Regulating digital therapeutics for mental health: Opportunities, challenges, and the essential role of psychologists.

With so many promising digital therapeutics for anxiety and obsessive-compulsive (OC) spectrum problems, there is an urgent need to consider how evolving regulatory oversight of digital therapeutics is poised to shift how these tools are developed, evaluated, reimbursed, and delivered. In this commentary, we discuss both opportunities and potential pitfalls associated with emerging government regulations of digital therapeutics for mental health, and we consider how applying the traditional 'prescription-based' medical approval paradigm to digital therapeutics for mental health could ultimately undermine and limit the broad accessibility of these software-based innovations that have been explicitly designed to expand the accessibility of care. For example, the vast majority of behavioural and mental health providers do not have 'prescription privileges' (a term originally rooted in pharmacologic practices), and as a result, under current regulations in the U.S. would not be authorized to make FDA-cleared digital therapeutics available to their patients. This is particularly concerning given that most digital therapeutics for mental health are directly rooted in psychological and behavioural science, yet psychologists would not be authorized to incorporate these innovations into their practice. We consider how synchronizing regulatory standards across countries may prove useful, and we conclude by arguing that multidisciplinary teams making regulatory decisions concerning digital therapeutics for mental health must include representation from the discipline and practice of psychology. PRACTITIONER POINTS: Emerging government regulations of digital therapeutics for mental health present both opportunities and potential pitfalls Applying the traditional 'prescription-based' medical approval paradigm to digital therapeutics for mental health could ultimately undermine the broad accessibility of these software-based innovations. Synchronizing regulatory standards across countries may prove useful. Multidisciplinary teams making regulatory decisions concerning digital therapeutics for mental health must include representation from the field of psychology.

Insomnia as a mediating therapeutic target for depressive symptoms: A sub-analysis of participant data from two large randomized controlled trials of a digital sleep intervention.

Insomnia predicts the onset of depression, commonly co-presents with depression and often persists following depression remission. However, these conditions can be challenging to treat concurrently using depression-specific therapies. Cognitive behavioural therapy for insomnia may be an appropriate treatment to improve both insomnia and depressive symptoms. We examined the effects of a fully-automated digital cognitive behavioural therapy intervention for insomnia (Sleepio) on insomnia and depressive symptoms, and the mediating role of sleep improvement on depressive symptoms in participants from two randomized controlled trials of digital cognitive behavioural therapy for insomnia. We also explored potential moderators of intervention effects. All participants met criteria for probable insomnia disorder and had clinically significant depressive symptomatology (PHQ-9 ≥ 10; n = 3,352). Individuals allocated to treatment in both trials were provided access to digital cognitive behavioural therapy. Digital cognitive behavioural therapy significantly improved insomnia (p < .001; g = 0.76) and depressive symptoms (p < .001; g = 0.48) at post-intervention (weeks 8-10), and increased the odds (OR = 2.9; 95% CI = 2.34, 3.65) of clinically significant improvement in depressive symptoms (PHQ-9 < 10). Improvements in insomnia symptoms at mid-intervention mediated 87% of the effects on depressive symptoms at post-intervention. No variables moderated effectiveness outcomes, suggesting generalizability of these findings. Our results suggest that effects of digital cognitive behavioural therapy for insomnia extend to depressive symptoms in those with clinically significant depressive symptomatology. Insomnia may, therefore, be an important therapeutic target to assist management of depressive symptoms.

Efficacy of digital cognitive behavioral therapy for moderate-to-severe symptoms of generalized anxiety disorder: A randomized controlled trial.

BACKGROUND: Cognitive behavioral therapy (CBT) is an efficacious intervention for generalized anxiety disorder (GAD). Digital CBT may provide a scalable means of delivering CBT at a population level. We investigated the efficacy of a novel digital CBT program in those with GAD for outcomes of anxiety, worry, depressive symptoms, sleep difficulty, wellbeing, and participant-specific quality of life. METHODS: This online, two-arm parallel-group superiority randomized controlled trial compared digital CBT with waitlist control in 256 participants with moderate-to-severe symptoms of GAD. Digital CBT (Daylight), was delivered using participants' own smartphones. Online assessments took place at baseline (Week 0; immediately preceding randomization), mid-intervention (Week 3; from randomization), post-intervention (Week 6; primary endpoint), and follow-up (Week 10). RESULTS: Overall, 256 participants were randomized and intention-to-treat analysis found Daylight reduced symptoms of anxiety compared with waitlist control at post-intervention, reflecting a large effect size (adjusted difference [95% CI]: 3.22 [2.14, 4.31], d = 1.08). Significant improvements were found for measures of worry; depressive symptoms, sleep difficulty, wellbeing, and participant-specific quality of life. CONCLUSION: Digital CBT (Daylight) appears to be safe and efficacious for symptoms of anxiety, worry, and further measures of mental health compared with waitlist control in individuals with GAD.

The Sleep Condition Indicator: reference values derived from a sample of 200 000 adults.

The Sleep Condition Indicator (SCI) is an eight-item rating scale that was developed to screen for insomnia disorder based on DSM-5 criteria. It has been shown previously to have good psychometric properties among several language translations. We developed age- and sex-referenced values for the SCI to assist the evaluation of insomnia in everyday clinical practice. A random sample of 200 000 individuals (58% women, mean age: 31 ± 13 years) was selected from those who had completed the SCI via several internet platforms. Descriptive and inferential methods were applied to generate reference data and indices of reliable change for the SCI for men and women across the age deciles 16-25, 26-35, 36-45, 46-55, 56-65 and 66-75 years. The mean SCI score for the full sample was 14.97 ± 5.93. Overall, women scored worse than men (14.29 ± 5.83 versus 15.90 ± 5.94; mean difference: -1.60, η2  = 0.018, Cohen's d = 0.272) and those of older age scored worse than those younger (-0.057 points per year, 95% confidence interval (CI): -0.059 to -0.055) relative to age 16-25 years. The Reliable Change Index was established at seven scale points. In conclusion, the SCI is a useful instrument for clinicians and researchers that can help them to screen for insomnia, compare completers to individuals of similar age and sex and establish whether a reliable change was achieved following treatment.

A preliminary investigation of the effects of the unified protocol on temperament.

Previous research has shown that two dimensions of temperament referred to as neuroticism/behavioral inhibition (N/BI) and extraversion/behavioral activation (E/BA) are key risk factors in the development and maintenance of anxiety and mood disorders (Brown & Barlow, 2009). Given such findings, these temperamental dimensions may represent promising treatment targets for individuals with emotional disorders; however, to date, few studies have investigated the effects of psychological treatments on temperamental constructs generally assumed to be "stable, inflexible, and pervasive" (American Psychiatric Association, 2000). The present study addresses this gap in the literature by examining the effects of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP; Barlow et al., 2011), a cognitive-behavioral therapy designed to target core processes of N/BI and E/BA temperaments, in a sample of adults with principal anxiety disorders and a range of comorbid conditions. Results revealed small effects of the UP on N/BI and E/BA compared with a waitlist control group at post-treatment. Additionally, decreases in N/BI and increases in E/BA during treatment were associated with improvements in symptoms, functioning, and quality of life. Findings provide preliminary support for the notion that the UP treatment facilitates beneficial changes in dimensions of temperament.

Rigorous and rapid evidence assessment in digital health with the evidence DEFINED framework.

Dozens of frameworks have been proposed to assess evidence for digital health interventions (DHIs), but existing frameworks may not facilitate DHI evidence reviews that meet the needs of stakeholder organizations including payers, health systems, trade organizations, and others. These organizations may benefit from a DHI assessment framework that is both rigorous and rapid. Here we propose a framework to assess Evidence in Digital health for EFfectiveness of INterventions with Evaluative Depth (Evidence DEFINED). Designed for real-world use, the Evidence DEFINED Quick Start Guide may help streamline DHI assessment. A checklist is provided summarizing high-priority evidence considerations in digital health. Evidence-to-recommendation guidelines are proposed, specifying degrees of adoption that may be appropriate for a range of evidence quality levels. Evidence DEFINED differs from prior frameworks in its inclusion of unique elements designed for rigor and speed. Rigor is increased by addressing three gaps in prior frameworks. First, prior frameworks are not adapted adequately to address evidence considerations that are unique to digital health. Second, prior frameworks do not specify evidence quality criteria requiring increased vigilance for DHIs in the current regulatory context. Third, extant frameworks rarely leverage established, robust methodologies that were developed for non-digital interventions. Speed is achieved in the Evidence DEFINED Framework through screening optimization and deprioritization of steps that may have limited value. The primary goals of Evidence DEFINED are to a) facilitate standardized, rapid, rigorous DHI evidence assessment in organizations and b) guide digital health solutions providers who wish to generate evidence that drives DHI adoption.

Stage models for major depression: Cognitive behavior therapy, mechanistic treatment targets, and the prevention of stage transition.

Stage models encourage a longitudinal perspective on the care of those with major depression: supporting vigilance to the risk for stage progression and the selection of interventions to address that risk. A central goal for this article is to evaluate the role of cognitive-behavior therapy (CBT) in addressing stage progression in the treatment of major depression. We summarize the evidence supporting depression-focused CBT for: (1) preventing depression onset, (2) treating syndromal depression, (3) treating residual symptoms, (4) preventing relapse, and (5) addressing pharmacologic treatment resistance. In addition, consistent with the goal of aiding prevention and intervention development by refining mechanistic treatment targets, we evaluate the role of two specific risk-factors for stage progression: insomnia and rumination. These risk factors have a feed-forward relationship with stress, both being amplified by stress and amplifying the negative consequences of stress. Moreover, each of these risk factors predict depression stage transmissions across multiple stages, and both are modifiable with treatment. Accordingly, insomnia and rumination appear to serve as excellent mechanistic targets for the prevention of depression stage progression. These findings are discussed in relation to current limitations and future research directions for targeting these risk factors and furthering the effective treatment of depression.

Cost-effectiveness of digital cognitive behavioral therapy (Sleepio) for insomnia: a Markov simulation model in the United States.

STUDY OBJECTIVES: To examine the cost-effectiveness and potential net monetary benefit (NMB) of a fully automated digital cognitive behavioral therapy (CBT) intervention for insomnia compared with no insomnia treatment in the United States (US). Similar relative comparisons were made for pharmacotherapy and clinician-delivered CBT (individual and group). METHODS: We simulated a Markov model of 100,000 individuals using parameters calibrated from the literature including direct (treatment) and indirect costs (e.g. insomnia-related healthcare expenditure and lost workplace productivity). Health utility estimates were converted into quality-adjusted life years (QALYs) and one QALY was worth $50,000. Simulated individuals were randomized equally to one of five arms (digital CBT, pharmacotherapy, individual CBT, group CBT, or no insomnia treatment). Sensitivity was assessed by bootstrapping the calibrated parameters. Cost estimates were expressed in 2019 US dollars. RESULTS: Digital CBT was cost beneficial when compared with no insomnia treatment and had a positive NMB of $681.06 (per individual over 6 months). Bootstrap sensitivity analysis demonstrated that the NMB was positive in 94.7% of simulations. Relative to other insomnia treatments, digital CBT was the most cost-effective treatment because it generated the smallest incremental cost-effectiveness ratio (-$3,124.73). CONCLUSIONS: Digital CBT was the most cost-effective insomnia treatment followed by group CBT, pharmacotherapy, and individual CBT. It is financially prudent and beneficial from a societal perspective to utilize automated digital CBT to treat insomnia at a population scale.

Feasibility and efficacy of a digital CBT intervention for symptoms of Generalized Anxiety Disorder: A randomized multiple-baseline study.

BACKGROUND AND OBJECTIVES: Cognitive behavioral therapy (CBT) is a first-line treatment for anxiety, but it is not widely available as clinical guidelines recommend. We examined the feasibility and efficacy of a novel smartphone-based fully automated digital CBT intervention, 'Daylight™', to improve symptoms of Generalized Anxiety Disorder (GAD). METHODS: In this multiple-baseline design, 21 adults (20 F; mean age 43yrs. range 19-65yrs.) with moderate-to-severe symptoms of GAD were randomized to one of three baseline durations (2-, 4-, or 6-weeks) and then received access to digital CBT. Participants completed daily ratings of anxiety and worry, weekly measures of anxiety, depressive symptoms, and sleep, and measures of anxiety, worry, wellbeing, quality of life, CBT skill acquisition, and work performance at initial assessment prior to baseline randomization, post-intervention, and follow-up. RESULTS: Digital CBT was found to be feasible in terms of engagement, satisfaction, and safety. For preliminary efficacy, improvements were detected in daily and weekly outcomes of anxiety for most participants. Despite individual differences, significant improvements occurred with the introduction of digital CBT and not during baseline. Overall, 70% of participants no longer had clinically significant symptoms of GAD, 61% no longer had significant depressive symptoms, and 40% no longer had significant sleep difficulty at post-intervention. LIMITATIONS: The study sample was recruited using the internet and was mostly female, limiting the generalizability of the findings. CONCLUSIONS: Findings support the feasibility and efficacy of Daylight. Further examination in randomized controlled trials is now warranted.

Development and Preliminary Evaluation of a Positive Emotion Regulation Augmentation Module for Anxiety and Depression.

Research has shown that positive emotions are important to optimal health, functioning, and well-being, and contribute to resilience against psychological dysfunction. Many clinical disorders, particularly anxiety and mood disorders, are associated with deficits in positive emotion that may contribute to disorder severity and prevent full recovery, and these deficits have received insufficient attention in treatment. The present study represents a preliminary evaluation of the feasibility and utility of adding a novel brief intervention module for enhancing positive emotion in anxiety and depressive disorders to existing evidence-based treatment. This intervention was evaluated in nine patients with a range of principal anxiety disorders who had previously completed an initial course of cognitive-behavioral treatment, utilizing a multiple baseline experimental-across-participants design. Results indicated that the intervention was effective in improving positive emotion regulation skills for five of nine participants. The intervention was also associated with further improvements in anxiety and depressive symptoms, positive and negative emotion, functioning, quality of life, and well-being. Participants reported high acceptability and satisfaction with the study intervention. Future research is needed to confirm the validity of these findings and evaluate the generalizability of these effects across patients and settings.

Development of a Single-Session, Transdiagnostic Preventive Intervention for Young Adults at Risk for Emotional Disorders.

Cognitive-behavioral prevention programs have demonstrated efficacy in reducing subclinical symptoms of anxiety and depression, and there is some evidence to suggest that they can lower the risk of future disorder onset. However, existing interventions tend to be relatively lengthy and target specific disorders or problem areas, both of which limit their potential for widespread dissemination. To address these limitations, we aimed to develop a single-session, transdiagnostic preventive intervention based on the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders for young adults at risk for developing anxiety and/or depressive disorders within a college setting. Results from this proof-of-concept study indicated that the intervention was viewed as highly satisfactory and acceptable. The intervention also was successful at delivering adaptive emotion management skills in its 2-hr workshop format. Future studies evaluating the efficacy of this novel transdiagnostic, emotion-focused prevention program are warranted.

The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders Compared With Diagnosis-Specific Protocols for Anxiety Disorders: A Randomized Clinical Trial.

Importance: Transdiagnostic interventions have been developed to address barriers to the dissemination of evidence-based psychological treatments, but only a few preliminary studies have compared these approaches with existing evidence-based psychological treatments. Objective: To determine whether the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) is at least as efficacious as single-disorder protocols (SDPs) in the treatment of anxiety disorders. Design, Setting, and Participants: From June 23, 2011, to March 5, 2015, a total of 223 patients at an outpatient treatment center with a principal diagnosis of panic disorder with or without agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, or social anxiety disorder were randomly assigned by principal diagnosis to the UP, an SDP, or a waitlist control condition. Patients received up to 16 sessions of the UP or an SDP for 16 to 21 weeks. Outcomes were assessed at baseline, after treatment, and at 6-month follow-up. Analysis in this equivalence trial was based on intention to treat. Interventions: The UP or SDPs. Main Outcomes and Measures: Blinded evaluations of principal diagnosis clinical severity rating were used to evaluate an a priori hypothesis of equivalence between the UP and SDPs. Results: Among the 223 patients (124 women and 99 men; mean [SD] age, 31.1 [11.0] years), 88 were randomized to receive the UP, 91 to receive an SDP, and 44 to the waitlist control condition. Patients were more likely to complete treatment with the UP than with SDPs (odds ratio, 3.11; 95% CI, 1.44-6.74). Both the UP (Cohen d, -0.93; 95% CI, -1.29 to -0.57) and SDPs (Cohen d, -1.08; 95% CI, -1.43 to -0.73) were superior to the waitlist control condition at acute outcome. Reductions in clinical severity rating from baseline to the end of treatment (ß, 0.25; 95% CI, -0.26 to 0.75) and from baseline to the 6-month follow-up (ß, 0.16; 95% CI, -0.39 to 0.70) indicated statistical equivalence between the UP and SDPs. Conclusions and Relevance: The UP produces symptom reduction equivalent to criterion standard evidence-based psychological treatments for anxiety disorders with less attrition. Thus, it may be possible to use 1 protocol instead of multiple SDPs to more efficiently treat the most commonly occurring anxiety and depressive disorders. Trial Registration: clinicaltrials.gov Identifier: NCT01243606.

The unified protocol for transdiagnostic treatment of emotional disorders: preliminary exploration of effectiveness for group delivery.

The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP) has demonstrated promising results among patients with heterogeneous anxiety and comorbid depressive disorders when delivered on an individual basis, but greater efficiencies may be achieved with group-based applications. The aim of the present study was to provide a preliminary exploration of the UP when delivered in a group format. Among diagnostically diverse patients (N = 11), the UP group treatment resulted in moderate to strong effects on anxiety and depressive symptoms, functional impairment, quality of life, and emotion regulation skills, as well as good acceptability and overall satisfaction ratings from patients. Three clinical cases are presented in detail to illustrate the group-based UP delivery, followed by a critical discussion of associated challenges and proposed guidelines for group administration, as well as directions for future research.

The Origins of Neuroticism.

In this article, we provide a fresh perspective on the developmental origins of neuroticism--a dimension of temperament marked by elevated stress reactivity resulting in the frequent experience of negative emotions. This negative affectivity is accompanied by a pervasive perception that the world is a dangerous and threatening place, along with beliefs about one's inability to manage or cope with challenging events. Historically, neuroticism has been viewed as a stable, genetically based trait. However, recent understanding of ongoing gene-environment interactions that occur throughout the life span suggests there may be a more complex and dynamic etiology. Thus, the purpose of this article is to offer a theory for understanding the development of neuroticism that integrates genetic, neurobiological, and environmental contributions to this trait. Given the strong correlation between neuroticism and the development of negative health outcomes--most notably, the full range of anxiety and mood disorders--an enhanced understanding of how neuroticism originates has implications for the treatment and prevention of a broad range of pathologies and, perhaps, even for the prevention of neuroticism itself.

Development and validation of the Overall Depression Severity and Impairment Scale.

The need to capture severity and impairment of depressive symptomatology is widespread. Existing depression scales are lengthy and largely focus on individual symptoms rather than resulting impairment. The Overall Depression Severity and Impairment Scale (ODSIS) is a 5-item, continuous measure designed for use across heterogeneous mood disorders and with subthreshold depressive symptoms. This study examined the psychometric properties of the ODSIS in outpatients in a clinic for emotional disorders (N = 100), undergraduate students (N = 566), and community-based adults (N = 189). Internal consistency, latent structure, item response theory, classification accuracy, convergent and discriminant validity, and differential item functioning analyses were conducted. ODSIS scores exhibited excellent internal consistency, and confirmatory factor analyses supported a unidimensional structure. Item response theory results demonstrated that the ODSIS provides more information about individuals with high levels of depression than those with low levels of depression. Responses on the ODSIS discriminated well between individuals with and without a mood disorder and depression-related severity across clinical and subclinical levels. A cut score of 8 correctly classified 82% of outpatients as with or without a mood disorder; it evidenced a favorable balance of sensitivity and specificity and of positive and negative predictive values. The ODSIS demonstrated good convergent and discriminant validity, and results indicate that items function similarly across clinical and nonclinical samples. Overall, findings suggest that the ODSIS is a valid tool for measuring depression-related severity and impairment. The brevity and ease of use of the ODSIS support its utility for screening and monitoring treatment response across a variety of settings.

Positive emotion regulation in emotional disorders: a theoretical review.

Conceptualizations of emotion regulation have led to the identification of cognitive and behavioral regulatory abnormalities that contribute to the development and maintenance of emotional disorders. However, existing research on emotion regulation in anxiety and mood disorders has primarily focused on the regulation of negative emotions rather than positive emotions. Recent findings indicate that disturbances in positive emotion regulation occur across emotional disorders, and may be a generative target for treatment research. The aims of this paper are to: 1. Present a transdiagnostic model of positive emotion disturbances in emotional disorders; 2. Review evidence for disturbances in positive emotion regulation in emotional disorders across categories of emotion regulation; and 3. Propose treatment strategies that may address these disturbances.

The Impact of the Unified Protocol for Emotional Disorders on Quality of Life.

It has become increasingly clear that mental health is more than just the absence of psychopathology and that there is clinical utility in examining positive aspects of mental health. The present study examined the effects of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders on quality of life in a randomized controlled trial that included individuals with a diverse range of emotional disorders. Results indicated that the Unified Protocol produced significant increases in quality of life when examining both within-individual effect sizes and between-conditions effect sizes compared to a waitlist condition. Furthermore, results indicated that post-treatment levels of quality of life predicted levels of functional impairment independently of diagnostic severity. These results provide further evidence of the importance of examining indicators of mental health in conjunction with markers of psychopathology and provide promising evidence that the Unified Protocol may promote improved mental health in addition to treating psychopathology.

Antidepressant effects on emotional temperament: toward a biobehavioral research paradigm for major depressive disorder.

BACKGROUND: Given the limited efficacy of current pharmacotherapy for major depressive disorder (MDD) and the historical decline in antidepressant development, there is increasing clinical urgency to develop more effective treatments. OBJECTIVES: To synthesize findings from clinical psychology and affective neuroscience related to the construct of emotional temperament; to examine the effects of antidepressants on the temperament dimensions of positive (PA) and negative affectivity (NA); and to propose a biobehavioral research paradigm for the treatment of MDD. METHODS: We begin with an introduction to PA and NA, which emphasizes their construct development, historical context, and relevance to psychopathology. We then review studies of antidepressant effects on PA and NA, and explore two related hypotheses: (1) Cause-correction: The antidepressant response may fundamentally occur through changes in emotional temperament, with subsequent spread to syndrome or symptom changes; (2) preferential effects: Antidepressants with different mechanisms of action may have preferential effects on PA or NA. RESULTS: Preliminary findings appear to support the cause-correction hypothesis; there is insufficient clinical evidence to support the preferential effects hypothesis. CONCLUSIONS: PA and NA are biologically based temperament dimensions, which modulate emotional, motivational, and behavioral responses to positive and negative incentives. They can be altered by antidepressants, and may independently contribute to depression improvement. In addition, the distinct biobehavioral features of PA and NA suggest that combined pharmacological and cognitive-behavioral treatments targeting these dimensions may have specific, and perhaps, synergistic antidepressant effects.

Transdiagnostic processes in emotional disorders and insomnia: results from a sample of adult outpatients with anxiety and mood disorders.

Conceptual similarities between recent models of insomnia and emotional disorders suggest there may be common factors that underlie or maintain these difficulties. Maladaptive cognitive and behavioral processes similar to those described in connection with emotional disorders have been cited as key mechanisms in the maintenance of primary insomnia. Unfortunately, research on this potential overlap is lacking. The present study examined the relationship among anxiety sensitivity (AS), dysfunctional beliefs, fatigue, safety behaviors, and insomnia severity in 59 outpatients with anxiety and mood disorders. Key insomnia processes (dysfunctional beliefs, fatigue, safety behaviors) were all related to insomnia severity in the comorbid sample, although AS was not. However, as hypothesized, AS did moderate the relationship of both dysfunctional beliefs and fatigue with insomnia severity. The relationships between key insomnia processes and insomnia severity was strongest among individuals high in AS. Results support the hypothesis that common mechanisms are involved for insomnia and emotional disorders. AS might function as a mechanism for the maintenance of sleep disturbance in the context of anxiety and mood disorders, suggesting a promising avenue for future research.