Happy to Do It
Semaglutide and Effort-Based Decision-Making in Major Depressive Disorder: A Randomized Clinical Trial
Hartej Gill et al.
JAMA Psychiatry, forthcoming
Design, Setting, and Participants: This study was a 16-week, double-blind, placebo-controlled, parallel-group randomized clinical trial. A total of 72 participants with a diagnosis of MDD [major depressive disorder] and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or higher were randomized to oral semaglutide (n = 35) or placebo (n = 37). Participants were recruited from the Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, a university-based mood disorders program. Participants were enrolled between March 14, 2022, and July 26, 2024. Data analysis was performed from January 7, 2025, through February 3, 2025.
Results: A total of 72 participants were randomized to oral semaglutide (n = 35 [49.7%]; mean [SD] age, 38.17 [11.79] years; 18 female participants [51.4%]) or placebo (n = 37 [51.3%]; mean [SD] age, 40.27 [9.32] years; 19 female participants [51.3%]). Semaglutide-treated participants exhibited a pattern of increased willingness to exert physical efforts with higher expected values of reward (treatment × visit × expected value interaction: χ2 = 12.024; P = .02). Computational modeling indicated that semaglutide’s effects on choice behavior were a result of reduced effort discounting. Sensitivity to effort was significantly reduced by treatment with semaglutide (β = −1.737; P = .03), whereas there was no treatment effect on sensitivity to probability (β = −0.776; P = .51).
Positive Affect Treatment for Depression, Anxiety, and Low Positive Affect: A Randomized Clinical Trial
Alicia Meuret et al.
JAMA Network Open, April 2026
Design, Setting, and Participants: This was an assessor-blinded, parallel-group, multisite, 2-arm randomized clinical superiority trial. Study recruitment was from December 2021 to January 2024, with final assessment in July 2024. Participants were recruited from academic outpatient treatment centers in Los Angeles, California, and Dallas, Texas, and included treatment-seeking adults with severely low positive affect and moderate to severe depression or anxiety that was functionally impairing. Analyses were conducted with intent-to-treat principles.
Intervention: Participants underwent 15 weekly individual therapy sessions of positive affect treatment (PAT) or negative affect treatment (NAT).
Results: In total, 98 participants (mean [SD] age, 32.8 [12.2] years; 65 [66.3%] female) were randomized to receive PAT (n = 51) or NAT (n = 47). Multivariate multilevel model analyses of the 3 clinical status variables as a multivariate outcome showed that clinical status improved more with PAT than NAT (b = −0.06 [95% CI, −0.11 to −0.01]; t3039 = 2.43; P = .02; d = 0.27) and that PAT had better (higher) scores on clinical status than NAT at the 1-month follow-up (b = −0.21 [95% CI, −0.41 to −0.02]; t3039 = 2.11; P = .04; d = 0.21). Improvements in reward anticipation-motivation (b = 0.02 [95% CI, 0.01-0.03]; t1307 = 4.36; P < .001; d = 0.40) and reward attainment (b = 0.04 [95% CI, 0.01-0.06]; t1405 = 3.16; P = .002; d = 0.18) targets were comparable for PAT and NAT. Of 7 reward and threat self-reported target measures, 6 mediated improvements in clinical status, but none of the behavioral or physiological measures did. There was limited evidence for moderated mediation.
Direct comparison of reconsolidation of traumatic memories and prolonged exposure therapy: A randomized controlled trial
Michael Roy et al.
Journal of Traumatic Stress, forthcoming
Abstract:
New therapies are needed for posttraumatic stress disorder (PTSD), particularly in military service members (SMs). Reconsolidation of traumatic memories (RTM) is a novel treatment with promising results in small clinical trials. We randomized 94 active duty or retired SMs (Mage = 45.80, 31.0% women) with PTSD to receive up to ten 90-min sessions of RTM (n = 48) or prolonged exposure (PE; n = 46) to ascertain whether RTM achieved a greater and/or faster response. The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) was used to establish eligibility and assess response at 2 weeks and 2, 6, and 12 months postintervention. The PTSD Checklist for DSM-5 was administered before Sessions 2, 4, 6, 8, and 10 to assess response rapidity. We hypothesized that RTM would achieve quicker responses and higher loss of diagnosis rates than PE. From baseline to postintervention, participants in both the RTM (39.13 vs. 22.38), d = 1.42, p < .001, and PE groups (39.26 vs. 22.45), d = 1.50, p < .001, showed improvement on the CAPS-5, with no between-group difference, p = .959. Response (RTM: 74.2%, PE: 72.4%), loss of diagnosis (RTM: 58.1%, PE: 51.7%), and withdrawal (RTM: 18.8%, PE: 32.6%) rates showed no significant differences. Gains were largely sustained through 12 months. RTM had more early responders (72.2%) than PE (27.8%), p = .005; 70.0% of participants addressed multiple traumas with RTM versus 30.0% for PE, p = .022. RTM and PE demonstrated comparable large effect sizes, but RTM achieved more early responses.
Television, health, and happiness: A natural experiment in West Germany
Adrian Chadi & Manuel Hoffmann
Journal of Public Economics, May 2026
Abstract:
While watching television is one of the most time-consuming human activities, its potential negative effects on well-being are discussed in the literature as a prime example of irrational behavior. We are the first to comprehensively address this possible paradox by exploiting a novel setting in the research on the effects of television for society: a natural experiment in the late 1980s where people in a few geographically restricted areas of West Germany received commercial TV via terrestrial frequencies. Rich panel data combined with precisely calculated frequency signals allow us to determine how regional availability of commercial TV affects time-use, before investigating the implications for individual well-being over time. Contrary to previous research, we find no evidence of negative health impacts when TV consumption increases. For life satisfaction, we even find a positive effect, which is robust across various sensitivity analyses and subgroups of TV viewers. By also considering evidence from expenditure data and from our own separately conducted surveys, we discuss the external validity of our findings as well as possible mechanisms and conclude that correlational evidence on the well-being effects of TV viewing could be driven by negative self-selection.
The Well-Being Effects of Digital Mental Health Care
Manuela Angelucci, Raissa Fabregas & Antonia Vazquez
University of Texas Working Paper, April 2026
Abstract:
AI-powered mental health apps have attracted growing interest as a low-cost way to expand care. Yet questions remain about their effectiveness, safety, and whether they may crowd out psychotherapy. We evaluate one such app in a randomized controlled trial among 1,964 Mexican women with mild to severe psychological distress. Over six months, app access improved mental health by 0.3 standard deviations with no evidence of harm, improved sleep quality, increased healthful behaviors, and reduced missed work, yielding considerably larger benefits than costs. Treated participants were also more likely to seek traditional psychotherapy, but this increase does not explain most of the mental health gains. App use was high in the first month but then declined, as is common in digital interventions. Despite this drop in use, treatment effects persisted. Participants continued to implement practices promoted by the app, suggesting that even short-term engagement can produce durable improvements through sustained behavioral change.