Search Results (471)

Background/Objectives: Antidepressants are widely prescribed medications that may affect psychomotor performance and driving ability depending on their pharmacological profile. This study investigated the prevalence and patterns of antidepressant use among drivers undergoing forensic toxicological evaluation and explored their potential implications for road safety. Methods: An observational study was conducted on n = 6316 drivers undergoing forensic toxicological assessment following licence suspension for driving under the influence (DUI) of alcohol and/or drugs between January 2023 and December 2025. Reported antidepressants were classified into selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), serotonin antagonist and reuptake inhibitors (SARIs), tricyclic antidepressants (TCAs), norepinephrine–dopamine reuptake inhibitors (NDRIs), noradrenergic and specific serotonergic antidepressants (NaSSAs), and monoamine oxidase inhibitors (MAOIs). Distribution patterns were analysed descriptively and discussed considering the available literature. Results: Antidepressant use was reported by n = 132 participants (2.1%). SSRIs were the most common class (44.0%), followed by SNRIs (26.5%) and SARIs (17.4%). TCAs (6.1%), NDRIs (3.7%), and NaSSAs (2.3%) were less common, while no MAOI use was reported. Among antidepressant users, n = 28 individuals (21.2%) tested positive for other psychoactive substances, including benzodiazepines, cocaine, and cannabinoids. Conclusions: The use of antidepressants was relatively uncommon in the study population. However, clinical evaluation remains important, particularly at the start of treatment and during dose adjustments to determine the potential for an increased risk while driving. Further studies integrating toxicological analyses and clinical data are needed to better define the relationship between antidepressant exposure, polysubstance use, and road safety. Full article

Background: Pharmacological treatments are frequently prescribed for adolescents with anorexia nervosa (AN), mainly to address psychiatry comorbidities and associated clinical features, although evidence supporting medication-specific effects remains limited. This retrospective study examined 12-month clinical trajectories associated with different pharmacological treatment patterns in a cohort of female adolescents with AN admitted to a tertiary university hospital. Methods: Clinical records of 102 female patients aged 12–18 years with AN were retrospectively reviewed. Participants were first classified according to whether they received any pharmacological treatment and were subsequently divided into six groups: no medication, antidepressants, antipsychotics, mood stabilizers, combination therapy, and medication switching. Body mass index (BMI), Clinical Global Impression—Severity (CGI-S), Children’s Global Assessment Scale (C-GAS), and item 40 of the Structured Interview for Anorexic and Bulimic Syndromes—Expert Form (SIAB-EX) were evaluated at admission (T0, before treatment initiation), at 6-month follow-up (T1), and at 12-month follow-up (T2). Results: BMI improved significantly over time across all treatment groups. Compared with participants who received any form of pharmacological treatment, the non-medicated group exhibited a significantly greater increase in mean CGI-S scores and significantly greater reductions in mean C-GAS and SIAB-EX scores. Baseline comparison among the six treatment groups showed significant differences in CGI-S, C-GAS, and SIAB-EX item 40 scores, indicating that the groups were not fully comparable in terms of initial clinical severity, global functioning, and physical hyperactivity. Patients in the medication-switching group generally showed smaller improvements, whereas findings in the mood-stabilizer group should be interpreted cautiously because of the very small sample size. Conclusions: In this real inpatients cohort, adolescents with AN showed clinical improvement over 12 months across different pharmacological treatment patterns. However, baseline differences between groups and the non-randomized retrospective design preclude causal conclusions regarding medication-specific effectiveness. These findings should be interpreted as descriptive clinical trajectories associated with treatment patterns selected in routine care. Further prospective studies with standardized treatment data and adequately powered subgroups are needed. Full article

Background/Objectives: Alcohol consumption and medication use have increased among older population, potentially increasing the risk of alcohol–drug interactions and adverse outcomes. Biological sex differences may further influence these effects. This study aimed to assess sex-related differences in medication use, comorbidities, and hepatic biomarkers among older adults with risky alcohol consumption. Methods: A cross-sectional, multicenter study was conducted in 455 adults aged ≥65 years. Sociodemographic and clinical characteristics, medication prescriptions, and hepatic biomarkers were collected. Results: Of the participants, 41% were women, with a mean age of 71 years. The median weekly alcohol consumption was 7 standard drink units. Overall, 90% were taking at least one medication, with antihypertensives being the most prescribed (62%). Significant sex differences were observed (p ≤ 0.01): men showed higher use of antidiabetic drugs (24%), anticoagulants (8%), and nitrates (4%), whereas women more frequently used anxiolytics (35%), non-steroidal anti-inflammatory drugs (22%), and antidepressants (18%). Although risky alcohol consumption was more prevalent among men, women had a higher overall medication use. Significant differences were also observed in hepatic biomarkers, with higher gamma-glutamyl transferase levels and a higher prevalence of elevated FIB-4 values among men (p ≤ 0.01). Conclusions: These findings highlight the importance of routinely assessing alcohol consumption and medication use in older adults and support incorporating a sex-specific perspective into clinical practice and future research. Full article

Background/Objectives: Although psychopharmacotherapy and physical activity may benefit children with mental disorders, the association of psychotropic medications with physical activity remains unclear. The study evaluated the association between exposure to antidepressants or central nervous system (CNS) stimulants and the likelihood of meeting the Centers for Disease Control and Prevention (CDC) physical activity guidelines (≥60 min of moderate-to-vigorous physical activity daily) among U.S. children. Methods: We used data from the 2017–March 2020 National Health and Nutrition Examination Survey (NHANES) to quantify medication use and physical activity duration. The exposure to antidepressants and CNS stimulants in children and their level of physical activity were captured via interviews with pediatric participants and their adult proxies. The proportion of children meeting the CDC-recommended physical activity level was compared between propensity-score-matched antidepressant users vs. non-users, as well as matched CNS-stimulant users and non-users, using Rao–Scott chi-square tests. Results: Among 3835 NHANES participants aged 2–17 years, representing approximately 59.4 million U.S. children, 0.89% used antidepressants, and 2.40% used CNS stimulants. After accounting for age, sex, race/ethnicity, body mass index (BMI), and family income, a smaller proportion of CNS stimulant users met physical activity guidelines compared with non-users (22.06% vs. 37.02%; p = 0.0075). Antidepressant use was not significantly associated with physical activity level (12.06% vs. 15.52%; p = 0.6342). Conclusions: These findings highlight the importance of monitoring activity patterns among youth prescribed CNS stimulants and antidepressants, particularly integrating physical activity promotion into public health strategies. Full article

Background and Objectives: This study aimed to estimate the prevalence of documented borderline personality disorder (BPD) diagnosis and study-defined BPD indicators among adults with depressive disorders in outpatient psychiatric care, and to quantify a subgroup who were indicator-positive but had no documented diagnosis (potential under-recognition). Materials and Methods: This retrospective, cross-sectional study included adult outpatients with depressive disorders receiving pharmacological treatment at Maharaj Nakorn Chiang Mai Hospital. BPD status was classified using (1) a documented BPD diagnosis in the electronic medical record (EMR) and (2) study-defined indicators, comprising a symptom-based indicator (documentation of ≥5 DSM-5 BPD criteria) and a prescribing-based indicator (antidepressant treatment with concurrent use of antipsychotics and/or mood stabilizers). Prevalence and overlap across diagnoses and indicators were summarized using a Venn distribution. Results: Among 1175 patients, 63 (5.4%) had a documented BPD diagnosis. Using EMR indicators, 84 (7.1%) met the symptom-based indicator and 325 (27.7%) met the prescribing-based indicator. In total, 374 (31.8%) had either a documented BPD diagnosis or at least one indicator, while 801 (68.2%) had neither. Overall, 370 (31.5%) met at least one indicator (symptom-based and/or prescribing-based). Among indicator-positive patients, 311 (84.1%) had no documented BPD diagnosis, representing 26.5% (311/1175) of the total cohort. Conclusions: Study-defined EMR indicators flagged a substantial subgroup with potential under-recognition of BPD features in depressive-disorder clinics. These indicators may help prioritize targeted assessment and structured diagnostic evaluation to support access to BPD-informed care and support referral to BPD-informed psychotherapy. Full article

Background/Objectives: Chronic low back pain (CLBP) affects approximately 20% of the global population and is a leading cause of years lived with disability. Long-term, real-world evidence for inhaled cannabis in patients refractory to conventional multimodal therapy remains scarce. We assessed the five-year efficacy and safety of inhaled cannabis in CLBP patients who had documented failure of ≥1 year of opioid analgesics, anticonvulsants, antidepressants, NSAIDs, and physiotherapy, with each patient serving as their own historical control. Methods: We analyzed prospectively collected clinical data from 241 consecutive adults with treatment-refractory CLBP (mean age 49.3 ± 14.9 years; 37.8% female; mean pain duration 15.1 years) initiated on inhaled medical cannabis (predominantly smoking, THC 4–22%, CBD 2–22%) in a single-center tertiary orthopedic clinic between 2020 and 2025 (Hasharon Hospital, Rabin Medical Center, Israel; IRB protocols 0807-21-RMC and 0634-25-RMC). Year-0 outcomes during conventional therapy were compared with outcomes at Years 1–5 on cannabis. Primary outcomes were the Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), and Brief Pain Inventory severity/interference (BPI-S/BPI-I). Concomitant-medication trajectories were a secondary outcome. The primary analysis was a mixed model for repeated measures (MMRM) with random intercept and slope, REML estimation, and time as a categorical fixed effect. Multiple imputation (MAR, m = 20, Rubin’s rules) was the primary missing-data approach; complete-case and tipping-point pattern-mixture sensitivity analyses were used. A multivariate Hotelling T² provided a joint test across the four correlated PROMs. Concomitant-medication discontinuation was modeled with GEE logistic regression and exact McNemar tests. Time to discontinuation was estimated by Kaplan–Meier and Cox regression. The Bonferroni-adjusted significance threshold for the four primary outcomes was α = 0.0125. BioWell gas-discharge-visualization (GDV) parameters were exploratory only. Results: Of 241 patients, 238 (98.8%) provided Year-5 data and 224 (92.9%) remained on cannabis at Year 5; only five patients (2.1%) discontinued for adverse events or inefficacy. All four primary PROMs improved markedly and durably. MMRM-estimated Year-5 minus Year-0 changes were: NRS −5.36 (95% CI −5.65, −5.07), ODI −17.68 (95% CI −19.73, −15.63), BPI-S −6.73 (95% CI −6.99, −6.47), and BPI-I −3.41 (95% CI −3.65, −3.16); all four contrasts had |z| ≥ 16.9 and p < 10⁻²⁰. MI-pooled estimates were within 0.05 of MMRM (FMI < 0.03 for all outcomes). Hotelling T² was F(4, 232) = 872.8, p < 10⁻²⁰. At Year 5, 89.2% achieved ≥30% NRS reduction, 77.2% ≥ 50%, and 93.4% met the NRS minimum clinically important difference (MCID); ODI MCID 65.6%, BPI-S MCID (≥1 pt) 98.3%, BPI-I MCID (≥1 pt) 91.3%. Concomitant opioid use fell from 100% at baseline to 4.6% at Year 5 (within-patient absolute risk reduction 95.4%, McNemar exact p = 1.16 × 10⁻⁶⁹), NSAID from 100% to 7.1%, SSRI/SNRI from 80.5% to 5.4%, and gabapentinoid from 38.6% to 2.5%. The ARR-derived NNT for opioid discontinuation was 1.05; this NNT is referenced to each patient’s own documented maximal-conventional-therapy state and is not equivalent to a between-arm randomized-trial NNT. Cannabis dose × time interaction was consistent with no pharmacological tolerance (β = −0.0044 per gram-month per year, p = 0.074). Across 1205 patient-years of cannabis exposure (calculated as 241 patients × 5 follow-up years from Year 1 through Year 5; baseline Year 0 represents pre-cannabis state and is not included in person-time on cannabis), 1338 organ-system AE events were recorded at 1.110/patient-year (Poisson 95% CI 1.05–1.17); 99.8% of graded events were mild (grade 1), with ocular (476 events, 0.40/PY), cognitive (460, 0.38/PY), and gastrointestinal (368, 0.31/PY) reactions predominating. The Year-3 retention dip reflected a documented telemedicine-clinic phenomenon during 2022–2024, with patients returning to in-person follow-up by Year 4–5. BioWell GDV discriminated NRS ≥ 4 only at chance level (BWS AUC 0.574, 95% CI 0.54–0.60; BWV AUC 0.51). Conclusions: In a treatment-refractory CLBP cohort with five-year longitudinal follow-up, inhaled cannabis was associated with large, sustained, and statistically robust improvements in pain, disability, and pain interference, accompanied by near-total displacement of opioids, NSAIDs, antidepressants, and gabapentinoids. These observational associations, although mechanically less susceptible to bias for the binary medication-discontinuation outcomes than for self-reported PROMs, cannot be interpreted causally in the absence of a concurrent randomized control arm and may reflect a combination of pharmacological effect, regression to the mean from a high pre-treatment baseline, expectancy and self-selection effects intrinsic to an actively chosen open-label therapy, and secular trends in pain reporting. The within-patient benefit-risk profile—ARR-derived NNT ≈ 1 for opioid sparing against a predominantly mild adverse-event burden—supports consideration of cannabis as a potentially clinically meaningful, opioid-sparing option in patients who have failed multimodal conventional therapy, pending confirmation in randomized comparative trials. Full article

Background/Objectives: Vestibular migraine is a common but often underrecognized cause of dizziness in otolaryngology practice. Although awareness has increased, variation in clinician training and management may contribute to inconsistent care. This study evaluated current diagnostic and treatment practices of Canadian otolaryngologists for vestibular migraine, including familiarity with diagnostic criteria, therapeutic approaches, perceived barriers, and educational needs. Methods: A national cross-sectional electronic survey was distributed to practicing and emeritus members of the Canadian Society of Otolaryngology–Head and Neck Surgery from February to April 2025. The 14-item survey assessed demographics, clinical exposure to dizzy patients, residency training, diagnostic familiarity, treatment patterns, referral practices, barriers to care, and preferred educational resources. Responses were anonymized and analyzed using descriptive statistics. Results: Forty-four otolaryngologists completed the survey (response rate: 7.4%). Most respondents reported being very familiar (59.1%) or moderately familiar (38.6%) with vestibular migraine diagnostic criteria, and 97.7% reported currently diagnosing and/or treating these patients. However, only 15.9% had received extensive residency training specific to migraine or vestibular migraine. Common treatments included lifestyle and dietary modification (90.9%), nutraceutical supplements (59.1%), tricyclic antidepressants (54.5%), and analgesics (52.3%). Vestibular rehabilitation therapy (29.5%) and calcitonin gene-related peptide-targeted therapies (<10%) were used less frequently. Major barriers were clinical time constraints (65.9%), lack of training or knowledge (54.5%), and diagnostic complexity (47.7%). Clinical guidelines (70.5%) and continuing medical education courses (65.9%) were identified as the most valuable supports. Conclusions: Among surveyed Canadian otolaryngologists engaged in dizziness and vestibular migraine care, substantial heterogeneity existed in training and management practices. Standardized guidance, enhanced education, and interdisciplinary collaboration may improve consistency of care and patient outcomes. Full article

Pharmacomicrobiomics is the study of drug–microbiome interactions. It examines the dynamic relationship between the drug, the host, and the microbiome, and has become a rapidly evolving area in the realm of pharmacology and personalized medicine. Emerging evidence demonstrates that the gut microbiome can influence the pharmacodynamics and pharmacokinetics of drugs through various mechanisms, while drugs can simultaneously alter microbial composition. Treatment approaches include regular targeted pharmaceutical therapies (e.g., antibiotics, antidepressants) and alternative treatment approaches (e.g., CAM treatments such as supplements and herbs). Microbiome-based medication treatment is an alternative treatment approach that has been studied extensively in the last decade. This article reviews the current knowledge on drug–microbiome interactions across multiple therapeutic systems, including cardiovascular, central nervous system, gastrointestinal, respiratory, endocrine, oncologic, musculoskeletal, anti-infective therapies, and supplements (such as melatonin). We also highlight the various pathways by which microbes can alter the mechanisms (such as drug absorption), bioavailability, efficacy, and incidence of adverse effects, along with highlighting the clinical implications of drug-induced dysbiosis. Full article

Background/Objectives: This study aimed to evaluate the frequency and predictors of adverse drug events (ADEs) related to medication abuse, misuse, and dependence, along with serious adverse events (SAEs), and to develop machine learning models to detect serious abuse, misuse, and dependence cases. Methods: This study included 455,415 ADE reports involving medications with high dependence potential reported to the Korea Adverse Event Reporting System (KIDS KAERS DB) between 2013 and 2022. Multivariate logistic regression was used to identify predictors. Three machine learning algorithms, random forest (RF), support vector machine, and eXtreme Gradient Boosting, were developed and evaluated. Results: Higher reporting likelihood of abuse-, misuse-, and dependence-related ADEs was observed with concomitant use of acetaminophen (OR 3.60, 95% CI 2.40–5.39), antidepressants (OR 1.75, 95% CI 1.17–2.61), antipsychotics (OR 4.97, 95% CI 3.21–7.17), and anticonvulsants (OR 3.42, 95% CI 2.42–4.81). Reports from the general public were associated with higher odds of abuse, misuse, and dependence than those from healthcare professionals (OR 4.59, 95% CI 3.04–6.94). Ketamine (ROR 14.03) and bromazepam (ROR 13.02) showed the highest likelihood of being classified as SAEs. Cardiovascular (ROR 30.36) and respiratory disorders (ROR 17.03) demonstrated the highest SAE reporting likelihood. RF model demonstrated the best predictive performance (AUC-ROC 0.928; accuracy 94.4%), with reporter type identified as a key feature. Conclusions: RF model demonstrated optimal predictive performance, with reporter type as the most important feature for detecting serious cases. This study emphasizes the importance of incorporating patient-reported data and polypharmacy surveillance to facilitate early detection of serious cases. Full article

Frailty is a multifactorial geriatric syndrome marked by reduced physiological reserves and increased vulnerability to adverse outcomes. This multicenter observational study adopted a One Health approach to examine the association between frailty and biological sex, denture use, and antidepressant medication, as well as their impact on bite force, in two transnational cohorts of physically active older adults. The sample included 499 individuals aged ≥60 years (295 from Brazil and 204 from Portugal), all with functional dentition and regular physical activity. Frailty was assessed using the adapted Fried phenotype and classified as non-frail (G0), pre-frail (G1), or frail (G2). Oral health, depressive symptoms (CES-D), bite force, and self-reported use of dentures and antidepressants were analyzed. Frailty was significantly associated with biological sex (p < 0.001), with higher prevalence among women, especially in G2. Antidepressant use was associated with frailty in the Portuguese cohort (p < 0.001) and in the total sample (p = 0.005), but not in Brazil. No significant association was observed between denture use and frailty. However, Brazilian participants without dentures showed significantly higher bite force (p < 0.001), indicating a functional oral health effect. Frailty was associated with female sex and antidepressant use, while bite force emerged as a complementary functional marker for geriatric assessment. Full article

Depression is notable for high rates of disability. The medical model typically characterizes depression as a physiological dysfunction or psychological disorder. However, both views fail to appreciate the phenomenology of depressed experience. Drawing on the existential phenomenology of Merleau-Ponty, this article contends that the lived experience of chronic depression is marked by a disturbance between the body-subject and the world. More specifically, the experience of depression is characterized by alienation from the world, self and others. While anti-depressants have long been the first line of treatment of depression, many governments subsidize cognitive behavioral therapy (CBT) as an adjunct treatment. CBT is said to be the gold standard psychotherapeutic treatment given that it is evidence-based, cost-effective, and short in duration. However, not only are these justifications questionable, but the theoretical underpinnings of CBT have ideological significance. Rather than approaching depressed persons as body-subjects, CBT casts service users as neo-liberal subjects, insofar as depression is characterized as disordered thinking that is independent of a person’s situated life. The emphasis on quickly returning people to work to reduce strain on welfare systems, while a valid economic concern, is not a valid therapeutic concern. The limited choice of subsidized psychotherapeutic options fails to recognize that depression is a heterogenous phenomenon, meaning that the CBT model of disordered thinking is not necessarily representative of the way in which depression manifests. Full article

Background/Objectives: Gabapentinoids are first-line treatments for neuropathic pain (NP); however, real-world evidence regarding their safety and effectiveness in complex clinical populations remains limited. This study aimed to evaluate the effectiveness and safety profile of gabapentinoid therapy in patients managed within a specialized pain relief institution. Methods: A retrospective cohort study (n = 109) was conducted (January 2024 to December 2024). Effectiveness was assessed via DN4 and VAS over one year. Time to improvement was analyzed using Kaplan–Meier curves. Results: The cohort (mean age 66.2 ± 15.3 years) presented 100% comorbidity and polypharmacy (66.1% opioids; 67.9% antidepressants). Although all patients showed improvement, only 35.8% achieved “maximal improvement.” Pregabalin demonstrated faster VAS reduction than gabapentin (p = 0.029), though long-term success was comparable (p = 0.30). Significantly, 100% of patients reported at least one adverse drug event (ADE), primarily somnolence (66.1%), though no serious ADEs occurred. Lower baseline pain scores were significant predictors of therapeutic success. Conclusions: Gabapentinoids are effective for long-term NP management; however, their use is consistently associated with non-serious ADEs. In specialized settings characterized by extensive CNS-active polypharmacy, proactive pharmacovigilance and multidisciplinary oversight are essential to balance analgesic effectiveness with medication safety. Full article

Objectives. The aim of our study was to track changes in ODQ scores in adolescents with depressive episodes taking sertraline, depending on CYP2C19 polymorphisms. Methods. This study included 88 adolescents (88% were female) aged 12–17 who were prescribed sertraline. Emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ) scale when the antidepressant was prescribed, after one, three, and 8 weeks, taking into account other medications used. Part 3 of the ODQ scale assessed the changes that occurred after the prescription of an antidepressant. All patients were genotyped for CYP2C19*2, *3, and *17. Based on genotypes, the phenotypes of the CYP2C19 isoenzyme were determined. Results. The ODQ score at the time of enrollment was higher (65[50;79] points) compared with after 8 weeks (38.5[32.5;56.5] points). Part 3 of the ODQ-26 questionnaire remained approximately the same for 8 weeks. Patients with higher ODQ-26 values at enrollment (73[56;83] vs. 59[44;71] points) were more likely to be prescribed antipsychotics. Differences in ODQ scores remained significant up to 3 weeks after enrollment (50.5[41.5;68] vs. 45.5[36;54] points). The comparison of ODQ scores and their dynamics did not show significant differences depending on CYP2C19*2 or *17 polymorphisms, or the type of CYP2C19 metabolism. Conclusions. There was no increase in emotional blunting according to the ODQ score among adolescents with depression who took sertraline for eight weeks. No significant correlations were found between the carrier status of CYP2C19 gene variants and the development of apathy induced by antidepressants. Full article

Background/Objectives: Real-world persistence of traditional oral migraine preventive medications is low in routine care. Prior large claims-based analyses demonstrated early discontinuation of oral prophylaxis, but such datasets neither included modern preventive options such as monoclonal antibodies (mAB) against calcitonin-gene-related peptide (CGRP), nor were able to capture clinically validated reasons for discontinuation. The primary aim was to compare real-world treatment persistence and discontinuation reasons due to adverse drug reactions (ADRs) or insufficient efficacy among three preventive therapy classes: subcutaneous CGRP mAB and oral high- (HEVP) and low-evidence preventive medications (LEVP). A secondary aim was to examine persistence patterns of individual substances within the HEVP cohort. Methods: This exploratory observational study used depersonalized real-world data from the German Pain e-Registry (GPeR), a national multicenter clinical registry. Persistence trajectories were evaluated over six months, together with cumulative proportions of ADR-related and inefficacy-related discontinuations. Pairwise comparisons across the three cohorts based on chi-square analyses, odds ratios, relative risks, effect sizes, and numbers needed to harm. Results: At six months, persistence was highest for CGRP monoclonal antibodies at 89.4%, compared with 43.0% for LEVP and 34.0% for HEVP (all p < 0.001). ADR-related discontinuation occurred in 7.0% with CGRP vs. 35.7/44.5% with LEVP/HEVP, and discontinuations due to insufficient efficacy occurred in 3.6% with CGRP vs. 21.3/21.5% with LEVP/HEVP, without influence of sex or migraine frequency. Substance-level analysis within HEVP showed the steepest early attrition for tricyclic antidepressants, followed by beta-blockers, with comparatively more favorable though still suboptimal persistence for topiramate and flunarizine. Conclusions: Real-world treatment persistence is markedly higher with CGRP mAB than with HEVP/LEVP. Oral preventives show high discontinuation rates due to both ADR and insufficient efficacy, indicating substantial limitations in real-world applicability. These findings highlight the clinical relevance of a modern mechanism-based migraine prevention with CGRP mAB. Full article

Background/Objectives: Intranasal esketamine has emerged as an effective treatment for patients with treatment-resistant depression (TRD), providing rapid symptom relief when conventional antidepressant strategies fail. While its pharmacological efficacy has been demonstrated in randomized controlled trials, less attention has been paid to the organizational, relational, and multidisciplinary aspects that influence its real-world implementation and clinical effectiveness. While practical recommendations for intranasal esketamine services exist, an implementation-ready framework integrating psychiatry, nursing, and psychotherapy across treatment phases is still lacking. This narrative review synthesizes the clinical and real-world evidence and proposes a phase-based integration framework with explicit role delineation and measurable implementation/fidelity indicators. Methods: We conducted a narrative review informed by a structured literature search in major databases from inception to the most recent update. Search terms combined ‘esketamine’/‘Spravato’ with ‘treatment-resistant depression’, ‘nursing’, ‘psychotherapy’, ‘multidisciplinary’, and ‘implementation’. Outcomes prioritized in the synthesis included depressive symptom severity/response, relapse prevention, safety/tolerability, anhedonia, suicidality monitoring, functional outcomes, and patient-reported experience/retention. Based on this evidence, an integrated, phase-based multidisciplinary framework for esketamine treatment was developed. Results: Available evidence supports the efficacy of intranasal esketamine in reducing depressive symptoms in TRD, with growing real-world data confirming its effectiveness and safety. Beyond global symptom improvement, studies highlight benefits on clinically relevant domains such as anhedonia and suicidality trajectories, as well as meaningful patient-reported outcomes. However, the complexity of esketamine delivery requires structured clinical pathways. The proposed model delineates complementary roles for medical supervision, nursing care, and psychotherapy across pre-treatment assessment, induction and session delivery, post-session integration, and maintenance phases, emphasizing safety, continuity of care, and patient-centred monitoring. Conclusions: Intranasal esketamine represents not only a pharmacological innovation but also a treatment that necessitates an integrated multidisciplinary approach. A structured phase-based multidisciplinary approach may support safer, more acceptable delivery of intranasal esketamine and potentially improve retention and patient experience; however, prospective implementation and comparative studies are needed to evaluate clinical effectiveness, feasibility, and cost-effectiveness. Full article