Objective: Obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD) are often comorbid. While exposure-based treatments can be effective for each, given that comorbid OCD and PTSD symptoms often interact dynamically, concurrent treatment may be most beneficial. The aim of the current analysis was to examine the naturalistic effectiveness of concurrently delivered exposure and response prevention (ERP) and prolonged exposure (PE) therapy among individuals with comorbid OCD and PTSD.

Objective: To evaluate pharmacokinetics of viloxazine extended-release (ER) in breast milk and plasma of healthy lactating women and calculate potential infant exposure. Methods: Healthy lactating women (N=15), who were ≥12 weeks postpartum, received viloxazine ER 600 mg/d (the maximum recommended adult dose, given as 3x200 mg capsules) for 3 days at the same time each morning. Pharmacokinetic parameters describing the timing and amount of viloxazine in plasma and breast milk were measured based on samples collected predose and for 24 hours postdose on Day 3.Measures of potential infant exposure were calculated, including estimated daily infant dose (EDID) and relative infant dose (RID; the percentage of the weight-adjusted maternal daily dose that an infant would likely receive through breast milk). Results: At steady state, the median Tmax, milk in breast milk for viloxazine ER was 5.53 h, and the geometric mean (coefficient of variation [CV]%) breast milk-to-plasma ratio was 0.338 (17.4), indicating limited partitioning of drug into breast milk. Using a standard estimate of 150 mL/kg/d infant milk intake, the geometric mean (CV%) EDID was 0.134 (34.4) mg/kg/d, yielding an RID of 1.53% (27.6)-a value indicating low infant exposure within the commonly accepted <5%-10% RID safety threshold. Mild treatment-related adverse events were reported by 80% of participants, most commonly somnolence (67%), nausea (20%), and dizziness (20%). No participants discontinued. Conclusion: Viloxazine transfer into breastmilk of healthy, lactating women following multiple, once-daily 600 mg viloxazine ER doses was low. Trial Registration: ClinicalTrials.gov identifier: NCT06259331.

Objective: People with schizophrenia often experience hostility and agitation, which can worsen their functioning. This post hoc analysis aimed to investigate the effects of brexpiprazole on functioning in schizophrenia in relation to hostility and agitation symptoms. Methods: Short-term data were pooled from three 6-week, randomized, double-blind, placebo-controlled trials of brexpiprazole tablets in adult inpatients with acute schizophrenia (DSM-IV-TR criteria), conducted at sites worldwide from July 2011 to December 2014. Long-term data were pooled from two 52-week, open-label extension trials conducted from September 2011 to February 2016. Functioning was measured using the Personal and Social Performance (PSP) scale, strengthened by removing the "disturbing and aggressive behaviors" domain to be independent of hostility and agitation. Participants were stratified according to baseline hostility, defined using the Positive and Negative Syndrome Scale (PANSS) hostility item, and agitation, defined using the PANSS-Excited Component subscale. Results: At baseline, 692/ 1,385 participants (50.0%) had hostility and 784 (56.6%) had agitation. At Week 6, PSP score change (least-squares mean difference [95% confidence interval]) favored brexpiprazole 2-4 mg/day versus placebo in participants with hostility (2.82 [0.58-5.07]; P = .014), without hostility (3.42 [1.37-5.48]; P = .001), and with agitation (4.05 [2.01-6.10]; P < .001), but not those without agitation (2.09 [-0.18 to 4.36]; P = .071). PSP score improved and stabilized over 58 weeks (408 participants analyzed). Conclusion: Brexpiprazole may improve functioning in adults with schizophrenia, even if they have hostility and agitation symptoms. Trial Registration: Data used in this post hoc analysis are from the following ClinicalTrials.gov identifiers: NCT01396421, NCT01393613, NCT01810380, NCT01397786, and NCT01810783.

Objective: Overdoses remain a major public health challenge. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been proposed as a treatment for opioid use disorder (OUD) based on preclinical research. Early observational research suggests that GLP-1RAs are associated with reduced opioid overdoses but warrants replication in different patient populations. Methods: This target trial emulation study used Veterans Health Administration (VA) data to include Veterans with a diagnosis of type 2 diabetes mellitus and OUD who initiated semaglutide and tirzepatide or a comparison diabetes medication (insulin, metformin, a sulfonylurea, a sodium-glucose transport 2 (SGLT2) inhibitor, or a dipeptidyl-peptidase 4 [DPP4] inhibitor) between January 1, 2020, and December 31, 2024. Each set of comparison groups was propensity score matched on relevant variables. Cox proportional hazards regression models were used to compare the time to all-cause overdose events in the 12 months after medication initiation. Results: After propensity score matching, semaglutide and tirzepatide were associated with significantly lower risk of all-cause overdose compared to insulin (hazard ratio [HR]=0.32; 95% CI=0.14-0.71; P=.006; n=630) and SGLT2 inhibitors (HR=0.25; 95% CI=0.09-0.68; P=.006; n=432). Semaglutide and tirzepatide were not associated with significantly lower risks than metformin (HR=0.75; 95% CI=0.38-1.45; n=1,016), sulfonylureas (HR=0.82; 95% CI=0.33-1.96; n=710), or DPP4 inhibitors (HR=1.20; 95% CI=0.52-2.78; n=858). Conclusion: Collectively, semaglutide and tirzepatide were associated with lower risk of all-cause overdose compared to insulin and SGLT2 inhibitors, but not metformin, sulfonylureas, or DPP4 inhibitors. These results suggest the possible role of GLP-1RAs in OUD but underscore the need for randomized controlled trials.

Objective: To compare effects of adjunctive active versus sham vagus nerve stimulation (VNS) on suicidal ideation (SI) in markedly treatment-resistant depression (TRD).

Objective: Trauma-focused psychotherapies are first-line treatments for posttraumatic stress disorder (PTSD). For veterans, however, response rates are low, and dropout tends to be high. Some evidence suggests that those with comorbid depression are less likely to complete treatment and improve less in trauma-focused treatments. This study examined treatment noncompletion and PTSD symptom outcomes among veterans with and without comorbid major depressive disorder (MDD) treated for PTSD with either a trauma-focused psychotherapy (prolonged exposure [PE]) or a non-trauma-focused psychotherapy (interpersonal psychotherapy [IPT]). We also examined depressive symptoms as an outcome. Methods: We conducted a secondary analysis of data from a randomized controlled trial comparing PE and IPT for the treatment of PTSD in veterans. Among 109 veterans starting treatment, 30 (52%) of 58 IPT patients and 21 (41%) of 51 PE patients were diagnosed with MDD. Those completing fewer than 8 sessions were considered noncompleters. Outcomes within each treatment and between treatments were compared by MDD status. Results: There were no differences in noncompletion by MDD status in IPT. In PE, failure to complete was numerically but nonsignificantly higher in those without MDD. MDD was associated with significantly less PTSD symptom improvement in PE (P=.04) but not in IPT at the end of treatment. Findings from a linear model incorporating posttreatment follow-up data, although not statistically significant, were consistent with the end-of-treatment findings. Comparisons between treatments among those with MDD showed partial support for an advantage of IPT for PTSD symptom improvement. There were no differences between the treatments in change in symptoms of depression. Conclusions: Findings are consistent with prior research showing that depression is associated with less PTSD symptom improvement in PE, a trauma-focused psychotherapy, but does not affect PTSD outcome in IPT. Although in need of replication in studies designed and statistically powered to test the role of MDD in PTSD treatment outcome, findings suggest a possible advantage for IPT relative to trauma-focused treatment for PTSD for those with comorbid MDD. Trial Registration: ClinicalTrials.gov identifier: NCTO2586064.

Background: Obesity and psychiatric disorders are major contributors to morbidity and premature mortality in the US and frequently co-occur, yet their joint mortality burden has not been systematically quantified nationally.

Objective: To examine whether benzodiazepine use within 30 days after mass trauma increases posttraumatic stress disorder (PTSD) risk and whether timing or persistence of use modifies this association.

Objectives: To examine county-level variations in and correlates of substance use disorders (SUDs) health service utilization by insurance payers (Medicaid, private insurance, and Medicare) and self-pay. Methods: Service utilization (the number of health care encounters, visits, admissions, or prescriptions) for SUDs was extracted from the Disease Expenditure 2017-2019 Project. We linked county-level data to drug overdose mortality rates and County Health Rankings, Area Health Resources Files, and Opioid Environment Policy Scan datasets. Descriptive and regression analyses were applied. Results: During 2017-2019, Medicaid (52.7%) and private insurance (32.3%) financed 85.0% of annual average SUD service expenditures examined, accounting for 50.6% of SUD service utilizations (in number). Across 3,143 counties, the average annual county-level number of SUD service utilizations was 5.2 (95% CI =5.1-5.3) per 1,000 county residents. Self-pay individuals had the highest average county-level number of SUD service utilizations (8.6, 95% CI =8.4-8.6 per 1,000 county residents), followed by Medicaid beneficiaries (6.9, 95% CI =6.6-7.1 per 1,000 county Medicaid enrollees) and those paid by private insurance (2.8, 95% CI =2.7-2.8 per 1,000 privately insured county residents). County-level percentage of uninsured adults was negatively associated with SUD service utilization overall (standardized β = -.45, the highest across examined variables, P<.0001), accounting for 23.0% of its variance. SUD-related health care resource indicators explained 2.3%. Conclusions: Across all examined payers, Medicaid funded a disproportionate share-over 50%-of SUD service expenditures. Findings quantified the substantial impact of county-level adult uninsured rates on SUD health service utilization, highlighting the pivotal role of health insurance in supporting access to and utilization of SUD services.