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.

Background: Current drug policy debates often center on whether hallucinogen-related hospital admissions indicate a causal relationship with psychosis. This study examines the extent to which observed associations between hallucinogen use and psychosis are mediated by preexisting psychiatric conditions, providing important evidence for psychedelic policy formulation. Methods: We conducted a retrospective analysis using MarketScan Medicaid and commercial claims databases from 2015-2019. The population-based sample included individuals receiving substance use disorder treatment with documented substance-related emergency admissions or hospitalizations. We compared psychosis-related admissions occurring 30 days to 6 months postindex event between individuals with hallucinogen-related admissions versus those with nonhallucinogen substance-related admissions. Cox regression models adjusted for demographics and clinical characteristics to determine whether prior psychiatric history explained observed associations. Results: Among 273,466 individuals with substance-related admissions, psychosis diagnoses were more prevalent following hallucinogen-related admissions (16.4%) compared to nonhallucinogen substance admissions (6.6%, P<.001). While unadjusted models showed increased psychosis risk for hallucinogen-related admissions (hazard ratio [HR]=1.22, 95% CI=1.19-1.25), this association became nonsignificant after adjusting for clinical characteristics (HR=0.97, 95% CI=0.95-1.00). Conclusions: Apparent associations between hallucinogen use and psychosis appear largely attributable to baseline psychiatric comorbidities rather than direct causal effects. These findings carry implications for evidence-based policy development, suggesting that observed epidemiologic associations may reflect underlying vulnerability factors rather than hallucinogen-induced psychosis. Policymakers should consider these results when interpreting population-level data regarding hallucinogen safety profiles and regulatory frameworks.

Objective: The placebo effect is established in psychiatry, yet its role in substance use disorders (SUDs) treatment remains unclear. The aim of this study was to evaluate changes in craving scores in placebo groups in randomized controlled trials (RCTs) across different SUDs in adults. Data sources: Eight different databases (PubMed, Embase, Web of Science, Cochrane Library, Emcare, MEDLINE, PsycINFO, and Academic Search) were systematically searched up to October 28, 2024, by 2 independent researchers. Study selection: Placebo-controlled, double-blind RCTs assessing craving in patients with SUDs were included based on predefined eligibility criteria, published in English, Dutch, Spanish, or German language. Search terms were a combination and synonyms of "craving," "addiction," and "placebo." From a total of 1945 unique records identified, 9 articles met our eligibility criteria. Data extraction: Data on demographic characteristics, study design, and outcome results were extracted. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for pre-post craving scores within each placebo group; a positive difference point towards improvement in the postplacebo period. Results: A total of n=495 placebo-treated participants were included from nine RCTs in three different SUDs (n=300 in alcohol, n=88 in cocaine, and n=107 in methamphetamine use disorder). Craving scores significantly decreased over time (meaning symptom improvement) in the placebo treatment group in alcohol use disorder (5 studies, SMD=0.93 [95% CI=0.33 to 1.54]) but did not reach statistical significance in cocaine use disorder (2 studies, SMD=0.61 [95% CI=-1.41 to 2.62]) or in (meth)amphetamine use disorder (2 studies, SMD=0.44 [95% CI=-3.43 to 4.32]). Conclusions: Placebo treatment led to reductions in craving scores across all three SUDs, although statistical significance was achieved only in alcohol use disorder. Given the low number of studies for cocaine and (meth)amphetamine use disorder, these estimates were captured with much uncertainty. These findings may inform the design of future RCTs and support the development of more individualized treatment approaches in clinical settings.

Objective: Postpartum depression (PPD) is a debilitating mood disorder with peripartum onset. Current treatment options are limited in PPD. GH001 is a synthetic inhalation formulation of the psychoactive molecule mebufotenin (5-MeO-DMT). This trial investigated the preliminary efficacy and safety of GH001 in adult females with PPD. Methods: This phase 2a, proof-of-concept, open-label trial enrolled women aged 18-45 years (March 2023 to August 2024) with a Mini-International Neuropsychiatric Interview-confirmed diagnosis of major depressive disorder with peripartum onset. Patients had Montgomery-Asberg Depression Rating Scale (MADRS) scores of ≥28 at baseline. GH001 was administered as an individualized dosing regimen of up to 3 escalating doses (6, 12, and 18 mg) on day 1. The primary end point was the change in MADRS total score from baseline to day 8. Secondary end points included antidepressant response (≥50% reduction), remission (MADRS total score ≤10), and safety and tolerability of GH001. Results: Ten patients were enrolled. Mean baseline MADRS total score was 36.7 (SD = 4.8). Mean MADRS total score change from baseline to day 8 was -35.4 points (SD = 5.5; P < .0001). All patients achieved response and were in remission on day 8, which was first observed 2 hours after their final dose on day 1. Inhalation of GH001 was well tolerated, and no serious adverse events (AEs) were reported. All treatment-emergent AEs were mild or moderate, with headache as the most frequently reported AE. Conclusion: GH001 demonstrated rapid and significant improvements in depressive symptoms and remission of PPD with an acceptable safety profile and parallel improvements across secondary end points. Trial Registration: ClinicalTrials.gov identifier: NCT05804708; EudraCT identifier: 2021-006879-42.

Sleep is an important biological function. This article considers practical matters related to the prescription of sedative-hypnotic drugs to patients with insomnia. This article also presents practical suggestions for the management of excessive sedation in patients who need pharmacologic treatments with sedating adverse effects when dose reduction is not an option. Issues examined include the choice of drug for sleep-onset insomnia and for sleep-maintenance insomnia; the choice of drug for insomnia in patients with psychiatric disorders; sedative-hypnotic dosing in contexts such as perturbation of multiple neurotransmitter systems; metabolic drug interactions with sedative-hypnotic drugs; gastrointestinal absorption of hypnotic drugs and time to onset of drowsiness; the effect of food on absorption and time to onset of drowsiness; the effect of glucagon-like peptide-1 receptor agonist (GLP-1RA) drugs on absorption and time to onset of drowsiness; the importance of half-life for the duration of action of the sedative-hypnotic drug; strategies to address oversedation with sedating psychotropic drugs; treating insomnia with classical monoamine oxidase inhibitors, especially tranylcypromine; optimization of sedative-hypnotic therapy; provision of patient guidance; and related matters. Readers are also reminded that sleep hygiene and cognitive-behavioral approaches should routinely be combined with sedative-hypnotic drug therapy to optimize insomnia care and improve treatment outcomes.