BackgroundSerious mental illness imposes a substantial burden. Pharmacologic treatments remain only partially effective and are associated with significant side effects, highlighting the need for novel treatment approaches. Ketogenic metabolic therapy (KMT) is emerging as an intervention for serious mental illness, with a growing evidence base and strong patient interest. A critical barrier to KMT implementation is the lack of health care professional (HCP) competence and readiness to discuss KMT with patients with serious mental illness. Existing training does not adequately address HCP competence in presenting KMT as a treatment option. This study describes the pilot-testing of “Live It, Launch It” (LI-LI), the first KMT training program designed to build self-reported competence to discuss KMT in psychiatric care for HCPs.MethodsLI-LI combines a 4-hour asynchronous educational course on KMT with a 4-week experiential group KMT intervention during which participants adhered to a ketogenic diet. LI-LI aimed to improve self-reported competence to utilize KMT and perceived ability to engage in shared decision-making with patients about incorporating KMT into their treatment plan.ResultsForty HCPs participated in the education course: 10 psychiatrists, 10 psychiatric pharmacists, 8 psychologists/therapists, and 12 other HCPs (e.g., nurse practitioners, physician assistants). Twenty-five initiated the diet intervention. Baseline competence scores (visual analog scale 0-100) were low, M(SE) = 17.40 (2.68), increasing to M(SE) = 68.08 (2.47) after education (d = 2.88, p <0.0001), and to M(SE) = 86.62 (1.82) post-diet (d = 1.08), with a very large whole-study effect (d = 3.49, p < 0.0001). Shared decision-making scores at baseline were M(SE) = 53.64 (2.89), increasing to M(SE) = 83.35 (1.83) after the educational course (d = 1.74, p <0.0001), and to M(SE) = 91.23 (2.05) after the diet phase (d = 0.73, p = 0.009), with a very large whole-study effect (d = 2.53, p < 0.0001). Feedback indicated that lived experience with KMT was helpful for implementation-readiness.DiscussionThe educational course on KMT was associated with increased self-reported competence and perceived shared decision-making in HCPs, and this was enhanced with combined education and lived experience. Implementation of this approach could accelerate KMT into clinical care. Results should be interpreted with caution as this was a small uncontrolled study with self-reported main outcomes.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT07116226, identifier NCT07116226.
Neural mechanisms of uncertain decision-making in anxious adolescents: an EEG study based on the balloon analogue risk task
BackgroundAdolescence is marked by heightened vulnerability to anxiety which can impair decision-making under uncertainty. The underlying neural oscillatory network-level mechanisms in anxious adolescents require further elucidation.MethodsWe recruited 40 adolescents (20 adolescents with clinically diagnosed anxiety disorders, 20 matched controls). Participants performed a gain/loss version of the Balloon Analogue Risk Task (BART) during EEG recording. Behavioral data, time-frequency EEG power in beta (13–30 Hz) and theta (4–7 Hz) bands, and phase-based functional connectivity were analyzed.ResultsAnxious adolescents exhibited significant behavioral avoidance, reflected in fewer pump attempts and lower BART scores compared to controls. EEG analysis revealed elevated beta-band power during gain decisions and enhanced beta-band occipito-temporal connectivity in the anxious group. In loss contexts, anxious adolescents showed increased theta-band parieto-temporal connectivity.ConclusionsAdolescent anxiety is associated with a generalized avoidance pattern during uncertain decision-making, characterized by distinct neural dynamics. Beta-band changes in gain contexts may reflect heightened vigilance, while theta-band connectivity in loss contexts may indicate amplified threat monitoring. These neural signatures may represent candidate neurophysiological signatures of anxiety-related alterations in decision-making under uncertainty, warranting further validation in longitudinal and predictive studies.
Editorial: Diversity and equity in autism research
Methamphetamine-withdrawal catatonia resolved with mixed amphetamine salts: a case report
Catatonia is a well-recognized psychiatric emergency with an evolving understanding of its underlying pathophysiology. However, withdrawal-associated catatonia remains poorly characterized. Here we describe a 32-year-old man with symptoms consistent with methamphetamine-withdrawal catatonia, a previously undescribed etiology, which resolved only after treatment with mixed amphetamine salts. The patient remained catatonic (Bush-Francis Catatonia Rating Scale [BFCRS] >10) for four months despite 38 sessions of electroconvulsive therapy, lorazepam up to 24 mg daily, and multiple augmentation strategies. An extensive medical and neurologic workup excluded alternative causes. Following initiation of mixed amphetamine salts, his BFCRS decreased from 15 to 6 within 48 hours, with sustained resolution and no recurrence of psychosis despite discontinuation of antipsychotics. This case suggests that methamphetamine withdrawal may represent an underrecognized cause of catatonia and that dopaminergic augmentation may have a therapeutic role in refractory cases.
New federal autism committee head has financial ties to leucovorin
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Teen social media bans are hot these days, with new regulations installed or soon to come in Australia, Indonesia, and the European Union. But how will we know these rules are working? And what does “working” even mean?
A Comparison of Group Cognitive Behavioural Therapy (CBT) and Structured Activity Group for Adults With Attention Deficit Hyperactivity Disorder (ADHD)
Conditions: ADHD
Interventions: Behavioral: Group CBT based on DBT-skills training; Behavioral: Activity group
Sponsors: Region Stockholm
Recruiting
Interventions: Behavioral: Group CBT based on DBT-skills training; Behavioral: Activity group
Sponsors: Region Stockholm
Recruiting
ADEPT Psilocybin-Assisted Therapy With DBT for Borderline Personality Disorder
Conditions: Borderline Personality Disorder; Borderline Personality Pathology; Depressive Symptoms; Emotion Dysregulation; Suicidal Ideation
Interventions: Drug: Psilocybin; Behavioral: Psilocybin-Assisted Therapy With Dialectical Behavior Therapy
Sponsors: University of Minnesota; Filament Health Corp.
Not yet recruiting
Interventions: Drug: Psilocybin; Behavioral: Psilocybin-Assisted Therapy With Dialectical Behavior Therapy
Sponsors: University of Minnesota; Filament Health Corp.
Not yet recruiting
Agreement Between a Mobile Self-Administered Comprehensive Geriatric Assessment Screening Tool and Geriatrician-Administered Assessment: Cross-Sectional Feasibility Study
Background: Comprehensive geriatric assessment (CGA) is a widely recommended, multidimensional approach for guiding clinical decision-making and management in older adults. However, its implementation remains limited by a shortage of geriatric specialists, the complexity of geriatric care, and the increasing demands of an aging population. Mobile self-administered tools offer a potential strategy to expand access to multidimensional geriatric evaluation, particularly in resource-limited settings. Objective: This study aimed to evaluate the feasibility and agreement of a mobile self-administered CGA screening tool compared with geriatrician-administered assessments among inpatient and outpatient older adults in Brazil. Methods: This cross-sectional study included 80 older adults recruited from inpatient and outpatient geriatric clinics in Brasília, Brazil. Participants completed a mobile CGA, which incorporated validated instruments covering functional status (Vulnerable Elders Survey–13 [VES-13]), cognition (Cognitive Change Questionnaire–8 [CCQ-8]), depressive symptoms (5-item Geriatric Depression Scale [GDS-5]), nutritional status (Mini Nutritional Assessment [MNA]), frailty (G8 screening tool), social support (Gijón Scale), falls, and vision and hearing. Within 48 hours, a geriatrician independently performed a geriatrician-administered CGA using the same instruments. Agreement between the 2 assessment methods was evaluated using Wilcoxon signed-rank tests, Spearman correlation coefficients, intraclass correlation coefficients (ICCs), and Cohen κ coefficients for categorical variables. Results: Participants had a mean age of 70 (SD 7) years; 58.8% (47/80) were female, and 65% (52/80) had ≤8 years of education. The mean completion time for the self-administered CGA was 18.5 (SD 7.5) minutes. Most participants rated the tool as easy or very easy to use (65/80, 81.3%) and reported satisfaction with the assessment process (n=79, 98.8%). High concordance was observed between the self-administered and geriatrician-administered CGA versions for most domains. Cohen κ coefficients demonstrated strong agreement for falls (κ=0.878; <.001), hearing impairment (κ=0.826), and vision impairment (κ=0.634). No significant differences were observed between the 2 assessment methods for functional status (VES-13), frailty screening (G8), depressive symptoms (GDS-5), and cognition (CCQ-8). Nutritional status and social vulnerability showed lower concordance than other CGA domains. Among inpatients, significant discrepancies were identified in both nutritional scores and Gijón social risk scores (≤.05), with participants reporting greater perceived vulnerability. For outpatients, significant differences were observed for nutritional status (MNA; P=.02) and frailty screening (G8; P=.046). Conclusions: A mobile self-administered CGA demonstrated good feasibility, high user satisfaction, and substantial agreement with geriatrician-administered assessments across multiple geriatric domains. The tool may support geriatric screening and triage in settings with limited specialist availability, particularly when used as a complement to comprehensive clinical assessment.
Supporting the Primary Outcomes of the Mirai Trial for the Adjunctive Digital Therapeutic Rejoyn (CT-152) in the Treatment of Major Depressive Disorder: Meaningful Change Analysis in the Montgomery-Åsberg Depression Rating Scale
Background: Rejoyn (CT-152) is a prescription digital therapeutic (DTx) adjunct to antidepressive medication authorized for patients with major depressive disorder. To better understand the patient benefit of DTx and other treatment modalities, current regulatory standards support the use of modern psychometric methods to interpret the clinical meaningfulness of treatment effects for patients. In the primary analysis of Rejoyn from the pivotal phase 3 Mirai trial (NCT04770285), Rejoyn showed a broad risk-to-benefit profile as demonstrated on multiple clinician- and patient-rated scales, including the primary efficacy outcome measure, the Montgomery-Åsberg Depression Rating Scale (MADRS). These findings supported US Food and Drug Administration authorization of Rejoyn as a prescription DTx. However, the clinical relevance of these changes in the MADRS score is not immediately interpretable in clinical practice. Here, we present the results from several post hoc analyses of the Mirai trial data to support the interpretation of clinically meaningful treatment differences on clinician- and patient-reported change in depressive symptoms. Objective: This study had two main objectives: (1) establish threshold parameters that allow for clinically meaningful interpretation of the Mirai results in clinical practice, based on the clinical trial end points of change from baseline in depressive symptoms, and (2) apply this threshold in a responder and sensitivity analysis in the intent-to-treat (ITT) population (which is more frequently reported in pharmacological trials) to further support the interpretation of change in unblinded analysis of the Mirai results. Methods: For the Mirai meaningful within-patient change (MWPC) analysis, anchor-based methods were used to define an MWPC threshold by exploring the associations between the MADRS and the clinician-rated Clinical Global Impression-Severity Scale (CGI-S) and the patient-reported Patient Health Questionnaire 9-Item Scale (PHQ-9). Additional post hoc efficacy analyses (including that of responders) are reported for the ITT population. Results: Using the MWPC thresholds of 8 and 10 points (derived with the CGI-S and PHQ-9 as anchor measures, respectively), the distribution of MADRS responders favored the Rejoyn group over the sham group, and the Rejoyn group had 24%‐47% higher odds of meaningful improvement on the MADRS. Post hoc ITT analyses also favored the Rejoyn group over the sham group for response rates and PHQ-9 and CGI-S score change from baseline. Conclusions: Results are consistent with the primary findings of the Mirai trial, supporting the efficacy of Rejoyn as an adjunctive treatment to antidepressive medication monotherapy for adults with major depressive disorder. The MWPC analyses offered a measure of meaningful change on the MADRS, providing a framework of clinical meaningfulness for the Mirai trial findings.
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STAT+: Pharmalittle: We’re reading about Novo plans to expand its pipeline, early Alkermes ADHD data, and more
Hello there and welcome to a new week. STAT reporter Andrew Joseph here in London filling in for Mr. Pharmalot for the day. Before we get to the headlines, an extra dose of encouragement to check out all the great pieces that STAT has to offer today, from Reed Jobs opining on the NIH budget to our new trust-in-science reporter Nick Florko outlining his own experience grappling with, as he puts it, “how frustrating it is to realize that modern medicine does not have all the answers.” Now to those headlines. …
Novo Nordisk is seeking to assure investors that it can regain its momentum in the coming years, outlining plans to expand its pipeline and find new products that it could sell more like consumer goods than traditional medicines, building off what’s occurring with its obesity treatments, STAT shares. At the company’s capital markets day in London, CEO Mike Doustdar said Novo would launch at least five multi-blockbusters by 2030 and deliver revenue growth on par with other major pharma firms. He also presented a strategy that involved investing more in disease areas outside diabetes and obesity and said the company “will be more active within business development,” an acknowledgment of investors’ concerns that Novo was too reliant on its landmark GLP-1 drugs and needed to develop other products.
Drugs called orexin agonists have been hailed for their ability to treat rare sleep disorders, but with new data, Alkermes is showing for the first time that the new class of therapies may benefit people with ADHD, STAT writes. In a randomized Phase 1 study, the company’s new drug, called ALKS 7290, was well tolerated and showed a signal of efficacy. Participants in the study started with a median score of 39 on a diagnostic known as the Adult ADHD Investigator Symptom Rating Scale, indicating that they had moderate to severe symptoms. After two weeks, those taking a high dose of 50 milligrams of ALKS 7290 experienced a 19-point reduction on the scale, indicating that their symptoms had become mild.