Stronger, longer, better opioid antagonists? Nalmefene is NOT a naloxone replacement.

The fatal overdose crisis claims nearly 200 lives daily in the United States (U.S). Evolutions in the illicit drug supply, such as the addition of sedative adulterants and a shift to synthetic opioids such as fentanyl, have driven increasing rates of both fatal and non-fatal overdose. Specifically, synthetic opioid usage of fentanyl was implicated in 68 % of the U.S. drug overdose deaths in 2022 alone. This has placed tremendous burden on communities, emergency medical services, and healthcare systems, and contributed to tragedy and grief both in the U.S. and worldwide. Despite the availability of effective opioid antagonist medications and standards of care, there has been increased interest in research and development of alternative opioid overdose reversal agents by the National Institutes of Health (NIH) in partnership with pharmaceutical manufacturers over the last decade. The U.S. Food and Drug Administration (FDA) recently approved nalmefene (Opvee) a mu-opioid receptor antagonist that boasts an extended half-life and stronger mu-receptor affinity compared to the standard of care use of naloxone for opioid reversal. In this article, we explore the medical need and ramifications of the introduction of longer-acting opioid antagonists in the current opioid overdose landscape. Existing data highlight the effectiveness of already available naloxone products as a safe and effective standard of care. These data support the notion that stronger, longer-acting agents may be unnecessary, and their existence may cause undue harm, such as more severe and/or prolonged withdrawal symptoms, lead to challenging patient interactions, and complicate the initiation of medications for opioid use disorder. More evidence is needed before healthcare professionals should implement the use of stronger, longer-acting opioid antagonists for reversing opioid overdose over evidence-based, cost-effective naloxone.

Integration of a Community Opioid Treatment Program into a Federally Qualified Health Center.

OBJECTIVES: With the increasing rates of opioid overdose deaths in the United States, barriers to treatment access for patients seeking medications for opioid use disorder (OUD), and challenges of initiating buprenorphine in patients who use fentanyl, it is essential to explore novel approaches to expanding access to methadone treatment. An opioid treatment program (OTP) and a federally qualified health center (FQHC) partnered to develop and implement an innovative integrated methadone and primary care treatment model. The process for integrating an OTP and FQHC to provide methadone treatment in the primary care setting will be discussed. METHODS: An OTP methadone dispensing site was co-located in the FQHC, utilizing a staffing matrix built on the expertise of each stakeholder. The OTP managed DEA and state regulatory processes, whereas the FQHC physicians provided medical treatment, including methadone treatment protocols, treatment plans, and primary care. Patient demographics, medical history, and retention data for those who entered the program between January 2021 and February 2023 were collected through chart review and analyzed with descriptive statistics. RESULTS: A total of 288 OTP-FHQC patients were enrolled during the study. Retention rates in methadone treatment at 90 and 180 days were similar to partner clinics. CONCLUSIONS: Collaboration between FQHCs and OTPs is operationally feasible and can be achieved utilizing the current staffing model of the FQHC and OTP. This model can increase access to treatment for OUD and primary care for an urban, underserved patient population.

Medication-assisted recovery for opioid use disorder: A guide.

Considering offering medical intervention for OUD to reduce mortality? It's essential to understand the clinical benefits, limitations, and regulation of available agents.

Phenotypic differences between pregnancy-onset and postpartum-onset major depressive disorder.

OBJECTIVE: To compare clinical features of major depression that begins during pregnancy to clinical features of postpartum-onset depression. The hormonal environments of pregnancy and postpartum periods are quite different and therefore may promote distinct subtypes of major depression. METHOD: Data were collected from medical records of 229 women who were evaluated in an academic medical center reproductive psychiatry clinic. All patients evaluated between 2005 and 2010 who were pregnant or in the first year postpartum and received a DSM-IV diagnosis of major depressive disorder were included. Comparisons between the pregnancy-onset and postpartum-onset subjects included demographics, psychiatric diagnostic history, psychosocial stressors, reproductive history, and current episode symptoms. Time of onset within trimesters of pregnancy and within the postpartum year as well as the effects of discontinuation of antidepressant medication were also examined. RESULTS: Women with major depressive episodes that began during pregnancy had higher rates of prior episodes of postpartum and nonperinatal major depression (both P values < .001). Major depression that began during pregnancy was also more commonly associated with psychosocial stressors. Obsessive-compulsive symptoms and psychotic symptoms were more common in postpartum-onset depression. These findings were also evident in the subgroup of 176 subjects who did not discontinue antidepressant medication during the year prior to development of perinatal depression. The onset of 94% of postpartum major depressive episodes occured within the first 4 months postpartum. Episodes of major depression during pregnancy were more likely to develop in the first trimester for women who discontinued antidepressant medication within the past year; otherwise, depression onset was more evenly distributed across trimesters. CONCLUSIONS: Women with a history of perinatal and nonperinatal major depression are more likely to relapse during pregnancy than postpartum, a finding that points to the need for closely monitoring these women for depression during pregnancy. In addition, these findings of differences in risk factors and clinical features suggest that postpartum-onset major depression may have a pathophysiology distinct from major depression that begins during pregnancy. Time of onset of perinatal depression should be considered in the design of genetic and treatment studies.

BDNF Val66Met impairs fluoxetine-induced enhancement of adult hippocampus plasticity.

Recently, a single-nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene (BDNF Val66Met) has been linked to the development of multiple forms of neuropsychiatric illness. This SNP, when genetically introduced into mice, recapitulates core phenotypes identified in human BDNF Val66Met carriers. In mice, this SNP also leads to elevated expression of anxiety-like behaviors that are not rescued with the prototypic selective serotonin reuptake inhibitor (SSRI), fluoxetine. A prominent hypothesis is that SSRI-induced augmentation of BDNF protein expression and the beneficial trophic effects of BDNF on neural plasticity are critical components for drug response. Thus, these mice represent a potential model to study the biological mechanism underlying treatment-resistant forms of affective disorders. To test whether the BDNF Val66Met SNP alters SSRI-induced changes in neural plasticity, we used wild-type (BDNF(Val/Val)) mice, and mice homozygous for the BDNF Val66Met SNP (BDNF(Met/Met)). We assessed hippocampal BDNF protein levels, survival rates of adult born cells, and synaptic plasticity (long-term potentiation, LTP) in the dentate gyrus either with or without chronic (28-day) fluoxetine treatment. BDNF(Met/Met) mice had decreased basal BDNF protein levels in the hippocampus that did not significantly increase following fluoxetine treatment. BDNF(Met/Met) mice had impaired survival of newly born cells and LTP in the dentate gyrus; the LTP effects remained blunted following fluoxetine treatment. The observed effects of the BDNF Val66Met SNP on hippocampal BDNF expression and synaptic plasticity provide a possible mechanistic basis by which this common BDNF SNP may impair efficacy of SSRI drug treatment.