Back2Action: effectiveness of physiotherapy blended with eHealth consisting of pain education and behavioural activation versus physiotherapy alone—protocol for a pragmatic randomised clinical trial for people with subacute or persistent spinal pain

IntroductionPsychosocial factors predict recovery in patients with spinal pain. Several of these factors are modifiable, such as depression and anxiety. However, primary care physiotherapists who typically manage these patients indicate that they do not feel sufficiently competent and equipped to address these factors optimally. We developed an eHealth intervention with a focus on pain education and behavioural activation to support physiotherapists in managing psychosocial factors in patients with spinal pain. This paper describes the protocol for a pragmatic randomised clinical trial, which evaluates the effectiveness of this eHealth intervention blended with physiotherapy compared with physiotherapy alone.Methods and analysisParticipants with non-specific low back pain and/or neck pain for at least 6 weeks who also have psychosocial risk factors associated with the development or maintenance of persistent pain will be recruited in a pragmatic multicentre cluster randomised clinical trial. The experimental intervention consists of physiotherapy blended with six online modules of pain education and behavioural activation. The control intervention consists of usual care physiotherapy. The primary outcomes are disability (Oswestry Disability Index for low back pain and Neck Disability Index for neck pain) and perceived effect (Global Perceived Effect). Outcomes will be assessed at baseline and at 2, 6 and 12 months after baseline. The results will be analysed using linear mixed models.Ethics and disseminationThe study is approved by the Medical Ethical Committee of VU Medical Center Amsterdam, The Netherlands (2017.286). Results will be reported in peer-reviewed journals, at national and international conferences, and in diverse media to share the findings with patients, clinicians and the public.Trial registration numberNL 5941; The Netherlands Trial Register.

5-HT2C receptor perturbation has bidirectional influence over instrumental vigour and restraint

The serotonin (5-HT) system, particularly the 5-HT2C receptor, has consistently been implicated in behavioural control. However, while some studies have focused on the role 5-HT2C receptors play in regulating motivation to work for reward, others have highlighted its importance in response restraint. To date, it is unclear how 5-HT transmission at this receptor regulates the balance of response invigoration and restraint in anticipation of future reward. In addition, it remains to be established how 5-HT2C receptors gate the influence of internal versus cue-driven processes over reward-guided actions. To elucidate these issues, we investigated the effects of administering the 5-HT2C receptor antagonist SB242084, both systemically and directly into the nucleus accumbens core (NAcC), in rats performing a Go/No-Go task for small or large rewards. The results were compared to the administration of d-amphetamine into the NAcC, which has previously been shown to promote behavioural activation. Systemic perturbation of 5-HT2C receptors—but crucially not intra-NAcC infusions—consistently boosted rats’ performance and instrumental vigour on Go trials when they were required to act. Concomitantly, systemic administration also reduced their ability to withhold responding for rewards on No-Go trials, particularly late in the holding period. Notably, these effects were often apparent only when the reward on offer was small. By contrast, inducing a hyperdopaminergic state in the NAcC with d-amphetamine strongly impaired response restraint on No-Go trials both early and late in the holding period, as well as speeding action initiation. Together, these findings suggest that 5-HT2C receptor transmission, outside the NAcC, shapes the vigour of ongoing goal-directed action as well as the likelihood of responding as a function of expected reward.

Interventional Indirect Effects: A Novel Approach to Optimise Complex Psychological Therapies to Treat Depression for Scale-up in Goa, India

Introduction: Understanding how and under what circumstances complex psychological therapies work (or not) is important to bring evidence-informed intervention to scale, especially in resource poor settings. However, current methods do not apply methodology that account for the underlying complexity of these interventions including the interplay between implementation outcomes, implementation strategies and mechanisms. Here we apply a robust mediation analysis to address these issues to data from the Healthy Activity Program (HAP) trial –a psychological intervention for depression delivered using task-shifting with lay counsellors in Goa India.Methods: Interventional in(direct) effects were used to simultaneously decompose the total effect of the intervention on depression symptoms measured through the Patient Health Questionnaire (PHQ-9). The following indirect effects were considered: fidelity of receipt including number of sessions and homework completed; behavioural activation according to an adapted version of the Behavioural Activation for Depression Short Form (BADS-SF), and extra sessions offered to participants who did not respond to the intervention. Results: Of the total effect of the intervention measured through the difference in PHQ-9 scores between treatment arms (mean difference: -2.2, 95% bias-corrected CI: -3.2, -0.8), 45% was mediated through improved levels of behavioural activation (-1.0, -1.3, -0.6). There was little evidence to support the mediating role of characteristics of the sessions nor the extra sessions offered to participants who did not respond to the treatment. ConclusionsFindings from our analyses have demonstrated how interventional (in)direct effects can be applied to understand how implementation research programmes can be optimised for scale-up. Our results highlight the importance of sessions focusing on behavioural activation to improve symptoms of depression. Targeting non-responders with strategies other than extra therapy sessions has the potential to improve depression outcomes at a population level.

Behavioural activation to prevent depression and loneliness among socially isolated older people with long-term conditions: The BASIL COVID-19 pilot randomised controlled trial

Background Older adults, including those with long-term conditions (LTCs), are vulnerable to social isolation. They are likely to have become more socially isolated during the Coronavirus Disease 2019 (COVID-19) pandemic, often due to advice to “shield” to protect them from infection. This places them at particular risk of depression and loneliness. There is a need for brief scalable psychosocial interventions to mitigate the psychological impacts of social isolation. Behavioural activation (BA) is a credible candidate intervention, but a trial is needed. Methods and findings We undertook an external pilot parallel randomised trial (ISRCTN94091479) designed to test recruitment, retention and engagement with, and the acceptability and preliminary effects of the intervention. Participants aged ≥65 years with 2 or more LTCs were recruited in primary care and randomised by computer and with concealed allocation between June and October 2020. BA was offered to intervention participants (n = 47), and control participants received usual primary care (n = 49). Assessment of outcome was made blind to treatment allocation. The primary outcome was depression severity (measured using the Patient Health Questionnaire 9 (PHQ-9)). We also measured health-related quality of life (measured by the Short Form (SF)-12v2 mental component scale (MCS) and physical component scale (PCS)), anxiety (measured by the Generalised Anxiety Disorder 7 (GAD-7)), perceived social and emotional loneliness (measured by the De Jong Gierveld Scale: 11-item loneliness scale). Outcome was measured at 1 and 3 months. The mean age of participants was aged 74 years (standard deviation (SD) 5.5) and they were mostly White (n = 92, 95.8%), and approximately two-thirds of the sample were female (n = 59, 61.5%). Remote recruitment was possible, and 45/47 (95.7%) randomised to the intervention completed 1 or more sessions (median 6 sessions) out of 8. A total of 90 (93.8%) completed the 1-month follow-up, and 86 (89.6%) completed the 3-month follow-up, with similar rates for control (1 month: 45/49 and 3 months 44/49) and intervention (1 month: 45/47and 3 months: 42/47) follow-up. Between-group comparisons were made using a confidence interval (CI) approach, and by adjusting for the covariate of interest at baseline. At 1 month (the primary clinical outcome point), the median number of completed sessions for people receiving the BA intervention was 3, and almost all participants were still receiving the BA intervention. The between-group comparison for the primary clinical outcome at 1 month was an adjusted between-group mean difference of −0.50 PHQ-9 points (95% CI −2.01 to 1.01), but only a small number of participants had completed the intervention at this point. At 3 months, the PHQ-9 adjusted mean difference (AMD) was 0.19 (95% CI −1.36 to 1.75). When we examined loneliness, the adjusted between-group difference in the De Jong Gierveld Loneliness Scale at 1 month was 0.28 (95% CI −0.51 to 1.06) and at 3 months −0.87 (95% CI −1.56 to −0.18), suggesting evidence of benefit of the intervention at this time point. For anxiety, the GAD adjusted between-group difference at 1 month was 0.20 (−1.33, 1.73) and at 3 months 0.31 (−1.08, 1.70). For the SF-12 (physical component score), the adjusted between-group difference at 1 month was 0.34 (−4.17, 4.85) and at 3 months 0.11 (−4.46, 4.67). For the SF-12 (mental component score), the adjusted between-group difference at 1 month was 1.91 (−2.64, 5.15) and at 3 months 1.26 (−2.64, 5.15). Participants who withdrew had minimal depressive symptoms at entry. There were no adverse events. The Behavioural Activation in Social Isolation (BASIL) study had 2 main limitations. First, we found that the intervention was still being delivered at the prespecified primary outcome point, and this fed into the design of the main trial where a primary outcome of 3 months is now collected. Second, this was a pilot trial and was not designed to test between-group differences with high levels of statistical power. Type 2 errors are likely to have occurred, and a larger trial is now underway to test for robust effects and replicate signals of effectiveness in important secondary outcomes such as loneliness. Conclusions In this study, we observed that BA is a credible intervention to mitigate the psychological impacts of COVID-19 isolation for older adults. We demonstrated that it is feasible to undertake a trial of BA. The intervention can be delivered remotely and at scale, but should be reserved for older adults with evidence of depressive symptoms. The significant reduction in loneliness is unlikely to be a chance finding, and replication will be explored in a fully powered randomised controlled trial (RCT). Trial registration ISRCTN94091479.

Causal meditation analysis to understand how different components of a complex psychological intervention improved symptoms (or not) of depression in Goa, India

BackgroundUnderstanding how and under what circumstances a highly effective psychological intervention, improved symptoms of depression is important to bring this evidence-informed intervention to scale, particularly in resource-poor settings. We aim to estimate the indirect effects of potentially important mediators to improve symptoms of depression in the Healthy Activity Program (HAP) trial.MethodsInterventional in(direct) effects were used to simultaneously decompose the total effect of the intervention on depression symptoms measured through the Patient Health Questionnaire (PHQ-9). The following indirect effects were considered: characteristics of sessions including the number of sessions and homework completed; behavioural activation according to an adapted version of the Behavioural Activation for Depression Short Form (BADS-SF), and extra sessions offered to participants who did not respond to the intervention.ResultsOf the total effect of the intervention measured through the difference in PHQ-9 scores between treatment arms (mean difference: -2.2, 95% bias-corrected CI: -3.2, -0.8), 45% was mediated through improved levels of behavioural activation (−1.0, -1.3, -0.6). There was no evidence to support the mediating role of characteristics of the sessions nor the extra sessions offered to participants who did not respond to the treatment.ConclusionsFindings from our robust mediation analyses, confirmed the importance of behavioural activation in improving depression symptoms. Contrary to published literature, our findings suggest that neither the number of sessions nor proportion of homework completed, improved outcomes. Moreover, results indicate that the extra sessions were insufficient to improve symptoms of depression for participants who did not respond to the intervention.