An online therapist-guided ultra-brief treatment for depression and anxiety: a randomized controlled trial.

BACKGROUND: There are many barriers to engaging in current psychological treatments, including time, cost, and availability. Ultra-brief treatments overcome some of these barriers by delivering therapeutic information and skills using significantly less time than standard-length treatments. We developed a therapist-guided online ultra-brief treatment for depression and anxiety and compared it to an existing 8-week, 5-lesson therapist-guided standard-length treatment and a waitlist control. METHODS: In a randomized controlled trial, adults with self-reported depression or anxiety were randomized (1:1:1) to the ultra-brief treatment, standard-length treatment, or waitlist control. The primary outcomes were depression symptoms and anxiety symptoms assessed at baseline, 5-weeks later, 9-weeks later (primary timepoint), and 3-months later. The trial was prospectively registered. RESULTS: Between 7 February 2022, and 16 August 2022, 242 participants were enrolled in the ultra-brief treatment (n = 85), standard-length treatment (n = 80), and waitlist control (n = 77). Participants were mostly women with an average age of 48.56 years. At 9-weeks post-baseline, participants in the ultra-brief treatment group reported significantly lower depression (between groups d = 0.41) and anxiety (d = 0.53) than the waitlist control. The ultra-brief treatment was non-inferior for anxiety at both 9-weeks and 3-months follow-up. Non-inferiority for depression was observed at 9-weeks. CONCLUSIONS: The online ultra-brief treatment resulted in significant reductions in depression and anxiety that were non-inferior to a longer treatment course after 9-weeks. Remotely delivered ultra-brief treatments have the potential to provide accessible and effective care for those who cannot, or would prefer not to, access longer psychological interventions.

Internet-Delivered Psychological Pain-Management for Young Adults With Chronic Pain: An Investigation of Clinical Trial Data.

Young adults report chronic pain at rates of around 12% but lack access to clinical services. There is interest in learning how this emerging adult population engages with and responds to treatment. Using data from young adults aged 18 to 30 years (Mage = 25.8, SD = 3.2), taken from 4 previous randomised controlled trials, the current study investigated the feasibility, acceptability, and efficacy of an internet-delivered psychological pain-management intervention for young adults with chronic pain. We compared young adults in a treatment group (n = 104) with 1) a young-adult wait-list control group (n = 48), and 2) a treatment group reflecting the average-aged participant from the previous trials (39-63 years, n = 561). Feasibility was determined through treatment engagement, adherence and completion, and acceptability through a treatment satisfaction measure. Clinical outcomes were disability, pain intensity, anxiety, and depression; assessed at pre-treatment, post-treatment, and 3-month follow-up. Generalised estimation equation analyses were undertaken, using multiple imputations to account for missing data. Young adults had high engagement and acceptability ratings, though 34% did not complete the intervention. The treatment group significant improved across all outcomes, compared with control, with improvements maintained at follow-up. Post-treatment improvements were equivalent for young-adult and average-aged adult treatment groups, with no significant differences in feasibility or acceptability outcomes. Findings indicate young adults can engage with and show improvements following a psychological pain-management intervention designed for all adults with chronic pain. Future research is encouraged to examine outcomes related to role functioning of young adults, and moderators of treatment acceptability and efficacy for this population. PERSPECTIVE: Secondary analysis of data from 4 RCTs found an Internet-delivered psychological pain-management intervention acceptable and clinically efficacious for improving disability, anxiety, depression and pain intensity in young adults (18-30) with chronic pain.

Cognitive behavioral therapies for depression and anxiety in people with chronic disease: A systematic review and meta-analysis.

OBJECTIVE: Anxiety and depression in chronic disease are common and burdensome co-morbidities. There has been growing interest in cognitive and behavioral therapies (CBTs) for anxiety and depression in chronic disease, however their efficacy has not been well-established. This study examined the efficacy of CBTs for depression and/or anxiety symptoms within chronic disease and explored the moderating role of clinical and methodological characteristics. METHODS: Following prospective registration, electronic databases were searched up to 2023 for randomized controlled trials (RCTs) examining CBTs for depression and/or anxiety in any adult chronic disease population. RESULTS: We included 56 RCTs. The overall effect of CBTs was g = 0.61 (95% CI, 0.49, 0.72) for depression and g = 0.56 (95% CI, 0.42, 0.70) for anxiety. A range of methodological features significantly moderated the effect sizes obtained, including type of control group and the outcome measure used. Risk of Bias ratings indicated some concerns regarding RCT conduct and reporting. CONCLUSIONS: CBTs lead to moderate improvements in both depression and anxiety symptoms among people with chronic disease. However, the efficacy of CBT should be interpreted considering certain study and sample characteristics. It is recommended that future studies make improvements to study methodology and reporting.

Depression and Anxiety Trajectories in Chronic Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: People living with chronic diseases are at an increased risk of anxiety and depression, which are associated with poorer medical and psychosocial outcomes. Many studies have examined the trajectories of depression and anxiety in people with specific diseases, including the predictors of these trajectories. This is valuable for understanding the process of adjustment to diseases and informing treatment planning. However, no review has yet synthesised this information across chronic diseases. METHODS: Electronic databases were searched for studies reporting trajectories of depression or anxiety in chronic disease samples. Data extracted included sample characteristics, results from trajectory analyses, and predictors of trajectories. Meta-analysis of the overall pooled prevalence of depression and anxiety trajectories was conducted, and qualitative synthesis of disease severity predictors was undertaken. RESULTS: Following search and screening, 67 studies were included (N = 61,201 participants). Most participants followed a stable nonclinical trajectory for depression (69.0% [95% CI: 65.6, 72.2]) and anxiety (73.4% [95% CI: 66.3, 79.5]). Smaller but meaningful subsamples followed a trajectory of depression and anxiety symptoms consistently in the clinical range (11.8% [95% CI: 9.2, 14.8] and 13.7% [95% CI: 9.3, 19.7], respectively). Several clinical and methodological moderators emerged, and qualitative synthesis suggested that few aspects of disease severity were associated with participants' trajectories. CONCLUSION: Most people with chronic disease follow a trajectory of distress that is low and stable, suggesting that most people psychologically adjust to living with chronic disease. Evidence also suggests that the nature and severity of the disease are not meaningful predictors of psychological distress.

The Timing and Magnitude of Improvements in Depression, Anxiety, Disability, and Pain Intensity During an Internet-delivered Program for Chronic Pain.

Numerous studies have found that pain management programs are an effective treatment option for people with chronic pain. However, little is known about when people experience improvements during these programs and why they are effective. Using a secondary analysis, the current study examined the timing and magnitude of symptom change during an 8-week internet-delivered psychological pain management program for people with chronic pain. The change in 4 outcomes was examined: depression (n = 881), anxiety (n = 561), disability (n = 484), and pain intensity (n = 484). The largest improvements in depression, anxiety, and disability were reported during the first half of treatment (ie, 4 weeks), whereas the largest reductions in pain intensity were reported during the second half of treatment. Half the participants had experienced a clinically meaningful improvement in depression or anxiety, and a third of participants had reported such an improvement in disability by midtreatment (ie, 5 weeks after baseline). In a subgroup analysis (n = 397), this pattern of change in depression and anxiety symptoms did not differ based on the level of therapist guidance. This study highlights the importance of the first few weeks of psychological pain management programs and encourages future work to examine how the mechanisms underpinning rapid change may be harnessed to optimize care for people with chronic pain. PERSPECTIVE: This study found that depression, anxiety, and disability improved rapidly during the first half of an 8-week internet-delivered pain management program, and most of the prepost change had occurred by midtreatment. This work highlights the therapeutic potential of the first few treatment sessions and prompts future research into a rapid responding.

The impact of obesity and overweight on response to internet-delivered cognitive behavioural therapy for adults with chronic health conditions.

BACKGROUND: There is growing evidence that internet-delivered cognitive behavioural therapy (iCBT) can improve functioning and reduce psychological distress in people with chronic health conditions. Obesity frequently co-occurs with chronic health conditions, yet its impact on response to psychological interventions in this population is not known. The current study examined associations between BMI and clinical outcomes (depression, anxiety, disability, and satisfaction with life) following a transdiagnostic iCBT program targeting adjustment to chronic illness. METHODS: Participants from a large randomised controlled trial, who provided information on height and weight, were included (N = 234; mean age= 48.32, SD = 13.80; mean BMI = 30.43, SD = 8.30, range 16.18-67.52; 86.8% female). The influence of baseline BMI range on treatment outcomes at post-treatment and 3-month follow-up was examined using generalized estimating equations. We also examined changes in BMI and in participants' perceived impact of weight on their health. RESULTS: Improvement in all outcomes occurred across BMI ranges; additionally, persons with obesity or overweight generally experienced greater symptom reductions than those within a healthy weight range. A greater proportion of participants with obesity achieved clinically significant change on key outcomes (e.g., depression: 32% [95% CI: 25%, 39%]) than participants with a healthy weight (21% [95% CI: 15%, 26%]) or overweight (24% [95% CI: 18%, 29%], p = 0.016). There were no significant changes in BMI from pre-treatment to 3-month follow-up, however there were significant reductions on the self-rated impact of weight on health. CONCLUSIONS: Persons with chronic health conditions and with obesity or overweight benefit at least as much as those with a healthy BMI from iCBT programs targeting psychological adjustment to chronic illness, even without changes in BMI. iCBT programs may be an important component in the self-management of this population, and may address barriers implicated in health behaviour change.

Can Internet-Delivered Pain Management Programs Reduce Psychological Distress in Chronic Pain? Exploring Relationships Between Anxiety and Depression, Pain Intensity, and Disability.

BACKGROUND: Adults with chronic pain who also report high pain intensity and disability are more likely to experience depression and anxiety symptoms. The present study examined changes in anxiety and depression symptoms after an Internet-delivered pain management program based on baseline pain intensity and disability severity categories. METHODS: We conducted a secondary analysis of data from four randomized controlled trials (N = 1,333). RESULTS: Greater pain intensity and disability were associated with increased odds of elevated anxiety or depression symptoms at baseline. Treatment led to greater reductions in anxiety and depression symptoms compared with a waitlist control, and these improvements occurred irrespective of baseline pain intensity or disability severity. Those individuals who reported ≥30% improvements in pain intensity or disability after treatment were more likely to also report ≥30% improvements in psychological symptoms. Importantly, most participants who achieved ≥30% improvements in depression and anxiety had not experienced such improvements in pain intensity or disability. CONCLUSION: These findings suggest that emerging Internet-delivered pain management programs can lead to reductions in psychological distress even when pain intensity and disability are severe or do not improve with treatment. This indicates the value of such treatments in treating distress and improving mental health in people with chronic pain.

The timing and magnitude of symptom improvements during an Internet-delivered transdiagnostic treatment program for anxiety and depression.

OBJECTIVE: In face-to-face treatments, mental health symptoms improve rapidly across the first few treatment sessions, and the pace of improvement slows with additional sessions. Some individuals also report clinically meaningful symptom improvements after only two or three treatment sessions. As the rate of symptom change has been given limited attention within digital treatments, the present study investigated the timing and magnitude of symptom change during an 8-week online treatment for anxiety and depression. METHOD: Three adult samples were derived from previous randomized controlled trials: generalized anxiety disorder (n = 165), major depression (n = 149), and mixed anxiety/depression (n = 262). Symptom scores were compared between consecutive weeks of treatment, and we examined the proportion of individuals who achieved a ≥ 25% or ≥ 50% improvement in symptoms each week. RESULTS: Across all three samples, symptoms improved more rapidly during the first half of treatment compared to the second half of treatment. Within the first 4 weeks, over half of the participants had experienced a ≥ 25% improvement in symptoms, and approximately a third of participants had experienced a ≥ 50% improvement in symptoms. This pattern of change was found irrespective of diagnostic status or outcome measure. CONCLUSIONS: A substantial number of people who receive internet-delivered treatments appear to experience rapid, large, and clinically significant symptom improvement early in treatment. These findings add to our theoretical understanding of symptom improvements during psychotherapy, and further research investigating the mechanisms of such change will inform the development of more effective treatments. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Sudden gains in therapist-guided versus self-guided online treatments for anxiety or depression.

OBJECTIVE: Sudden gains are large, rapid, and sustained symptom improvements, and are associated with improved treatment outcomes across a range of mental health problems. Current theories suggest that therapists are required for sudden gains to be sustained, and to result in improved treatment outcomes. We compared the prevalence and consequences of sudden gains in therapist-guided versus self-guided internet-delivered treatments for anxiety and depression. METHOD: Samples from four previous randomized controlled trials were analyzed: generalized anxiety disorder (n = 259), panic disorder (n = 109), social anxiety disorder (n = 175), and major depressive disorder (n = 209). The prevalence, timing, and reversal rates of sudden gains were compared across therapist-guided and self-guided groups. Generalized estimating equations were used to examine the impact of guidance level and sudden gain status on posttreatment outcomes. RESULTS: Sudden gains were similarly prevalent in therapist-guided and self-guided treatments. In all four diagnostic samples, sudden gains most frequently occurred between Weeks 2 and 3 of treatment, and the rate of reversals did not differ based on the presence of guidance. The association between sudden gains and treatment outcome varied by disorder, such that sudden gains were associated with improved outcomes (irrespective of guidance condition) for participants with social anxiety disorder and major depression, but not generalized anxiety disorder or panic disorder. CONCLUSIONS: Sudden gains can occur, and are maintained, during internet-delivered psychotherapy even in the absence of therapist guidance. Furthermore, sudden gains may be associated with different patterns of symptom improvement depending on diagnostic presentation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A meta-analytic review of randomized clinical trials of online treatments for anxiety: Inclusion/exclusion criteria, uptake, adherence, dropout, and clinical outcomes.

Over the last decade there has been rapid growth in the number of clinical trials examining internet-delivered interventions for anxiety. While there have been numerous analyses of treatment efficacy, few studies have examined treatment engagement. The current meta-analysis examined participant eligibility, uptake, adherence, and drop-out in clinical trials of internet-delivered treatments for anxiety. This meta-analysis used random effects models to obtain estimates of participant inclusion, uptake, adherence, drop-out, and within-group treatment effect size. Moderator analyses examined the effects of anxiety disorder type, treatment type, and level of clinician guidance. After screening, 140 trials with 199 treatment arms (N = 11,021) were included. An average of 46% (95% CI 42, 50) of interested people were included in the clinical trials. In the active treatment arms, 98% (95% CI 97, 99) of participants began treatment, 81% (95% CI 78, 85) of the assigned treatments were completed, 21% (95% CI 18, 23) of individuals dropped out at post-treatment based on questionnaire non-completion, and an overall within-group effect size of g = 1.03 (95% CI 0.94, 1.13) was obtained. Several moderators of interest were significant (e.g., clinical guidance, anxiety disorder type), and there was substantial heterogeneity in estimates. In conclusion, a large number of inclusion and exclusion criteria have been used in trials of internet-delivered treatments for anxiety. Once recruited into a trial, however, most people appear to begin, adhere, and complete internet-delivered treatment for anxiety. Further research exploring various eligibility criteria and their impact on engagement and efficacy is warranted.

German translation and validation of the brief Epilepsy Anxiety Survey Instrument (brEASI).

BACKGROUND: Anxiety disorders remain undiagnosed in routine clinical practice in up to two thirds of affected patients with epilepsy despite their significant impact on medical and psychosocial outcomes. The study objective was to translate and validate the German 8-item "brief Epilepsy Anxiety Survey Instrument" (brEASI) to facilitate effective screening for the presence of anxiety disorders in German-speaking patients. METHODS: After expert translation into German, the brEASI was completed by consecutive adult inpatients with epilepsy hospitalized for seizures at an academic reference epilepsy center. Patients also completed the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), the Generalized Anxiety Disorder scale (GAD-7) for external validity, and underwent a standardized interview (Mini-DIPS-OA) as a gold standard to determine the presence of an ICD-10 anxiety disorder (generalized anxiety disorder (GAD), panic disorder, agoraphobia, and social phobia). Receiver operating characteristics (ROC) were calculated to determine the diagnostic accuracy of the brEASI, including the associated area under the curve (AUC) statistics to determine the potential of the brEASI to identify ICD-10 anxiety disorders diagnosed by interview. For comparative purposes, these analyses were also conducted for the GAD-7. RESULTS: Of 80 recruited adult inpatients with epilepsy, 18 (23 %) were found to have a current anxiety disorder through standardized interview. In this study, both brEASI and GAD-7 showed a better diagnostic performance at a cutoff of >5 than at the previously reported cutoff values of >6 and >9, respectively. The AUC of the German brEASI was outstanding (AUC = 0.90, 95 % confidence interval (CI) = 0.82-0.96) for detecting all anxiety disorders and excellent for detecting non-GAD disorders (AUC = 0.85, CI = 0.76-0.92) at a cutoff of >5. At this optimal cutoff of >5 the brEASI demonstrated better sensitivity and specificity (89 % and 84 %) for identifying anxiety disorders than the GAD-7 (83 % and 74 %). The final German version of the brEASI is free to download at https://www.v-neuro.de/veroeffentlichungen/. CONCLUSION: The German version of the brEASI represents a valid and reliable epilepsy-specific anxiety screening instrument. A positive screening result should be followed by further diagnostic procedures. Appropriate therapeutic steps should be initiated if the presence of an anxiety disorder or other psychiatric disorders is confirmed.

Understanding the untreated course of anxiety disorders in treatment-seeking samples: A systematic review and meta-analysis.

BACKGROUND: Very little is known about the course of anxiety disorders when they go untreated, despite the significant theoretical and practical value of this information, such as for treatment planning and benchmarking purposes. This meta-analysis aimed to examine the course of anxiety disorders in treatment-seeking samples using the control groups of treatment studies for anxiety disorders. METHODS: Following pre-registration, we systematically searched the literature for RCTs of treatment for anxiety disorders. Studies were included if they randomised participants to a control arm, where treatment was not received (i.e. waitlist control or no-treatment control). Meta-analyses were conducted to determine the magnitude of symptom change over the control period (Hedges' g), and rate of response (pooled prevalence). Effects were compared between anxiety disorders, alongside other potential moderators. RESULTS: Following search and screening, 173 RCTs met criteria (n = 15,250) for data extraction. Overall, untreated participants demonstrated significant, but small improvements to anxiety symptoms (g = 0.17, 95% CI 0.14, 0.21). Significant differences were observed between anxiety disorders, and according to other methodological features of the included trials. CONCLUSIONS: Results suggest that anxiety disorders are unlikely to remit without treatment, with some disorders remitting to a lesser extent than others. While this review is limited to a treatment-seeking sample, results provide theoretical and practical value for researchers and treatment providers.

The Chronic Conditions Course: A Randomised Controlled Trial of an Internet-Delivered Transdiagnostic Psychological Intervention for People with Chronic Health Conditions.

INTRODUCTION: Psychological adjustment to chronic health conditions is important, as poor adjustment predicts a range of adverse medical and psychosocial outcomes. Psychological treatments demonstrate efficacy for people with chronic health conditions, but existing research takes a disorder-specific approach and they are predominately delivered in face-to-face contexts. The internet and remotely delivered treatments have the potential to overcome barriers to accessing traditional face-to-face treatment. OBJECTIVE: The current study examined the efficacy and acceptability of an internet-delivered transdiagnostic psychological intervention to promote adjustment to illness, based on cognitive behaviour therapy principles. METHODS: In a two-arm randomised controlled trial, participants (n = 676) were randomly allocated to the 8-week intervention or a waitlist control. Treatment included five core lessons, homework tasks, additional resources, and weekly contact with a psychologist. Primary outcomes included depression, anxiety, and disability, assessed at pre-treatment, post-treatment, 3-month follow-up, and 12-month follow-up. RESULTS: The treatment group reported significantly greater improvements in depression (between-groups d = 0.47), anxiety (d = 0.32), and disability (d = 0.17) at post-treatment (all ps <0.001). Improvements were sustained over the 3-month and 12-month follow-ups. High treatment completion rates (69%) and levels of satisfaction (86%) were reported by participants in treatment. The intervention required a mean clinician time of 56.70 min per participant. CONCLUSIONS: The findings provide preliminary and tentative support for the potential of internet-delivered transdiagnostic interventions to promote adjustment to chronic health conditions. Further research using robust control groups, and exploring the generalisability of findings, is needed before firm conclusions can be drawn.

Examining the psychometric properties of brief screening measures of depression and anxiety in chronic pain: The Patient Health Questionnaire 2-item and Generalized Anxiety Disorder 2-item.

OBJECTIVE: Individuals with chronic pain experience anxiety and depressive symptoms at rates higher than the general population. The Patient Health Questionnaire 2-item (PHQ-2) and Generalized Anxiety Disorder 2-item (GAD-2) are brief screening measures of depression and anxiety, respectively. These brief scales are well-suited for use in routine care due to their brevity and ease of administration, yet their psychometric properties have not been established in heterogeneous chronic pain samples when administered over the Internet. MATERIALS AND METHODS: Using existing data from randomized controlled trials of an established Internet-delivered pain management program (n = 1333), we assessed the reliability, validity, diagnostic accuracy, and responsiveness to treatment change in the PHQ-2 and GAD-2, as well as the long-form counterparts. Exploratory analyses were conducted to obtain cutoff scores using those participants with diagnostic data (n = 62). RESULTS: The PHQ-2 and GAD-2 demonstrated appropriate reliability (eg, Cronbach's α = 0.79-0.84), validity (eg, higher scores in individuals with a diagnosis; p < 0.001), and responsiveness to treatment change (eg, pre- to post-treatment scores, p < 0.001). The psychometric properties of the short forms compared well with the longer forms. Cutoff scores on the short forms were consistent with general population samples, while cutoff scores on the long forms were higher than previously observed using general population samples. All four scales favored specificity over sensitivity. CONCLUSIONS: The PHQ-2 and GAD-2 demonstrated acceptable psychometric properties in the current sample, as did the long forms. Based on our findings, the PHQ-2 and GAD-2 can be used as screening tools with chronic pain samples when administered over the Internet.

Internet-delivered cognitive and behavioural based interventions for adults with chronic pain: a systematic review and meta-analysis of randomized controlled trials.

ABSTRACT: This study examined the efficacy of internet-delivered cognitive and behavioural interventions for adults with chronic pain AND explored the role of clinical and study characteristics as moderators of treatment effects. PubMed, Embase, PsycINFO, CENTRAL and CINAHL were searched to identify randomized controlled trials published up to October 2021. A meta-analysis of 36 studies (5778 participants) was conducted, which found small effect sizes for interference/disability (Hedges' g = 0.28; 95% confidence interval [CI] 0.21-0.35), depression ( g = 0.43; 95% CI 0.33-0.54), anxiety ( g = 0.32; 95% CI 0.24-0.40), pain intensity ( g = 0.27; 95% CI 0.21-0.33), self-efficacy ( g = 0.39; 95% CI 0.27-0.52) and pain catastrophizing ( g = 0.31; 95% CI 0.22-0.39). Moderator analyses found that interventions which involved clinician guidance had significantly greater effect sizes for interference/disability ( g = 0.38), anxiety ( g = 0.39), and pain intensity ( g = 0.33) compared with those without ( g = 0.16, g = 0.18, and g = 0.20, respectively). Studies using an inactive control had greater effects for depression ( g = 0.46) compared with active control trials ( g = 0.22). No differences were found between treatments based on traditional cognitive behaviour therapy vs acceptance and commitment therapy. Sample size, study year, and overall risk of bias (Cochrane rating) did not consistently moderate treatment effects. Overall, the results support the use of internet-delivered cognitive and behavioural interventions as efficacious and suggest guided interventions are associated with greater clinical gains for several key pain management outcomes.

A systematic review and meta-analysis of the success of blinding in antidepressant RCTs.

Successful blinding in double-blind RCTs is crucial for minimizing bias, however studies rarely report information about blinding. Among RCTs for depression, the rates of testing and success of blinding is unknown. We conducted a systematic review and meta-analysis of the rates of testing, predictors, and success of blinding in RCTs of antidepressants for depression. Following systematic search, further information about blinding assessment was requested from corresponding authors of the included studies. We reported the frequency of blinding assessment across all RCTs, and conducted logistic regression analyses to assess predictors of blinding reporting. Participant and/or investigator guesses about treatment allocation were used to calculate Bang's Blinding Index (BI). The BI between RCT arms was compared using meta-analysis. Across the 295 included trials, only 4.7% of studies assessed blinding. Pharmaceutical company sponsorship predicted blinding assessment; unsponsored trials were more likely to assess blinding. Meta-analysis suggested that blinding was unsuccessful among participants and investigators. Results suggest that blinding is rarely assessed, and often fails, among RCTs of antidepressants. This is concerning considering controversy around the efficacy of antidepressant medication. Blinding should be routinely assessed and reported in RCTs of antidepressants, and trial outcomes should be considered in light of blinding success or failure.

The Pain Course: a randomised controlled trial and economic evaluation of an internet-delivered pain management program.

ABSTRACT: There is interest in the potential of Internet-delivered programs to cost-effectively increase access to pain management for people with chronic pain. However, few large-scale clinical and economic evaluations have been undertaken. Using a randomised controlled trial design, the current study (n = 659) examined the clinical efficacy, cost-effectiveness, and cost utility of an Internet-delivered pain management program for people with mixed chronic pain conditions when delivered with optional clinician support. The treatment group reported significant improvements in disability, depression, anxiety, average pain intensity, and quality-adjusted life years (QALYs), compared with control, and exhibited relatively high levels of treatment engagement and satisfaction. Each additional clinical improvement (defined as ≥ 30% improvement) produced by the intervention, over control, was associated with a cost of $48, $27, $38, and $83 for disability, depression, anxiety, and average pain intensity, respectively. Gaining one QALY was associated with a cost of $152 or $11,910 per QALY when an 80% probability criterion for cost utility was applied. The program itself was associated a relatively small, fixed, cost per patient but was not cost saving over the brief intervention period. The findings support the clinical efficacy and cost-effectiveness of Internet-delivered programs with "on demand" clinician support as a way to increase access to pain management. Key limitations of the current study include the use of a waitlist-control group, a short follow-up period, and the focus on governmental healthcare costs. Further evaluation of these programs is necessary if they are scaled up and offered as routine care.

Association of Single-blind Placebo Run-in Periods With the Placebo Response in Randomized Clinical Trials of Antidepressants: A Systematic Review and Meta-analysis.

Importance: Single-blind placebo run-in (PRI) periods are common in randomized clinical trials (RCTs) of treatment for depression. They aim to increase sensitivity to detect drug effects; however, the association of PRI periods with study outcomes remains unclear. This is concerning given the costs of PRI periods to patients and investigators. Objective: To examine the association of the use of PRI periods with the placebo response, drug response, and drug-placebo difference among RCTs of antidepressants. Data Sources: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and PsycINFO, as well as repositories of unpublished studies, were systematically searched up to July 2021. Study Selection: Included studies were double-blind, placebo-controlled RCTs of antidepressant medication among adults with depressive disorders. Data Extraction and Synthesis: Data were extracted into a coding sheet, including the characteristics of studies, the characteristics of PRI periods, and the outcomes of studies. Main Outcomes and Measures: Study outcomes were the primary depression symptom measure reported by the RCT. These outcomes were used to calculate effect sizes (Hedges g) of the within-group drug response and placebo response as well as the drug-placebo difference. Random-effects meta-analysis was used to calculate effect sizes, and subgroup analyses were used to compare outcomes depending on use of PRI periods. Results: A total of 347 trials (representing 89 183 participants) were included; 174 studies (50%) reported using a single-blind PRI period. Response outcome data were available for 189 studies. Studies using PRI periods reported a smaller placebo response (g = 1.05 [95% CI, 0.98-1.11]; I2 = 82%) than studies that did not use a PRI period (g = 1.15 [95% CI, 1.09-1.21]; I2 = 81%; P = .02). Subgroup analysis showed a larger drug response size among studies that did not use a PRI period (g = 1.55 [95% CI, 1.49-1.61]; I2 = 85%) than those that did use a PRI period (g = 1.42 [95% CI, 1.36-1.48]; I2 = 81%; P = .001). The drug-placebo difference did not differ by use of PRI periods (g = 0.33 [95% CI, 0.29-0.38]; I2 = 47% for use of a PRI period vs g = 0.34 [95% CI, 0.30-0.38]; I2 = 54% for no use of PRI periods; P = .92). The likelihood of response to drug vs placebo also did not differ between studies that used a PRI period (odds ratio, 1.89 [95% CI, 1.76-2.03]) and those that did not use a PRI period (odds ratio, 1.77 [95% CI, 1.65-1.89]; P = .18). Conclusions and Relevance: This study suggests that RCTs using PRI periods yield smaller within-group changes across both placebo and drug groups compared with RCTs without PRI periods. The reduction in effect size across groups was equivalent in magnitude. Consequently, PRI studies do not observe larger drug-placebo differences, suggesting that they do not increase trial sensitivity. As such, given the resources and probable deception required and risk to external validity, the practice of using PRI periods in RCTs of antidepressants should be ended.