Management Of Major Depressive Disorder Research Articles

Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes.

The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults. CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process. The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted. The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.

Emotion-induced frontal α asymmetry as a candidate predictor of relapse after discontinuation of antidepressant medication

One in three patients relapse after antidepressant discontinuation. Thus, the prevention of relapse after achieving remission is an important component in the long-term management of Major Depressive Disorder (MDD). However, no clinical or other predictors are established. Frontal reactivity to sad mood as measured by fMRI has been reported to relate to relapse independently of antidepressant discontinuation and is an interesting candidate predictor. Patients (n=56) who had remitted from a depressive episode while taking antidepressants underwent EEG recording during a sad mood induction procedure prior to gradually discontinuing their medication. Relapse was assessed over a six-months follow-up period. 35 healthy controls were also tested. Current source density of the EEG power in the α band (8-13Hz) was extracted and alpha-asymmetry was computed by comparing the power across two hemispheres at frontal electrodes (F5 and F6). Sad mood induction was robust across all groups. Reactivity of α-asymmetry to sad mood did not distinguish healthy controls from patients with remitted MDD on medication. However, the 14 (25%) patients who relapsed during the follow-up period after discontinuing medication showed significantly reduced reactivity in α- asymmetry compared to patients who remained well. This EEG signal provided predictive power (69% out-of-sample balanced accuracy and a positive predictive value of 0.75). A simple EEG-based measure of emotional reactivity may have potential to contribute to clinical prediction models of antidepressant discontinuation. Given the very small sample size, this finding must be interpreted with caution and requires replication in a larger study.

Psychedelic Therapy: A Primer for Primary Care Clinicians-Historical Perspective and Overview.

Psychedelic drugs have recently emerged as plausibly effective pharmacological agents for the management of depression, anxiety, and other neuropsychiatric conditions, including those that are treatment-resistent. The latter half of the 20th century marked a revolution in the treatment of mental illnesses, exemplified by the introduction of selective serotonin reuptake inhibitors and other pharmacological agents. Nevertheless, mental illness remains a major public health crisis, affecting nearly one billion individuals worldwide. Because of the decades-long status of several psychedelics as Schedule I drugs, there have not been very many large, double-blind, randomized controlled trials of psychedelics. Owing to small sample sizes, there may be rare yet serious adverse events that have not been reported in the clinical trials thus far. Esketamine, a dissociative hallucinogen drug, was approved for the management of major depressive disorder by the Food and Drug Administration in 2019. As of January 2024, two Phase III trials of 3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug that inhibits the serotonin transporter, have been completed; the results indicate that MDMA is superior to existing pharmacological treatments for post-traumatic stress disorder. A phase III trial of psilocybin, a naturally occurring serotonin receptor partial agonist, is currently underway. The following series details the current state of research in psychedelic therapeutics, including lysergic acid diethylamide (LSD), N-N-dimethyltryptamine (DMT) and ayahuasca, psilocybin, ibogaine, MDMA, and ketamine. While initial clinical trials of psychedelics for depression were very promising, trials of psilocybin with larger sample sizes (100+ participants) suggest that its remission rate is 25%-29%. This is about the same as the remission rate of antidepressants, which is roughly 30% according to the landmark STAR*D trial. Psychedelic drugs and structural derivatives offer a great deal of promise for the management of a wide range of psychiatric morbidities. It is imperative that clinicians become familiar with these novel agents and learn how to integrate psychedelic therapy with the rest of their care through open communication and referral.

Patient Perceptions of Microbiome-Based Therapies as Novel Treatments for Mood Disorders: A Mixed Methods Study: Perceptions des patients sur les thérapies basées sur le microbiome pour les troubles de l'humeur : une étude à méthodes mixtes.

Medications are critical for treating major depressive disorder (MDD) and bipolar disorder (BD). Unfortunately, 30% to 40% of individuals do not respond well to current pharmacotherapy. Given the compelling growing body of research on the gut-brain axis, this study aims to assess patient perspectives regarding microbiome-based therapies (MBT) such as probiotics, prebiotics, dietary changes, or fecal microbiota transplantation (FMT) in the management of MDD and BD. This single-centred observational study used quantitative and qualitative assessments to examine patient perceptions of MBT. Participants diagnosed with MDD or BD completed an anonymous questionnaire obtaining demographics, prior medication history, and symptom burden. Self-assessment questionnaires specific to each diagnosis were also used: Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR), Altman Self-Rating Mania Scale (ASRM), and General Anxiety Disorder Questionnaire (GAD-7). A logistic regression model analysed the association of MBT acceptance with disorder type, QIDS-SR, and GAD-7 scores. A bootstrap method assessed the proportion of MBT acceptance. The qualitative assessment consisted of 30-minute interviews to elicit perceptions and attitudes towards MBT. The qualitative assessment achieved information power with n = 20. Results from the 63-item MBT questionnaire (n = 43) showed probiotics (37.2%) as the top choice, followed by FMT (32.6%), dietary change (25.6%), and prebiotics (4.6%). A majority of participants (72.1%) expressed willingness to try MBT for their mood disorder, however, logistic regression analysis did not identify statistically significant predictors for MBT acceptance among disorder type, QIDS-SR, and GAD-7. There is an increased focus on the gut microbiota's role in mood disorders' etiology and treatment. Promising research and patient interest underscore the necessity for exploring and educating on patient perspectives and the factors influencing attitudes towards MBT.

Measurement-Based Care for Depression in Youth: Practical Considerations for Selecting Measures to Assess Depression, Associated Features and Functioning.

Identification and management of major depressive disorder (MDD) in children and adolescents remains a significant area of public health need. The process for identifying depression (e.g. screening) and management (e.g. measurement based care [MBC]) is substantially enhanced by utilization of clinical measures and rating scales. Measures can be self- or caregiver reported or clinician rated. They can aid recognition of at-risk individuals for future assessment and assist in clinical diagnosis and management of depression. In addition to assessing symptoms of depression, rating scales can be used to assess important associated features (e.g. anxiety, trauma) and functional outcomes (e.g. quality of life, performance/productivity). In this manuscript, we discuss practical considerations for clinicians and researchers when selecting rating instruments for assessing depression, associated factors, functioning, and treatment outcomes (i.e. adherence and side effects) as part of MBC in youth and provide a summary of rating scales commonly used in research and clinical settings.

SSRI Efficacy in Treating Major Depressive Disorder: Preliminary Findings

Background: Conflicting evidence on the relative effectiveness of second-generation antidepressants has made initial management of major depressive disorder (MDD) complex and frequently results in a trial-and-error-based approach to treatment. With recent literature suggesting serotonin plays no significant role in the etiology of depression, further investigation of selective serotonin reuptake inhibitors (SSRIs) as a firstline treatment of MDD is warranted.
 Methods: A retrospective chart review of patients 18 years or older visiting the Fort Wayne Family Medicine Center and completing a Patient Health Questionnaire (PHQ) or Generalized Anxiety Disorder scale (GAD) from January 2020 through May 2023 was performed. Comparative analysis of PHQ and GAD scores was performed to determine if any differences in treatment management outcomes were present between SSRI therapy and other treatment approaches.
 Results: 1,502 patients met the inclusion criteria. Due to time constraints, a sample of 45 patients (10 males, 35 females) was selected and preliminary results are as follows: After initiating treatment with an SSRI, 14 (42.4%) PHQ scores and 7 (24.1%) GAD scores demonstrated improved disease severity. After initiating treatment with another antidepressant class, 10 (31.3%) PHQ scores and 17 (48.6%) GAD scores demonstrated improved disease severity. There was no significant difference (p=0.351) in treatment outcomes between antidepressant class in terms of PHQ results, but a significant difference (p=0.044) was found between groups with regards to GAD results.
 Conclusions: This study describes preliminary findings on the current patterns of care for mental health within a primary care setting and demonstrates antidepressant classes appear equally efficacious in treating depression. However, anxiety management outcomes appear to be influenced by antidepressant class administered. Future analysis will include the entire available dataset and produce more robust results from which to improve patient-specific and community health outcomes.

Expert opinion on the management of major depressive disorder in Indian settings

Expert opinion on the management of major depressive disorder in Indian settings

Management of major depressive disorders in pregnant or breastfeeding women in primary care: A systematic meta-review

BackgroundMajor depressive disorders (MDDs) are common during the perinatal period, with a prevalence around 12 %. General practitioners are increasingly involved in the management of these disorders, but no specific recommendations have been developed for primary care. The objective was to review the literature on the detection, treatment and follow-up of MDD in pregnant and breastfeeding women in primary care. MethodsA systematic meta-review was carried out to synthesize the findings of systematic reviews, meta-analyses, and Good Practice Guidelines published between 2002 and 2021. PubMed, Cochrane and ISI Web of Science databases were searched. Methodological and quality assessment was done using the AGREE II, PRISMA and R-AMSTAR grids. A narrative synthesis was elaborated. ResultsIn total, 34 articles were included. The use of psychotherapy alone by cognitive-behavioral therapy (CBT) or interpersonal psychotherapy (ITP) was recommended as first-line therapy in mild and moderate MDD in 7 guidelines included in our review. The 14 systematic reviews, meta-analyses included confirm their efficacy with a slight superiority of CBT as compared to IPT (OR, 2.00; 95 % CI, 1.61 to 2.48); Standardized mean differences (SMD) between -2.86 (95 % CI from -4.41 to -1.31) and -0.61 (95 % CI from 0.73 to -0.49), depending on the study) (OR, 0.68; 95 % CI, 0.55 to 0.84); SMD between 0.39 (95 % CI 0.18 to 0.61) and 1.41 (95 % CI % from 0.96 to 1.86)). All of the Good Practice Guidelines included recommend pharmacotherapy in second intention, if it represents the most suitable therapeutic option. Selective serotonin reuptake inhibitors (in particular sertraline) are preferred, because there are suitable during pregnancy and breastfeeding in 6 of the systematic reviews included, nevertheless, they all mention the lack of high-quality clinical trial in their limits. The same limitation was highlighted in the 8 studies that focused on complementary medicine. ConclusionThis study provides a synthesis on the management of MDD in pregnant and breastfeeding women in primary care. Further high-quality studies are needed on antidepressants drugs use and complementary medicines to elicit their respective role during the perinatal period.

Development of Visible Spectrophotometric Methods for the Determination of Tricyclic Antidepressants Based on Formation of Molecular Complexes with p-Benzoquinones

Tricyclic antidepressants are commonly employed in the management of major depressive disorders. The present work describes two visible (VIS) spectrophotometric techniques that utilize the formation of charge transfer complexes between four antidepressant compounds, namely, amitriptyline hydrochloride (AMI), imipramine hydrochloride (IMI), clomipramine hydrochloride (CLO), and trimipramine maleate (TRI) acting as electron donors and two p-benzoquinones, namely, p-chloranilic acid (pCA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), serving as electron acceptors. The stoichiometry of the compounds produced exhibited a consistent 1:1 ratio in all instances, as established by Job’s method. Molar absorptivities, equilibrium association constants, and several other spectroscopic properties were determined for all complexes. The developed spectrophotometric techniques were validated intra-laboratory and successfully applied for quantitative assessment of the four antidepressant active ingredients in several commercial pharmaceutical formulations. The methods are relatively simple, fast, and use readily available laboratory instrumentation, making them easily applicable by most quality control laboratories worldwide.

A narrative review of digital biomarkers in the management of major depressive disorder and treatment-resistant forms

IntroductionDepression is the leading cause of worldwide disability, until now only 3% of patients with major depressive disorder (MDD) experiences full recovery or remission. Different studies have tried to better understand MDD pathophysiology and its resistant forms (TRD), focusing on the identification of candidate biomarkers that would be able to reflect the patients’ state and the effects of therapy. Development of digital technologies can generate useful digital biomarkers in a real-world setting. This review aims to focus on the use of digital technologies measuring symptom severity and predicting treatment outcomes for individuals with mood disorders.MethodsTwo databases (PubMed and APA PsycINFO) were searched to retrieve papers published from January 1, 2013, to July 30, 2023, on the use of digital devices in persons with MDD. All papers had to meet specific inclusion criteria, which resulted in the inclusion of 12 articles.ResultsResearch on digital biomarkers confronts four core aspects: (I) predicting diagnostic status, (II) assessing symptom severity and progression, (III) identifying treatment response and (IV) monitoring real-word and ecological validity. Different wearable technologies have been applied to collect physiological, activity/sleep, or subjective data to explore their relationships with depression.DiscussionDepression’s stable rates and high relapse risk necessitate innovative approaches. Wearable devices hold promise for continuous monitoring and data collection in real world setting.ConclusionMore studies are needed to translate these digital biomarkers into actionable interventions to improve depression diagnosis, monitoring and management. Future challenges will be the applications of wearable devices routinely in personalized medicine.

Deciphering the neural mechanisms of miR-134 in major depressive disorder with population-based and person-specific imaging transcriptomic techniques

MiR-134 has emerged as a potential molecular biomarker for the detection and management of major depressive disorder (MDD). Nevertheless, the specific effects of miR-134 as a regulatory element on brain function and its implications for the clinical presentation of MDD are not yet fully understood. In order to investigate the potential neural mechanisms that contribute to the relationship between miR-134 and MDD, we employed a parallel two-stage cross-scale multi-omics approach. This involved utilizing the anterior cingulate cortex (ACC) functional connectivity as a means to connect microscopic molecular structures with macroscopic brain function in two separate cohorts: the MDD-I dataset (56 MDD patients and 51 healthy controls) and the MDD-II dataset (57 MDD patients and 52 healthy controls). We found a stable ACC functional dysconnectivity pattern of MDD and established the hierarchical cross-scale association from molecular organizations of miR-134 target genes to macroscopic brain functional dysconnectivity and associated behavior, as revealed by population-based analysis. Additionally, our person-specific imaging transcriptomic study revealed that individual exosomal miR-134 expression levels impact on individual clinical symptoms of MDD by modulating ACC-related functional dysconnectivity. Together, our findings provide compelling evidence of the correlation between miR-134 and depression across multi scales within the gene-brain-behavior context.

A review on a selected Ayurvedic herbal formula in the management of Kaphaja Unmada (Major depressive disorder): A critical analysis

The widespread psychiatric disease known as major depressive disorder (MDD) is associated with a high rate of morbidity and mortality with correlation to Kaphaja Unmāda. According to family, twin and adoption studies, genetic variables are crucial in the emergence of MDD and may provide crucial details regarding the disease's pathophysiology. Bacopa monniera (Brāhmi) and Evolvulus alsinoides (Vishnukrānthi) were the ingredients of a decoction from a traditional formula and this review's objective was to investigate how well the herbal formula of decoction effective to treat MDD. Information about MDD and Kaphaja Unmāda was acquired from Ayurvedic scriptures, contemporary texts and earlier research studies (from primary and secondary sources). A survey of the literature was done on those two herbs in the selected decoction and then examined for their Pancha Padārtha (5 elements of herb) and pharmacological qualities regarding in the management of MDD. Ayurvedic Pancha Padārtha study has revealed that selected herbal formula has anti-depressant qualities because of their compatibility with Mēdhya (nootropic action) Prabhāva (special action). The majority of studies have demonstrated the anti-depressant effects of herbal formula, but reviewed articles have also highlighted additional qualities that aid in lowering the symptoms of MDD. According to the literature review and Pancha Padārtha analysis, selected herbal formula is useful in the treatment of MDD.

Determinants of Health-Seeking Behavior in Major Depressive Disorder: An Observational Study.

Major depressive disorder (MDD) is one of the most common illnesses in the world anda major cause of years lived with disability.It is necessary to diagnose and treat depression promptly. To identify and compare factors affecting health-seeking behavior in patients suffering from MDD. An observational cross-sectional study was conducted. The study population was divided into two groups: early and late health seekers (cut off: three months). Patient Health Questionnaire - 9 (PHQ-9) as well as Perceived and Personal Depression Stigma Scores were calculated.Data were analyzed and the chi-square test and z-test were used to calculate statistical significance. There were 102 participants. The majority were female (62.75%) and the maximum number of participants were from the age group of 26-45 years (65.69%). There were more early help seekers (61.76%) than late help seekers (38.24%). The majority of early help seekers were married individuals. Distance played a vital role in help-seeking behavior. A significant association was also found between participants' personal stigma and late treatment seeking. The most common reason for delaying medical attention was that patients thought that they could cure themselves, followed by a lack of awareness. Delay and hesitance observed concerning health-seeking behavior are assumed to be associated with factors such as gender, income, family or marital status, stigma, lack of awareness, beliefs and practices, and deficient health facilitiescausing delays in the diagnosis and management of MDD. The research supported that involving primary health care centers, spreading awareness about the disease, and increasing psychiatric facilities, along with a special emphasis on factors as mentioned like gender, marital status, stigma, and feasibility of reaching facility as distance plays a major role in causing delay, and can help decrease the duration of symptom from the onset, initiating appropriate treatment, and improving prognosis.

Antidepressant Strategies for Treatment of Acute Depressive Episodes Among Veterans.

The 2016 VA/DoD Clinical Practice Guideline for Management of Major Depressive Disorder offers consensus-based recommendations when response to the initial antidepressant medication is suboptimal; however, little is known about "real-world" pharmacological strategies used by providers treating depression in the Veterans Affairs Health Care System (VAHCS). We extracted pharmacy and administrative records of patients diagnosed with a depressive disorder and treated at the Minneapolis VAHCS between January 1, 2010 and May 11, 2021. Patients with bipolar disorder, psychosis-spectrum, or dementia diagnoses were excluded. An algorithm was developed to identify antidepressant strategies: monotherapy (MONO); optimization (OPM); switching (SWT); combination (COM); and augmentation (AUG). Additional data extracted included demographics, service utilization, other psychiatric diagnoses, and clinical risk for hospitalization and mortality. The sample consisted of 1298 patients, 11.3% of whom were female. The mean age of the sample was 51 years. Half of the patients received MONO, with 40% of those patients receiving inadequate doses. OPM was the most common next-step strategy. SWT and COM/AUG were used for 15.9% and 2.6% of patients, respectively. Overall, patients who received COM/AUG were younger. OPM, SWT, and COM/AUG occurred more frequently in psychiatric services settings and required a greater number of outpatient visits. The association between antidepressant strategies and risk of mortality became nonsignificant after accounting for age. Most of the veterans with acute depression were treated with a single antidepressant, while COM and AUG were rarely used. The age of the patient, and not necessarily greater medical risks, appeared to be a major factor in decisions about antidepressant strategies. Future studies should evaluate whether implementation of underutilized COM and AUG strategies early in the course of depression treatment are feasible.

Long-term safety and efficacy, including anhedonia, of vortioxetine for major depressive disorder: findings from two open-label studies

Objective Evaluate the long-term safety and efficacy of vortioxetine in the management of major depressive disorder (MDD) in two open-label one-year studies, including a post-hoc analysis of its effects on symptoms related to anhedonia. Methods Both studies were 52-week, open-label, flexible-dose extension studies to evaluate the safety and efficacy of vortioxetine in adult patients with MDD following prior double-blind studies. Patients in the first study (NCT00761306) were flexibly treated with vortioxetine 5 or 10 mg/day (N = 74), and patients in the second study (NCT01323478) received vortioxetine 15 or 20 mg/day (N = 71). Results The safety and tolerability profile of vortioxetine was similar between the two studies; treatment-emergent adverse events with the highest incidence were nausea, dizziness, headache, and nasopharyngitis. Across both studies, improvements achieved during the preceding double-blind studies period were maintained, and additional improvements were observed with open-label treatment. Patients showed a mean ± SD reduction (improvement) in Montgomery and Åsberg Depression Rating Scale (MADRS) total score from open-label baseline to Week 52 of 4.3 ± 9.2 points in the 5–10 mg study, and 10.9 ± 10.0 in the 15–20 mg study. Post-hoc MMRM analyses of MADRS anhedonia factor scores also showed continued improvements over long-term treatment; patients showed a mean ± SE reduction from an open-label baseline to Week 52 of 3.10 ± 0.57 points in the 5–10 mg study, and 5.62 ± 0.60 in the 15–20 mg study. Conclusions Data from both studies confirm the safety and efficacy of flexibly dosed vortioxetine over 52 weeks of treatment and demonstrate that MADRS anhedonia factor scores continue to improve with long-term maintenance treatment.

Ego-defense mechanisms and brief psychotherapies for the management of major depressive disorder in adults: A longitudinal and quasi-experimental study

ObjectiveTo evaluate the effect of psychotherapies on ego defense mechanisms and the reduction of depressive symptoms in a 12-month follow-up period. MethodsThis longitudinal and quasi-experimental study nested within a randomized clinical trial included a clinical sample of adults (18–60 years) diagnosed with major depressive disorder using the Mini-International Neuropsychiatric Interview. Two models of psychotherapy were used: Supportive Expressive Dynamic Psychotherapy (SEDP) and Cognitive Behavioral Therapy (CBT). Defense Style Questionnaire 40 was used to analyze defense mechanisms and the Beck Depression Inventory was used to measure the depressive symptoms. ResultsThe total sample comprised 195 patients (113 SEDP and 82 CBT), with the mean age was 35.63 (11.44) years. After adjustments, increased mature defenses was significantly associated with reduced depressive symptoms at all follow-up times (p < 0.001) and the decrease in immature defenses was significantly associated with the reduction of depressive symptoms at all follow-up times (p < 0.001). While neurotic defenses were not associated with a reduction in depressive symptoms at any time of follow-up (p > 0.05). ConclusionBoth models of psychotherapy were effective in increasing mature defenses and decreasing immature ones, as well as decreasing depressive symptoms at all evaluation times. With this, it is understood that a greater understanding of these interactions will allow a more adequate diagnostic and prognostic evaluation and the design of useful strategies that adapt to the patient's reality.

Evaluating the pediatric mental health care continuum at an American health system.

To describe trends in the pediatric mental health care continuum and identify potential gaps in care coordination. We used electronic medical record data from October 2016 to September 2019 to characterize the prevalence of mental health issues in the pediatric population at a large American health system. This was a single institution case study. From the electronic medical record data, primary mental health discharge and readmission diagnoses were identified using International Classification of Diseases (ICD-9-CM, ICD-10-CM) codes. The electronic medical record was queried for mental health-specific diagnoses as defined by International Classification of Diseases classification, analysis of which was facilitated by the fact that only 176 mental health codes were billed for. Additionally, prevalence of care navigation encounters was assessed through electronic medical record query, as care navigation encounters are specifically coded. These encounter data was then segmented by care delivery setting. Major depressive disorder and other mood disorders comprised 49.6% and 89.4% of diagnoses in the emergency department and inpatient settings respectively compared to 9.0% of ambulatory care diagnoses and were among top reasons for readmission. Additionally, only 1% of all ambulatory care encounters had a care navigation component, whereas 86% of care navigation encounters were for mental health-associated reasons. Major depressive disorder and other mood disorders were more common diagnoses in the emergency department and inpatient settings, which could signal gaps in care coordination. Bridging potential gaps in care coordination could reduce emergency department and inpatient utilization through increasing ambulatory care navigation resources, improving training, and restructuring financial incentives to facilitate ambulatory care diagnosis and management of major depressive disorder and mood disorders. Furthermore, health systems can use our descriptive analytic approach to serve as a reasonable measure of the current state of pediatric mental health care in their own patient population.

Delta Opioid Receptor-Mediated Antidepressant-Like Effects of Diprenorphine in Mice.

Major depressive disorder is a highly common disorder, with a lifetime prevalence in the United States of approximately 21%. Traditional antidepressant treatments are limited by a delayed onset of action and minimal efficacy in some patients. Ketamine is effective and fast-acting, but there are concerns over its abuse liability. Thus, there is a need for safe, fast-acting antidepressant drugs. The opioid buprenorphine shows promise but also has abuse liability due to its mu-agonist component. Preclinical evidence indicates that the delta-opioid system contributes to mood disorders, and delta-opioid agonists are effective in preclinical models of depression- and anxiety-like states. In this study, we test the hypothesis that the mu-opioid antagonist diprenorphine by virtue of its partial delta opioid agonist activity may offer a beneficial profile for an antidepressant medication without abuse liability. Diprenorphine was confirmed to bind with high affinity to all three opioid receptors, and functional experiments for G protein activation verified diprenorphine to be a partial agonist at delta- and kappa-opioid receptors and a mu-antagonist. Studies in C57BL/6 mice demonstrated that an acute dose of diprenorphine produced antidepressant-like effects in the tail suspension test and the novelty-induced hypophagia test that were inhibited in the presence of the delta-selective antagonist, naltrindole. Diprenorphine did not produce convulsions, a side effect of many delta agonists but rather inhibited convulsions caused by the full delta agonist SNC80; however, diprenorphine did potentiate pentylenetetrazole-induced convulsions. Diprenorphine, and compounds with a similar pharmacological profile, may provide efficient and safe rapidly acting antidepressants. SIGNIFICANCE STATEMENT: The management of major depressive disorder, particularly treatment-resistant depression, is a significant unmet medical need. Here we show that the opioid diprenorphine, a compound with mu-opioid receptor antagonist activity and delta- and kappa-opioid receptor partial agonist activities, has rapid onset antidepressant-like activity in animal models. Diprenorphine and compounds with a similar pharmacological profile to diprenorphine should be explored as novel antidepressant drugs.

Association between childhood trauma and medication adherence among patients with major depressive disorder: the moderating role of resilience

BackgroundSuboptimal medication adherence is a major reason for failure in the management of major depressive disorder (MDD), childhood trauma might be an essential risk factor of suboptimal medication adherence. This study aimed to comprehensively explore the associations between different types of childhood trauma and medication adherence among patients with MDD, and to test whether resilience has moderating effects on the foregoing associations.MethodsParticipants were from the Depression Cohort in China (ChiCTR registry number 1900022145), 282 MDD patients with completed both baseline and 12-weeks follow-up investigations were included in this study. The diagnosis of MDD was assessed by trained psychiatrists using the Mini-International Neuropsychiatric Interview (M.I.N.I.). Childhood trauma was evaluated using the Childhood Trauma Questionnaire-28 item Short Form (CTQ-SF), and resilience was evaluated using the Connor-Davidson Resilience Scale (CD-RISC). Demographic characteristics, depression symptoms, anxiety symptoms, suicidal ideation, suicidal attempt, insomnia symptoms, and painful somatic symptoms were also investigated. Participants were divided into groups of optimal and suboptimal adherence based on their Medication Adherence Rating Scale scores. Logistic regression and stratified analyses were performed.ResultsA total of 234 participants (83%) reported suboptimal medication adherence. After adjusting for covariates, CTQ total scores (AOR = 1.03, 95%CI = 1.01–1.06), CTQ measures of sexual abuse (AOR = 1.17, 95%CI = 1.01–1.37), and CTQ measures of physical neglect (AOR = 1.12, 95%CI = 1.02–1.23) were all associated with an increased likelihood of suboptimal adherence. There were significant moderating effects of resilience on the associations of childhood trauma (P = 0.039) and physical neglect (P = 0.034) with medication adherence. The stratification analyses showed that CTQ total scores and CTQ measures of physical neglect were independently associated with an increased risk of suboptimal adherence among patients with MDD with low-resilience or moderate-resilience, while not significantly associated with suboptimal adherence in those with high-resilience.ConclusionChildhood trauma was a significant risk factor of suboptimal adherence among patients with MDD, and resilience moderated the foregoing association. Obtaining a history of childhood trauma and assessing resilience may help identify patients with suboptimal adherence when providing MDD pharmacotherapy. Psychiatrists may consider enhancing resilience to cope with the adverse effects of childhood trauma on medication adherence.

The Management of Major Depressive Disorder: Synopsis of the 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

In February 2022, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline (CPG) for the management of major depressive disorder (MDD). This synopsis summarizes key recommendations. Senior leaders within the VA and the DoD assembled a team to update the 2016 CPG for the management of MDD that included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy CPGs. The guideline panel developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and distilled 36 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Select recommendations that were identified by the authors to represent key changes from the prior CPG are presented in this synopsis. The scope of the CPG is diverse; however, this synopsis focuses on key recommendations that the authors identified as important new evidence and changes to prior recommendations on pharmacologic management, pharmacogenomics, psychotherapy, complementary and alternative therapies, and the use of telemedicine.