Jasper A. J. Smits

Anxiety and related disorders are highly prevalent (Baxter et al., 2012) and associated with significant distress and disability (Bandelow & Michaelis, 2015; Olatunji et al., 2007). Fortunately, in...

Single-session interventions (SSIs) have become increasingly popularpsychotherapeutic interventions in recent years due to their potential in providing a therapeuticand problem-focused experience in one encounter. However, less focus has been given todissemination and implementation outcomes for SSIs within existing healthcare settings. Thisstudy evaluated the effectiveness and suitability for broad implementation of a personalizedSingle Session Cognitive Behavioral Intervention (SSCBI) for depression and anxiety,delivered in a university-based training clinic in Singapore. Using a mixed-methods design,adult therapy clients (N = 24) completed pre-treatment and follow-up measures assessingdepression, anxiety, and cognitive and affective subjective well-being. Quantitative analysesshowed reductions in both symptoms of depression (d = 0.94, p < .001) and anxiety (d = 0.45,p = .038). Semi-structured interviews were conducted with clients (n = 9) and clinicians (n =9), and thematic analysis identified twelve key themes mapped to five implementationoutcomes: acceptability, appropriateness, feasibility, fidelity, and adoption. Both clients andclinicians reported high acceptability of the intervention, highlighting its structure, relevance,and utility in supporting coping skill development. Clinicians felt the protocol was feasible andappropriate for clients with relatively less complex presentations, with full protocol adherenceachieved across all therapeutic sessions. Recruitment (63.5%) and completion (78.1%) ratesexceeded the pre-registered feasibility benchmarks. These findings provide preliminaryevidence supporting our personalized SSCBI as an effective and scalable brief psychologicalintervention, particularly suited for resource-limited settings. Future research shouldinvestigate its longer-term impact, cost-effectiveness, and broader applicability in communityand primary care contexts.

Fear extinction is foundational to exposure therapy; therefore, the study of strategies to optimize fear extinction is relevant for clinical practice. This article provides a critical review of translational research on pharmacological enhancement of fear extinction, concentrating mostly on d -cycloserine, the agent with the most extensive evidence base across levels of analysis. Despite early promise, results across preclinical, human laboratory, and clinical trials have been mixed. We identify factors that may account for these inconsistent findings, including differences in study design, selection of subjects, sample size, and measurement approaches. We emphasize the need for a rigorous mechanistic research agenda that both assesses extinction processes—acquisition, consolidation, and retrieval—as distinct mechanistic targets and examines the relation between changes in these fear extinction processes and clinical outcomes. Finally, we discuss opportunities to advance translational research in this area by leveraging extant collaborative infrastructures to improve the quality, the efficiency, and ultimately the availability of effective clinical strategies.

Background: The identification of moderators of exposure-based cognitive behavioral therapy (EXCBT) outcomes has the potential to (1) guide the judicious application of the limited resource that is EXCBT and (2) identify additional treatment targets for ameliorating the deleterious effects of an identified moderator, thereby enhancing clinical response. Experimental and clinical studies have yielded intriguing findings for the moderating influence of positive affect on EXCBT outcomes. Mixed findings for state positive affect (at the time of extinction or exposure trials) as a predictor of EXCBT outcomes stand in contrast to evidence that baseline levels of trait positive affect may be a more effective predictor. As such, questions remain about the best way to assess positive affect as a potential treatment moderator. Objective: This study was designed to investigate (1) the relative value of state and trait positive affect for predicting the outcome of a single-session virtual reality exposure intervention for public speaking anxiety in adults attending college and (2) the role of 3 related constructs—optimism, hopefulness, and mental health self-efficacy—that may explain the predictive significance of trait positive affect. Methods: State affect will be manipulated at an experimental level using affect induction procedures; trait positive affect will be measured at baseline. Three dependent measures—a primary outcome of public speaking anxiety and secondary outcomes of social phobia and self-reported valence—will be examined. This study relies on a team science approach and is being conducted across 12 collaborating sites through the Exposure Therapy Consortium, allowing for replication of all findings across diverse study sites worldwide. Results: Data collection for this study began in October 2024 and ended in August 2025. We expect to complete data analysis and submit results for publication in approximately November 2025. Conclusions: This study will help clarify the relationship among positive affect (state and trait), exposure learning, and 3 related constructs (optimism, hopefulness, and mental health self-efficacy). These findings will illuminate strategies for future treatment improvement and enhanced efficacy.

Chronic musculoskeletal pain (MSKP) is a common and challenging condition often occurring with generalized anxiety disorder (GAD). Cognitive behavior therapy (CBT) is a first-line treatment for GAD, but limitations on the potential availability or engagement in CBT have encouraged consideration of remote and autonomous treatment options. Yet, little is known about preferences for different modalities of CBT. This study evaluated relative preferences for in-person, telehealth, or digital CBT among individuals with comorbid MSKP and anxiety. Using local and national online advertising, we recruited a sample of 85 individuals with MSKP and self-reported clinical levels of anxiety (mean age: 40.3, 74.4% female, 67.1% White). Results indicated a significant preference for in-person therapy over digital treatment. Nonetheless, multiple indices of higher pain-related fear and distress were linked to a greater relative preference for digital therapy. Dissemination of scalable digital treatment for anxiety for adults with MSKP may find the best reception among individuals with these characteristics.

Background: Many patients with major depressive disorder (MDD) do not respond sufficiently to first-line treatments. Due to its biological and psychological mechanisms, exercise may enhance the effectiveness of other MDD treatments. In a pragmatic randomised superiority trial, we evaluated the clinical and cost-effectiveness of exercise therapy adjunct to guideline-concordant care as usual (CAU) for MDD in specialised mental health care. Methods: MDD outpatients (N = 112; Mage = 37; 51% female) were randomized to CAU (96.9% psychotherapy, 59% pharmacotherapy) or CAU + EX (CAU plus 12 weeks of exercise therapy: one supervised and two home-based aerobic sessions/week). Depressive symptoms were assessed using the Inventory of Depressive Symptomatology-Self Report. Remission was evaluated during follow-up by blinded assessors using the Structured Clinical Interview for DSM-5. The economic evaluation followed a societal perspective. Results: Patients in the CAU + EX condition were significantly more likely than those in CAU to meet the exercise prescription; however, only 22% fully adhered to it. Depressive symptoms decreased from severe to moderate depression in both conditions, with no significant difference between the conditions on symptom reduction (b = −0.22, [−0.72, 0.29]) or remission rate (OR = 0.06, [−0.20, 0.32]). Evidence for cost-effectiveness was found in the per-protocol (≥ six supervised exercise sessions) but not in the intention-to-treat sample. Conclusions: Adjunct exercise therapy does not provide additional clinical benefits or cost-effectiveness in specialized mental health care. Low adherence to the exercise prescription limits its potential. Cost-effectiveness may be achievable with higher adherence, warranting emphasis on strategies to improve adherence in this population.

Fear extinction is foundational to exposure therapy and thus studying strategies to optimize fear extinction is relevant for clinical practice. This paper provides a critical review of translational research on pharmacological enhancement of fear extinction, concentrating mostly on D-cycloserine (DCS), the agent with the most extensive evidence base across levels of analyses. Despite early promise, results across preclinical, human laboratory, and clinical trials have been mixed. We identify factors that may account for these inconsistent findings, including differences in study design, selection of subjects, sample size, and measurement approaches. We emphasize the need for a rigorous mechanistic research agenda that assesses extinction processes – acquisition, consolidation, and retrieval – as distinct mechanistic targets, and examines the relation between changes in these fear extinction processes and clinical outcomes. Finally, we discuss opportunities to advance translational research in this area leveraging extant collaborative infrastructures to improve quality, efficiency and ultimately the availability of effective clinical strategies.

Background: Evidence based treatments for smoking cessation have high relapse rates. Targeting cue-induced craving, a strong predictor of relapse, may be critical to promoting sustained abstinence. We previously found that isradipine, an FDA-approved antihypertensive, enhanced the effect of virtual reality cue exposure therapy (VR-CET) on cue-induced craving. In this secondary analysis we tested whether this augmentation strategy was more beneficial for participants with high (relative to low) baseline cue-induced craving.Methods: After a 24-h abstinence challenge, participants (N = 78) completed a single session of VR-CET with isradipine or placebo, and returned for a 24-h follow-up to repeat the procedure in a medication-free state. We conducted a moderator analysis to test the hypothesis that the effect of isradipine on cue-induced craving at follow-up would be larger among participants with higher (relative to lower) baseline cue reactivity.Results: In the model of cue-induced craving at follow-up, the Group × Baseline Cue Reactivity interaction was significant, p = .045. Among participants with higher baseline cue-induced craving, isradipine resulted in a large, significant reduction in mean craving across the 10 trials (M difference = -18.17, 95% CI [−31.38, −4.95], p = .01, d = -1.46). Among participants with lower baseline cue-induced craving were not significantly different across groups (M difference = 1.38, 95% CI [−12.98, 15.75], p = .85, d = 0.11). Conclusions: Results suggest isradipine enhances VR-CET, particularly for individuals with higher baseline levels of cue-induced craving. Future studies testing relapse-prevention strategies that target higher cue-induced craving with isradipine are warranted.

Background: Many patients with major depressive disorder (MDD) do not respond sufficiently to first-line treatments. Due to its biological and psychological mechanisms of change, exercise therapy may enhance the effectiveness of other treatments in depression. In a pragmatic randomised superiority trial, we evaluated the clinical and cost-effectiveness of exercise therapy adjunct to guideline-concordant care as usual (CAU) for MDD in specialised mental health care.Methods: Outpatients with MDD (N = 112; Mage = 37 years; 51% female) were randomised to CAU, consisting primarily of psychotherapy (96.9%) and pharmacotherapy (59%), or CAU augmented with 12 weeks of exercise therapy (CAU+EX). Exercise therapy entailed one 45-minute supervised and two home-based moderate-intensity (i.e., 64–76% of HRmax) aerobic exercise sessions per week. Depressive symptoms were assessed every three weeks during the 12-week intervention and quarterly during the 12-month follow-up using the Inventory of Depressive Symptomatology-Self Report (IDS-SR). Remission was evaluated during follow-up by trained assessors using the Structured Clinical Interview for DSM-5 (SCID-5-S). The economic evaluation was conducted from a societal perspective.Results: Patients in the CAU+EX condition were significantly more likely than CAU to meet the exercise prescription, but still only 22% of patients adhered to the prescription. Depressive symptoms decreased from severe to moderate depression in both conditions, with no significant difference between the conditions on symptom reduction or remission rate. Evidence for cost-effectiveness was found in the per-protocol (≥ six supervised exercise sessions) but not in the intention-to-treat sample.Conclusions: Adjunct exercise therapy does not provide additional clinical benefits or cost-effectiveness for all MDD patients in specialized mental health care, who typically receive pharmacotherapy and psychotherapy. Low adherence to the exercise prescription limits its potential. Cost-effectiveness may be achievable with higher adherence, warranting emphasis on strategies to improve adherence, such as exploring how to personalize exercise protocols.

Exercise directly improves mood and cognition. Providing exercise immediately before cognitive behavior therapy (CBT) sessions may therefore enhance the clinical responsiveness to CBT. The present pilot study examined the feasibility and direction of effect of exercise+CBT versus CBT in depressed outpatients using a stepped wedged design. Thirty-three patients received either group-based CBT (12-16 weeks) or group-based exercise+CBT within specialized mental healthcare settings. Weekly therapist-supervised exercise sessions (45 min, moderate intensity, running/indoor cycling) were provided directly before the CBT sessions, with encouragement for home-exercise. Feasibility was assessed through recruitment, retention, and safety, alongside treatment adherence and treatment effects on clinically relevant outcomes. Recruitment yielded 37% of eligible patients with similar retention rates across conditions. No adverse events were reported. The exercise+CBT condition attended 63% of supervised exercise sessions (72% at moderate/vigorous intensity) and fewer CBT sessions (42%) compared to the CBT condition (54%). The conditions showed similar improvements in depressive symptoms, rumination, and CBT skills over time. Our study shows in a specialized mental health care routine practice population that providing exercise before CBT sessions is feasible, warranting a future randomized controlled trial.