西平后,氯氮平的水平显著下降,因此有必要将氟伏沙明的剂量增加到 50 毫克。五周后,患者被送入一家综合医院,诊断为麻痹性回肠炎。灌肠治疗证明有效。药物浓度分析表明,入院前几周诺氯氮平的浓度增加了 2.5 倍,导致氯氮平/诺氯氮平比例倒置。由于患者服用卡马西平后临床症状有所改善,因此继续使用氯氮平、卡马西平和氟伏沙明进行治疗。与此同时,患者开始接受强化泻药治疗。两周后,患者因疑似麻痹性回肠炎和呕吐再次入住综合医院,再次出现氯氮平/去氯氮平比例倒置的情况。我们讨论了导致该患者发生麻痹性回肠梗阻的潜在机制,包括氯氮平和诺氯氮平对毒蕈碱 M3 受体的拮抗作用,以及诺氯氮平对δ-阿片受体的激动作用。本病例强调了氯氮平/去甲氯氮平比率和去甲氯氮平绝对水平作为氯氮平治疗患者便秘和麻痹性回肠症风险因素的潜在重要性。
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Therapeutic Advances in Psychopharmacology
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