There is a need for deeper understanding of neurological and psychological aspects of pedophilic disorder (PeD) to improve management of the disorder and thereby prevent child sexual abuse. Functional magnetic resonance imaging (fMRI) measures have been suggested as imaging biomarkers that may contribute towards this goal. A previous study using degarelix, a testosterone suppressing drug, showed promising results in decreasing the risk of committing child sexual abuse among individuals with PeD. In this study, we evaluate functional connectivity (FC) related to PeD and degarelix treatment.

We used independent component analysis on resting state (rs)fMRI data acquired at baseline as well as two and ten weeks after injection of degarelix (or placebo) to evaluate FC alterations related to PeD and the degarelix treatment effect.

FC was altered in relation to several resting state networks in individuals with PeD compared to healthy controls at baseline. At follow-up time points, however, group comparisons were inconclusive and did after FDR correction not render statistically significant FC alterations when comparing patients to controls or related to degarelix treatment, child sexual abuse (CSA) dynamic risk scores or comorbidities.

We found FC alterations in PeD compared to healthy controls at baseline, however, no consistent, treatment specific FC signature of degarelix was demonstrated.

Digital interventions for promoting relaxation are increasingly popular, yet few combine multiple sensory modalities. This study evaluated the effectiveness of a fully digital relaxation program combining hypnotherapy with aromatherapy and explored whether the scent can induce a conditioned relaxation effect.

In this four-arm randomized controlled trial (N = 504), participants were assigned to one of four groups for a 4-week intervention: (a) combined (hypnotherapy + aromatherapy), (b) hypnotherapy-only, (c) aromatherapy-only, or (d) control (minimal intervention pause). Sessions were self-guided and delivered online every 2 days. The primary outcome was subjective calmness, assessed via the calmness–restlessness subscale of the Multidimensional Mood Questionnaire. Secondary outcomes included perceived stress (PSS-10) and well-being (WHO-5). A fifth week with aromatherapy-only exposure was conducted in the combined and aromatherapy-only groups to test for conditioning.

At post-intervention, both hypnotherapy-involved groups reported significant greater calmness than controls. The combined group showed a mean difference of β = 2.08 (95% CI: 0.50–3.65, p = 0.010, d = 0.38), while the hypnotherapy-only group showed β = 1.80 (95% CI: 0.24–3.37, p = 0.024, d = 0.33). Both effects were consistent across intention-to-treat and per-protocol analyses. Within-group improvements in calmness were also observed across all groups. No significant differences emerged from the conditioning test in week 5.

Digital hypnotherapy improved relaxation, with modest added benefit from aromatherapy. The results support the use of multisensory digital tools to enhance subjective calmness. However, no evidence for conditioned effects of the scent was observed under the current conditions.

Individuals with severe mental illnesses (SMIs) experience anxiety that impairs functioning and quality of life. This cluster randomized trial evaluated exposure-based cognitive behavioral therapy (ebCBT) integrated into assertive community treatment (ACT) teams to reduce anxiety.

Fifteen ACT teams were allocated to ebCBT + ACT (k = 8, n = 50) or ACT-only (k = 7, n = 43). The intervention followed four steps: situation identification, four-component analysis (behavior, cognition, emotion, physical symptoms), psychoeducation, and graded exposure. Staff received 50 h training and bimonthly supervision over 12 months. Co-primary outcomes were trait and social anxiety; secondary outcomes were psychiatric symptoms, functioning, quality of life, and recovery.

The ebCBT + ACT group showed significant improvements in State–Trait Anxiety Inventory–Trait scores at 12 months (AMD = −5.30, 95% CI = −8.71 to −1.90, p = 0.002, d = −0.64) and 18 months (AMD = −7.22, 95% CI = −12.1 to −2.34, p = 0.004, d = −0.60). Brief Fear of Negative Evaluation scores showed near-significant improvement at 18 months (AMD = −3.70, 95% CI = −7.44 to 0.04, p = 0.052, d = −0.40). Secondary outcomes, including global functioning, recovery, and quality of life, also improved. Cost-effectiveness analyses indicated favorable cost-effectiveness for anxiety outcomes.

Embedding ebCBT within ACT services may reduce anxiety-related fear and avoidance and enhance recovery-related outcomes in individuals with SMI. These findings support the feasibility and clinical value of integrating structured psychological interventions into intensive community-based outreach services.

Patients with advanced liver disease (ALD) may benefit from the early integration of supportive care toward the end of life. Engagement with supportive and palliative care could decrease disease-related distress and alleviate pressure on the health system. This trial evaluated whether a transdisciplinary supportive care model, aligned with standard care and guided by patient- and carer-identified needs, could optimize health service utilization and outcomes for patients and carers living with ALD.

A 90-day multicenter, mixed-methods pilot randomized controlled trial, “Liver Life,” was conducted at 1 regional tertiary and 1 rural referral hospital in NSW, Australia. The intervention group received patient- and carer-centered supportive care interventions during 5 scheduled allied health-led outpatient visits, alongside ongoing standard care. This paper reports health service utilization and associated costs, and participant-reported measures.

Over 90 days, emergency department presentations were reduced by 66% (incidence rate ratio: 0.34 [0.13–0.80]), and hospital admissions by 64% (incidence rate ratio: 0.36 [0.12–0.98]). Intervention patients were 5 times more likely to have more days “alive and out of hospital” than those receiving standard care alone (odds ratio: 5.34 [1.43–22.1]). As a result, the overall cost of health service use per intervention patient was less than half that of standard care alone.

The Liver Life trial demonstrated the feasibility, acceptability, efficacy, and potential cost savings of a transdisciplinary supportive care model for ALD patients and their caregivers. Future research should investigate the sustainability and transferability of this approach to other populations and other chronic diseases.

Psychedelic-assisted psychotherapy has shown potential for psychiatric disorders. However, the magnitude of symptom change in control groups remains poorly understood. We aim to evaluate within-group effects in control groups and compare them to treatment groups in psychedelic trials.

A systematic search was conducted up to 1 July 2025. The study protocol was preregistered in PROSPERO (CRD420251111853).

Fourteen randomized controlled trials (n = 643) were included. Direct between-arm meta-analyses showed greater symptom reductions in treatment compared with control across outcomes, including depressive symptoms (number of study arms [k] = 13; SMD = −0.82; 95% CI = −1.17, −0.47; I2 = 60.1%), posttraumatic stress disorder (PTSD) symptoms (k = 10; SMD = −0.89; 95% CI = −1.14, −0.65; I2 = 0%), and anxiety symptoms (k = 5; SMD = −0.66; 95% CI = −0.94, −0.38; I2 = 0%). Subgroup analyses showed limited evidence that effects differed by placebo type for depressive or PTSD symptoms. Descriptive within-group analyses indicated symptom reductions from baseline in both control and treatment groups, with larger within-group improvements observed in treatment groups across outcomes; notably, larger within-group reductions in PTSD symptoms were observed in inactive placebo groups. Sensitivity analyses showed consistent results.

Control groups in psychedelic trials demonstrated substantial symptom improvement, which may reflect non-specific trial factors (including expectancy and concurrent psychotherapy). These findings emphasize the importance of robust control conditions in psychedelic research and the need for nuanced interpretation of treatment effects.

Major depressive disorder (MDD) exhibits significant heterogeneity in treatment responses, necessitating multiple pharmacological trials to achieve therapeutic success. Pharmacogenetic (PGx) testing has emerged as a promising tool to personalize antidepressant (AD) treatments, though its clinical utility remains controversial.

This study assessed the efficacy of PGx-guided treatment in improving clinical outcomes among 287 MDD patients within the PANDORA trial, a prospective randomized, participant- and rater-blinded, controlled trial conducted in Italy. A total of 268 adults with moderate-to-severe MDD were randomized into Treated as Usual (TAU) or Treated with Genetic Test Guide (TGTG). Patients were assessed using the Hamilton Depression Rating Scale (HAM-D17), Beck Depression Inventory II (BDI-II), Beck Anxiety Inventory, MINI-ICF-APP for psychosocial functioning, and the UKU Side Effects Rating Scale, at baseline and at 4, 8, and 12 weeks.

Both groups demonstrated significant symptom improvement over the 12-week period. No significant differences were observed between the groups in terms of response and remission rates, measured by HAM-D17 and BDI-II, at weeks 8 and 12. Notably, in the BDI-II symptom cluster analysis, significant differences were found only in neurovegetative symptoms, with TGTG patients showing greater improvement at the 4-week and 8-week follow-up visits. Among patients with severe baseline symptoms, those in the TGTG group exhibited greater symptom reduction and higher response rates at week 8.

These findings suggest that while PGx testing did not significantly improve overall treatment efficacy in MDD compared to TAU, it may offer benefits in managing patients with severe symptoms and specific symptom domains.

Embolization of the middle meningeal artery (EMMA) is an emerging neuroendovascular therapy for chronic subdural hematoma (CSDH). Recently, three landmark randomized trials (MAGIC-MT, EMBOLISE, STEM) were published. We performed a systematic review and meta-analysis of randomized trials for EMMA.

The authors systematically searched MEDLINE, EMBASE, Cochrane and ClinicalTrials.gov (National Library of Medicine) through March 6, 2025. Prospective randomized controlled trials comparing EMMA and standard care versus standard care alone were included. Primary (symptomatic recurrence, symptomatic progression, major adverse event, neurological deterioration, stroke, myocardial infarction and/or death) and secondary endpoints (serious adverse events, stroke, death from any cause and death from neurological causes) were analyzed. The review was registered on PROSPERO (CRD42024512049).

Four randomized trials (Lam et al., MAGIC-MT, EMBOLISE, STEM) were meta-analyzed. A total of 1468 patients were included. The primary endpoint was met in 50 patients (7.5%) in the EMMA group compared to 106 patients (15.5%) in the control group (RR 0.49 [95% CI, 0.36–0.67]; P < 0.001, I2 = 0.0%), with a number needed to treat of 13. There was no difference in serious adverse events (RR 0.88 [95% CI 0.68–1.13]; P = 0.31, I2 = 50.2%), stroke (RR 1.51 [95% CI 0.46–5.01]; P = 0.50, I2 = 0.0%), death from any cause (RR 1.03 [95% CI 0.37–2.85]; P = 0.95, I2 = 58.1%) or death from neurological causes (RR 1.29 [95% CI 0.53–3.09]; P = 0.58, I2 = 25.4%).

EMMA is effective in reducing symptomatic recurrence, progression and/or reoperation among patients with CSDH and is not associated with a greater incidence of serious adverse events, stroke or death.

Psychosocial interventions for people with mental illness are increasingly focusing on facilitating recovery and self-care. Despite evidence from Europe on the short-term effects of recovery self-planning programs for people discharged from crisis resolution teams, similar programs and supporting evidence in other countries or healthcare contexts are lacking, particularly regarding cultural adaptation and long-term assessment. This randomized controlled trial compared a 4-month peer-facilitated, recovery-focused self-illness management (Peer-RESIM) program for Chinese adults with first-episode psychosis with psychoeducation (PE) and treatment as usual (TAU).

Patients (N = 198) were recruited from four Integrated Community Centres for Mental Wellness in Hong Kong and randomly assigned to the Peer-RESIM, PE, or TAU group (66/group). The primary outcomes were recovery and functioning levels; the secondary outcomes were psychotic symptoms, problem-solving ability, rehospitalization rate, and service satisfaction. Assessments were conducted at baseline and immediate, 9, and 18 months postintervention.

The generalized estimating equation test revealed that the Peer-RESIM group reported significantly greater improvements in recovery, functioning, problem-solving ability, psychotic symptoms, average duration of rehospitalizations, and service satisfaction (p = 0.01–0.04, small to large effect sizes) than the TAU group at all three posttests and the PE group at 18 months postintervention.

The Peer-RESIM can enhance long-term recovery and self-care in adults with early-stage psychosis.

The optimal duration for maintaining antidepressant treatment in individuals with obsessive-compulsive disorder (OCD) who achieve symptom stabilization remains unclear.

This systematic review and pairwise meta-analysis of double-blind randomized placebo-controlled trials (DBRPCTs) compared antidepressant maintenance and antidepressant discontinuation groups in terms of relapse rate at each DBRPCT study endpoint (primary outcome), OCD symptom improvement, all-cause discontinuation, and adverse event-related discontinuation. Furthermore, relapse rates at 4, 8, 12, 16, 20, and 24 weeks were compared between the groups. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated. The absolute risk reduction (ARR) and number needed to treat to benefit (NNTB) for relapse rates were also estimated.

Nine trials (n = 1084; mean age: 32.8 years; proportion of males: 53.3%) were included. The antidepressant maintenance group had lower relapse rates at each DBRPCT study endpoint (RR [95% CI] = 0.53 [0.42–0.68]; ARR = 21.0%; NNTB = 5) and lower all-cause and adverse event-related discontinuation rates than the antidepressant discontinuation group. The maintenance group also exhibited lower relapse rates at 4 weeks (RR [95% CI] = 0.47 [0.31–0.70]; ARR: not significant; NNTB: not significant), 8 weeks (0.42 [0.31–0.57]; 12.0%; 8), 12 weeks (0.43 [0.32–0.56]; 18.0%; 6), 16 weeks (0.41 [0.32–0.52]; 25.0%; 4), 20 weeks (0.43 [0.34–0.53]; 26.0%; 4), and 24 weeks (0.42 [0.33–0.52]; 27.0%; 4) than the discontinuation group. Moreover, the maintenance group outperformed the discontinuation group regarding OCD symptom improvement.

Individuals with OCD may benefit from continued antidepressant treatment, provided that it is well tolerated.

The management of persistent physical symptoms poses a challenge in many healthcare settings, including primary care. Psychological treatments that involve exposure have shown promise for several conditions where patients suffer from persistent physical symptoms and unwanted responses to these. It is unclear, however, to what extent exposure therapy has effects beyond existing routine care interventions and who benefits the most.

A randomized controlled trial at a primary care center in Stockholm, Sweden compared 10 weeks of internet-delivered exposure therapy (n = 80) to healthy lifestyle promotion (HLP; n = 81) for patients bothered by at least one persistent physical symptom. The primary outcome was the mean reduction in subjective somatic symptom burden (Patient Health Questionnaire 15) as measured week-by-week up to the post-treatment assessment. Secondary outcomes included symptom preoccupation, anxiety, depression symptoms, and functional impairment.

Patients contributed 1544 datapoints during treatment. The primary analysis showed no significant advantage of exposure therapy versus HLP in the reduction of mean somatic symptom burden (d = 0.14; p = 0.220). In secondary analyses, exposure showed superiority in the reduction of symptom preoccupation (d = 0.31; p = 0.033) but not anxiety, depression symptoms, or functional impairment. A higher somatic symptom burden or symptom preoccupation before treatment was predictive of a larger advantage of exposure versus HLP.

Exposure therapy does not appear to show noteworthy average benefit over HLP, with the exception of symptom preoccupation. Substantial benefits are seen in patients with very high symptom burden or symptom preoccupation.

Providing psychotherapy at 50 sessions in a year (starting twice weekly) led to faster and greater improvements in depression and personality functioning compared to 25 sessions, starting weekly for patients with depression and personality disorder (PD). This study reports long-term dosage effects at 18 and 24 months.

In a pragmatic, double-randomized clinical trial, 246 outpatients with depression and PD were assigned to (1) 25 or 50 sessions and (2) Short-term Psychodynamic Supportive Psychotherapy (SPSP) or Schema Therapy (ST). Depression severity was assessed with the Beck Depression Inventory-II. Secondary outcomes included diagnostic remission of depression (MINI-plus), PD (SCID-II/SCID-5-P), and treatment-specific measures. Intention-to-treat analyses were conducted.

At 18 and 24 months, BDI-II means did not differ between dosage groups (19.0 for 25 sessions versus 19.1 for 50 sessions; d = −0.01; 95% CI = −0.35-0.37, p = 0.96). The lower-dosage group improved during follow-up (−2.6 BDI points, p = 0.031), which may be partly attributed to additional therapy received by a subgroup. Remission rates at 24 months were 66% for depression and 76% for PD, with no differences between conditions.

Higher psychotherapy dosage led to faster initial improvements, but long-term outcomes were not superior to those achieved with a lower dosage. These results should be interpreted with caution, as unregulated treatment during follow-up reduced the power to detect significant dosage effects. Both SPSP and ST provide viable alternatives to treatments focused solely on depression.

Adolescents are at a heightened risk of suicide reattempts following hospital discharge, but few evidence-based interventions exist. This study evaluated the efficacy of the self-awareness of mental health (SAM) program combined with treatment as usual (TAU) versus TAU alone in reducing reattempts among high-risk adolescents.

A randomized clinical trial was conducted across nine Spanish hospitals (January 2021–March 2024) with 261 adolescents (12–17 years) who had attempted suicide within the last 15 days. Participants were assigned to SAM + TAU (n=128) or TAU (n=133), with 12-month follow-up. The primary outcome was suicide reattempts within 12 months; secondary analyses examined time to reattempt and associated risk factors.

After 12-months, no significant differences were found in reattempt rates [22.6% (SAM) versus 27.8% (TAU); OR=0.610, 95%CI (0.321–1.151), p=0.127] or time to reattempt [HR=0.606, 95%CI (0.390–1.021), p=0.060]. In SAM, attentional impulsivity emerged as a significant risk factor [HR=1.126, 95% CI (1.004–1.263), p=0.043], while nonplanning impulsivity was protective [HR=0.878, 95%CI (0.814–0.948), p<0.001]. In TAU, increased suicide risk was linked to suicidal intentionality [HR=1.341, 95%CI (1.009–1.782), p=0.044] and more prior attempts [HR=1.230, 95%CI (1.039–1.457), p=0.016]. Conversely, fewer psychiatric diagnoses emerged as a protective factor [HR=0.821, 95%CI (0.677–0.996), p=0.045].

While no significant differences were found between groups, SAM identified important psychological factors influencing suicide risk. These findings provide a foundation for targeted interventions to prevent reattempts in adolescents.