Do single-case experimental designs lead to randomised controlled trials of cognitive behavioural therapy interventions for adolescent anxiety and related disorders recommended in the National Institute of Clinical Excellence guidelines? A systematic review

BACKGROUND: Although Cognitive Behavioural Therapy (CBT) is effective for 60% of adolescents with anxiety disorders, only 36% are in remission post-intervention. This indicates that more effective treatments are needed which should be reflected in the NICE guidelines. We hypothesised that Single-case experimental designs (SCEDs) may provide a framework for accelerating the development of novel interventions. The primary purpose of this review was to investigate whether SCEDs are currently followed by randomised controlled trials (RCTs) of CBT intervention for adolescent anxiety disorders named in the NICE guidelines. The secondary objective was to investigate whether using SCEDs prior to RCTs could be a helpful approach. METHOD: For the primary search of SCEDs five databases were used (PsycINFO, PubMed, PsycArticles, Web of Science and ProQuest). Nineteen articles met eligibility criteria including a total of 107 participants. For the secondary search of RCTs named in the NICE guidelines for adolescent anxiety disorders 53 articles met inclusion criteria and were included in the systematic review. RESULTS: The 19 SCED studies included in the review were conducted with participants with a diverse range of anxiety disorders and across a range of CBT formats. Two of the SCEDs were followed by RCTs, but neither of these were named in the NICE guidelines for anxiety disorders. All of the SCEDs identified were rated as low quality with none meeting the criteria for the highest or second highest quality rating. From the secondary searches, none of the RCTs named in the NICE guide were preceded by SCEDs. CONCLUSIONS: It was concluded that currently SCEDs were not followed by RCTs of CBT interventions named in the NICE guidelines for adolescent anxiety disorders. However, it was suggested that SCEDs may provide an important framework for the development of more effective interventions for adolescents with anxiety

The development and preliminary evaluation of Cognitive Behavioural Therapy (CBT) for Chronic Loneliness in Young People

Background: Approximately 10% of young people ‘often’ feel lonely, with loneliness being predictive of multiple physical and mental health problems. Research has found CBT to be effective for reducing loneliness in adults, but interventions for young people who report loneliness as their primary difficulty are lacking. // Method: CBT for Chronic Loneliness in Young People was developed as a modular intervention. This was evaluated in a single-case experimental design (SCED) with seven participants aged 11–18 years. The primary outcome was self-reported loneliness on the Three-Item Loneliness Scale. Secondary outcomes were self-reported loneliness on the UCLA-LS-3, and self- and parent-reported RCADS and SDQ impact scores. Feasibility and participant satisfaction were also assessed. // Results: At post-intervention, there was a 66.41% reduction in loneliness, with all seven participants reporting a significant reduction on the primary outcome measure (p < .001). There was also a reduction on the UCLA-LS-3 of a large effect (d = 1.53). Reductions of a large effect size were also found for parent-reported total RCADS (d = 2.19) and SDQ impact scores (d = 2.15) and self-reported total RCADS scores (d = 1.81), with a small reduction in self-reported SDQ impact scores (d = 0.41). Participants reported high levels of satisfaction, with the protocol being feasible and acceptable. // Conclusions: We conclude that CBT for Chronic Loneliness in Young People may be an effective intervention for reducing loneliness and co-occurring mental health difficulties in young people. The intervention should now be evaluated further through a randomised controlled trial (RCT)

Evaluating the Efficacy of a Guided and Unguided Internet-Based Self-help Intervention for Chronic Loneliness: Protocol for a 3-Arm Randomized Controlled Trial.

BACKGROUND Loneliness, or perceived social isolation, is prevalent in both the general population and clinical practice. Although loneliness has repeatedly been associated with mental and physical health, research on interventions that reduce loneliness effectively is still rather scarce. OBJECTIVE This study aims to evaluate the efficacy of a guided and an unguided version of the same internet-based cognitive behavioral self-help program for loneliness (SOLUS-D) for adults. METHODS A total of 250 participants will be randomly assigned to 1 of 2 intervention groups (SOLUS-D with guidance or SOLUS-D without guidance) or a wait-list control group (2:2:1 allocation ratio). Adult participants experiencing high levels of loneliness will be recruited from the general population. Individuals currently experiencing at least moderately severe depressive symptoms, an ongoing severe substance use disorder, previous or current bipolar or psychotic disorder, or acute suicidality will be excluded from the trial. Assessments will take place at baseline, 5 weeks (midassessment), and 10 weeks (postassessment). The primary outcome is loneliness assessed using the 9-item University of California, Los Angeles Loneliness Scale at the posttreatment time point. Secondary outcomes include depressive symptoms, symptoms of social anxiety, satisfaction with life, social network size, and variables assessing cognitive bias and social behavior. The maintenance of potentially achieved gains will be assessed and compared at 6 and 12 months after randomization in the 2 active conditions. Potential moderators and mediators will be tested exploratorily. Data will be analyzed on an intention-to-treat basis. RESULTS Recruitment and data collection started in May 2021 and are expected to be completed by 2022, with the 12-month follow-up to be completed by 2023. As of the time of submission of the manuscript, 134 participants were randomized. CONCLUSIONS This 3-arm randomized controlled trial will add to the existing research on the efficacy of loneliness interventions. Furthermore, it will shed light on the role of human guidance in internet-based treatments for individuals with increased levels of loneliness and the possible mechanisms of change. If SOLUS-D proves effective, it could provide a low-threshold, cost-efficient method of helping and supporting individuals with increased levels of loneliness. TRIAL REGISTRATION ClinicalTrials.gov NCT04655196; https://clinicaltrials.gov/ct2/show/NCT04655196. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/36358

6-OHDA-induced dopaminergic neurodegeneration in <i>Caenorhabditis elegans</i> is promoted by the engulfment pathway and inhibited by the transthyretin-related protein TTR-33

<div><p>Oxidative stress is linked to many pathological conditions including the loss of dopaminergic neurons in Parkinson’s disease. The vast majority of disease cases appear to be caused by a combination of genetic mutations and environmental factors. We screened for genes protecting <i>Caenorhabditis elegans</i> dopaminergic neurons from oxidative stress induced by the neurotoxin 6-hydroxydopamine (6-OHDA) and identified the <u>t</u>rans<u>t</u>hyretin-<u>r</u>elated gene <i>ttr-33</i>. The only described <i>C</i>. <i>elegans</i> transthyretin-related protein to date, TTR-52, has been shown to mediate corpse engulfment as well as axon repair. We demonstrate that TTR-52 and TTR-33 have distinct roles. TTR-33 is likely produced in the posterior arcade cells in the head of <i>C</i>. <i>elegans</i> larvae and is predicted to be a secreted protein. TTR-33 protects <i>C</i>. <i>elegans</i> from oxidative stress induced by paraquat or H₂O₂ at an organismal level. The increased oxidative stress sensitivity of <i>ttr-33</i> mutants is alleviated by mutations affecting the KGB-1 MAPK kinase pathway, whereas it is enhanced by mutation of the JNK-1 MAPK kinase. Finally, we provide genetic evidence that the <i>C</i>. <i>elegans</i> cell corpse engulfment pathway is required for the degeneration of dopaminergic neurons after exposure to 6-OHDA. In summary, we describe a new neuroprotective mechanism and demonstrate that TTR-33 normally functions to protect dopaminergic neurons from oxidative stress-induced degeneration, potentially by acting as a secreted sensor or scavenger of oxidative stress.</p></div

Internetbaserade interventioner mot ensamhet : Effektivitet och latenta psykopatologiska profiler hos de behandlingssökande

Loneliness is an adverse emotional reaction thought to stem from an unwanted and impoverished social situation. Though it commonly makes brief appearances across the lifespan for most people, it has received increasing attention as a factor relevant to somatic and psychological well-being when assuming a more chronic form. For this reason, developing ways of alleviating loneliness is an important item on the research agenda tied to this phenomenon. Psychological interventions, and cognitive behavioural therapy (CBT) in particular, have been proposed to have potential for this. This thesis sought to evaluate the effects of two different kinds of internet-based interventions targeting loneliness: one based on CBT, and one based on interpersonal psychotherapy (IPT). In addition to this general aim, Study I also investigated the presence of different subgroups in the sample of people seeking help within the framework of projects. Using the statistical method known as Latent Profile Analysis we discovered five profiles consisting of symptoms of common psychiatric disorders and loneliness. The profiles mainly differed as a function of symptom severity, though one of the larger groups was also characterised primarily by their high ratings of social anxiety. The results suggest that the sample seeking help for their loneliness can exhibit both clinical and non-clinical levels of common mental health problems. Study II served as the pilot evaluation of an ICBT programme for loneliness. A total of 73 participants were included in a randomised controlled trial where the participants were randomised to either 8 weeks of active treatment or a wait-list control group. The results indicated significantly lower loneliness ratings after the treatment phase for the ICBT condition with a moderate-to-large effect size compared to the control group. Significant differences favouring the ICBT condition were also noted for two of the four secondary measures. Study III followed up on the participants two years after the conclusion of the initial treatment period. At this point, the control group had also received access to a version of the ICBT programme with therapist support on-demand. The results indicated that the decrease in loneliness was sustained, along with similarly lasting effects on the secondary outcomes of interest. Study IV aimed to replicate the findings from the second study with a similar ICBT programme. However, this study also employed an internet-based IPT intervention to allow for conclusions regarding the possibility of reducing loneliness by other means than CBT. A sample of 170 participants were recruited and randomised to one the treatment conditions or to a waitlist control group. The results indicated that the ICBT condition had a significantly steeper reduction in loneliness than both the waitlist and the IPT condition after the conclusion of the treatment. Both active conditions produced a significant increase in quality of life. In conclusion, internet-based psychological interventions can be efficacious for reducing loneliness, though the efficacy was only found for participants who received access to the ICBT condition in Study II and IV. The benefits from this treatment programme were sustained up to two years after the conclusion of the intervention. For these reasons, ICBT is proposed to be a good candidate for offering help to people experiencing distressing feelings of loneliness.Ensamhet är en aversiv känsloreaktion som har sitt ursprung i en oönskad social situation. I kronisk form har den påkallat uppmärksamhet som en faktor med implikationer för fysisk och psykisk hälsa. På grund av detta har tillvägagångssätt för att minska ensamhet blivit en viktig punkt på forskningsagendan kopplad till detta fenomen. Psykologiska interventioner, och mer specifikt kognitiv beteendeterapi (KBT), har hävdats ha potential för att åstadkomma detta. Denna avhandling utvärderade effekterna av två internetbaserade interventioner inriktade mot ensamhet: en baserad på KBT och en baserad på interpersonell psykoterapi (IPT). Dessutom intresserade sig en av studierna för den deltagarheterogenitet som fanns i termer av psykiatriska symptom. Personerna som sökte hjälp inom ramarna för studierna kunde delas in i fem undergrupper som främst skiljde sig åt gällande hur grav symptombörda de uppvisade, men i viss mån även sett till vilken typ av psykiatriska symptom som dominerade. Resultaten från de kliniska prövningarna pekar på att det framtagna KBT-programmet har positiva effekter i form av minskad ensamhet och psykiatrisk samsjuklighet. Effekterna kvarstod även över tid. IPT-programmet var inte lika framgångsrikt

Knowledge acquisition following internet-based cognitive behavioural therapy for loneliness-A secondary analysis of a randomised controlled trial

Background and objectives: Knowledge about a condition and how to treat it is part of most cognitive behavioural therapies. This is particularly relevant for self-help treatments such as internet-based CBT, which is commonly delivered in the form of didactic materials. The role of knowledge acquisition in treatment outcomes is an understudied area. The present study sought to investigate knowledge acquisition as part of an ICBT trial targeting loneliness and discern its role in the outcome of treatment. Methods: We used secondary data from a randomised controlled trial of ICBT targeting loneliness with 73 participants. A knowledge test including certainty ratings was constructed and used to investigate whether knowledge increased for the treatment group in comparison to the control group, whether changes in knowledge predicted changes in loneliness during the treatment phase, and how the acquired knowledge related to outcomes at a two-year follow-up. Multiple linear regression models were used to analyse the data. Results: The treatment group had significantly higher knowledge scores compared to the waitlist group at posttreatment, both in terms of correct answers (Cohens d = 0.73) and certainty-weighted sum scores (Cohens d = 1.20). Acquired knowledge did not predict reductions in loneliness in the short-term, and neither loneliness ratings nor use of treatment techniques in the long-term. Limitations: The sample size was relatively small, which limits the statistical inferences. Conclusions: Knowledge of treatment relevant principles increase as part of the treatment in ICBT for loneliness. This increase was not related to other short- and long-term outcomes.Funding Agencies|Linkoping University</p

Exploring Latent Profiles of Psychopathology in a Sample of Lonely People Seeking Treatment

Loneliness is a common experience in populations experiencing mental health problems. Associations with symptoms of psychopathology are prevalent, but little is known about the diversity of symptom profiles in people suffering from prolonged and distressing loneliness. The current study sought to investigate the existence of subgroups of loneliness and common forms of psychopathology in a sample of adults (n = 332) seeking treatment for their loneliness. Using latent profile analysis, five profiles were identified and differences in demographic factors were investigated. The profiles differed mainly in the severity of symptoms of depression, worry, and social anxiety, with the largest profile exhibiting minimal-to-mild symptoms (n = 109) across these indicators. The second largest group was characterized primarily by high ratings of social anxiety (n = 90). Overall, three of the five profiles, encompassing roughly half of the sample, scored at a clinical level on mental health symptom measures. Age was inversely related to symptom severity among the profiles, indicating that the older subgroups of the sample exhibited milder symptoms, particularly on social anxiety. The results provide insight into the heterogeneity of the clinical symptoms of people suffering from loneliness and add important knowledge that could help inform how to best intervene to help this population.Funding Agencies|Linkoping University</p

Efficacy of an Internet-based self-help intervention with human guidance or automated messages to alleviate loneliness: a three-armed randomized controlled trial.

Loneliness is a prevalent and stigmatized phenomenon associated with adverse (mental) health outcomes. However, evidence-based interventions to alleviate loneliness are scarce. This randomized controlled trial (ClinicalTrials.gov-ID: NCT04655196) evaluated the efficacy of an internet-based cognitive behavioral self-help intervention (ICBT) to reduce loneliness by comparing two intervention groups with guidance or automated messages against a waitlist control group. Adults (N = 243) suffering from loneliness were recruited from the general public and then randomly assigned (2:2:1) to a 10-week ICBT with human guidance (GU) or automated messages (AM) or to a waitlist control group (WL). Loneliness, assessed with the UCLA-9, was the primary outcome. Outcomes were assessed at baseline and 10 weeks (post) and analyzed using mixed-effects models. The pooled intervention conditions resulted in lower loneliness scores at post-assessment than the WL (Cohen's d = 0.57, 95% CI [0.25; 0.89]) and reduced depressive symptoms, social anxiety, social avoidance behavior, and rejection sensitivity (d = 0.32-0.52). The GU group had lower loneliness scores at post-assessment than the AM group (d = 0.42, 95% CI [0.13; 0.70]). ICBT effectively alleviated loneliness, and guidance increased the reduction in loneliness compared to automated messages. Alleviating loneliness with ICBT further seems to reduce the overall burden of psychopathological symptoms

Lonesome no more? : A two-year follow-up of internet-administered cognitive behavioral therapy for loneliness

The current study sought to investigate the long-term effects of an internet-administered programme based on CBT principles for which the initial efficacy has been reported in Kall, Jagholm, et al. (In press). Seventy-three participants who were recruited on the basis of experiencing frequent and prolonged loneliness were contacted to complete questionnaires measuring loneliness, quality of life, and symptoms of psychopathology two years after the conclusion of the initial treatment period. Additional items regarding use of the treatment techniques and strategies contained in the programme during the follow-up period was included. In total, 44 participants provided data for the loneliness measure at follow-up. The outcome data were analyzed with a piecewise mixed effects model to provide estimates of change for the continuous measures. Linear multiple regression analysis was used to investigate the relationship between use of treatment techniques and reliable change on the primary outcome measure. The results showed decreases in loneliness during the follow-up period for the sample as a whole. Additionally, an increase in quality of life and a decrease in social anxiety were noted, but no significant changes of depressive symptoms or generalized anxiety. Effect sizes for the observed changes from baseline to follow-up were in the moderate to large range for all measures. Reported use of the treatment techniques was not significantly related to reliable change in loneliness after the two-year period. In conclusion, the results of the study support the utility of internet-based CBT targeting loneliness and indicate that the benefits from the intervention can be enduring

The development of Cognitive Behavioural Therapy (CBT) for chronic loneliness in children and young people: Protocol for a single-case experimental design.

Loneliness is a significant problem for young people and is associated with a range of physical and mental health difficulties. Meta-analyses have identified that interventions aimed at young people who report loneliness as their primary problem are lacking within the literature. In adults, the most effective interventions for loneliness are those which target the underlying maladaptive social cognitions. Therefore, we have developed a modular Cognitive Behavioural Therapy (CBT) intervention for children and young people. The aim of this study is to conduct a multiple baseline single-case experimental design (SCED) to assess the efficacy, feasibility and acceptability of this intervention. In total 6-8 11-18-year-olds and their families will be recruited. The design consists of AB+ post-intervention, where A is the baseline phase, B is the intervention phase and then a post-intervention phase. Participants will complete a baseline assessment, before being randomised to one of four different baseline lengths (12 days, 19 days, 26 days or 33 days). Participants will then complete an average of 12 sessions of CBT, with the aim being to reduce their feelings of loneliness. Participants will then complete a 12-day post-intervention phase. Participant loneliness will be repeatedly assessed throughout the three phases of the intervention using the Three-item Loneliness Scale, which will be the primary outcome. Secondary outcomes will be reliable and clinically meaningful change on the UCLA Loneliness Scale, Revised Child Anxiety and Depression Scale (RCADS) and Strengths and Difficulties Questionnaire (SDQ). Feasibility and participant satisfaction will also be assessed and reported. Trial registration: ClinicalTrails.gov trial registration number: NCT05149963 (Date registered: 07.12.2021). https://www.clinicaltrials.gov/ct2/show/NCT05149963?term=cbt&cond=loneliness&draw=2&rank=1