To examine regional differences in cannabis use and probable cannabis use disorder (CUD) in US veterans. Participants (N = 2,441) were drawn from a nationally representative sample of US veterans who participated in the...To examine regional differences in cannabis use and probable cannabis use disorder (CUD) in US veterans. Participants (N = 2,441) were drawn from a nationally representative sample of US veterans who participated in the 2022 National Health and Resilience in Veterans Study, conducted from August 11 to September 12, 2022. Weighted estimates indicated that 85.5% reported no cannabis use, 11.6% reported cannabis use, and 2.9% screened positive for probable CUD. Chi-square tests were conducted to assess differences in cannabis use and probable CUD across 9 US Census Bureau-defined regions: New England, Middle Atlantic, East and West North Central, South Atlantic, East and West South Central, Mountain, and Pacific. Significant regional differences were observed in cannabis use and CUD across the 9 regions (χ= 73.33, < .001). Veterans in the Pacific region exhibited the highest rates of cannabis use (18.6%) compared to all other regions except New England (8.2%-13.4%, s < .05). The Pacific region also had significantly higher rates of probable CUD (8.8%) relative to all other regions (0.7%-3.5%, s < .05). These findings demonstrate substantial regional differences in cannabis use and probable CUD among US veterans and underscore the importance of routine screening for cannabis-related problems in health care settings serving veterans, particularly in higher-prevalence regions of the United States.
During the past 2 decades, there has been intense interest in the clinical significance of the concurrence of manic symptoms in depressed patients. introduced a mixed features specifier for both bipolar depression and m...During the past 2 decades, there has been intense interest in the clinical significance of the concurrence of manic symptoms in depressed patients. introduced a mixed features specifier for both bipolar depression and major depressive disorder. Studies of the mixed features specifier have generally found a low prevalence of mixed depression. One approach toward increasing the sensitivity of the mixed features criteria is to lower the classification threshold. In the present study, we examine the impact of lowering the diagnostic threshold from 3 to 2 criteria on the prevalence and validity of the mixed features specifier for depression. Four hundred fifty-nine psychiatric patients in a depressive episode were interviewed by a trained diagnostic rater who administered semistructured interviews including the Mixed Features Specifier Interview. The patients were rated on clinician rating scales of depression, anxiety, and irritability and measures of psychosocial functioning, suicidality, and family history of bipolar disorder. When the diagnostic threshold was lowered from 3 to 2 symptoms, the prevalence of mixed features based on the majority of episode time frame tripled from 3.9% to 13.1% (n=60). Based on a past week time frame, the prevalence of mixed features more than doubled from 9.4% to 22.9% (n=105) upon lowering the threshold from 3 to 2 criteria. However, there was no difference between the patients with 2 mixed features and patients with 0 or 1 mixed features on family history of bipolar disorder, psychosocial impairment, presence of comorbid disorders, age of onset, or history of suicide attempts or psychiatric hospitalization. The results of the present study do not support lowering the diagnostic threshold for the mixed features specifier in depressed patients from 3 to 2 criteria.
Marques MG, Özerdem A, Kung S
… +10 more, Vande Voort JL, Betcher HK, Gentry M, Veldic M, Moore KM, Croarkin PE, Penaluna BK, Cavalcanti S, Frye MA, Singh B
J Clin Psychiatry
· 2026 Jan · PMID 41603781
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Treatment-resistant depression (TRD) affects one-third of patients with major depressive disorder, leading to increased morbidity, health care costs, and suicide risk. TRD lacks a standardized definition, complicating tr...Treatment-resistant depression (TRD) affects one-third of patients with major depressive disorder, leading to increased morbidity, health care costs, and suicide risk. TRD lacks a standardized definition, complicating treatment selection. Current guidelines often group treatments broadly without clear prioritization, and evidence gaps persist, particularly regarding newer interventions and real-world clinical complexity. A simulated case-based discussion, modeling a modified Delphi consensus, was conducted to offer a clinical perspective to this gap. A panel of 10 psychiatrists, directly engaged in the treatment of TRD at the Mayo Clinic Depression Center, participated in the surveys. Results represent expert opinion from participants. The process included an initial group review of TRD, where participants reviewed and presented a summary on each TRD treatment option, followed by discussion. Using a structured clinical vignette of a patient with TRD after 3 antidepressant trials, statements regarding next-step treatments were created through iterative ranking of options. Six vignette variations reflecting common clinical considerations (eg, metabolic disease, age) were included. Agreement was measured in 3 anonymous survey rounds, with group discussions in between. Strong consensus emerged recommending augmentation with second-generation antipsychotics, transcranial magnetic stimulation, and ketamine/ esketamine as next-step treatments in the base vignette. Treatment preferences shifted to include nonaugmentative antidepressants and electroconvulsive therapy based on changes in patient characteristics. This study highlights the importance of tailoring treatment strategies for TRD to patient factors that extend beyond conventional guideline tiers. Integrating multidisciplinary perspectives and patient preferences holds promise for enhancing therapeutic selection and advancing personalized care in TRD.
de Granda-Beltrán AM, Peñuelas-Calvo I, Taracena-Cuerda M
… +7 more, Merayo-Cano JM, Carrillo-Notario L, Hidalgo Muñoz PA, Bello HJ, Rodríguez-Jiménez R, Baca-García E, Porras-Segovia A
Suicide is a major public health concern with a significant global impact. Among children and adolescents, an increasing incidence of suicidal behavior is being observed. Several studies have noted an increase in the num...Suicide is a major public health concern with a significant global impact. Among children and adolescents, an increasing incidence of suicidal behavior is being observed. Several studies have noted an increase in the number of emergency department (ED) consultations involving children and adolescents presenting with self-injurious thoughts and behaviors (SITB). However, few studies have yet described risk factors associated with these repeated visits. Our sample included all patients under 18 years of age who visited the Child and Adolescent Mental Health ED at Hospital Universitario 12 de Octubre between January 2, 2022, and November 30, 2023. A baseline interview was conducted by an attending psychiatrist during the patient's first emergency visit, followed by a review of their digital medical records 6 months later by the hospital's clinical staff. A total of 713 patients were treated in the ED during the study period, of whom 429 (60.16%) presented with suicidal behavior. Within 6 months of the initial ED visit, 25.4% of patients returned due to SITB. Specifically, 21.7% of those who initially attended for SITB returned for the same reason. Among patients who initially presented with suicidal ideation or suicide attempts, 25.8% and 25.3%, respectively, returned within 6 months. The variables independently associated with returning to the ED for SITB after the initial visit were nonheterosexual sexual orientation (odds ratio [OR]=2.10; 95% CI, 1.14-3.87) and prior SITB (OR=2.14; 95% CI, 1.27-3.60). In our study, we found that a significant number of children and adolescents who come to the ED for SITB return for the same reason within 6 months. There is also a certain amount of switching between different types of SITB consultations, particularly from ideation to attempt. This should alert us to the significant recurrence of these consultations and the fact that mental health resources continue to be insufficient to address these behaviors.
Psychiatric drug development is critical for addressing the global burden of mental illness, but the degree of recent innovation is not well understood. Prior studies have highlighted concerns over the stagnation of new...Psychiatric drug development is critical for addressing the global burden of mental illness, but the degree of recent innovation is not well understood. Prior studies have highlighted concerns over the stagnation of new therapeutic approaches, particularly compared to other medical specialties. What is the degree of innovation in psychiatric drug development? This observational study cross referenced 3 drug development databases to identify new and existing therapeutics approved for psychiatric indications between January 1, 2012, and December 31, 2024. To assess each drug's degree of innovation, the primary outcome was the proportion of drugs classified as "first-in-class" with secondary measures including US Food and Drug Administration (FDA) priority review status, orphan drug designations, inclusion on the WHO's Model List of Essential Medicines, and therapeutic benefit and clinical usefulness ratings by experts. A total of 22 new psychiatric drugs and supplemental indications were identified. Of these, 7 (31.8%) were categorized as first-in-class, 2 (9.1%) were considered an advance-in-class, and 13 (59.1%) were considered addition to-class. Three drugs (13.6%) received FDA priority review, 1 (4.5%) was designated as an orphan drug, and 0 were included on the WHO's Model List of Essential Medicines. For clinical utility, of drugs with available data, none of them received a rating of "clinically helpful," and 3/22 (13.6%) were rated "clinically not helpful." Innovation in psychiatric drug development in the past 13 years was limited, with most new drugs representing incremental advances rather than groundbreaking innovations. Compared to other medical fields, psychiatric drug development appears to lag in terms of novelty and clinical impact.
To examine the effectiveness of therapist-delivered video therapy habit reversal training (HRT) in large real-world samples of children, adolescents, and adults with trichotillomania and excoriation disorder (ED). The s...To examine the effectiveness of therapist-delivered video therapy habit reversal training (HRT) in large real-world samples of children, adolescents, and adults with trichotillomania and excoriation disorder (ED). The sample included 543 patients with trichotillomania (57 children, 75 adolescents, 411 adults) and 528 patients with ED (40 children, 46 adolescents, 442 adults). Treatment followed a protocol of weekly HRT sessions, transitioning to biweekly sessions. The Repetitive Body Focused Behavior Scale was administered at baseline, weeks 5-7, and weeks 14-16 and during maintenance periods through week 52. Mean treatment duration was 14.64±2.50 weeks (7.71±2.61 sessions) for trichotillomania and 14.54±2.69 weeks (7.73±2.68 sessions) for excoriation. At weeks 14-16, trichotillomania showed a median 33.33% severity reduction (interquartile range [IQR]=11.11%-54.55%; 44.08% achieving ≥35% reduction) with large effects (Hedges = 1.01, 95% CI [0.88-1.14]). Excoriation showed a median 33.33% reduction (IQR=12.50%-57.14%; 48.66% achieving ≥35% reduction) with large effects (Hedges = 1.16, 95% CI [1.02-1.30]). Improvements were maintained through week 52 (trichotillomania: =1.51 [CI, 1.23-1.79]; excoriation: =1.56 [1.29-1.84]). Both conditions showed improvements in depression, anxiety, and stress (=0.22-0.29). All age groups improved, with effect sizes ranging from =0.78-1.12 for trichotillomania and =0.68-1.54 for excoriation. This analysis shows promising evidence that therapist-delivered video therapy HRT is associated with reductions in both hair-pulling and skin-picking severity and improvements in related symptoms in a real-world setting. The large treatment effects and improvements across the lifespan for both conditions suggest this delivery format may help address barriers to accessing evidence-based care for body-focused repetitive behaviors.
J Clin Psychiatry
· 2026 Jan · PMID 41532843
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Early prognostic indicators of nonresponse to buprenorphine treatment for opioid use disorder can inform targeted efforts to improve outcomes. Opioid use in the first 2-3 weeks of treatment predicts later outcomes, yet i...Early prognostic indicators of nonresponse to buprenorphine treatment for opioid use disorder can inform targeted efforts to improve outcomes. Opioid use in the first 2-3 weeks of treatment predicts later outcomes, yet it is unclear what frequency of opioid use confers risk. We aimed to (1) identify thresholds for the frequency of early opioid use that optimally predict later sustained use and (2) quantify associations between thresholds and continuous treatment outcomes. We used data from 2 clinical trials of buprenorphine (N=562; mean age=34 years; 38% female), which were conducted from 2006-2009 and 2007-2011. Area under the receiver operating characteristic curve analyses identified optimal thresholds for opioid frequency during the first 4 weeks in predicting sustained use during weeks 5-12 (ie, 4 consecutive weeks with an opioid-positive or missing urine drug screen). Negative binomial regressions examined associations between early nonresponse and opioid-free and retention weeks. Sustained opioid use was optimally predicted by ≥1 day of opioid use in the first 2 weeks (sensitivity=0.747; specificity=0.688; positive predictive value [PPV]=0.524; negative predictive value [NPV]=0.856) and ≥2 days of use in the first 3 weeks (sensitivity=0.649; specificity=0.810; PPV=0.611; NPV=0.834). Both thresholds were negatively associated with opioid-free and retention weeks. Even very low levels of opioid use in the first 2-3 weeks of buprenorphine treatment signal risk for poor outcomes. Emphasizing abstinence or near abstinence early in treatment might help promote long-term stability. Identified thresholds can be used to identify patients who may benefit from treatment adjustments and close monitoring.
To evaluate the effects of a 6-month digital multidomain cognitive intervention on cognitive function and psychosocial outcomes in older adults at high risk of dementia. A 2-arm, randomized clinical trial was conducted...To evaluate the effects of a 6-month digital multidomain cognitive intervention on cognitive function and psychosocial outcomes in older adults at high risk of dementia. A 2-arm, randomized clinical trial was conducted at Fujian Provincial Hospital and 4 community health care centers (April 2024 to December 2024). Participants (N=166, aged ≥60 years, modified dementia risk score >79) were enrolled and randomized 1:1 to a 6-month digital multidomain cognitive intervention and control group. Primary outcomes included general cognitive function (Montreal Cognitive Assessment [MoCA]) scores; secondary outcomes covered memory (Rey-Osterrieth Complex Figure Test [ROCFT] and Auditory Verbal Learning Test), language (Verbal Fluency Test and Boston Naming Test), executive function and attention (Shape Trails Test), visuospatial skill (ROCFT), mobility (Activity of Daily Living and Berg Balance Scale), psychosocial status (15-item Geriatric Depression Scale, Zung Self-Rating Anxiety Scale, UCLA Loneliness Scale, and Quality of Life-Alzheimer's Disease), and health-promoting behaviors (Health-Promoting Lifestyle Profile II and Self-Rated Abilities for Health Practices). Intention-to-treat analysis with random forest imputation was performed. A total of 154 participants (92.77%) completed the trial. Compared to the control group, the intervention group demonstrated significant improvements in general cognitive function, visuospatial memory, and loneliness, including MoCA (=2.106, =.037), ROCFT immediate and long-delay recall (=-2.789, =.05; =2.797, =.05), and UCLA Loneliness Scale (=-2.641, =.008). No statistically significant between-group differences emerged in other indicators. A 6-month digital multidomain intervention significantly enhanced general cognitive function and visuospatial memory and reduced loneliness in older adults at high risk for dementia. These results highlight the potential of WeChat-based delivery models to provide feasible, acceptable, and widely applicable solutions for dementia risk reduction in aging populations. ClinicalTrials. gov identifier: NCT06442943.
Pregabalin is a gabapentinoid. It does not act on GABA receptors; rather, it inhibits calcium influx into neurons by acting on the α2δ-1 subunit of voltage-gated calcium channels. This reduces release of excitatory neuro...Pregabalin is a gabapentinoid. It does not act on GABA receptors; rather, it inhibits calcium influx into neurons by acting on the α2δ-1 subunit of voltage-gated calcium channels. This reduces release of excitatory neurotransmitters, thereby, perhaps, explaining the sedative, anxiolytic, anticonvulsant, and other properties of the drug. Pregabalin has been approved for neuropathic pain, fibromyalgia, partial-onset seizures, and generalized anxiety disorder, and is used, off-label, for pain in many other contexts and for alcohol use disorder, pruritus, restless legs syndrome, and sleep disorders. It may also be abused. About 0.04%-0.14% of women may use pregabalin during pregnancy. This article examines outcomes of pregnancies that were exposed to pregabalin. A meta-analysis of 7 cohort studies found that, even in unadjusted analysis, pregabalin was not associated with an increased risk of major congenital malformations. This finding was confirmed in later studies; or, if the unadjusted risk was significantly elevated, it was no longer so in adjusted analysis. Many studies found that anytime gestational exposure to pregabalin was not associated with a significantly elevated risk of other important birth outcomes such as stillbirth, low birth weight, preterm birth, small for gestational age, low Apgar score, and microcephaly; or the risks were elevated before but not after adjustment for covariates and confounds; or the risks were not significant relative to disease controls. Similarly, studies found that anytime gestational exposure to pregabalin was associated with no increase in risk, or with a significantly increased risk of attention-deficit/ hyperactivity disorder and related disorders, autism spectrum disorder and related disorders, and intellectual disability before but not after adjustment for covariates and confounds. As a limitation, pregabalin-exposed pregnancy sample sizes were small in all studies. On the positive side, safety impressions were obtained despite negligible adjustment for genetic, illness behavior, and environmental confounds.
Health care professionals face elevated suicide risk, yet longitudinal studies during occupational crises are lacking. We investigated factors associated with suicide attempts and psychiatric hospitalizations in health c...Health care professionals face elevated suicide risk, yet longitudinal studies during occupational crises are lacking. We investigated factors associated with suicide attempts and psychiatric hospitalizations in health care workers seeking emotional support during COVID-19. We prospectively evaluated 3,087 Brazilian health care professionals enrolled in a digital mental health trial (May-July 2020). Participants were recruited nationwide from May 2020 to December 2021. From this cohort, 2,815 with complete baseline data comprised the intention-to-treat (ITT) sample. Outcomes were assessed at 4, 12, and 24 weeks. Baseline predictors included demographics, Patient Health Questionnaire-9 item 9 (suicidal ideation), Patient-Reported Outcomes Measurement Information System T-scores (depression, anxiety, irritability, sleep), life satisfaction, and burnout. Cox models examined associations; inverse probability weighting addressed attrition. Additive interaction was quantified using relative excess risk due to interaction (RERI). In the total sample, 53 participants (1.59%) attempted suicide. In the ITT sample (86% female, mean age 36.5), 46 (1.63%) attempted suicide (64 events), and 60 (2.22%) required psychiatric hospitalization. Nearly every day ideation (hazard ratio [HR]=39.58, 95% CI, 14.03-111.64, <.001), severe sleep disturbances (HR=17.39, 95% CI, 2.05-147.46, =.009), and male sex (HR=2.08, 95% CI, 1.01-4.26, =.046) independently predicted attempts. The 24-week attempt probability reached 57.1% for individuals with both ideation and sleep problems versus 1.2% with neither, with 40% of the combined risk attributable to synergistic interaction (RERI=11.51). Notably, 28.3% of attempts occurred among individuals denying baseline ideation. For hospitalizations, only nearly every day ideation remained significant (HR=8.11, 95% CI, 3.10-21.18, <.001). Results remained robust after weighting. Daily suicidal ideation and severe sleep disturbances synergistically elevate suicide risk among health care professionals. Findings support a comprehensive assessment incorporating sleep disturbances and multicomponent interventions targeting both domains simultaneously. ClinicalTrials.gov identifiers: NCT04635618, NCT04632082.
This study aims to characterize the rate of successful rechallenge considering the risk of recurrence of cutaneous adverse reactions with reintroduction of lamotrigine, as well as how to characterize cutaneous reactions...This study aims to characterize the rate of successful rechallenge considering the risk of recurrence of cutaneous adverse reactions with reintroduction of lamotrigine, as well as how to characterize cutaneous reactions appropriately, and important considerations in deciding whether to attempt reintroduction of lamotrigine. A systematic review was conducted of PubMed, SCOPUS, and Web of Science databases. Search terms included lamotrigine, rash, and rechallenge or reintroduction. The resulting articles (59) were imported into Covidence. After screening and application of inclusion/exclusion criteria, 11 articles were included. Variables extracted included study design, age of patient, lamotrigine dosing regimen, concomitant valproate use, use of other concomitant enzyme-inducing antiepileptic drugs, rash timing after starting lamotrigine, rash description, rash diagnosis, dermatologist evaluation, skin biopsy, hospitalization, time from initial rash onset until rechallenge, rechallenge lamotrigine dosing regimen, and response. There were 106 cases of rechallenge of lamotrigine. Over half (57%) of patients were female, and the average age was 35 years. Time from discontinuation of lamotrigine until rechallenge ranged from 1 week to 26 months, and there were 12 cases that continued lamotrigine without interruption or by reducing the dose. Patients who were rechallenged with lamotrigine successfully typically started the rechallenge with either 5 mg or 12.5 mg daily with a gradual upward titration until reaching desired dose. Successful rechallenge occurred in 84% of cases; reasons for unsuccessful rechallenge included severe or intolerable rash or other symptoms. Only 3 out of 106 cases had a dermatologist confirm the initial rash diagnosis. Lamotrigine has been rechallenged safely in select cases; however, it is critical to confirm that the initial rash did not have specific features of a severe rash in order to proceed with safe reintroduction of lamotrigine. This article analyzes the cases in the literature to date and gives recommendations for how to assess whether to rechallenge lamotrigine.
Functional recovery has emerged as a critical treatment goal in schizophrenia, extending beyond symptom reduction to encompass independent living, vocational and educational attainment, social integration, and overall qu...Functional recovery has emerged as a critical treatment goal in schizophrenia, extending beyond symptom reduction to encompass independent living, vocational and educational attainment, social integration, and overall quality of life. Despite advances in pharmacotherapy, many people with schizophrenia continue to experience significant functional impairments driven by persistent symptoms, cognitive deficits, comorbidities, stigma, and adverse social determinants. Psychosocial interventions have been shown to be effective in improving functional outcomes but are not extensively utilized. To address these challenges, a consensus panel of experts in psychiatry and psychology reviewed the evidence base and developed practical recommendations for optimizing functional outcomes. Panel discussions highlighted 4 domains of functional drivers in schizophrenia: intrinsic, behavioral, comorbid/consequential, and societal/contextual, and evaluated psychosocial interventions with demonstrated benefits relative to these domains. Amidst lingering questions about further refinement and optimal individualization, evidence clearly supports the use of cognitive behavioral therapy, cognitive remediation, social skills training, supported employment and housing, and family-focused interventions; likewise, evidence supports the use of psychoeducation, motivational interviewing, mindfulness- and acceptance-based therapies, and lifestyle interventions, such as structured exercise. Implementation remains limited due to workforce shortages, resource constraints, and a lack of integration into routine care. The panel recommends a comprehensive, patient-centered approach that integrates pharmacological treatment with evidence-based psychosocial strategies, guided by measurement-based care and individualized treatment planning. Validated functional assessment tools and emerging digital therapeutics offer scalable methods to monitor and enhance outcomes. By addressing both intrinsic and extrinsic drivers of disability, clinicians can more effectively support people with schizophrenia in achieving functional recovery and an improved quality of life.