Supplementary Material for: Reducing distress from auditory verbal hallucinations: A multicentre, parallel, single-blind, randomised controlled feasibility trial of Relating Therapy

Introduction
There is significant demand for interventions that reduce distress related to auditory verbal hallucinations (AVH). AVH-distress is associated with the way voice hearers relate with AVH. We aimed to establish the feasibility of a randomised controlled trial to demonstrate that adding ‘Relating Therapy” (RT) to Treatment as Usual (TAU) is superior to TAU in reducing AVH distress.
Methods
We conducted a multicentre, parallel, single-blind, randomised controlled feasibility trial in five mental health centres in Germany. Participants were ≥16 years of age, had persistent and distressing AVH, and a diagnosis of a schizophrenia-spectrum disorder. RT was delivered over a maximum of 16 sessions within 5 months. Blind assessments were conducted at baseline, at 5 and 9 months. Feasibility outcomes were the numbers of patients recruited and retained, safety and therapist adherence. The primary endpoint was the distress factor score of the AVH-subscale of the Psychotic Symptoms Rating Scales at 9 months.
Results
Eighty-five of 177 enrolled participants were randomised into RT+TAU (n=43) or TAU (n=42). Feasibility was excellent with 87% retention at 9 months, 86% reaching ‘treatment uptake’, 98% therapist adherence and no unexpected serious adverse reactions. Compared to TAU, RT+TAU showed non-significant trends towards less AVH-distress (b=-2.40, SE=1.52, p = 0.121, 90% CI (-4.94 to 0.15) and stronger improvement on all but one secondary outcomes.
Conclusion
A randomised controlled trial of RT is feasible, safe, and well accepted. Our results provide an encouraging basis to further test the efficacy of RT in a definitive multicentre trial.

引言
当前针对缓解言语性听幻觉（auditory verbal hallucinations, AVH）相关痛苦的干预手段存在显著临床需求。言语性听幻觉相关痛苦与幻听体验者对待幻听的方式密切相关。本研究旨在验证一项随机对照试验的可行性，以证实于常规治疗（Treatment as Usual, TAU）基础上联用关联疗法（Relating Therapy, RT），相较于单纯常规治疗，更可减轻言语性听幻觉相关痛苦。

方法
本研究在德国5家精神卫生中心开展了一项多中心、平行对照、单盲随机对照可行性试验。入组参与者年龄≥16岁，存在持续性且伴痛苦的言语性听幻觉，且被诊断为精神分裂症谱系障碍。关联疗法在5个月内最多完成16次会谈。分别在基线、5个月及9个月时进行盲法评估。可行性结局指标包括入组与留存患者数、安全性及治疗师依从性。主要终点为9个月时精神病性症状评定量表（Psychotic Symptoms Rating Scales）言语性听幻觉分量表的痛苦因子分。

结果
177名入组参与者中，85名被随机分配至RT+常规治疗组（n=43）与单纯常规治疗组（n=42）。可行性表现优异：9个月留存率达87%，86%的参与者达成治疗接受，治疗师依从性为98%，未出现意料之外的严重不良反应。与单纯常规治疗组相比，RT+常规治疗组的言语性听幻觉相关痛苦程度呈降低趋势，但未达统计学显著性（回归系数b=-2.40，标准误SE=1.52，p=0.121，90%置信区间[-4.94, 0.15]）；且除1项次要结局指标外，其余所有次要结局指标的改善程度均更显著。

结论
关联疗法的随机对照试验具备可行性、安全性且临床接受度良好。本研究结果为后续在确证性多中心试验中检验关联疗法的疗效提供了令人鼓舞的依据。