INTEGRATIVE SYSTEMATIC REVIEW ON PHARMACOLOGICAL, PSYCHOTHERAPEUTIC AND NEUROSTIMULATORY TREATMENT OPTIONS IN TREATMENT-RESISTANT ANXIETY DISORDERS.

IF 17.4 1区医学 Q1 PSYCHIATRY

Psychotherapy and Psychosomatics Pub Date : 2025-09-14 DOI:10.1159/000547926

Miriam A Schiele,Harry A Fagan,David S Baldwin,Katharina Domschke

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Abstract

Treatment resistance in anxiety disorders (TR-AD) constitutes a major clinical challenge conferring a considerable burden regarding quality of life and societal health costs. This systematic review provides an overview of pharmacological, psychotherapeutic and neurostimulatory treatment options in adults with treatment-resistant generalized anxiety disorder (TR-GAD), panic disorder (TR-PD) / agoraphobia and social anxiety disorder (TR-SAD). A total of 26 randomised controlled trials (RCTs) and 36 open label studies were identified, with, however, mostly small sample sizes and several methodological limitations. According to RCTs, selective serotonin reuptake inhibitors (SSRI) or clomipramine are effective in TR-PD after failure to respond to cognitive behavioral therapy (CBT). In pharmacological TR-SAD, switching from one SSRI to another or to venlafaxine was found helpful in open label trials. RCTs further suggest augmentation with quetiapine, risperidone, olanzapine or pregabalin in TR-GAD, pindolol in TR-PD and clonazepam in TR-SAD. Open label studies in TR-AD provide preliminary evidence for ketamine or augmentation with nefazodone, reboxetine, buspirone, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, divalproex sodium, levetiracetam, zonisamide, flumazenil, pregabalin, cannabidiol and acamprosate. For pharmacological TR, CBT was effective in several RCTs. Following non-response to CBT, first evidence suggests effectiveness of Acceptance and Commitment Therapy and Mindfulness-Based Cognitive Therapy. Only inconclusive support was identified for repetitive transcranial magnetic stimulation (rTMS) in TR-AD. In summary, this integrative review may provide an evidence base for expert recommendations, inform clinical guidelines, and inspire further research into innovative, personalized treatment of TR-AD increasing response rates and lowering the considerable individual and public health burden of anxiety disorders.

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难治性焦虑障碍的药理学、心理治疗和神经刺激治疗方案的综合系统评价。

焦虑障碍（TR-AD）的治疗耐药性构成了一项重大的临床挑战，给生活质量和社会健康成本带来了相当大的负担。本系统综述了成人难治性广泛性焦虑障碍（TR-GAD）、惊恐障碍(TR-PD) /广场恐怖症和社交焦虑障碍（TR-SAD）的药理学、心理治疗和神经刺激治疗方案。共有26项随机对照试验（RCTs）和36项开放标签研究被确定，然而，大多数样本量小，并且有一些方法学上的局限性。根据随机对照试验，选择性5 -羟色胺再摄取抑制剂（SSRI）或氯丙咪嗪对认知行为治疗（CBT）无效的TR-PD有效。在药理学TR-SAD中，在开放标签试验中，从一种SSRI切换到另一种SSRI或文拉法辛是有帮助的。随机对照试验进一步表明，在TR-GAD中增加喹硫平、利培酮、奥氮平或普瑞巴林，在TR-PD中增加品多洛尔，在TR-SAD中增加氯硝西泮。dr - ad的公开标签研究提供了氯胺酮或与奈法唑酮、瑞波西汀、丁螺环酮、阿立哌唑、奥氮平、喹硫平、利培酮、齐拉西酮、双丙戊酸钠、左乙拉西坦、唑尼沙胺、氟马西尼、普瑞巴林、大麻二酚和阿坎普罗酸增加的初步证据。对于药理学TR， CBT在几个随机对照试验中是有效的。在对CBT无反应之后，第一个证据表明接受和承诺疗法和基于正念的认知疗法是有效的。只有不确定的证据支持重复经颅磁刺激（rTMS）治疗TR-AD。总之，这项综合评价可能为专家建议提供证据基础，为临床指南提供信息，并启发进一步研究TR-AD的创新、个性化治疗，以提高反应率，降低焦虑障碍的个人和公共卫生负担。

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来源期刊

Psychotherapy and Psychosomatics 医学-精神病学

CiteScore

29.40

自引率

6.10%

发文量

期刊介绍： Psychotherapy and Psychosomatics is a reputable journal that has been published since 1953. Over the years, it has gained recognition for its independence, originality, and methodological rigor. The journal has been at the forefront of research in psychosomatic medicine, psychotherapy research, and psychopharmacology, and has contributed to the development of new lines of research in these areas. It is now ranked among the world's most cited journals in the field. As the official journal of the International College of Psychosomatic Medicine and the World Federation for Psychotherapy, Psychotherapy and Psychosomatics serves as a platform for discussing current and controversial issues and showcasing innovations in assessment and treatment. It offers a unique forum for cutting-edge thinking at the intersection of medical and behavioral sciences, catering to both practicing clinicians and researchers. The journal is indexed in various databases and platforms such as PubMed, MEDLINE, Web of Science, Science Citation Index, Social Sciences Citation Index, Science Citation Index Expanded, BIOSIS Previews, Google Scholar, Academic Search, and Health Research Premium Collection, among others.