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当标准治疗不足时:难治性强迫症中超治疗剂量选择性5-羟色胺再摄取抑制剂的叙述性综述

When Standard Is Not Enough: A Narrative Review of Supratherapeutic SSRI Doses in Resistant Obsessive Compulsive Disorder.

作者信息

Gualtieri Giacomo, Cuomo Alessandro, Pardossi Simone, Fagiolini Andrea

机构信息

Department of Molecular Medicine, University of Siena School of Medicine, 53100 Siena, Italy.

出版信息

J Clin Med. 2025 May 30;14(11):3858. doi: 10.3390/jcm14113858.

Abstract

: OCD is a chronic psychiatric disorder, often requiring long-term pharmacological treatment. Although selective serotonin reuptake inhibitors (SSRIs) are considered first-line agents, 40 to 60% of patients show only partial or no response when treated at standard dosages. In such cases, supratherapeutic doses of SSRIs have been proposed as an alternative strategy. However, the evidence supporting this approach remains limited and fragmented. This review aims to evaluate the rationale, clinical efficacy, tolerability, and practical considerations associated with high-dose SSRI use in OCD. : A structured narrative review was conducted using targeted literature searches in PubMed and Scopus. Studies were included if they reported on the use of high-dose SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline) in patients with OCD and provided efficacy and/or tolerability data. Clinical trials, observational studies, and case reports were all reviewed. : Evidence shows that higher doses of SSRIs are significantly more effective than low or medium doses in reducing OCD symptoms-especially in individuals who have only partially responded to standard treatment. Smaller clinical studies and case reports have also demonstrated that supratherapeutic dosing, beyond typical regulatory limits, can be both effective and well tolerated in treatment-resistant OCD. : High-dose SSRI treatment may be a valuable option for selected OCD patients who do not respond to standard therapy. However, careful patient selection, regular monitoring, and further controlled studies are necessary to better define its long-term safety and effectiveness. In this context, increasingly advanced technologies-such as therapeutic drug monitoring and pharmacogenetic testing for relevant polymorphisms-may support more individualized and safer treatment strategies.

摘要

强迫症是一种慢性精神疾病,通常需要长期药物治疗。尽管选择性5-羟色胺再摄取抑制剂(SSRIs)被视为一线药物,但40%至60%的患者在接受标准剂量治疗时仅表现出部分反应或无反应。在这种情况下,已有人提出使用超治疗剂量的SSRIs作为替代策略。然而,支持这种方法的证据仍然有限且零散。本综述旨在评估与强迫症患者使用高剂量SSRIs相关的理论依据、临床疗效、耐受性及实际考量因素。

使用PubMed和Scopus进行有针对性的文献检索,开展了一项结构化叙述性综述。纳入的研究需报告在强迫症患者中使用高剂量SSRIs(西酞普兰、艾司西酞普兰、氟西汀、氟伏沙明、帕罗西汀或舍曲林)的情况,并提供疗效和/或耐受性数据。对临床试验、观察性研究和病例报告均进行了综述。

证据表明,高剂量SSRIs在减轻强迫症症状方面比低剂量或中等剂量显著更有效,尤其是对那些对标准治疗仅部分有反应的个体。小型临床研究和病例报告也表明,超出典型监管限度的超治疗剂量在难治性强迫症治疗中既有效且耐受性良好。

对于某些对标准治疗无反应的强迫症患者,高剂量SSRI治疗可能是一个有价值的选择。然而,需要仔细选择患者、定期监测,并开展进一步的对照研究,以更好地确定其长期安全性和有效性。在这种背景下,越来越先进的技术,如治疗药物监测和相关多态性的药物遗传学检测,可能支持更个体化和更安全的治疗策略。

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