Psychological therapy for mood instability within bipolar spectrum disorder: a randomised, controlled feasibility trial of a dialectical behaviour therapy-informed approach (the ThrIVe-B programme)

Trial design

We conducted a feasibility study with a two-arm, randomised, parallel, controlled trial design. Participants were randomised in a 1:1 ratio to TAU only (control arm) or TAU plus the ThrIVe-B programme (intervention arm). Outcome measures were administered at baseline and at 3, 6, 9 and 15 months after randomisation. The primary end point was predetermined to be at 9 months. The full trial protocol is reported elsewhere (Wright et al. 2018).

A panel of individuals with lived experience of mood disorders advised on study design and delivery throughout the trial.

Participants

Participants were required to be aged 18 years or older, with a diagnosis of BD (I, II, other specified BD) or Cyclothymic Disorder, according to the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) (American Psychiatric Association 2013), and to have a period of at least 2 days during which symptom criteria for hypomania/mania were met. They were required to have current BPMI, defined as either meeting DSM-V criteria 1 and 2 for Cyclothymic Disorder, or having a score of at least 1.3 [the mean for individuals with Bipolar disorder in previous research (Henry et al. 2008)] on the bipolar subscale of the short form of the Affective Lability Scale (ALS) (Oliver and Simons 2004). Participants had to be willing to engage in psychological therapy that focusses primarily on ongoing mood instability and its consequences, and be willing and able to attend scheduled group therapy sessions. Sufficient competency in English to be able to complete study measures without the need for translation was required, as was registration with a primary care physician in the study catchment area. Exclusion criteria included current substance dependence, other ongoing psychological therapy for BD at study entry, lack of capacity to consent to treatment or research participation, and acute mania or depression (DSM-V). Participants engaging in frequent, significant self-harming behaviour, at high risk of suicide, or posing a significant risk to other group members were not eligible. Initially patients receiving ongoing, co-ordinated care in secondary mental health services were excluded from participation because the ThriVe-B programme was aimed at those at the interface between primary and secondary care, however this criterion was removed at month 9 of the 11 month recruitment phase to facilitate recruitment.

Participants were recruited from two sites in the United Kingdom, Cumbria and Devon. Both are relatively rural however Cumbria has a population density less than half that of Devon’s. Recruitment was via primary care services, secondary care mental health services and self-referral. Following an expression of interest, participants providing written agreement to be contacted by the study team were sent information about the study and invited to attend a baseline eligibility assessment interview. Those not referred from secondary care (and thus who had not recently participated in a specialist Psychiatric assessment) completed a telephone screening interview prior to the eligibility assessment to increase the likelihood that those invited for a time-consuming face-to-face assessment would be eligible. At the eligibility assessment written, informed consent was sought, eligibility criteria were checked and baseline measures completed.

Planned sample size

On the basis of our previous work (Wright et al. 2020) we estimated an attrition rate of 17% with respect to the 9 month primary end point. A sample of 48 would allow estimation of this level of attrition for a future definitive trial with a precision of ± 15% with 95% certainty. The 48 participants (24 per arm) would represent recruitment to three ThrIVe-B groups at full capacity (8 per group: 2 in Devon and 1 in Cumbria).

Intervention

The intervention (ThrIVe-B) was delivered in addition to TAU. The content of the ThrIVe-B programme is described in detail in the logic model in Additional file 1. In brief, modules covered Mindful Awareness, Day to Day Mood Regulation. Tolerating Intense Moods, and Wise Relationships The programme consisted of 15 weekly group meetings and up to eight individual sessions of up to 45 min held either face-to-face or by telephone, according to participant preference for modality, number and duration. All participants were expected to attend the initial and final individual meeting. There was a group “booster” session 3 months after the final group meeting, and midway through the programme participants were offered a “supporters” session which friends or family could attend. To help generalisation of learning, participants were given a folder of written materials. In addition we used a custom-built smartphone application (‘ThrIVe-B app’) to prompt participants to use skills at times of extreme mood, between therapy sessions. The app asked participants to rate their mood from − 10 to + 10 each day between 0 and 10 times, with number of ratings per day determined by the user. Users specified ‘high’ and ‘low’ mood thresholds and when these were surpassed, users saw a feedback screen containing advisory messages they had pre-programmed either alone or with therapist support, which could contain techniques from the therapy programme (see Additional file 2). A version of this app, with reduced functionality, was also used to monitor mood stability over 7-day periods at baseline and at follow-up for all participants.

Therapy was delivered by four qualified mental health professionals with previous specialist training in cognitive behavioural therapy and related approaches (two therapists per group). A 5 day bespoke, face-to-face training programme was provided by the main author of the ThrIVe-B therapy protocol, which covered background information about Bipolar disorder, the therapeutic stance within DBT-informed approaches, therapy components, and skills in group facilitation. Weekly supervision occurred throughout therapy delivery. Before each group session participants completed the Beck Depression Inventory (Beck et al. 1961) and Altman Scale for Rating Mania (Altman et al. 1997).

Participants in the TAU arm received their usual NHS care, with no stipulation from the trial regarding the minimum constituents of this. In addition, in order that the two arms were broadly equivalent in time spent using the app between assessment points, those in the TAU arm were invited to use it for mood monitoring only (no additional therapeutic functionality) between months 3 and 9. As per the intervention arm, participants could set number of alerts per day from 0 to 10. Other than the experimental intervention no treatments were withheld.

Outcomes

Primary outcome measures. Numbers of patients identified, approached, consented, randomised and completed were used to assess feasibility, as was participant attrition from the trial and from treatment. Acceptability was assessed by questionnaires at baseline, 9 month follow-up and on ineligibility or withdrawal from the study. Items with quantitative ratings at 9 month follow-up were rated on a five point scale and asked about acceptability and satisfaction (anchored from “not at all” to “extremely”) and likelihood of recommending the trial to eligible friends and family. To assess patient valuation of outcomes, at the 9-month follow-up point participants were asked to rank the four candidate outcome measures (see below) and a measure of anxiety symptoms, the Generalised Anxiety Disorder 7-item scale (GAD-7) (Spitzer et al. 2006) in order of priority, in terms of where they would most want to see change following psychological treatment. Participants were also asked to estimate the smallest change on each measure that would feel meaningful.

A subset of 14 participants from both sites took part in a semi-structured interview exploring their experiences of the research study and therapy in more detail. Referring clinicians were asked for their views of the therapy and research process using a brief survey form, and ThrIVe-B therapists took part in an interview about their experiences and views of the therapy, training and supervision.

Adherence to treatment was measured in terms of number of therapy sessions attended; because some individual sessions were optional, “possible sessions” (continuation rule 4) was defined as all 15 group sessions, booster session and initial and final individual sessions (18 sessions in total).

The ThrIVe-B app was used to gather data on momentary mood in order to assess mood stability. All participants were invited to use the app for 1 week at baseline and at 9-month follow-up, to give comparable 1 week periods of mood stability data that did not overlap with periods of therapeutic app use. Mood stability measured by the ThrIVe-B app is a potential secondary outcome in a definitive trial, therefore we tested the feasibility and acceptability of gathering these data, as indicated by completion rates and participant feedback.

Secondary outcome measures. The following were candidate primary outcome measures for a future definitive trial and were completed at baseline and all follow-up points: the Patient Health Questionnaire 9-item scale (PHQ-9) (Spitzer et al. 1999) which measures depressive symptoms; the short-form Affective Lability Scale; the Bipolar Recovery Questionnaire (BRQ) (Jones et al. 2013); and the brief Quality of Life in Bipolar disorder scale (QoL-BD) (Michalak et al. 2010). Participants also completed the GAD-7. At baseline, 9 and 15 months, the Bech Mania Rating Scale (BMRS) (Bech et al. 1978), the Hamilton Depression Rating Scale (HDRS) (Hamilton 1986) (both observer-rated), and the Brief Adherence Rating Scale for medication adherence (BARS) (Byerly et al. 2008) were completed, as was relevant sections of the Structured Clinical Interview for DSM-V (First et al. 2014). This was used both to assess eligibility criteria, and to identify affective episodes during the follow-up period.

To assess feasibility of health outcome measures for a future cost-effectiveness analysis was assessed with two measures: the EuroQoL 5-dimension 3-level (EQ-5D-3L) (Oppe and Devlin 2007),Footnote 1 and the 36-item Short Form Health Survey (SF-36) (Garratt et al. 1993), these were administered at baseline and follow-up points. In addition, participants were asked to complete a resource use questionnaire (last 6 months or since last assessment point) for assessing the feasibility of collecting accurate health and social service use. Finally information on resource use and costs of delivering the ThrIVE-B programme were also collected.

Quantitative process measurement

Measurement of putative mechanisms of change was included in order to inform measurement in a definitive trial. These were completed at baseline and all follow-up points. We included measures of impulsive behavioural response to high and low mood (Positive and Negative Urgency, Premeditation, Perseverance, Sensation-Seeking impulsive behaviour scales [UPPS-P] (Cyders et al. 2007); Behavioral Activation in Depression Scale [BADS] (Kanter et al. 2007)) as this is a key process that ThrIVe-B aims to disrupt. In DBT this is achieved in part by building mindful awareness skills, hence we measured this using the Kentucky Inventory of Mindfulness Skills (KIMS) (Baer et al. 2004). We assessed social rhythm stability using the adapted Social Rhythm Metric (SRM) (Monk et al. 1990) and emotional problem solving using the Means-Ends Problem Solving task (MEPS: baseline, 9 and 15 months only) (Kehrer and Linehan 1996).

The schedule for administration of study measures is shown in Additional file 3.

Procedure

Prior to conducting the trial ethical approval was obtained from the National Research Ethics Service (Ref: 219816) and local departmental research ethics committees. Assessments were face to face, by telephone, by post or online, dependent upon participant preference. In-person contact was required at baseline and at months 9 and 15 in order to complete the interview-based measures. At 9 months the questionnaire on experiences of the study was completed and a subset of participants completed the semi-structured interview.

Randomisation, concealment of allocation, and blinding

Participants were randomised on a 1:1 ratio, with minimisation by trial site and medication status (any medication for Bipolar disorder prescribed: yes/no). To ensure concealment, eligible participants were randomised via a validated password website hosted by Exeter Clinical Trials Unit. The first ten participants were allocated using simple randomisation; the remainder were allocated using the minimisation procedure, maintaining a stochastic element to the algorithm to allow concealment. Participants were randomised prior to the start of each therapy group, and informed by an unblinded researcher.

Researchers conducting follow-up assessments were blind to allocation and participants were reminded of this at each follow-up contact. All unblindings were recorded and where possible, researchers who remained blinded to that participant’s status conducted future follow-up assessments. All statistical analyses were performed by a statistician using groups indicated by an anonymised code.

Statistical and economic methods

The primary analyses were performed after 9-month follow-up. Further analyses were performed after the final 15-month follow-up. No interim analyses were conducted. All analyses were on an intention-to-treat basis; included outcomes were reported according to randomised allocation, regardless of the treatment actually received. No attempts to address missing data, such as multiple imputation, were made. The economic analysis took the NHS and social care perspective.

At 9-month follow-up only, an inferential analysis was performed for continuous outcomes only, reporting the relevant 95% CI for the between-group mean difference (intervention minus TAU), but no p value. Inferential analyses included the randomisation covariates of site and baseline medication status.

Qualitative analysis

Qualitative interviews and written responses on the feedback questionnaires were analysed using a framework approach (Ritchie and Spencer 2002). A preliminary set of a priori themes was drawn up, based on interview/questionnaire questions (e.g. expectations of therapy; most helpful aspects; unhelpful aspects). Data were entered onto a spreadsheet, creating a matrix of rows (participants) and columns (themes) and populating it with summarised responses. During the process, higher-order themes and sub-themes were inductively generated. These were then tabulated, with exemplary quotes and analytic notes, and visually mapped to explore relationships between them.

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