Self-guided Internet-based cognitive behavior therapy (iCBT) for migraine interventions could improve access to care, but there is poor evidence of their efficacy.

A three-arm randomized controlled trial compared: iCBT focused on psychoeducation, self-monitoring and skills training (SPHERE), iCBT focused on identifying and managing personal headache triggers (PRISM) and a waitlist control. The primary treatment outcome was a ≥ 50% reduction in monthly headache days at 4 months post-randomization.

428 participants were randomized (mean age = 30.1). 240 participants (56.2%) provided outcome data at 4 months. Intention-to-treat (ITT) analysis with missing data imputed demonstrated that the proportion of responders with a ≥ 50% reduction was similar between combined iCBTs and waitlist (48.5/285, 17% vs. 16.6/143, 11.6%, p = 0.20), but analysis of completers showed both iCBT programs to be superior to the waitlist (24/108, 22.2% vs. 13/113, 11.5%, p = 0.047). ITT analysis with missing data imputed showed no difference between the two iCBTs (SPHERE: 24.8/143, 17.3% vs. PRISM: 23.7/142, 16.7%, p = 0.99). Uptake rates of the iCBTs were high (76.9% and 81.69% logged in at least once into SPHERE and PRISM, respectively), but adherence was low (out of those who logged in at least once, 19.01% [21/110] completed at least 50% modules in SPHERE and 7.76% [9/116] set a goal for trying out a given trigger-specific recommendation in PRISM). Acceptability ratings were intermediate.

Self-guided iCBTs were not found to be superior in our primary ITT analysis. Low adherence could explain the lack of effects as completer analysis showed effects for both interventions. Enhancement of adherence should be a focus of future research.

In VIVRE (NCT04448431), vortioxetine was associated with significantly higher rates of symptomatic and functional remission, better daily and social functioning, and greater treatment satisfaction than desvenlafaxine in patients with major depressive disorder (MDD) and partial response to selective serotonin reuptake inhibitor (SSRI) therapy. This analysis further explored the relative improvement in patient functioning with vortioxetine versus desvenlafaxine.

VIVRE was a randomized, double-blind study of vortioxetine (10 or 20 mg/day) versus desvenlafaxine (50 mg/day) in adults with MDD and partial response to initial SSRI monotherapy. Mean percentage changes from baseline to week 8 in Functioning Assessment Short Test (FAST) total and domain scores were analyzed by treatment group in the overall population and in working patients.

In the overall population, the mean reduction in FAST total score from baseline after 8 weeks of treatment was 37.2% in vortioxetine-treated patients versus 31.8% in desvenlafaxine-treated patients (P = 0.04). Significantly greater improvements versus desvenlafaxine were seen in vortioxetine-treated patients for FAST autonomy, cognitive functioning, and interpersonal-relationships scores (all P < 0.05). In working patients, the mean reduction in FAST total score from baseline at week 8 was 38.7% versus 32.1% in the vortioxetine and desvenlafaxine groups, respectively (P = 0.04). Significant correlations were seen between absolute changes in patient functioning, and those in depression severity and health-related quality of life.

Vortioxetine was significantly better than desvenlafaxine in improving overall functioning as well as daily, social, and cognitive functioning in patients with MDD with inadequate response to prior SSRI therapy.

Theory and research indicated that executive functioning (EF) correlated with, preceded, and stemmed from worry in generalized anxiety disorder (GAD). The present secondary analysis (Zainal & Newman, 2023b) thus determined whether EF domains mediated the effect of a 14-day (5 prompts/day) mindfulness ecological momentary intervention (MEMI) against a self-monitoring control (SM) for GAD.

Participants (N = 110) diagnosed with GAD completed self-reported (Attentional Control Scale, GAD Questionnaire, Perseverative Cognitions Questionnaire) and performance-based tests (Letter-Number Sequencing, Stroop, Trail Making Test-B, Verbal Fluency) at baseline, post-treatment, and one-month follow-up (1MFU). Causal mediation analyses determined if pre-post changes in EF domains preceded and mediated the effect of MEMI against SM on pre-1MFU changes in GAD severity and trait repetitive negative thinking (RNT).

MEMI was more efficacious than SM in improving pre–post inhibition (β = −2.075, 95% [−3.388, −0.762], p = .002), working memory (β = 0.512, 95% [0.012, 1.011], p = .045), and set-shifting (β = −2.916, 95% [−5.142, −0.691], p = .010) but not verbal fluency and attentional control. Within groups, MEMI but not SM produced improvements in all examined pre–post EF outcomes except attentional control. Only pre–post improvements in inhibition mediated the effect of MEMI against SM on pre-1MFU reductions in GAD severity (β = −0.605, 95% [−1.357, −0.044], p = .030; proportion mediated = 7.1%) and trait RNT (β = −0.024, 95% [−0.054, −0.001], p = .040; proportion mediated = 7.4%). These patterns remained after conducting sensitivity analyses with non-linear mediator-outcome relations.

Optimizing MEMI for GAD might entail specifically boosting inhibition plausibly by augmenting it with dialectical behavioral therapy, encouraging high-intensity physical exercises, and targeting negative emotional contrast avoidance.

Despite high levels of psychological distress, mental health service use among Syrian refugees in urban settings is low. To address the mental healthcare gap, the World Health Organization developed group problem management plus (gPM+), a scalable psychological intervention delivered by non-specialist peer facilitators. The study aimed to evaluate the effectiveness of gPM+ in reducing symptoms of depression and anxiety among Syrian refugees in Istanbul, Türkiye.

A randomized controlled trial was conducted among 368 distressed (Kessler Psychological Distress Scale, K10 > 15) adult Syrian refugees with impaired functioning (World Health Organization Disability Assessment Schedule, WHODAS 2.0 > 16). Participants were recruited between August 2019 and September 2020 through a non-governmental organization providing services to refugees. Participants were randomly allocated to gPM+ and enhanced care as usual (gPM+/E-CAU) (184 participants) or E-CAU only (184 participants). Primary outcomes were symptoms of depression and anxiety (Hopkins Symptom Checklist (HSCL-25)) at 3-month follow-up. Secondary outcomes were post-traumatic stress disorder (PTSD) symptoms (PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders-5; PCL-5), functional impairment (WHODAS 2.0), and self-identified problems (psychological outcome profiles).

Intent-to-treat analyses showed no significant effect of gPM+ on symptoms of anxiety, depression, PTSD and self-identified problems. Yet, there was a significant reduction in functional impairment in gPM+/E-CAU compared to E-CAU at 3-month follow-up (adjusted mean difference 1.66, 95 % CI 0.04, 3.27, p = 0.045, d = 0.19). Post-hoc subgroup analyses among participants with probable baseline depression or anxiety showed that there was a small but significant reduction in depression (adjusted mean difference −0.17, 95 % CI −0.32, −0.02, p = 0.028, d = 0.27) and anxiety (adjusted mean difference −0.21, 95 % CI −0.37, −0.05, p = 0.009, d = 0.30) symptoms comparing gPM+/E-CAU to E-CAU only at 1-week post assessment, but not at 3-month follow-up. There was a significant difference between conditions on functional impairment at 3-month follow-up, favouring gPM+/E-CAU condition (adjusted mean difference −1.98, 95 % CI −3.93, −0.02, p = 0.048, d = 0.26).

In this study in an urban setting in Türkiye, gPM+ did not alleviate symptoms of depression and anxiety among Syrian refugees experiencing psychological distress and daily living difficulties. However, participants with higher distress at baseline seemed to benefit from gPM+, but treatment gains disappeared in the long term. Current findings highlight the potential benefit of tailored psychosocial interventions for highly distressed refugees in volatile low-resource settings.

Sleep pattern alteration is a core feature of bipolar disorder (BD), often challenging to treat and affecting clinical outcomes. Suvorexant, a hypnotic agent that decreases wakefulness, has shown promising results in treating primary insomnia. To date, data on its use in BD are lacking. This study evaluated the efficacy and tolerability of adjunctive suvorexant for treatment-resistant insomnia in BD patients.

Thirty-six BD outpatients (19 BDI, 69.4% female, 48.9 [±15.2] years) were randomized for 1 week to double-blind suvorexant (10–20 mg/day) versus placebo. Then, all subjects who completed the randomized phase were offered open suvorexant for 3 months. Subjective total sleep time (sTST) and objective total sleep time (oTST) were assessed.

During the randomized control trial (RCT) phase, an overall increase in the oTST emerged, which was statistically significant for the Cole–Kripke algorithm (p = 0.035). The comparison between the suvorexant and placebo groups was limited by significant differences between measurements at baseline. During the open phase, no significant improvement was detected relative to either sTST and oTST. No adverse events nor major intolerances were reported.

Efficacy results are inconsistent. During the RCT phase, only a small increase in the objective oTST emerged, while during the open phase, no significant improvement was detected. While this is the first ever study of suvorexant in BD-related insomnia, the limitation of the small sample and the high rate of dropouts limits the generalizability of these findings. Larger studies are needed to assess suvorexant in treating BD-related insomnia.

Problematic drinking frequently co-occurs with depression among young adults, but often remains unaddressed in depression treatment. Evidence is insufficient on whether digital alcohol interventions can be effective in this young comorbid population. In a randomized controlled trial, we examined the effectiveness of Beating the Booze (BtB), an add-on digital alcohol intervention to complement depression treatment for young adults.

Participants were randomized to BtB + depression treatment as usual (BTB + TAU, n = 81) or TAU (n = 82). The primary outcome was treatment response, a combined measure for alcohol and depression after 6-month follow-up. Secondary outcomes were number of weekly drinks (Timeline Follow-back) and depressive symptoms (Center for Epidemiologic Studies Depression scale). Treatment response was analyzed using generalized linear modeling and secondary outcomes using robust linear mixed modeling.

Low treatment response was found due to lower than expected depression remission rates. No statistically significant between-group effect was found for treatment response after 6-month follow-up (odds ratio 2.86, p = 0.089, 95% confidence interval [CI] 0.85–9.63). For our secondary outcomes, statistically significant larger reductions in weekly drinks were found in the intervention group after 3-month (B = −4.00, p = 0.009, 95% CI −6.97 to −1.02, d = 0.27) and 6-month follow-up (B = −3.20, p = 0.032, 95% CI −6.13 to −0.27, d = 0.23). We found no statistically significant between-group differences on depressive symptoms after 3-month (B = −0.57, p = 0.732, 95% CI −3.83 to 2.69) nor after 6-month follow-up (B = −0.44, p = 0.793, 95% CI −3.69 to 2.82).

The add-on digital alcohol intervention was effective in reducing alcohol use, but not in reducing depressive symptoms and treatment response among young adults with co-occurring depressive disorders and problematic alcohol use.

Pre-registered on October 29, 2019 in the Overview of Medical Research in the Netherlands (OMON), formerly the Dutch Trial Register(https://onderzoekmetmensen.nl/en/trial/49219).

Theories propose that judgment of and reactivity to inner experiences are mediators of the effect of mindfulness-based interventions on generalized anxiety disorder (GAD). However, no study has tested such theories using brief, mindfulness ecological momentary intervention (MEMI). We thus tested these theories using a 14-day MEMI versus self-monitoring app (SM) control for GAD.

Participants (N = 110) completed self-reports of trait mindfulness (Five Facet Mindfulness Questionnaire), GAD severity (GAD-Questionnaire-IV), and trait perseverative cognitions (Perseverative Cognitions Questionnaire) at prerandomization, posttreatment, and 1-month follow-up (1MFU). Counterfactual mediation analyses with temporal precedence were conducted.

Improvement in pre–post mindfulness domains (acceptance of emotions, describing feelings accurately, acting with awareness, judgment of inner experience, and reactivity to inner experience) predicted pre-1MFU reduction in GAD severity and pre-1MFU reduction in trait perseverative cognitions from MEMI but not SM. MEMI reduced pre–post reactivity to inner experiences (but not other mindfulness domains) significantly more than SM. Only reduced pre–post reactivity significantly mediated stronger efficacy of MEMI over SM on pre-1MFU reductions in GAD severity (indirect effect: β = −2.970 [−5.034, −0.904], p = .008; b path: β = −3.313 [−6.350, −0.276], p = .033; percentage mediated: 30.5%) and trait perseverative cognitions (indirect effect: β = −0.153 [−0.254, −0.044], p = .008; b path: β = −0.145 [−0.260, −0.030], p = .014; percentage mediated: 42.7%). Other trait mindfulness domains were non-significant mediators.

Reactivity to inner experience might be a mindfulness-based intervention change mechanism and should be targeted to optimize brief MEMIs for GAD.

Addressing aggressive behavior in adolescence is a key step toward preventing violence and associated social and economic costs in adulthood. This study examined the secondary effects of the personality-targeted substance use preventive program Preventure on aggressive behavior from ages 13 to 20.

In total, 339 young people from nine independent schools (M age = 13.03 years, s.d. = 0.47, range = 12–15) who rated highly on one of the four personality traits associated with increased substance use and other emotional/behavioral symptoms (i.e. impulsivity, anxiety sensitivity, sensation seeking, and negative thinking) were included in the analyses (n = 145 in Preventure, n = 194 in control). Self-report assessments were administered at baseline and follow-up (6 months, 1, 2, 3, 5.5, and 7 years). Overall aggression and subtypes of aggressive behaviors (proactive, reactive) were examined using multilevel mixed-effects analysis accounting for school-level clustering.

Across the 7-year follow-up period, the average yearly reduction in the frequency of aggressive behaviors (b = −0.42; 95% confidence interval [CI] −0.64 to −0.20; p < 0.001), reactive aggression (b = −0.22; 95% CI 0.35 to −0.10; p = 0.001), and proactive aggression (b = −0.14; 95% CI −0.23 to −0.05; p = 0.002) was greater for the Preventure group compared to the control group.

The study suggests a brief personality-targeted intervention may have long-term impacts on aggression among young people; however, this interpretation is limited by imbalance of sex ratios between study groups.

Eating disorder (ED) research has embraced a network perspective of psychopathology, which proposes that psychiatric disorders can be conceptualized as a complex system of interacting symptoms. However, existing intervention studies using the network perspective have failed to find that symptom reductions coincide with reductions in strength of associations among these symptoms. We propose that this may reflect failure of alignment between network theory and study design and analysis. We offer hypotheses for specific symptom associations expected to be disrupted by an app-based intervention, and test sensitivity of a range of statistical metrics for identifying this intervention-induced disruption.

Data were analyzed from individuals with recurrent binge eating who participated in a randomized controlled trial of a cognitive-behavioral smartphone application. Participants were categorized into one of three groups: waitlist (n = 155), intervention responder (n = 49), and intervention non-responder (n = 77). Several statistical tests (bivariate associations, network-derived strength statistics, network invariance tests) were compared in ability to identify change in network structure.

Hypothesized disruption to specific symptom associations was observed through change in bivariate correlations from baseline to post-intervention among the responder group but were not evident from symptom and whole-of-network based network analysis statistics. Effects were masked when the intervention group was assessed together, ignoring heterogeneity in treatment responsiveness.

Findings are consistent with our contention that study design and analytic approach influence the ability to test network theory predictions with fidelity. We conclude by offering key recommendations for future network theory-driven interventional studies.

Growing evidence points to the pivotal role of vitamin D in the pathophysiology and treatment of major depressive disorder (MDD). However, there is a paucity of longitudinal research investigating the effects of vitamin D supplementation on the brain of MDD patients.

We conducted a double-blind randomized controlled trial in 46 MDD patients, who were randomly allocated into either VD (antidepressant medication + vitamin D supplementation) or NVD (antidepressant medication + placebos) groups. Data from diffusion tensor imaging, resting-state functional MRI, serum vitamin D concentration, and clinical symptoms were obtained at baseline and after an average of 7 months of intervention.

Both VD and NVD groups showed significant improvement in depression and anxiety symptoms but with no significant differences between the two groups. However, a greater increase in serum vitamin D concentration was found to be associated with greater improvement in depression and anxiety symptoms in VD group. More importantly, neuroimaging data demonstrated disrupted white matter integrity of right inferior fronto-occipital fasciculus along with decreased functional connectivity between right frontoparietal and medial visual networks after intervention in NVD group, but no changes in VD group.

These findings suggest that vitamin D supplementation as adjunctive therapy to antidepressants may not only contribute to improvement in clinical symptoms but also help preserve brain structural and functional connectivity in MDD patients.

We compared dissociative seizure specific cognitive behavior therapy (DS-CBT) plus standardized medical care (SMC) to SMC alone in a randomized controlled trial. DS-CBT resulted in better outcomes on several secondary trial outcome measures at the 12-month follow-up point. The purpose of this paper is to evaluate putative treatment mechanisms.

We carried out a secondary mediation analysis of the CODES trial. 368 participants were recruited from the National Health Service in secondary / tertiary care in England, Scotland, and Wales. Sixteen mediation hypotheses corresponding to combinations of important trial outcomes and putative mediators were assessed. Twelve-month trial outcomes considered were final-month seizure frequency, Work and Social Adjustment Scale (WSAS), and the SF-12v2, a quality-of-life measure providing physical (PCS) and mental component summary (MCS) scores. Mediators chosen for analysis at six months (broadly corresponding to completion of DS-CBT) included: (a) beliefs about emotions, (b) a measure of avoidance behavior, (c) anxiety and (d) depression.

All putative mediator variables except beliefs about emotions were found to be improved by DS-CBT. We found evidence for DS-CBT effect mediation for the outcome variables dissociative seizures (DS), WSAS and SF-12v2 MCS scores by improvements in target variables avoidance behavior, anxiety, and depression. The only variable to mediate the DS-CBT effect on the SF-12v2 PCS score was avoidance behavior.

Our findings largely confirmed the logic model underlying the development of CBT for patients with DS. Interventions could be additionally developed to specifically address beliefs about emotions to assess whether it improves outcomes.

Hypoxia is a frequently reported complication during the intubation procedure in the emergency department (ED) and may cause bad outcomes. Therefore, oxygenation plays an important role in emergency airway management. The efficacy of oxygenation with high-flow nasal cannula (HFNC) in the ED has been studied, though the evidence is limited. The study aim was to compare two methods of preoxygenation in patients undergoing rapid sequence intubation (RSI) in the ED: (1) HFNC and (2) bag-valve mask (BVM) oxygenation.

This is a single-center, prospective, randomized controlled trial (RCT) in adult ED patients requiring RSI. Patients were randomized to receive preoxygenation with either HFNC or BVM. While HFNC therapy was continued during the intubation procedure, BVM oxygenation was interrupted for laryngoscopy. The primary outcome was the lowest peripheral oxygen saturation (SpO2) level during intubation. Secondary outcomes were incidence of desaturation (SpO2<90%) and severe hypoxemia (SpO2<80%) throughout the procedure, intubation time, rate of failed intubation, and 30-day survival rates.

A total of 135 patients were randomized into two groups (HFNC n = 68; BVM n = 67). The median lowest SpO2 value measured during intubation was 96% (88.8%-99.0%) in the HFNC group and 92% (86.0%-97.5%) in the BVM group (P = .161). During the intubation procedure, severe hypoxemia occurred in 13.2% (n = 9) of patients in the HFNC group and 8.9% (n = 6) in the BVM group, while mild hypoxemia was observed in 35.8% (n = 24) of the BVM group and 26.5% (n = 18) of the HFNC group. However, there was no statistically significant difference between the groups in terms of hypoxemia development (P = .429 and P = .241, respectively). No significant difference was reported in the rate of failed intubation between the groups. Thirty-day mortality was observed in 73.1% of the BVM group and 57.4% of the HFNC group, with a borderline statistically significant difference (difference 15.7; 95% CI of the difference: −0.4 to 30.7; P = .054).

The use of HFNC for preoxygenation, when compared to standard care with BVM oxygenation, did not improve the lowest SpO2 levels during intubation. Also, the use of HFNC during intubation did not provide benefits in reducing the incidence of severe hypoxemia. However, the 30-day survival rates were slightly better in the HFNC group compared to the BVM group.

Trauma is prevalent amongst early psychosis patients and associated with adverse outcomes. Past trials of trauma-focused therapy have focused on chronic patients with psychosis/schizophrenia and comorbid Post-Traumatic Stress Disorder (PTSD). We aimed to determine the feasibility of a large-scale randomized controlled trial (RCT) of an Eye Movement Desensitization and Reprocessing for psychosis (EMDRp) intervention for early psychosis service users.

A single-blind RCT comparing 16 sessions of EMDRp + TAU v. TAU only was conducted. Participants completed baseline, 6-month and 12-month post-randomization assessments. EMDRp and trial assessments were delivered both in-person and remotely due to COVID-19 restrictions. Feasibility outcomes were recruitment and retention, therapy attendance/engagement, adherence to EMDRp treatment protocol, and the ‘promise of efficacy’ of EMDRp on relevant clinical outcomes.

Sixty participants (100% of the recruitment target) received TAU or EMDR + TAU. 83% completed at least one follow-up assessment, with 74% at 6-month and 70% at 12-month. 74% of EMDRp + TAU participants received at least eight therapy sessions and 97% rated therapy sessions demonstrated good treatment fidelity. At 6-month, there were signals of promise of efficacy of EMDRp + TAU v. TAU for total psychotic symptoms (PANSS), subjective recovery from psychosis, PTSD symptoms, depression, anxiety, and general health status. Signals of efficacy at 12-month were less pronounced but remained robust for PTSD symptoms and general health status.

The trial feasibility criteria were fully met, and EMDRp was associated with promising signals of efficacy on a range of valuable clinical outcomes. A larger-scale, multi-center trial of EMDRp is feasible and warranted.

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.

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.

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.

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.

Choosing an appropriate electronic data capture system (EDC) is a critical decision for all randomized controlled trials (RCT). In this paper, we document our process for developing and implementing an EDC for a multisite RCT evaluating the efficacy and implementation of an enhanced primary care model for individuals with opioid use disorder who are returning to the community from incarceration.

Informed by the Knowledge-to-Action conceptual framework and user-centered design principles, we used Claris Filemaker software to design and implement CRICIT, a novel EDC that could meet the varied needs of the many stakeholders involved in our study.

CRICIT was deployed in May 2021 and has been continuously iterated and adapted since. CRICIT’s features include extensive participant tracking capabilities, site-specific adaptability, integrated randomization protocols, and the ability to generate both site-specific and study-wide summary reports.

CRICIT is highly customizable, adaptable, and secure. Its implementation has enhanced the quality of the study’s data, increased fidelity to a complicated research protocol, and reduced research staff’s administrative burden. CRICIT and similar systems have the potential to streamline research activities and contribute to the efficient collection and utilization of clinical research data.