Background

There is a large clinical need for improved treatments for patients with persecutory delusions. We aimed to test whether a new theoretically driven cognitive therapy (the Feeling Safe Programme) would lead to large reductions in persecutory delusions, above non-specific effects of therapy. We also aimed to test treatment effect mechanisms.

Methods

We did a parallel, single-blind, randomised controlled trial to test the Feeling Safe Programme against befriending with the same therapists for patients with persistent persecutory delusions in the context of non-affective psychosis diagnoses. Usual care continued throughout the duration of the trial. The trial took place in community mental health services in three UK National Health Service trusts. Participants were included if they were 16 years or older, had persecutory delusions (as defined by Freeman and Garety) for at least 3 months and held with at least 60% conviction, and had a primary diagnosis of non-affective psychosis from the referring clinical team. Patients were randomly assigned to either the Feeling Safe Programme or the befriending programme, using a permuted blocks algorithm with randomly varying block size, stratified by therapist. Trial assessors were masked to group allocation. If an allocation was unmasked then the unmasked assessor was replaced with a new masked assessor. Outcomes were assessed at 0 months, 6 months (primary endpoint), and 12 months. The primary outcome was persecutory delusion conviction, assessed within the Psychotic Symptoms Rating Scale (PSYRATS; rated 0–100%). Outcome analyses were done in the intention-to-treat population. Each intervention was provided individually over 6 months. This trial is registered with the ISRCTN registry, ISRCTN18705064.

Findings

From Feb 8, 2016, to July 26, 2019, 130 patients with persecutory delusions (78 [60%] men; 52 [40%] women, mean age 42 years [SD 12·1, range 17–71]; 86% White, 9% Black, 2% Indian; 2·3% Pakistani; 2% other) were recruited. 64 patients were randomly allocated to the Feeling Safe Programme and 66 patients to befriending. Compared with befriending, the Feeling Safe Programme led to significant end of treatment reductions in delusional conviction (−10·69 [95% CI −19·75 to −1·63], p=0·021, Cohen's d=–0·86) and delusion severity (PSYRATS, −2·94 [–4·58 to −1·31], p<0·0001, Cohen's d=–1·20). More adverse events occurred in the befriending group (68 unrelated adverse events reported in 20 [30%] participants) compared with the Feeling Safe group (53 unrelated adverse events reported in 16 [25%] participants).

Interpretation

The Feeling Safe Programme led to a significant reduction in persistent persecutory delusions compared with befriending. To our knowledge, these are the largest treatment effects seen for patients with persistent delusions. The principal limitation of our trial was the relatively small sample size when comparing two active treatments, meaning less precision in effect size estimates and lower power to detect moderate treatment differences in secondary outcomes. Further research could be done to determine whether greater effects could be possible by reducing the hypothesised delusion maintenance mechanisms further. The Feeling Safe Programme could become the recommended psychological treatment in clinical services for persecutory delusions.

Funding

NIHR Research Professorship and NIHR Oxford Health Biomedical Research Centre.

中文翻译：

---

理论驱动的认知疗法（感觉安全计划）与交友治疗持续性被害妄想的比较：一项平行、单盲、随机对照试验

 背景

临床上非常需要改善被害妄想患者的治疗方法。我们的目的是测试一种新的理论驱动的认知疗法（感觉安全计划）是否会导致被害妄想的大幅减少，而不是治疗的非特异性效果。我们还旨在测试治疗效果机制。

 方法

我们进行了一项平行、单盲、随机对照试验，以测试“感觉安全计划”与与同一治疗师成为非情感性精神病诊断背景下持续被害妄想患者的关系的效果。在整个试验期间继续进行常规护理。该试验在三个英国国家卫生服务信托机构的社区心理健康服务机构进行。如果参与者年满 16 岁，有被害妄想（根据 Freeman 和 Garety 的定义）至少 3 个月，并且至少有 60% 的定罪率，并且根据转诊临床初步诊断为非情感性精神病，则被纳入研究范围团队。患者被随机分配到感觉安全计划或交友计划，使用排列块算法，块大小随机变化，由治疗师分层。试验评估人员对分组分配情况不知情。如果分配被取消屏蔽，则取消屏蔽的评估员将被新的屏蔽评估员取代。在 0 个月、6 个月（主要终点）和 12 个月时评估结果。主要结果是被害妄想定罪，根据精神病症状评定量表（PSYRATS；评级 0-100%）进行评估。在意向治疗人群中进行了结果分析。每次干预均单独提供超过 6 个月。该试验已在 ISRCTN 注册中心注册，ISRCTN18705064。

 发现

从2016年2月8日至2019年7月26日，130名被害妄想患者（78名[60%]名男性；52名[40%]名女性，平均年龄42岁[SD 12·1，范围17-71]；86%招募了白人、9% 黑人、2% 印度人；2·3% 巴基斯坦人；2% 其他人）。 64 名患者被随机分配到“感觉安全”计划，66 名患者被分配到“交友”计划。与交友相比，感觉安全计划导致治疗结束时妄想信念显着减少（−10·69 [95% CI -19·75 至 -1·63]，p=0·021，Cohen's d =–0· 86) 和妄想严重程度 (PSYRATS, -2·94 [–4·58 至 -1·31], p<0 id=86>d =–1·20)。与感觉安全组（16 名 [25%] 参与者报告 53 件无关不良事件）相比，友好组发生了更多不良事件（20 名 [30%] 参与者报告了 68 件无关不良事件）。

 解释

与交友相比，“感觉安全”计划显着减少了持续的迫害妄想。据我们所知，这些是对持续性妄想症患者最大的治疗效果。我们试验的主要限制是比较两种积极治疗时的样本量相对较小，这意味着效应大小估计的精确度较低，并且检测次要结果中的中等治疗差异的功效较低。可以进行进一步的研究，以确定是否可以通过进一步减少假设的妄想维持机制来产生更大的效果。感觉安全计划可以成为临床服务中针对被害妄想症的推荐心理治疗方法。

 资金

NIHR 研究教授和 NIHR 牛津健康生物医学研究中心。