Fondation FondaMental, Créteil, France; Faculté de Médecine, Marseille Univ, EA 3279, Service d'Épidémiologie et d'Économie de la Santé, Marseille, France; Service Universitaire de santé mentale et physique, Centre Expert Dépression Résistante, CHU Sainte-Marguerite, APHM, Université Aix-Marseille, F-13009 Marseille, France.
Fondation FondaMental, Créteil, France; Service Universitaire de santé mentale et physique, Centre Expert Dépression Résistante, CHU Sainte-Marguerite, APHM, Université Aix-Marseille, F-13009 Marseille, France.
Prog Neuropsychopharmacol Biol Psychiatry. 2023 Aug 30;126:110779. doi: 10.1016/j.pnpbp.2023.110779. Epub 2023 Apr 27.
Benzodiazepine long-term use (BLTU) is a public health challenge. We lack data on the consequences of LBTU on the trajectory of treatment-resistant depression (TRD).
To determine the prevalence of BLTU in a nationwide non-selected population of patients with TRD, to determine the rate of patients succeeding at withdrawing benzodiazepines at one year and to determine if persistent BLTU is associated with poorer mental health outcomes.
The FACE-TRD cohort is a national cohort of TRD patients recruited in 13 resistant depression expert centers between 2014 and 2021 and followed-up at one year. A standardized one-day long comprehensive battery was carried out, including trained-clinician and patient-reported outcomes, and patients were reevaluated at one year.
At baseline, 45.2% of the patients were classified in the BLTU group. In multivariate analysis, compared to patients without BLTU, patients with BLTU were more frequently classified in the "low physical activity" group (adjusted odds ratio (aOR) = 1.885, p = 0.036), and had higher primary healthcare consumption (B = 0.158, p = 0.031) independently of age, sex and antipsychotic consumption. We found no significant difference for personality traits, suicidal ideation, impulsivity, childhood trauma exposure, earlier age at first major depressive episode, anxiety and sleep disorders (all p > 0.05). Despite recommendations for withdrawal, <5% of BLTU patients withdraw benzodiazepines during the one-year follow-up. Persistent BLTU at one-year was associated with higher depression severity (B = 0.189, p = 0.029), higher clinical global severity (B = 0.210, p = 0.016), higher state-anxiety (B = 0.266, p = 0.003), impaired sleep quality (B = 0.249, p = 0.008), increased peripheral inflammation (B = 0.241, p = 0.027), lower functioning level (B = -0.240, p = 0.006), decreased processing speed (B = -0.195, p = 0.020) and verbal episodic memory (B = -0.178, p = 0.048), higher absenteeism and productivity loss (B = 0.595, p = 0.016) and lower subjective global health status (B = -0.198, p = 0.028).
Benzodiazepines are over-prescribed in TRD (in almost a half of the patients). Despite recommendations for withdrawal and psychiatric follow-up, <5% of patients successfully stopped taking benzodiazepines at one-year. Maintaining BLTU may contribute to the worsening of clinical and cognitive symptoms and of daily functioning in TRD patients. Progressive and planed withdrawal of benzodiazepines seems therefore strongly recommended in TRD patients with BLTU. Pharmacological and non-pharmacological alternatives should be promoted when possible.
苯二氮䓬类药物的长期使用（BLTU）是一个公共卫生挑战。我们缺乏关于 LBTU 对治疗抵抗性抑郁症（TRD）轨迹影响的数据。
在全国范围内非选择性 TRD 患者人群中确定 BLTU 的流行率，确定一年内成功停用苯二氮䓬类药物的患者比例，并确定持续 BLTU 是否与较差的心理健康结果相关。
FACE-TRD 队列是一个全国性的 TRD 患者队列，于 2014 年至 2021 年在 13 个抗抑郁专家中心招募，并在一年时进行随访。进行了为期一天的综合测试，包括经过培训的临床医生和患者报告的结果，患者在一年时再次进行评估。
在基线时，45.2%的患者被归类为 BLTU 组。在多变量分析中，与没有 BLTU 的患者相比，BLTU 患者更频繁地被归类为“低体力活动”组（调整后的优势比（aOR）=1.885，p=0.036），并且独立于年龄、性别和抗精神病药物的使用，初级保健消费更高（B=0.158，p=0.031）。我们发现人格特质、自杀意念、冲动、儿童期创伤暴露、首次重度抑郁发作年龄较早、焦虑和睡眠障碍方面无显著差异（均 p>0.05）。尽管建议停药，但在一年的随访期间，<5%的 BLTU 患者停止使用苯二氮䓬类药物。一年内持续 BLTU 与更高的抑郁严重程度（B=0.189，p=0.029）、更高的临床总体严重程度（B=0.210，p=0.016）、更高的状态焦虑（B=0.266，p=0.003）、睡眠质量受损（B=0.249，p=0.008）、外周炎症增加（B=0.241，p=0.027）、功能水平降低（B=-0.240，p=0.006）、处理速度下降（B=-0.195，p=0.020）和情景记忆受损（B=-0.178，p=0.048）、更高的缺勤率和生产力损失（B=0.595，p=0.016）和主观总体健康状况降低（B=-0.198，p=0.028）相关。
苯二氮䓬类药物在 TRD 中被过度处方（近一半的患者）。尽管建议停药和精神病随访，但一年内只有<5%的患者成功停止服用苯二氮䓬类药物。维持 BLTU 可能会导致 TRD 患者的临床和认知症状以及日常功能恶化。因此，在有 BLTU 的 TRD 患者中，应强烈建议逐渐和有计划地停用苯二氮䓬类药物。当可能时，应提倡使用药物和非药物替代方法。
