搜索结果：Journal of addiction medicine

This study explored the utilization of medication for addiction treatment (MAT) by participants in one state physician health program (PHP) over the course of 30 years, and reviewed patterns of use and monitoring outcomes. Data were extracted from the PHP records of 45 physicians and 37 pharmacists with substance use disorder (SUD), with or without co-occurring pain disorder, who used opioid [partial] agonist or antagonist medication, with or without other MAT. Variables of interest included demographics, type/length of monitoring, use of medications during monitoring, results of neurocognitive testing, and monitoring outcomes. Descriptive statistics were used to characterize PHP participants. χ2 tests, Fisher exact test, and t tests were used for group comparisons. Findings demonstrated positive outcomes among the PHP participants, regardless of MAT use status, with over 70% graduating monitoring or currently in good standing. A minority completed their initial monitoring but returned to the PHP due to return-to-use (n=4, 4.9%), discontinued monitoring against recommendations (n=4, 4.9%), or were turned over to the licensing board due to noncompliance with monitoring (n=4, 4.9%). There were 5 deaths (unrelated to substance use). Periods of MAT use were not associated with worse outcomes or additional impairment. All FDA-approved MAT should be considered for physicians and pharmacists monitored by a PHP, on an individual basis, when deemed clinically appropriate. Extended-release formulations may be particularly helpful for this population. Results may help clarify misunderstandings and controversies surrounding the use of MAT for PHP participants, while also advancing patient-centered, evidence-based care.

Patterns of smartphone use vary across ages; however, adolescents and young adults may be at particular risk, with more behavioral addictions and adverse health effects. This study explored the prevalence of smartphone addictions among health adolescent professional students and examined how problematic smartphone usage interferes with their level of physical activity as well as health-related quality of life. A cross-sectional Analytical study based on self-perceived outcome measures such as the smartphone addiction scale-short version, the 'International Physical Activity Questionnaire-short form', and 'Patient-Reported Outcomes Measurement Information System 29'-item profile was done with a sample of 400 participants. A total of 400 individuals (125 Males & 275 females) with mean age being 20.8 + 2.06 years recruited for the study. Smartphone addiction was most prevalent in dentistry students (43 %), followed by medicine (32 %) and allied health science (30.5 %), with no statistically significant differences in the addiction rate among the three programs. Compared with smartphone-addicted individuals, nonaddicted individuals had marginally greater physical function (mean difference =0.670, p<0.001), and those addicted to smartphones had significantly higher. anxiety (mean difference = 2.776, p<0.001), depression (mean difference =2.264, p< 0.001), and fatigue (mean difference =2.264, p<0.001). Physical activity was found to have no statistically significant difference between addicted and non-addicted individuals and except for sleep disturbance, none of the domains of PROMISE-29 showed any statistically significant correlation with physical activity. The findings highlight the need for recommendation for setting a time limit for the usage of smartphones for formal and informal academic activities, as well as policy measures to promote normal smartphone use.

The folding pattern of the anterior cingulate cortex is variable among individuals. The paracingulate sulcus (PCS), in particular, can be difficult to identify because of this variability. In this paper, we assessed the benefits of a new protocol to identify the PCS and measure its length using 3D reconstructions of the brain obtained through the BrainVISA software. Both the previous state-of-the-art protocol and the new protocol were applied to identify the PCS in subjects from a UK cohort (n&#x2009;=&#x2009;50), with the length of the PCS computed automatically by BrainVISA after PCS identification. We assessed inter-rater reliability for PCS length under both protocols and the correlation of PCS length values output by the two protocols. Inspection of the results indicated an advantage of the new protocol as there are 8 out of 100 hemispheres in which the old protocol detects a PCS due to the mislabelling of the intra-limbic sulcus as the cingulate sulcus and the new protocol does not. This advantage is conferred by the incorporation of identification of the intra-limbic sulcus (when present) in the new protocol. For instances where the protocols agreed on the presence of a PCS, the new protocol for PCS length obtained intra-class correlations of 0.85 and 0.86 on respectively untrained and trained experimenters, compared to 0.81 when trained experimenters used the previous protocol. The PCS length correlation between both protocols was 0.73 for the entire sample and 0.85 after excluding instances where the protocols disagreed on the presence of a PCS. These findings suggest that taking into account the intra-limbic sulcus and taking advantage of 3D sulcal visualisation may help improve reliable PCS identification, and that the new protocol is a reliable tool that is likely to prove useful in research into cingulate and paracingulate cortical folding.

Substance use treatment and harm reduction strategies are vital tools in addressing the overdose crisis, however, effectiveness depends on access and uptake. Little is known about perceptions of harm reduction and substance use treatment efforts among people who use drugs (PWUD) in minoritized communities and how to enhance acceptability and uptake of evidence-based care. Our aim was to explore perceptions of drug use, PWUD and approaches to harm reduction and treatment in an urban, predominantly Black neighborhood heavily impacted by overdose. We conducted one-on-one, semi-structured interviews with a purposive sample of participants living or working in West and Southwest Philadelphia, focusing on factors influencing uptake of substance use services. Interviews were recorded, transcribed, and analyzed using thematic analysis. We completed 19 interviews. Mean participant age was 46, 79% of the sample were women; 83% were Black/AA. Half of participants worked with PWUD in health or social service roles (50%), and the majority had lived experience of substance use personally or with a close friend or family member (83%). Participants reported several factors of attitudes toward substance use, PWUD, and addiction care in the community. First, participants frequently referenced the legacy of the punitive drug policies regarding current community apprehension about substance use services. Participants reported a high degree of community stigma towards PWUD, as well as a view of harm reduction as an endorsement of drug use rather than a public health effort. Stigma also shaped cultural norms, limiting acceptability of care-seeking among PWUD. In addition, participants highlighted the toll of systemic racism, noting that it contributed to generational trauma, substance use, and overall vulnerability to addiction and overdose. Finally, participants emphasized the importance of community-driven initiatives, culturally appropriate services, and expanded outreach to actively address and dismantle the structural inequities. Overall, participants from West and Southwest Philadelphia described how the combined impact of the war on drugs, systemic racism, and medical system mistrust has shaped the experiences of Black PWUD and their communities. Participants highlighted the need for equitable, culturally responsive public health policies that safeguard the provision of harm reduction services for Black PWUD.

In March 2025, the expiration of federal pilot funding for Safer Supply Programs (SSPs), combined with restrictive provincial legislative changes to harm reduction service provision in Ontario, disrupted care for thousands of clients at risk of toxic drug poisoning. This study examines the impacts of these changes on client health, social stability, and overdose risk across a continuum of access. We conducted 30 semi-structured virtual interviews between September and November 2025 with clients who were enrolled in an SSP prior to March 31, 2025. Participants were recruited via purposive and snowball sampling. Data were analyzed using Braun and Clarke's reflexive thematic analysis to explore experiences across three distinct groups: those who maintained continuity with their prescriber or SSP, those who transitioned to a new prescriber or SSP, and those who lost access entirely. Experiences of harm were directly proportional to the degree of service disconnection. Participants who maintained access (n&#x2009;=&#x2009;10) retained clinical stability, but reported chronic anxiety and "survivor's guilt" regarding peers who lost care. Participants who transitioned to an alternative prescriber (n&#x2009;=&#x2009;13) experienced a "medicalization of harm reduction" characterized by increased surveillance (e.g., urine screens, monitored dosing), revoked take-home doses, and the loss of trusted relationships, which undermined their autonomy and stability. Those who lost access entirely (n&#x2009;=&#x2009;7) experienced significant harms, such as the loss of an entire ecosystem of care (i.e., medication, primary care, and community), an immediate return to the unregulated fentanyl market, and engagement in survival strategies that can lead to criminalization. Notably, 100% (n&#x2009;=&#x2009;5) of participants who reported an overdose following the policy changes belonged to this group. The loss of federal funding for SSPs in Ontario did not solely reduce medication availability; it severed the structural and relational network that supported participants' reintegration into health care services that they previously felt uncomfortable accessing due to stigma, surveillance and mistreatment. Findings reveal a "continuum of disconnection" where the removal of wraparound supports and the reintroduction of punitive clinical practices function as forms of structural violence. Sustainable, low-barrier models are urgently needed to prevent further morbidity and mortality.

The methadone:metabolite ratio (MMR) is a laboratory value assessed pre-dose to discriminate between individuals who are rapid or slow metabolizers. It is a proposed alternative to peak:trough serum methadone ratios to assess the impact of individual genetics on methadone metabolism to guide dosing frequency of methadone in adults. Pregnancy represents a state of dynamic metabolism of many drugs, including methadone, but there is little study of the MMR in pregnancy. We aimed to (1) assess how well MMR assessed during methadone initiation in pregnancy correlates with the gold standard of assessing metabolism (peak:trough ratio which requires 2 blood draws), (2) describe MMR as assessed during initiation of methadone across gestation to see if it reflected altered metabolism in pregnancy, and (3) determine whether differences in MMR correlated with measures of therapeutic effect, which would suggest it is a potentially useful tool to guide dosing regimens of methadone in pregnancy. This is a prospective study of pregnant patients with singleton gestation admitted for methadone initiation starting with a dose of 30&#xa0;mg and increasing by 10&#xa0;mg every 4 hours as needed based on withdrawal symptoms, with an increase in the daily dose the next day. Plasma samples of methadone and the metabolite EDDP were obtained pre-morning dose and 4 hours post-dose. MMR was evaluated both as a continuous variable and categorical: MMR<5: ultra-rapid metabolizer, MMR 5-11: extensive metabolizer, MMR 12-16: intermediate metabolizer, MMR&#x2265;16 ultra-slow metabolizer. Additional endpoints of Clinical Opioid Withdrawal Scale (COWS) and pupil dilation were assessed. Multivariable generalized estimating equations used for analyses. From March 2023 to May 2024 31 patients with 107 samples available were included. MMRtrough increased with methadone dose the prior 24 hours [0.01 (0.01, 0.02), P<0.001] and decreased with advancing trimester of admission [-2.95 (-5.00, -0.90), P=0.005 for second vs. first trimester and -2.78 (-4.98, -0.58), P=0.01 for third vs. first trimester]. A greater proportion of results reflected an ultra-rapid metabolizing state in the second and third trimester compared with the first (77% and 71% vs. 23%, P<0.001). MMR was highly correlated with log-corrected methadone peak:trough throughout gestation, regardless of trimester [B coefficient -3.36 (-5.65 to -1.06), P=0.004]. Regarding clinical effects-pupil dilation was significantly associated with methadone dose, with an expected pupilar constriction associated with increasing methadone dose [-0.55 (-0.75, -0.34) P<0.001]. There was significantly reduced pupillary constriction (relative larger post-dose diameter) identified in the third trimester versus first [adjusted mean difference 0.67 (0.20, 1.13)]. There was no significant association between MMR and pupillary change. MMR was associated with time needed to achieve a stable dose, with those who were extensive metabolizers requiring greater time to stable dose compared with ultra-rapid metabolizers [mean difference 3.37 (0.61-6.13) d, P=0.02]. Although MMR has historically been used to reflect genetic variants impacting methadone metabolism, in pregnancy it reflects the increased metabolism with advancing gestation and is associated with clinical/therapeutic effect. MMR may be a useful marker to guide methadone dosing protocols in pregnancy to optimize therapeutic effect.

Alcohol and opioid use disorders (AUD, OUD) cause significant morbidity and mortality among Veterans, yet only a minority receive evidence-based treatment. Beginning in February 2022, we piloted a telemedicine pharmacist-physician management model (PPMM) in 6 Veterans Health Administration (VHA) primary care community-based outpatient clinics (CBOCs) across one VHA Health Care System to improve rural Veteran access to medications for opioid and alcohol use disorder (MOAD). Veterans with AUD and/or OUD receiving primary care in participating CBOCs during the year following implementation were eligible for referral. Data obtained from study records and VHA electronic health records assessed patient sociodemographic and clinical characteristics and MOAD receipt among referred Veterans. There were 2274 Veterans diagnosed with AUD (n = 2062) and/or OUD (n = 307) receiving primary care from CBOCs during the study period. Of this population, 111 (4.9%) Veterans were referred and received PPMM services (AUD: n = 93; OUD: n = 9; AUD and OUD: n = 9), the mean age was 52 years, 92% were male, 68% White, and 39% lived in rural zip codes. Of the 102 Veterans referred to PPMM with AUD, 71% received medication. Of the 18 Veterans referred with OUD, 78% received medication. Most Veterans who were newly initiated on MOAD (N = 74) received medication within 72 h (N = 50, 68%). In this pilot implementation of same-day telemedicine PPMM, high rates of MOAD receipt were seen among referred Veterans. However, most Veterans with AUD/OUD seen in participating clinics were not referred. Further evaluation of barriers and/or facilitators to referral are needed to increase program uptake.

The coronavirus disease 2019 (COVID-19) pandemic has strongly challenged health systems, but Italian community mental health services, rooted in the Basaglia reform and the World Health Organization (WHO) QualityRights framework, may have preserved a high perception of care quality and respect for human rights. This study compared users' perceptions of quality of care, human rights, and resource adequacy in public mental healthcare facilities during and after the pandemic in Sardinia, Italy. A cross-sectional survey was conducted in 2025 among users attending three community mental health services (Nuoro and Sanluri Local Health Networks) and one university hospital facility (Cagliari). Data were compared with a previous survey carried out in the same network during the COVID-19 pandemic (2021). Users completed a brief sociodemographic form and the "Well-Being at Work and Respect for Human Rights Questionnaire" (WWRR, user version), inspired by the United Nations (UN) Convention on the Rights of Persons with Disabilities and WHO QualityRights. Group differences were analyzed using chi-square tests and one-way analysis of variance (ANOVA). The final 2025 sample included 118 users, compared with 200 users in 2021. Mean satisfaction scores for overall care and organizational aspects (WWRR items 1-3) remained very high in both surveys (>5/6) without significant differences. Perceived respect for users' rights (item 4) and staff rights (item 5) significantly increased post-pandemic (5.26&#x202f;&#xb1;&#x202f;1.10 vs. 5.51&#x202f;&#xb1;&#x202f;0.98, p&#x202f;=&#x202f;0.042; and 4.89&#x202f;&#xb1;&#x202f;1.22 vs. 5.35&#x202f;&#xb1;&#x202f;1.04, p&#x202f;=&#x202f;0.001, respectively). Perception of resource adequacy (item 6, reverse-coded) also improved (2.68&#x202f;&#xb1;&#x202f;1.10 vs. 2.06&#x202f;&#xb1;&#x202f;0.98, p&#x202f;<&#x202f;0.001), although it remained the most critical domain. Item 7 indicated an evolving demand for a more diversified workforce, with psychologists being the most frequently requested professionals, and an emerging perceived need to increase multiple professionals across multiple categories and administrative/management staff. Users of Sardinian community mental health services reported persistently high satisfaction and an increased perception of respect for human rights after the COVID-19 pandemic, despite ongoing concerns about limited resources. These findings highlight the resilience of community-based mental healthcare and underscore the need for structural investment and the strengthening of the multidisciplinary workforce strengthening to sustainably align service provision with international human rights standards.

Housing instability is associated with adverse mental health and increased health care use. Policies that reduce eviction risk may affect mental health-related health care utilization. Eviction moratoria enacted during the COVID-19 pandemic provide a natural experiment to examine these associations. To examine whether the lifting of eviction moratoria during the pandemic was associated with changes in mental health care utilization. A synthetic difference-in-differences approach was used, with state-week level, nationwide data of all-payer records of individuals with a mental health diagnosis or medication prescription in March to August 2020 and June to December 2021. The data were analyzed from November 2024 to November 2025. Two phases of eviction moratorium expirations were analyzed. Phase 1 included staggered expiration of state eviction moratoria from March to August 2020; phase 2 assessed the expiration of the federal eviction moratorium in August 2021, when some states maintained their own state-level eviction moratoria after the federal expiration. State-level or federal-level eviction moratorium expirations. Weekly, state-level counts of unique patients who had (1) any outpatient mental health visit, (2) any psychotropic medication prescription, (3) outpatient visits associated with mood-related disorders, (4) outpatient visits associated with serious mental illness (SMI), and (5) suicide-related visits. Of 8&#x202f;963&#x202f;310 individuals, 62% were female, and the mean (SD) age was 42.8 (21.5) years. Expiration of moratoria was associated with statistically significant increases in the weekly number of patients who were prescribed a psychotropic medication (0.57% in phase 1 and 1.17% in phase 2) and the number of patients who received outpatient care for SMI (3.42% in phase 1 and 3.13% in phase 2). By contrast, no measurable changes were observed in the overall patient count for mental health-related outpatient visits, outpatient visits associated with mood-related conditions, or suicide-related visits. The results of this differences-in-differences study suggest that the expiration of eviction moratoria was associated with increases in the mean number of patients with psychotropic medication prescriptions and outpatient visits for SMI. These findings underscore the importance of housing for psychiatric treatments and highlight the broader health care implications of housing policy decisions.

The purpose of this study was to assess the efficacy of metacognitive training for psychosis (MCT). The primary goal was to study the severity and the different dimensions of delusions. The secondary goal was to study its impact on self-esteem and depressive symptoms. This study was planned as a multicentre randomized controlled clinical trial. A sample of 122 patients with a recent-onset diagnosis of schizophrenia spectrum disorders was randomized to receive an MCT intervention (N&#x2009;=&#x2009;65) or a psychoeducational intervention (N&#x2009;=&#x2009;57). Patients were assessed at three different time points (baseline, post-treatment and 6&#x2009;months follow-up) with the following measures: the Psychotic Symptoms Rating Scale-Delusion subscale (PSYRATS-Del), the Beck Depression Inventory (BDI-II) and the Rosenberg Self-Esteem Scale (RSE). A generalized linear model comparing the MCT group and psychoeducational group in the main measures across all three assessment moments was constructed, controlling for the number of sessions they attended. In comparison with the psychoeducational group, MCT improved in several dimensions of delusions at the follow-up: amount of preoccupation about delusions (p&#x2009;=&#x2009;0.048), duration of preoccupation about delusions (p&#x2009;=&#x2009;0.048) and conviction (p&#x2009;=&#x2009;0.048). No differences between groups were found in self-esteem or depression at any time-point, but both interventions improved self-esteem-in the follow-up. In recent-onset psychosis patients, MCT demonstrated the expected benefits in conviction, as 'sowing seeds of doubt' is the core MCT mechanism of change. Despite functioning differently, both interventions improved patients' self-esteem. No superiority of MCT was discovered in self-esteem or depression in the short-term follow-up studied.

This study investigated the acceptability and preliminary efficacy of a peer recovery support services (PRSS) intervention focused on enhancing retention on medication for opioid use disorder (MOUD) through a pilot RCT. Individuals on MOUD who were newly living in a recovery residence or a long-term residential program (ie, ASAM level 3.1) were randomized to either MOUD-focused PRSS or usual care only for 24 weeks (168&#xa0;d). Negative binomial and logistic regression analyses using data from 40 adults (n=20 in PRSS and n=20 in TAU) tested for group differences on the primary outcome of cumulative days of MOUD adherence and secondary outcomes of other MOUD retention metrics, opioid use and return to regular use, and intervention acceptability assessed with an investigator-created satisfaction survey. Results revealed no group differences on primary or secondary outcomes, with those in PRSS reporting M=126 days of MOUD adherence compared with M=127 days in TAU. Overall satisfaction levels averaged 6.71 out of a possible 7. The results of this study did not support our hypothesis that PRSS would enhance MOUD adherence; however, this is likely due to a ceiling effect. Participants from both groups had higher-than-expected MOUD adherence (&#x223c;75% of days). Participants who received the PRSS intervention rated it very highly, and notably, were not opposed to the integration of MOUD into PRSS. These results suggest that the PRSS intervention was acceptable and feasible, but that it should be further developed and tested for patients who face more barriers to MOUD retention.

The renewal of psychedelic medicine has garnered significant scientific interest, with large efforts dedicated to the understanding of the complex subjective experiences induced by these substances. The Altered States of Consciousness (ASC) questionnaire represents the most comprehensive instrument for measuring such experiences yet lacks a validated French translation despite its centrality to research. A psychometric validation of the French 5D-ASC and 11 OAV subscales was conducted using data from 777 participants recruited through online platforms. Participants completed the 94-item questionnaire based on a past naturalistic psychedelic experience induced by a classical or non-classical psychedelic substance. Confirmatory factor analysis (CFA) of established factorial structures, multiple-indicator multiple-cause (MIMIC) modeling assessing measurement invariance across substance categories, and comprehensive reliability analyses were used. The 11-subscale solution demonstrated better fit compared to higher-order structures (CFI&#xa0;=&#xa0;0.882, RMSEA&#xa0;=&#xa0;0.051, SRMR&#xa0;=&#xa0;0.061), though comparative fit indices remained marginally below conventional thresholds. Internal consistency was excellent for global scores (&#x3b1;&#xa0;=&#xa0;0.95) and satisfactory across individual subscales (&#x3b1;&#xa0;=&#xa0;0.63-0.84). Construct validity was supported by theoretically consistent inter-scale correlations and convergent validity with single-item validators. MIMIC modeling revealed modest differential item functioning but confirmed measurement invariance, with latent factor differences aligning with known pharmacological profiles. This study provides preliminary evidence for the psychometric validity of the French 5D-ASC. These findings enable future research examining the relationship between subjective experience and therapeutic outcomes in francophone contexts, contributing to the international standardization of psychedelic research instruments.

Early recognition of alcohol use disorder (AUD) in women can reduce the risk of developing alcohol-related liver disease (ALD). For many women, reproductive health visits, including cervical cancer screening may be their only health care contact. We aimed to evaluate the prevalence of AUD and ALD in women undergoing cervical cancer screening and whether these visits represent missed opportunities for AUD identification. This is a retrospective analysis of adult women aged 21-65 who underwent cervical cancer screening in the nationwide MarketScan Database 7/1/2013-12/31/2021. ICD coding was used to identify inpatient/outpatient AUD/ALD diagnoses. Median time to AUD/ALD diagnosis was calculated, and the cumulative incidence of inpatient AUD/ALD following an initial outpatient encounter was estimated using the Kaplan-Meier method. A total of 11,429,720 women underwent cervical cancer screening (mean age 41.7&#xa0;y). AUD was identified in approximately 1 in 50 women, one-quarter of whom required hospitalization. Notably, 30.7% of women hospitalized for AUD previously saw a provider for cervical cancer screening where AUD was not diagnosed. ALD was present in 0.1% (1 in 1,000) of women screened for cervical cancer, with about half requiring hospitalization. Among those hospitalized for ALD, 24.5% previously saw a provider for cervical cancer screening where AUD had not been identified. A notable proportion of women hospitalized for AUD/ALD had a prior cervical cancer screening visit where AUD was not identified, representing a missed opportunity for intervention. Standardized screening and referral for treatment at these visits may reduce downstream consequences of harmful alcohol use.

Dopaminergic medication used in disorders like Parkinson's disease (PD) and restless legs syndrome can cause impulsive-compulsive behaviour (ICB), often with strong negative effects on patients' quality of life. This narrative review presents translational evidence on iatrogenic ICB, taking findings from epidemiological, clinical, neuroimaging and preclinical studies into consideration. Epidemiological and clinical studies find dopamine agonists with high D2/3-selectivity to be most strongly linked to ICB. Their effect on ICB has often been shown to be dose-dependent, but the impact of combining different dopaminergic drugs or applying extended-release formulations is less clear. Intervention studies support tapering or replacing dopamine agonists for ICB reduction, whereas no efficacious pharmacotherapy has been identified for ICB treatment specifically. Adequate animal models for mimicking different types of ICB are available, and point, in line with human neuroimaging studies, towards an involvement of striatum and prefrontal cortex in iatrogenic ICB. Overall, complementary research designs have led to profound evidence regarding the occurrence of ICB in PD and establishing methods transferable to other, less-studied patient populations. A combined approach integrating insights from human studies and animal models could contribute to developing dopaminergic drugs with lower ICB risk but also specific pharmacotherapies for impulsivity or compulsivity in the future. Diseases like Parkinson's disease and restless legs syndrome are treated with drugs that affect dopamine activity in the brain. As a side effect, these drugs can lead to a lower impulse control, manifested, for example, as gambling disorder or hypersexuality. This article summarises research on these side effects, collected through a variety of scientific methods. The drug type with the highest risk for behavioural side effects has been identified, but many details remain unclear, especially in patients with other disorders than Parkinson's disease. Results from both human brain imaging and animal models start to reveal brain pathways involved.

Continuation treatment with sertraline plus olanzapine is associated with lower risk of relapse of remitted psychotic depression than sertraline plus placebo. We examined the effect of continuation pharmacotherapy on health-related quality of life (HRQOL) in remitted psychotic depression. One hundred and twenty-six men and women, aged 18 to 85&#xa0;years, who had achieved sustained remission of psychotic depression with open-label treatment with sertraline plus olanzapine were randomized to continue sertraline plus either olanzapine or placebo. HRQOL was measured with the 36-item Short Form Health Survey (SF-36) at randomization baseline and study termination. The primary outcome was change in each of the eight SF-36 domains. Linear regression examined the relationship between randomized treatment and change in SF-36 domain scores. Sertraline plus olanzapine was associated with better outcomes in the Role Emotional (RE) and Mental Health (MH) domains than sertraline plus placebo. Relapse was associated with marked decline in both RE and MH scores. RE and MH scores at study termination were more than two standard deviations below the population mean in approximately one quarter of participants in the sertraline plus placebo group. In individuals with remitted psychotic depression, continuation treatment with sertraline plus olanzapine was associated with better outcomes in HRQOL domains directly relevant to mental health than treatment with sertraline plus placebo. These findings suggest that the benefit of sertraline plus olanzapine in preventing relapse of psychotic depression is associated with benefit in HRQOL.

To quantify the impact of the adulterated fentanyl supply, through the eras of xylazine and medetomidine predominance, on critical care charges associated with treatment of opioid withdrawal. A longitudinal retrospective analysis was conducted at 2 intensive care units (ICUs) in Philadelphia, PA, USA, from April 1, 2017, to September 30, 2025. Primary outcomes included median per quarter and per patient charges and median quarterly ICU admissions with a primary or secondary ICD-10 diagnosis of opioid withdrawal (F11.23) from Q2 2017 to Q3 2025. These dates were correlated with quarterly drug supply adulterant prevalence reports by the Philadelphia Department of Public Health (PDPH). Secondary outcomes included ICU length of stay. Median quarterly ICU charges for F11.23 increased from $1,383,688 (1,138,614-1,602,562), during the period when the drug supply only included fentanyl (BX), to $2,883,659 (2,625,205-3,466,314) during the period of xylazine dominance (XE), to $17,168,020 (11,302,464-19,963,551) (H=23.50, P <0.001) in the period following the emergence of medetomidine (ME). Increasing cost was driven primarily by an increase in patient admissions (median 62 admissions XE per quarter vs. 261 ME), rather than median charge per patient for (XE $28,336 vs. ME $44,525, P =0.167). The adulteration of synthetic opioids with medetomidine was associated with a dramatic increase in ICU admissions and charges related to opioid withdrawal diagnoses. These changes represent a substantial public health challenge that may require systematic changes to health system resource allocation and withdrawal protocols.

With the increase in fentanyl use, methadone remains one of the standards of care for opioid use disorder and may confer some advantages over buprenorphine. Yet the wide range of patient metabolism makes individual prescribing unpredictable. Induction and subsequent dose adjustments have historically been guided using a "start low and go slow" approach to minimize the risk of overdose, with individual metabolic differences unassessed. However, heroin's replacement by fentanyl in the illegal market has resulted in unprecedented levels of physical dependence necessitating higher doses and more rapid inductions. Methadone metabolism is unpredictable, largely due to phenotypic and genotypic variability of cytochrome P450 enzyme activity. Early research found a 17-fold variation in serum level for a given dose, corroborated recently by finding an equally wide range of individual metabolic speeds. Little work has been done documenting how this variability affects clinical response. Dosing practices have remained "pharmacokinetically blind" to a patient's capacity to metabolize a medication with a narrow therapeutic window and potentially serious consequences of underdosing or overdosing. Serum-based measures of methadone can provide objective information on individual metabolism. These tests include trough levels, peak levels, a methadone/metabolite ratio, and a peak/trough ratio. Genetic testing for variant alleles that alter metabolism (pharmacokinetics) or alter mu receptor activity (pharmacodynamics) can identify patients whose ability to metabolize methadone is either impaired or augmented. This review discusses the laboratory tools available to guide safe induction protocols and subsequent prescribing.

Disruptions in social and circadian rhythms are increasingly recognized as key contributors to depressive symptomatology and impaired quality of life, particularly in older adults, for whom daily regularity represents a crucial determinant of psychological and functional stability. Understanding the interplay between rhythm dysregulation, mood disturbances, and perceived well-being may inform preventive strategies in aging populations. This study aimed to examine the association between social rhythm dysregulation, depressive symptoms, and perceived quality of life in a sample of community-dwelling older adults. A cross-sectional observational study was conducted among 119 older adults (mean age 72.26 &#xb1; 4.72 years) enrolled in an active aging program. Social rhythms were assessed using the Brief Social Rhythm Scale (BSRS), depressive symptoms with the Patient Health Questionnaire-9 (PHQ-9), and health-related quality of life with the SF-12 Health Survey. Pearson correlation analyses and multiple linear regression models were applied. Greater social rhythm dysregulation was significantly associated with higher depressive symptom levels (r = 0.41, p < 0.001) and lower perceived quality of life (r = -0.39, p < 0.001). In multivariate analyses, both rhythm dysregulation (&#x3b2; = -0.1863, p < 0.001) and depressive symptoms (&#x3b2; = -0.2885, p = 0.037) independently predicted poorer quality of life. In community-dwelling older adults, irregular social rhythms and depressive symptoms are independently and jointly associated with reduced quality of life. These findings highlight social rhythm regulation as a relevant and potentially modifiable target for preventive and supportive interventions aimed at promoting mental well-being and resilience in later life.

Kratom (Mitragyna speciosa) is increasingly used in the United States as a dietary supplement for pain, mood regulation, and opioid withdrawal. Its alkaloids, mitragynine and 7-hydroxymitragynine (7-OH), demonstrate &#x3bc;-opioid receptor activity, with 7-OH exhibiting substantially greater opioid-like potency than mitragynine. There are concerns from the US Food and Drug Administration (FDA) regarding dependence and adverse effects. Purified 7-OH products may bypass metabolic pathways and deliver disproportionately strong opioid effects compared with natural kratom preparations, increasing the risk of dependence. Despite these concerns, 7-OH remains federally unscheduled, though listed as a "Drug of Concern" by the DEA. Although there is no standardized clinical guidance, buprenorphine has been used to manage kratom and 7-OH withdrawal with varying initiation strategies. To describe the clinical course and outcomes of buprenorphine initiation among patients with problematic 7-OH use, focusing on initiation timing, dosing strategies, and symptom monitoring. Retrospective chart review of patients treated at a low-barrier telehealth addiction medicine clinic between April and October 2025. Nine patients with purified 7-OH product use (as opposed to kratom use) met the inclusion criteria. The mean age was 33.5 years; 7 patients were identified as male. Low-dose initiation was used in 6 cases and standard initiation in 3 cases. Successful initiation and stabilization occurred in 88.9%, with no precipitated withdrawal or adverse events. Symptom improvement was reported in 8 of the total cases at a median 6-week follow-up. Buprenorphine initiation for problematic 7-OH use was feasible, well tolerated, and associated with symptom improvement, supporting development of pragmatic clinical approaches for this emerging substance use disorder.