Double-Blind Placebo-Controlled Study of Memantine in Trichotillomania and Skin-Picking Disorder
This study found that memantine treatment resulted in statistically significant reductions in hair pulling and skin-picking symptoms compared with placebo, with relatively high efficacy (based on number needed to treat), and was well tolerated.
KEY FINDINGS: This study found that memantine treatment resulted in statistically significant reductions in hair pulling and skin-picking symptoms compared with placebo, with relatively high efficacy (based on number needed to treat), and was well tolerated. The glutamate system may prove to be a beneficial target in the treatment of compulsive behaviors.
BACKGROUND: Trichotillomania and skin-picking disorder are underrecognized and often disabling conditions in which individuals repeatedly pull at their hair or pick at their skin, leading to noticeable hair loss or tissue damage. To date there is a severe paucity of evidence-based treatments for these conditions. In this study, the authors sought to determine whether memantine, a glutamate modulator, is more effective than placebo in reducing hair-pulling and skin-picking behavior.
DETAILS: One hundred adults with trichotillomania or skin-picking disorder (86 women; mean age, 31.4 years [SD=10.2]) were enrolled in a double-blind trial of memantine (dosing range, 10-20 mg/day) or placebo for 8 weeks. Participants were assessed with measures of pulling and picking severity. Outcomes were examined using a linear mixed-effects model. The prespecified primary outcome measure was treatment-related change on the NIMH Trichotillomania Symptom Severity Scale, modified to include skin picking. Compared with placebo, memantine treatment was associated with significant improvements in scores on the NIMH scale, Sheehan Disability Scale, and Clinical Global Impressions severity scale in terms of treatment-by-time interactions. At study endpoint, 60.5% of participants in the memantine group were "much or very much improved," compared with 8.3% in the placebo group (number needed to treat=1.9). Adverse events did not differ significantly between the treatment arms.
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Source: Grant, J. E., Chesivoir, E., Valle, S., et al. (2023). Double-Blind Placebo-Controlled Study of Memantine in Trichotillomania and Skin-Picking Disorder. Am J Psychiatry. 2023; 180(5): 348-356. Published: May, 2023. DOI: 10.1176/appi.ajp.20220737.
Cardiovascular, Bone, and Mortality Outcomes in Older Adults
A UK emulated target trial involving 19,027 adults found that initial levothyroxine dosing above 1.0 microgram per kg per day was associated with increased long-term risks of cardiovascular events, bone outcomes, and all-cause mortality. The findings highlight the importance of cautious dose selection and individualized titration in older adults, although prospective studies are needed to confirm these associations.
KEY FINDINGS: Among adults older than 50 years initiating levothyroxine, an initial dose exceeding 1.0 μg/kg per day was associated with higher long-term risks of cardiovascular events, bone outcomes, and all-cause mortality compared with lower initial dosing. The findings support careful consideration of initial dose and subsequent titration in older patients. However, the observational design does not establish that higher dosing directly caused these outcomes, and prospective studies are needed to validate the findings.
BACKGROUND: Levothyroxine is commonly prescribed for hypothyroidism, but determining an appropriate initial dose in older adults remains challenging. Both insufficient and excessive thyroid hormone replacement may adversely affect cardiovascular health, bone integrity, and survival. This study used an emulated target trial approach to evaluate the association between initial weight-based levothyroxine dosing and long-term clinical outcomes in adults older than 50 years.
DETAILS: This observational study used data from The Health Improvement Network, a UK primary care database, covering January 1, 2006, through December 31, 2021. Eligible participants were adults older than 50 years with diagnosed hypothyroidism, at least one recorded thyroid-stimulating hormone (TSH) measurement exceeding 4.0 mU/L, and a new levothyroxine prescription during the study period. The investigators compared patients initiating levothyroxine at more than 1.0 μg/kg per day with those receiving 1.0 μg/kg per day or less. Dosing was assessed using both total bodyweight and lean bodyweight. Participants were followed for up to 10 years for cardiovascular events, bone outcomes, and all-cause mortality. Inverse probability of treatment weighting was used to adjust for baseline confounders, and weighted Cox proportional hazards models were applied to estimate outcome associations.
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A total of 19,027 records were eligible, including 14,296 women (75%) and 4,731 men (25%). The cardiovascular analysis included 15,463 adults, the bone health analysis included 14,947, and all 19,027 participants were included in the mortality analysis. Unweighted event rates were higher among patients initiating levothyroxine at more than 1.0 μg/kg per day than among those receiving lower doses. Cardiovascular events occurred in 20% versus 18%, bone outcomes in 13% versus 9%, and all-cause mortality in 18% versus 17%, respectively. Higher initial dosing was associated with increased risk of cardiovascular events (adjusted hazard ratio [HR], 1.18; 95% CI, 1.08-1.29), bone outcomes (HR, 1.29; 95% CI, 1.16-1.43), and all-cause mortality (HR, 1.17; 95% CI, 1.09-1.25).
Using total bodyweight-based dosing, the weighted 10-year absolute risk differences between the higher- and lower-dose groups were 1.3% (95% CI, 0.3-3.0) for cardiovascular events, 3.0% (95% CI, 1.6-4.5) for bone outcomes, and 3.4% (95% CI, 1.7-5.1) for all-cause mortality. Similar associations were observed in analyses using lean bodyweight-based dosing.
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Source: Holley, M., Wilkes, S., Moss, E. D., et al. Weight-based levothyroxine dosing and long-term cardiovascular, bone, and mortality outcomes in older adults: an emulated target trial using UK primary care data. The Lancet Primary Care. 2026; 2(8): 100194. Published: August, 2026. DOI: 10.1016/j.lanprc.2026.100194.
Smartphone-Based Circadian Rhythm Stabilization May Reduce Mood Episode Recurrence
A 12-month randomized trial found that a personalized smartphone app designed to stabilize circadian rhythms was associated with fewer recurrent mood episodes in adults with major depressive disorder or bipolar disorder. The findings support further evaluation of digital circadian interventions as an adjunct to standard psychiatric care.
KEY FINDINGS: In this 12-month randomized trial, a smartphone intervention providing personalized circadian rhythm stabilization feedback was associated with fewer recurrent mood episodes and fewer days spent in recurrent episodes among adults with MDD or BD. The findings support further evaluation of personalized digital chronotherapy as an adjunct to standard psychiatric care. The study was conducted in a relatively small sample, and additional research will be important to assess effectiveness across broader and more diverse patient populations.
BACKGROUND: Recurrence of depressive and bipolar mood episodes remains a major challenge in long-term psychiatric care. Because disruptions in circadian rhythms are associated with mood instability, researchers developed the Circadian Rhythm for Mood (CRM) smartphone app to provide individualized mood forecasts and personalized feedback aimed at stabilizing circadian patterns. This randomized clinical trial evaluated whether the intervention could reduce recurrent mood episodes in adults with major depressive disorder or bipolar disorder.
DETAILS: This multicenter, double-blind, sham-controlled randomized clinical trial included 93 adults with MDD or BD. Participants were randomly assigned to an active CRM app group (47 participants) or a sham-app group (46 participants) for 12 months. The CRM app used passive sensor data and machine-learning algorithms to generate individualized 3-day mood forecasts and personalized circadian rhythm stabilization feedback. The sham app had an identical interface but provided nonactionable feedback generated by a dummy algorithm. The primary outcome was the number of recurrent mood episodes during follow-up.
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The modified intention-to-treat analysis included 80 participants, with 38 in the active CRM group and 42 in the sham group. The sham group had a significantly higher rate of recurrent mood episodes than the active CRM group, with an incidence rate ratio of 3.39 (95% CI, 1.86-6.17). Cumulative recurrent episode-days per person-year were also greater with the sham intervention, with a duration rate ratio of 2.76 (95% CI, 1.19-6.40). Time to recurrence differed between groups, with a hazard ratio of 3.03 (95% CI, 1.58-5.81). No significant adverse effects were observed.
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Source: Yeom, J. W., Jeong, J., Moon, E., et al. Circadian Rhythm Stabilization App to Prevent Mood Episode Recurrence in Patients With Mood Disorders: A Multicenter, Double-Blind, Sham-Controlled, Randomized Clinical Trial. American Journal of Psychiatry. 2026; 183(9): 657-667. Published: September, 2026. DOI: 10.1176/appi.ajp.20251008.
AI-Assisted Colonoscopy for Colorectal Lesion Detection in Lynch Syndrome
A multicentre randomized trial of 733 patients with Lynch syndrome found that AI-assisted colonoscopy did not significantly increase adenoma detection compared with high-definition white-light colonoscopy alone (33.8% vs 30.9%; P=0.41). AI-based lesion characterization showed good sensitivity and specificity but did not clearly improve on expert optical diagnosis in specialized surveillance settings.
KEY FINDINGS: In this international randomized trial conducted at specialized Lynch syndrome surveillance centres, adding AI-assisted detection to high-definition white-light colonoscopy did not significantly increase adenoma detection. Although the CADx system demonstrated good sensitivity and specificity for lesion differentiation, it did not clearly provide an advantage over expert optical diagnosis in this specialist setting. The findings indicate that the benefit of AI-assisted colonoscopy may depend on the expertise and clinical setting in which it is deployed.
BACKGROUND: Individuals with Lynch syndrome undergo regular colonoscopic surveillance because of their increased risk of colorectal cancer. Artificial intelligence (AI)-based computer-aided detection (CADe) has improved adenoma detection in average-risk colorectal cancer screening, but evidence in Lynch syndrome surveillance has been limited. The CADLY2 trial evaluated whether AI-assisted colonoscopy could improve adenoma detection and whether computer-aided optical diagnosis (CADx) could accurately differentiate neoplastic from non-neoplastic colorectal lesions.
DETAILS: This international, multicentre, open-label, randomized controlled trial was conducted at nine specialized hereditary cancer surveillance centres in Belgium, Germany, the Netherlands, and Spain. Adults aged 18 years or older with genetically confirmed Lynch syndrome undergoing surveillance colonoscopy were randomly assigned to high-definition white-light (HD-WL) colonoscopy alone or HD-WL colonoscopy assisted by the CAD EYE AI system. CADe was used during withdrawal to identify lesions, while CADx was used after lesion detection to assist with optical differentiation. The primary outcome was adenoma detection rate, defined as the proportion of patients with at least one histopathologically confirmed adenoma.
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Between May 9, 2023, and October 30, 2025, 757 patients were randomly assigned to HD-WL colonoscopy (377) or AI-assisted colonoscopy (380). The primary analysis included 733 patients: 369 in the HD-WL group and 364 in the AI-assisted group. Adenoma detection occurred in 30.9% of patients undergoing HD-WL colonoscopy compared with 33.8% receiving AI-assisted colonoscopy. The odds ratio was 1.14 (95% CI, 0.83-1.57; P=0.41), indicating no statistically significant improvement in adenoma detection with CADe. In the lesion-level analysis, CADx differentiated neoplastic from non-neoplastic lesions with a sensitivity of 85.9% (95% CI, 82.0-89.1) and specificity of 91.4% (95% CI, 89.4-93.0). Three adverse events occurred in the AI-assisted group, including two mild post-polypectomy bleeding events and one serious pulmonary embolism or deep venous thrombosis considered unrelated to the procedure. No adverse events were reported in the HD-WL group.
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Source: Hüneburg, R., van Bokhorst, Q. N. E., Pellisé, M., et al. Artificial intelligence-assisted detection and optical differentiation of colorectal lesions in Lynch syndrome surveillance (CADLY2): a multicentre, open-label, randomised controlled superiority trial. The Lancet Gastroenterology & Hepatology. 2026; 11(10): 875-886. Published: October, 2026. DOI: 10.1016/S2468-1253(26)00163-9.
Overdiagnosis of Papillary Thyroid Cancer in the United States
A US simulation study estimated that 72% to 94% of papillary thyroid cancer cases diagnosed between 1991 and 2019 were overdiagnosed. Reducing ultrasonography for nonpalpable thyroid nodules was modeled to substantially lower PTC incidence, with less than a 0.1% change in overall mortality. The findings highlight the potential role of reducing unnecessary imaging and diagnosis while recognizing that the estimates are model-based.
KEY FINDINGS: The findings indicate that PTC overdiagnosis remained substantial even after accounting for a possible underlying increase in true disease incidence. The modeling suggests that limiting unnecessary ultrasonography referrals for nonpalpable thyroid nodules could reduce detection of cancers unlikely to affect population mortality, potentially reducing unnecessary diagnoses and treatment-related burdens without a meaningful modeled increase in overall mortality. Because these findings are based on a simulation model rather than observed outcomes from an intervention, they should be interpreted as population-level estimates rather than evidence that reducing imaging is appropriate for individual patients.
BACKGROUND: Papillary thyroid cancer (PTC) incidence in the United States has increased substantially over recent decades, largely driven by detection of small, early-stage tumors, while population-level mortality has remained relatively stable. This pattern has raised concern that some thyroid cancers detected through imaging may never have become clinically significant. This study used a validated simulation model to estimate the extent of PTC overdiagnosis in the United States and examine the potential effects of reducing thyroid ultrasonography for nonpalpable thyroid nodules.
DETAILS: Researchers used the Papillary Thyroid Carcinoma Microsimulation Model (PATCAM) to evaluate PTC incidence among US adults aged 18 years or older from 1991 through 2019. The model accounted for changes in underlying thyroid cancer risk and estimated the proportion and absolute number of PTC cases considered overdiagnosed, defined in the model as cancers whose detection and treatment did not affect population mortality. The investigators also modeled the potential effects of reducing thyroid ultrasonography referrals for nonpalpable thyroid nodules.
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Between 1991 and 2019, the model estimated that 72% to 94% of diagnosed PTC cases were overdiagnosed. The estimated proportion was 75% to 95% among women and 63% to 90% among men. The corresponding absolute rate of overdiagnosis was 13 to 17 per 100,000 women and 3 to 5 per 100,000 men, translating to an estimated 443,212 to 573,705 women and 107,804 to 154,504 men overdiagnosed with PTC during the 28-year period. The model further estimated that reducing thyroid ultrasonography for nonpalpable nodules by 33% would reduce PTC incidence in 2019 by 17%, from 18 to 15 per 100,000 individuals. A 67% reduction in ultrasonography was associated with a modeled 41% reduction in incidence, from 18 to 11 per 100,000. In both scenarios, the modeled change in overall mortality was less than 0.1%.
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Source: Francis, D. O., Davies, L., Zhang, Y., et al. Overdiagnosis of Papillary Thyroid Cancer. JAMA Network Open. 2026; 9(2): e2559852. Published: February 24, 2026. DOI: 10.1001/jamanetworkopen.2025.59852
Depressive Symptoms Associated With Cognitive Impairment in Cerebral Amyloid Angiopathy
A study of 168 adults found that patients with cerebral amyloid angiopathy had substantially more depressive symptoms and poorer cognitive performance than cognitively normal controls. Possible depression was associated with impairment in episodic memory, executive function, and processing speed, and partially mediated the relationship between CAA and cognition. Greater depressive symptoms were also associated with MRI markers of cortical and small-vessel brain injury.
KEY FINDINGS: People with CAA in this study had substantially more depressive symptoms and poorer cognitive performance than cognitively normal controls. Depressive symptoms explained a small but significant portion of the association between CAA and impairment in episodic memory and executive function, suggesting that mood symptoms may contribute to cognitive difficulties in CAA. Greater depressive symptom severity was also associated with MRI markers of cortical and small-vessel brain injury. Because the study was cross-sectional, the findings do not establish whether CAA-related brain injury causes depression or whether depressive symptoms contribute to subsequent cognitive decline.
BACKGROUND: Cerebral amyloid angiopathy (CAA), a small-vessel disease characterized by β-amyloid deposition in cerebral vessel walls, is associated with cognitive impairment and dementia. Depression can independently affect memory and executive function, but the relationship between depressive symptoms, CAA-related brain injury, and cognition has been less clearly defined. This study examined whether depressive symptoms were associated with cognitive performance in people with CAA and whether depression helped explain the relationship between CAA and cognitive impairment.
DETAILS: Researchers analyzed baseline data from a prospective longitudinal cohort recruited through memory and stroke-prevention clinics at two Canadian centers. The analysis included adults aged ≥55 years with probable CAA and cognitively normal controls. Cognitive performance was evaluated across episodic memory, executive function, and processing speed, while depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). A score ≥5 was classified as "possible depression." The primary analysis included 168 participants: 85 with CAA and 83 cognitively normal controls. The mean age was 73.5 years among participants with CAA and 68.8 years among controls. Additional analyses exam-ined relationships between depressive symptoms and CAA-related MRI markers in 81 participants with CAA.
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Participants with CAA had substantially higher odds of possible depression than controls, with an odds ratio of 15.71 (95% CI, 4.26-80.05; P<0.001). Their GDS-15 scores were also 2.71 times higher than those of controls (95% CI, 2.10-3.51; P<0.001). Possible depression was associated with poorer performance across all three cognitive domains. After adjustment for age, sex, and education, associations were observed for episodic memory (β=-1.03; 95% CI, -1.53 to -0.53; P<0.001), executive function (β=-1.11; 95% CI, -1.65 to -0.58; P<0.001), and processing speed (β=-0.73; 95% CI, -1.24 to -0.21; P=0.006). Mediation analysis suggested that depressive symptoms accounted for 11% of the association between CAA and episodic memory and 9% of the association between CAA and executive function. No significant mediation was observed for processing speed, where depression accounted for approximately 2% of the association.
Among participants with CAA, greater depressive symptom severity was also associated with lower mean cortical thickness, cortical superficial siderosis, and a higher CAA-related small-vessel disease burden. Specifically, the count ratio was 1.33 (95% CI, 1.09-1.62; P=0.005) per SD decrease in cortical thickness, 2.04 (95% CI, 1.35-3.09; P<0.001) for cortical superficial siderosis, and 1.16 (95% CI, 1.00-1.35; P=0.047) for higher CAA small-vessel disease score.
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Source: Nukala, N., Muir, R. T., Beaudin, A. E., et al. Associations Between Cerebral Amyloid Angiopathy, Cognitive Impairment, and Depressive Symptoms. Neurology. 2026; 107(5): e218354. Published: September, 2026. DOI: 10.1212/WNL.0000000000218354.
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