Radically open dialectical behaviour therapy for refractory depression: the RefraMED RCT

Abstract

Background About one-third of patients who are depressed do not respond to antidepressant medication (ADM) and traditional psychotherapy shows limited benefits. However, most randomised trials have excluded the most sick patients, especially with comorbid personality disorder. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting emotionally overcontrolled personality, which is common in refractory depression. Objective To evaluate the efficacy, cost-effectiveness and therapeutic mechanisms of RO DBT for patients with refractory depression. Design The Refractory depression: Mechanisms and Efficacy of RO DBT (RefraMED) trial was a multicentre, parallel-group, randomised trial in which participants were randomised to receive either RO DBT plus treatment as usual (TAU) or TAU alone. Participants were assessed at 7, 12 and 18 months after randomisation. Therapeutic mechanisms were explored in causal analyses. Setting Participants were recruited from three secondary care NHS organisations in the UK: Dorset, Hampshire and North Wales. Participants Patients were eligible if they were aged ≥ 18 years, had a Hamilton Rating Scale for Depression (HRSD) score of at least 15, had a current diagnosis of major depressive disorder in the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I, were suffering either refractory or chronic depression and, in their current episode, had taken an adequate dose of ADM for at least 6 weeks without relief. Patients who met criteria for dramatic-erratic personality disorder (Cluster B), bipolar disorder or psychosis or who had a primary diagnosis of substance dependence or abuse were excluded. Interventions The intervention, RO DBT, comprised 29 weekly individual sessions lasting 1 hour and 27 weekly skills classes lasting 2.5 hours. Participants allocated to TAU could access any treatment offered by the NHS or privately. Main outcome measures The reported HRSD score 12 months after randomisation and cost per quality-adjusted life-year (QALY). Results A total of 250 participants were allocated at random: 162 (65%) participants were randomised to RO DBT plus TAU and 88 (35%) were randomised to TAU. The difference between RO DBT and TAU in the primary outcome at 12 months was not statistically significant. Nevertheless, after 7 months, participants randomised to RO DBT had substantially, and significantly, reduced depressive symptoms, relative to TAU, by 5.40 HRSD points [standardised mean difference 1.03 points, 95% confidence interval (CI) 0.94 to 9.85 points; p = 0.02]. Thereafter, RO DBT remained the better treatment with net, but non-significant, reductions of 2.15 HRSD points (standardised mean difference 0.41 points, 95% CI –2.28 to 6.59 points; p = 0.29) after 12 months and 1.69 points (standardised mean difference 0.32 points, 95% CI –2.84 to 6.22 points; p = 0.42) after 18 months. Participants allocated to TAU could access any treatment offered by the NHS or privately. Participants randomised to RO DBT reported significantly better psychological flexibility and emotional coping than TAU participants; these differences increased over time. From the perspective of the NHS and personal social services, RO DBT was not cost-effective; the incremental cost-effectiveness ratio was £220,000 per QALY, which is considerably above the willingness-to-pay threshold of £30,000 set by the National Institute for Health and Care Excellence (NICE). RO DBT participants reported eight possible serious adverse reactions compared with none by TAU participants; however, we believe that this imbalance was a result of major differences in reporting opportunities. The Data Monitoring and Ethics Committee agreed that there was no reason to suspect that RO DBT was harmful. Conclusions Although RO DBT achieved the target effect size (Cohen’s d) with a d of 0.4 at the primary end point of 12 months, this was not significant. RO DBT was not cost-effective by NICE criteria. Nevertheless, RO DBT enhanced psychological flexibility and emotional coping, which are potential mechanisms of change. Limitations Analysing only 190 participants, instead of the target of 245, reduced the statistical power of the trial. Future work Future studies should aim to refine RO DBT, by maintaining clinical effectiveness while reducing costs, and to evaluate it for a wider range of overcontrolled disorders over a longer period. Trial registration Current controlled trials ISRCTN85784627. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership, and will be published in full in Efficacy and Mechanism Evaluation; Vol. 5, No. 7. See the NIHR Journals Library website for further project information.

Treatment of personality pathology through the lens of the hierarchical taxonomy of psychopathology: Developing a research agenda

“…Preliminary research also suggests that techniques in radically open dialectical behaviour therapy (RO DBT) such as social signalling, trust signalling and interpersonal effectiveness can enhance social connectedness. [53][54][55] Low detachment Although, in general, low detachment may be a socially desirable interpersonal quality, individuals maladaptively low in detachment tend to be interpersonally intense and have lower quality or shallow relationships. Such intense interpersonal styles may be found in histrionic and dependent PD, BPD and narcissistic exhibitionism, and excessive excitement seeking might be seen in Stephanie N. Mullins-Sweatt et al 1 Communication analysis 1 Interpersonal effectiveness [2][3][4] Complementarity 1 Social signalling [2][3][4] Interpersonal group therapy 1 Trust signalling [2][3][4] Low detachment Behavioural experiments 5 Cognitive restructuring 5 Interpersonal group therapy 6…”

“…While five clinical trials have been conducted on RO DBT, including evidence of preliminary support for anorexia nervosa 54 and a randomized control trial for treatment-resistant depression, 53 the largest and most recent randomized control trial found no significant differences between RO DBT and treatment-as-usual groups. 55 However, evidence supporting change in theorized mechanisms of the treatment (psychological flexibility and emotional coping) were found. 55 Given the rigidity and socially reinforcing elements characteristic of low disinhibition, a transdiagnostic treatment may ultimately be most efficacious.…”

“…55 However, evidence supporting change in theorized mechanisms of the treatment (psychological flexibility and emotional coping) were found. 55 Given the rigidity and socially reinforcing elements characteristic of low disinhibition, a transdiagnostic treatment may ultimately be most efficacious. targets for pharmacologic interventions and/or individual psychotherapy.…”

Refractory depression – mechanisms and efficacy of radically open dialectical behaviour therapy (RefraMED): findings of a randomised trial on benefits and harms

“…All participants received TAU, including prescribed antidepressant medication or psychotherapy. 13 Participants in the control group could also access any treatment from the NHS or privately, except standard DBT. At each follow-up assessors asked participants to report their antidepressant medication and adherence to it, and psychotherapy accessed since their previous assessment or in the 6 months before their baseline assessment.…”

“…10,11 This trial aimed to assess the efficacy of RO DBT for refractory depression, 12 and whether RO DBT causes identifiable harms. 13…”