This is the first systematic review on the prevalence and clinical characteristics of 14 syndromes included in the Diagnostic Criteria for Psychosomatic Research (DCPR) across different settings. A systematic search was...This is the first systematic review on the prevalence and clinical characteristics of 14 syndromes included in the Diagnostic Criteria for Psychosomatic Research (DCPR) across different settings. A systematic search was conducted using Web of Science to identify all English-language citing articles for DCPR key references (from 1995 to 2025). A manual search of the literature was also performed. Studies were eligible if they reported the prevalence and clinical characteristics of the DCPR syndromes. The initial search identified 604 reports. After removing duplicates, 524 reports were screened, and 375 full-text articles were examined. Ninety-six studies met the criteria for inclusion in the systematic review. Data on sample size, number of cases and prevalence of each DCPR syndrome, setting, assessment methods and time(s), and overlaps between DCPR and were extracted. Studies were grouped according to clinical domains (ie, stress and psychological manifestations, illness behavior and somatization, personality features). Results were reported as median prevalence and range for each DCPR syndrome based on available studies. DCPR syndromes were found to be common in clinical settings, with higher prevalence than psychiatric diagnoses. The DCPR allowed identification of allostatic overload, demoralization, irritable mood, illness behavior, and various manifestations of somatization that otherwise would have gone undetected using standard diagnostic methods. Findings from this systematic review indicate that the DCPR are an essential integration to the customary psychiatric taxonomy, particularly in the setting of medical disease, with prognostic and therapeutic implications. The DCPR provide a unique clinimetric framework for optimal use of clinical judgment.
Major depressive disorder with peripartum onset (also known as postpartum depression [PPD]) () is a debilitating condition that can be characterized by difficulty transitioning out of a negative affective state. Given th...Major depressive disorder with peripartum onset (also known as postpartum depression [PPD]) () is a debilitating condition that can be characterized by difficulty transitioning out of a negative affective state. Given the rapid clinical response typically observed with brexanolone, the treatment period provides a rare opportunity to study the dynamics of this transition. The present study examined the timing and pattern of symptom changes, including leading and residual symptoms and associated changes in self-reported maternal functioning. Using a single-arm, open-label, descriptive pilot study, 10 women with moderate-to-severe PPD received a 60-hour intravenous infusion of brexanolone following the FDA-approved regimen. Symptoms comprising the affective state were assessed at high frequency before, during, and after the infusion to track the timing and sequence of symptom changes. Exploratory analyses used repeated-measures analysis of variance with Greenhouse-Geisser correction and post hoc comparisons with adjustment for multiple measures. Data were collected from July 2022 to November 2023. All participants showed clinical response, and most reached remission within 44 hours. Symptom improvement was broad, though no single symptom consistently led the affective shift. The timing of maximal change in subjective satisfaction with mood often differed from changes in standard symptom scales. Significant (<.001) improvements were observed in anhedonia (↓89%), rumination (↓29%), and (↑56%) maternal functioning, all of which persisted at 30-day follow-up. This study provides novel insights into the rapid and individualized symptom trajectories during recovery from PPD following brexanolone infusion. These findings could have broader implications for understanding the pathophysiology of mood disorders and for developing targeted interventions that modulate brain dynamics to promote recovery from pathological affective states. ClinicalTrials.gov identifier: NCT05543746.
Kapustin D, Rashidi-Ranjbar N, Wang W
… +18 more, Binns MA, McLaughlin PM, Abrahao A, Grimes D, Lang A, Marras C, Masellis M, Orange JB, Rajji TK, Roberts A, Saposnik G, Swartz RH, Tang-Wai DF, Tartaglia MC, Troyer A, Zinman L, Fischer CE, Kumar S
Neuropsychiatric symptoms (NPS) constitute a major challenge in Alzheimer disease (AD). We applied a component-based symptom paradigm by deriving Neuropsychiatric Inventory Questionnaire (NPI-Q) clusters and evaluating t...Neuropsychiatric symptoms (NPS) constitute a major challenge in Alzheimer disease (AD). We applied a component-based symptom paradigm by deriving Neuropsychiatric Inventory Questionnaire (NPI-Q) clusters and evaluating their longitudinal associations with regional brain volumes and functional outcomes (instrumental activities of daily living, activities of daily living [ADLs]). Participants with AD (N=111) were from the Ontario Neurodegenerative Disease Research Initiative. NPS were assessed using the NPI-Q. Symptom clusters were identified via principal components analysis at baseline. Magnetic resonance imaging-derived volumes for 34 cortical and 9 subcortical regions were obtained annually over 3 years. Longitudinal associations between NPS clusters and functional outcomes were examined using linear mixed-effects models adjusting for age, sex, Montreal Cognitive Assessment (MoCA), education, visit number, and cholinesterase inhibitor use. Four clusters explained 62% of variance: hyperactivity (disinhibition, irritability, motor disturbance, agitation), psychosis (hallucinations, delusions, euphoria), neurovegetative (apathy, appetite), and affective (depression, anxiety, nighttime behavior). The hyperactivity cluster was associated with the left middle temporal (β=-0.24, =.025) and right nucleus accumbens (β=-0.28, =.007). The neurovegetative cluster was associated with the left middle temporal (β=-0.50, <.001) and right nucleus accumbens (β=-0.55, <.001). The affective cluster showed the strongest associations with the left rostral anterior cingulate (β=-0.42, =.002) and right medial orbitofrontal cortex (β=-0.47, =.001). All clusters predicted iADL outcomes; clusters 1, 3, and 4 also predicted ADL outcomes. Greater NPS burden, male sex, age, lower MoCA, and later visits predicted worse function. NPS in AD separate into hyperactivity, psychosis, neurovegetative, and affective clusters, supporting a cluster-based paradigm linking co-occurring behavioral symptoms with brain structure and functional decline.
Persons with mental health disorders are at increased risk of dental disease, including lost teeth. Dental implants are the preferred option for most persons who have lost teeth. Recent studies suggest that antidepressan...Persons with mental health disorders are at increased risk of dental disease, including lost teeth. Dental implants are the preferred option for most persons who have lost teeth. Recent studies suggest that antidepressant drugs, especially the selective serotonin reuptake inhibitors, are associated with an increased risk of dental implant failure. This article provides a background about the epidemiology of loss of teeth, the causes of tooth loss, the need to replace lost teeth, and the use of dental implants to replace lost teeth. Two meta-analyses of retrospective cohort studies of the association between antidepressant use and implant failure are examined in detail. One meta-analysis included 6 studies and the other, 10 studies. An additional retrospective cohort study, published after the meta-analyses, is also examined. In summary, there is consistent evidence for a higher risk of implant failure in patients taking antidepressants, and for a higher number of implants failing in patients taking antidepressants, relative to patients not taking antidepressants. Broad findings were that, at the patient level, implant failure occurred in 6%-23% of antidepressant users vs 2%-8% of nonusers, and at the implant level, implant failure occurred in 6%-22% of antidepressant users vs 2%-9% of nonusers. Because unadjusted risks were more than doubled in antidepressant users, it implies that, in the real world, antidepressant use is a clinically important marker for risk of implant failure; it is hard to draw cause and effect inferences from the studies reviewed because of inadequacies in study designs and statistical methods. Action points are that antidepressant users should be educated about the risk of implant failure, and vigorous efforts should be made to identify and negate, to the extent possible, other risk factors for implant failure in these patients. Suggestions are offered for future research in the field.
To compare rehospitalization outcomes and medication practice patterns between long-acting injectable antipsychotics (LAIs) and oral antipsychotics (OAs) in US patients with bipolar I disorder (BD-I). This retrospective...To compare rehospitalization outcomes and medication practice patterns between long-acting injectable antipsychotics (LAIs) and oral antipsychotics (OAs) in US patients with bipolar I disorder (BD-I). This retrospective cohort study using the Premier Hospital database (October 2020-September 2023) grouped adults (aged ≥18 years) hospitalized with BD-I by discharge medication: OA, LAI, or second-generation LAI (SG LAI). LAI and SG LAI patients were propensity score matched (1:4) to OA patients. Rehospitalization rates and risk (BD-I-related and all-cause) within 30, 60, and 90 days were assessed. Medication continuation vs switching at rehospitalization was also analyzed. Among 98,088 eligible patients, 78.1% were in the OA and 2.4% in the LAI group. BD-I-related rehospitalization rates were lower for LAI users at 30 (3.9% vs 5.0%, =.033) and 60 days (5.9% vs 7.2%, =.030) vs OAs. SG LAI users showed reductions in rehospitalizations at 30 (3.6% vs 5.4%; =.010), 60 (5.2% vs 7.5%; =.008), and 90 (6.8% vs 9.1%; =.015) days. Risk of first BD-I rehospitalization within 30-90 days was reduced for LAI (hazard ratio [HR]: 0.784-0.856) and SG LAI (HR: 0.653-0.742) groups vs OAs. LAIs, especially SG formulations, are associated with reduced rehospitalization in BD-I compared to OAs, supporting their broader use to improve adherence and reduce readmissions.
Marcus SC, Wiesel Cullen S, Xie M
… +6 more, Liu T, Williams NJ, Schmutte T, Ungar LH, Cardamone NC, Olfson M
J Clin Psychiatry
· 2026 Mar · PMID 41784443
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To identify and compare predictors of nonfatal and fatal suicidal events within 180 days of emergency department (ED) visits for mental health disorders. This longitudinal cohort analysis assessed risk of nonfatal and f...To identify and compare predictors of nonfatal and fatal suicidal events within 180 days of emergency department (ED) visits for mental health disorders. This longitudinal cohort analysis assessed risk of nonfatal and fatal suicide events among a national sample of 511,559 patients presenting to an ED between 2015 and 2022 with 1 or more mental health disorder. Machine learning models were used to predict events incorporating demographic and clinical characteristics, incremental value of clinical feature sets, feature importance rankings across models, and accuracy with which a model trained to predict nonfatal outcomes predicted suicide deaths. Nonfatal attempts within 6 months of an ED visit were identified using electronic health records (n=4,525), while fatal events were identified from the National Death Index (n=434). The final sample of 872,627 ED episodes represented 511,559 individuals. The full model with 143 features achieved stronger performance for nonfatal events (area under the curve [AUC]=0.874) than for suicide deaths (AUC=0.787). The relative importance of features was highly correlated across models (=0.82), with 73% of overlap between the top 15 predictors for nonfatal and fatal events. When the nonfatal model was applied to fatal outcomes on the same sample, performance declined (AUC=0.724), indicating limited generalizability despite similar predictors (sensitivity=78.1%, specificity=67.3%). Although nonfatal and fatal suicidal events share predictors, their predictive strength and function differ. These differences underscore challenges in using models trained on nonfatal outcomes to identify risk of suicide death and contribute to the ongoing debate over whether suicidal thoughts and behaviors reflect a continuum of severity or distinct clinical pathways.
This preliminary open-label study examined whether 12 weeks of cannabis abstinence was associated with posttraumatic stress disorder (PTSD) symptom improvement in people with comorbid PTSD and cannabis use disorder (CUD)...This preliminary open-label study examined whether 12 weeks of cannabis abstinence was associated with posttraumatic stress disorder (PTSD) symptom improvement in people with comorbid PTSD and cannabis use disorder (CUD) (N=21). Participants received progressive contingency reinforcement payments for successful abstinence at weeks 4, 8, and 12. Abstinence was defined as a 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) level ≤50 ng/mL with no self-reported cannabis use. PTSD symptoms were evaluated using the Clinician-Administered PTSD Scale for (CAPS-5), capturing total severity, symptom count, and cluster scores. Data were collected from January 2022 to April 2025. Participants who achieved abstinence (n=11) reported significantly greater reductions in total PTSD symptom severity and symptom count relative to those who did not (n=10). CAPS-5 total scores decreased from 36.2 to 10.5 among abstainers versus 34.6 to 21.8 among nonabstainers (=.001). Time-by-group interactions revealed more pronounced improvements in avoidance, negative mood and cognition, and hyperarousal among abstainers. Reexperiencing symptoms improved across both groups over time, with no significant difference by abstinence status. Sustained cannabis abstinence was associated with significant reductions in PTSD symptom severity and frequency over 12 weeks. While not definitive, the results raise questions about the assumption that long-term cannabis use improves symptoms or functioning in PTSD. The data instead suggest that continued cannabis use could limit recovery in some domains. This underscores the need to routinely assess cannabis use during PTSD treatment and to educate patients on the potential consequences of continued use. Larger randomized trials are warranted to replicate and extend these findings and to investigate mechanisms through which abstinence may relate to symptom changes in PTSD with CUD. ClinicalTrials.gov identifier: NCT05162651.
This study describes recent trends in benzodiazepine prescribing to US adults and characterizes patients who receive benzodiazepines and other central nervous system (CNS) depressants. This repeated cross-sectional stud...This study describes recent trends in benzodiazepine prescribing to US adults and characterizes patients who receive benzodiazepines and other central nervous system (CNS) depressants. This repeated cross-sectional study analyzed benzodiazepine use by adults (ages ≥18 years) in the 2018-2022 Medical Expenditure Panel Surveys, which are nationally representative surveys of the civilian noninstitutionalized population. We examined sex-adjusted annual trends (2018-2022) in benzodiazepine use by age group (ages 18-35, 36-55, and ≥56 years) and pooled marginal differences by age group in any benzodiazepine use and in benzodiazepine use and other CNS-depressant medications, stratified by sociodemographic and clinical characteristics. The analysis involved 104,231 participants. Between 2018 and 2022, annual benzodiazepine use by US adults decreased from 4.7% to 3.4%. This included a greater decrease for adults ages ≥56 years (7.2% to 4.7%) than for those ages 36-55 years (4.4% to 3.4%) or 18-35 years (2.1% to 1.8%). Approximately 41.6% adults treated with benzodiazepines also received other CNS-depressant medications in the same year including a higher percentage aged 36-55 years (44.6%) or ≥56 years (42.9%) than 18-35 years (30.0%). Most benzodiazepine-treated adults with fair or poor general health (72.0%) or with serious psychological distress (62.9%) also received other CNS-depressant medications. Benzodiazepine treatment decreased among US adults between 2018 and 2022, with a greater decline among adults ≥56 years than those 36-55 or 18-35 years. Prescription of benzodiazepines to adults who also received other CNS depressants was common, especially among adults in fair or poor general health or with serious psychological distress.
Long-acting injectable (LAI) antipsychotics are increasingly recommended for patients in the early phase of schizophrenia. We examined how the timing of LAI initiation affects treatment discontinuation and hospitalizatio...Long-acting injectable (LAI) antipsychotics are increasingly recommended for patients in the early phase of schizophrenia. We examined how the timing of LAI initiation affects treatment discontinuation and hospitalization duration in first-episode schizophrenia. Using the Korean Health Insurance Review and Assessment Service claims database, we identified 6,380 patients with first-episode schizophrenia receiving continuous LAI treatment. The interval from diagnosis to LAI initiation was categorized into 6 groups (<1, 1-2, 2-3, 3-4, 4-5, and >5 years). Treatment discontinuation and the proportion of psychiatric hospitalization days during continuous LAI use were analyzed using Cox and linear regression models. Earlier LAI use increased over time, but the duration of continuous treatment declined. Patients who started LAIs >2 years after diagnosis had lower risks of discontinuation than those within the first year (2-3 years: hazard ratio [HR]=0.77 [0.69-0.87]; 3-4 years: HR=0.77 [0.68-0.86]; 4-5 years: HR=0.70 [0.61-0.79]; >5 years: HR=0.66 [0.59-0.74]). Later initiation was associated with greater psychiatric hospitalization burden, particularly among patients with prior hospitalizations (1-2 years: β=0.039, =.039; 3-4 years: β=0.057, =.010; >5 years: β=0.162, <.001), and within the >5-year group, longer delays further increased hospitalization days (β=1.87×10, <.001). Although delayed initiation was linked to better treatment adherence, early LAI use reduced hospitalization burden, supporting guidelines advocating earlier LAI treatment in schizophrenia.
The E-value is most simply described as the smallest strength of association that 1 or more unmeasured confounds must have with both risk factor and outcome to nullify a significant relationship between the risk factor a...The E-value is most simply described as the smallest strength of association that 1 or more unmeasured confounds must have with both risk factor and outcome to nullify a significant relationship between the risk factor and the outcome in a fully adjusted regression. Thus, the E-value is a measure of how robust a finding may be against unmeasured confounding. This article provides the reader with a primer on the E-value, and with a cheat sheet that simplifies concepts. The full definition of the E-value is stated, and each element in the definition is explained. The E-value is most commonly applied to statistics such as the relative risk, odds ratio, and hazard ratio but can be applied to other statistics, as well. The E-value is usually calculated for 2 estimates: the statistic that measures risk and the limit of the 95% confidence interval (CI) of the statistic that is closest to the null. The former E-value tells us how strong unmeasured confounding should be to bring the value of the statistic to null. The latter E-value tells us how strong unmeasured confounding should be to bring the null value into the 95% CI, thereby making a statistically significant finding nonsignificant. This article also explains the calculation and the interpretation of the E-value. A detailed discussion is provided on what unmeasured confounding means with reference to the E-value. The specificity of the E-value to the context of the study, and the variables adjusted for, is emphasized. Interpretation of the E-value should be based on the plausibility of existence of the unmeasured confounds and the prevalence of these confounds in the population. E-values, surprisingly, are not commonly reported. They should be reported by researchers, requested by reviewers and editors, and calculated by readers to understand how robust statistically significant findings are against unmeasured confounding.
Transcranial magnetic stimulation (TMS) is an FDA-cleared neuromodulation technique with expanding clinical applications beyond major depressive disorder. Despite increasing utilization, there has been no published, devi...Transcranial magnetic stimulation (TMS) is an FDA-cleared neuromodulation technique with expanding clinical applications beyond major depressive disorder. Despite increasing utilization, there has been no published, device-agnostic analysis of TMS-related adverse events (AEs) using the FDA's Manufacturer and User Facility Device Experience (MAUDE) database. To characterize the real-world safety profile of TMS devices based on MAUDE-reported AEs, including symptom patterns, manufacturer-level variations, device issues, and reporting delays, while contextualizing findings through a review of technological advancements in TMS. All reports under device code OBP were extracted from MAUDE through April 2025. After deduplication, 200 unique reports were analyzed descriptively. A focused literature review was also conducted to trace safety and innovation trends in TMS device development. Of 200 reports, 94.7% involved injury, 4.1% malfunction, and 1.2% death. Common symptoms included anxiety (8.2%), neurocognitive changes (8.0%), seizures (6.9%), headache (6.9%), and tinnitus (5.6%). Neuronetics accounted for 45.5% of reports, likely reflecting market share. Median reporting delay was 1.4 months, with some exceeding 6 years. The literature review identified major innovations, including figure-of-eight and H-coils, double-containment coils, seizure risk screening, and advanced circuitry (eg, insulated-gate bipolar transistors and metal-oxide-semiconductor field-effect transistors) enabling magnetic resonance imaging-guided and accelerated protocols. Exploratory developments include wearable systems, auricular stimulation, and artificial intelligence-based individualization. MAUDE data provide novel insights into TMS safety in real-world settings. Although serious AEs are rare, standardized reporting and continued device innovation are essential to ensure safe and effective clinical use.
Unwanted intrusive thoughts (UITs) of intentional infant-related harm are common among birthing parents. Evidence to date has failed to find any association with physical aggression toward the infant. However, the relati...Unwanted intrusive thoughts (UITs) of intentional infant-related harm are common among birthing parents. Evidence to date has failed to find any association with physical aggression toward the infant. However, the relationship between UITs of infant-related sexual harm and sexual behaviors toward the infant has yet to be assessed. This is the purpose of the current study. Data were collected from February 9, 2014, to February 14, 2017, via a prospective, province-wide, unselected cohort of N = 763 English-speaking birthing parents, n = 502 of whom provided data for the current analysis. Interview assessments of UITs of infant-related sexual harm were administered at approximately 7 weeks postpartum and 4 months postpartum. Sexual harming behaviors toward the infant were assessed via an anonymized questionnaire at the end of the study. UITs of infant-related sexual harm were reported by 9.2% (n = 38; 95% CI, 6.6-12.4) of participants. We found no evidence of an association between UITs of this nature and sexual behavior toward one's infant (Fisher exact, = 1.00). Only 1 participant reported engaging in sexual behavior toward their infant, and they did not report any UITs of infant-related sexual harm. Study findings add to growing evidence that UITs of infant-related harm are common, and when these thoughts are unwanted and intrusive, they are not associated with an increased risk of actually harming one's infant. Although findings suggest that this is also true for UITs of infant-related sexual harm and sexual behavior, due to the small sample employed in this research, replication with a larger sample is needed.