Testing similarity in longitudinal networks: The Individual Network Invariance Test.

The comparison of idiographic network structures to determine the presence of heterogeneity is a challenging endeavor in many applied settings. Previously, researchers eyeballed idiographic networks, computed correlations, and used techniques that make use of the multilevel structure of the data (e.g., group iterative multiple model estimation and multilevel vector autoregressive) to investigate individual differences. However, these methods do not allow for testing the (in)equality of idiographic network structures directly. In this article, we propose the Individual Network Invariance Test (INIT), which we implemented in the R package INIT. INIT extends common model comparison practices in structural equation modeling to idiographic network structures to test for (in)equality between idiographic networks. In a simulation study, we evaluated the performance of INIT on both saturated and pruned idiographic network structures by inspecting the rejection rate of the χ² difference test and model selection criteria, such as the Akaike information criterion (AIC) and Bayesian information criterion (BIC). Results show INIT performs adequately when t = 100 per individual. When applying INIT on saturated networks, the AIC performed best as a model selection criterion, while the BIC showed better results when applying INIT on pruned networks. In an empirical example, we highlight the possibilities of this new technique, illustrating how INIT provides researchers with a means of testing for (in)equality between idiographic network structures and within idiographic network structures over time. To conclude, recommendations for empirical researchers are provided. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Neuropsychological Assessments of Cognitive Impairment in Major Depressive Disorder: A Systematic Review and Meta-Analysis with Meta-Regression.

INTRODUCTION: Cognitive dysfunction or deficits are common in patients with major depressive disorder (MDD). The current study systematically reviews and meta-analyzes multiple domains of cognitive impairment in patients with MDD. METHODS: PubMed/MEDLINE, PsycINFO, Cochrane Library, Embase, Web of Science, and Google Scholar were searched from inception through May 17, 2023, with no language limits. Studies with the following inclusion criteria were included: (1) patients with a diagnosis of MDD using standardized diagnostic criteria; (2) healthy controls (i.e., those without MDD); (3) neuropsychological assessments of cognitive impairment using Cambridge Neuropsychological Test Automated Battery (CANTAB); and (4) reports of sufficient data to quantify standardized effect sizes. Hedges' g standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs) were used to quantify effect sizes of cognitive impairments in MDD. SMDs were estimated using a fixed- or random-effects models. RESULTS: Overall, 33 studies consisting of 2,596 subjects (n = 1,337 for patients with MDD and n = 1,259 for healthy controls) were included. Patients with MDD, when compared to healthy controls, had moderate cognitive deficits (SMD, -0.39 [95% CI, -0.47 to -0.31]). In our subgroup analyses, patients with treatment-resistant depression (SMD, -0.56 [95% CI, -0.78 to -0.34]) and older adults with MDD (SMD, -0.51 [95% CI, -0.66 to -0.36]) had greater cognitive deficits than healthy controls. The effect size was small among unmedicated patients with MDD (SMD, -0.19 [95% CI, -0.37 to -0.00]), and we did not find any statistical difference among children. Cognitive deficits were consistently found in all domains, except the reaction time. No publication bias was reported. CONCLUSION: Because cognitive impairment in MDD can persist in remission or increase the risk of major neurodegenerative disorders, remediation of cognitive impairment in addition to alleviation of depressive symptoms should be an important goal when treating patients with MDD.

Real-World Evidence on Clinical Outcomes of Commonly Used Antidepressants in Older Adults Initiating Antidepressants for Depression: A Nationwide Cohort Study in Denmark.

OBJECTIVE: The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing the 1-year risk of selected clinically relevant outcomes. METHODS: This cohort study used nationwide Danish registry data and included all older adults who redeemed a first-time (since 1995) antidepressant prescription with an indication of depression between 2006 and 2017. Only the 10 most frequently redeemed antidepressants were included in the analyses. Outcomes included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events, and all-cause mortality. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated using Poisson regression models, controlling for potential confounders. RESULTS: The study sample included 93,883 older adults (mean age, 78.0 years, SD=7.5 years; 56% female). The most frequently prescribed antidepressants were selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%), and two atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%). Compared with users of sertraline (the reference drug in this analysis, as Danish guidelines recommend it as the first-choice treatment for depression), users of most of the other nine antidepressants had a significantly higher risk of discontinuation (e.g., mirtazapine: IRR=1.55, 95% CI=1.50-1.61; venlafaxine: IRR=1.22, 95% CI=1.12-1.32), switching (amitriptyline: IRR=1.45, 95% CI=1.15-1.81; venlafaxine: IRR=1.47, 95% CI=1.20-1.80), augmentation, cardiovascular events, and mortality. Overall, mirtazapine and venlafaxine users had the most adverse outcomes compared with sertraline users. These results remained consistent in analyses stratified by sex and age (≤75 years vs. >75 years). CONCLUSIONS: This real-world evidence suggests that clinical outcomes may vary among initiators of commonly used antidepressants in older adults, which may inform benefit-risk evaluation at treatment initiation, and highlights the importance of careful selection of antidepressant treatment.

Rumination in bipolar disorder associated with brain network and behavioural measures of inhibitory executive control.

OBJECTIVE: Rumination is a passive form of negative self-focused cognition that predicts depressive episodes for individuals with bipolar disorder (BD). Individuals with BD also have impaired inhibitory executive control; rumination in BD may therefore reflect executive dysfunction. We investigated the relationship between a neural measure of executive functioning (functional connectivity between the frontoparietal control network [FPCN] and the default mode network [DMN] during an effortful task), behavioural measures of executive functioning (the Behavior Rating Inventory of Executive Function) and rumination (the Ruminative Responses Scale). METHODS: Fifteen individuals with BD and fifteen healthy controls underwent MRI scans during mental distraction. Using CONN toolbox, between-network FPCN-DMN connectivity values were calculated. We conducted Pearson's r bivariate correlations between connectivity values, BRIEF and RRS scores. RESULTS: RRS scores were positively correlated with BRIEF Behavioral Regulation Index (BRI) scores. In individuals with BD, there was a positive correlation between FPCN-DMN functional connectivity during distraction and BRIEF BRI scores. FPCN-DMN functional connectivity was also positively correlated with RRS ruminative brooding scores. Healthy controls did not show significant correlations between these behavioural and neural measures of executive functioning and rumination. CONCLUSION: For individuals with BD, the greater the tendency to ruminate and the higher the executive dysfunction, the stronger the connectivity between an executive control network and a network involved in rumination during an unrelated cognitive task. This could reflect continual attempts to inhibit ruminative thinking and shift back to the distraction task. Therefore, engagement in rumination may reflect failed inhibitory executive control.

Patterns of pharmacotherapy for bipolar disorder: A GBC survey.

OBJECTIVES: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well-characterized individuals with BD in North America, Europe, and Australia. METHODS: Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. Individual site and regional pooled proportional meta-analyses with generalized linear mixed methods were conducted to identify prescription patterns. RESULTS: This study included 10,351 individuals from North America (n = 3985), Europe (n = 3822), and Australia (n = 2544). Overall, participants were predominantly female (60%) with BD-I (60%; vs. BD-II = 33%). Cross-sectionally, mood-stabilizing anticonvulsants (44%), second-generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First-generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD-II (47%) compared to BD-I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort. CONCLUSIONS: Mood-stabilizing anticonvulsants, second-generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first-generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence-based guidelines to help improve treatment practices in BD.

Association between lithium treatment and renal, thyroid and parathyroid function: A cohort study of 6659 patients with bipolar disorder.

OBJECTIVES: Although potential adverse effects of lithium treatment on renal and endocrine systems have been extensively investigated, most prior studies are limited by selected populations and short follow-up. METHODS: Within the Psychiatric Services of the Central Denmark Region, we identified all patients with bipolar disorder and ≥1 serum-lithium (se-Li) measurements between January 1, 2013, and July 20, 2022, and reference patients with bipolar disorder matched on age, sex, and baseline creatinine. Outcomes were diagnoses of renal, thyroid and parathyroid disease, and blood tests measuring creatinine, estimated glomerular filtration rate (eGFR), thyroid-stimulating hormone (TSH), parathyroid hormone (PTH) and calcium. Analyses included unadjusted multilevel regression to describe changes in biochemical markers, and adjusted Cox regression to compare rates of disease/biochemical outcomes between lithium users and reference patients. RESULTS: Among 1646 lithium users (median age 36 years, 63% women) and 5013 reference patients, lithium users had decreasing TSH and eGFR, stable PTH, and increasing calcium levels over time. Lithium use was associated with increased rates of renal, thyroid and parathyroid disease, and levels of biochemical markers outside normal ranges (hazard rate ratios: 1.07-11.22), but the absolute number of severe outcomes was low (e.g., chronic kidney disease: N = 10, 0.6%). Notably, the rate of blood testing was substantially higher among lithium users than among reference patients (e.g., mean number of creatinine tests during the second year of follow-up: lithium users = 2.5, reference patients = 1.4). CONCLUSIONS: Severely adverse renal and endocrine outcomes are rare during lithium treatment. Observational studies of long-term lithium treatment are prone to detection bias.

Diagnosis and Treatment of Bipolar Disorder: A Review.

Importance: Bipolar disorder affects approximately 8 million adults in the US and approximately 40 million individuals worldwide. Observations: Bipolar disorder is characterized by recurrent episodes of depression and mania or hypomania. Bipolar depressive episodes are similar to major depressive episodes. Manic and hypomanic episodes are characterized by a distinct change in mood and behavior during discrete time periods. The age of onset is usually between 15 and 25 years, and depression is the most frequent initial presentation. Approximately 75% of symptomatic time consists of depressive episodes or symptoms. Early diagnosis and treatment are associated with a more favorable prognosis. Diagnosis and optimal treatment are often delayed by a mean of approximately 9 years following an initial depressive episode. Long-term treatment consists of mood stabilizers, such as lithium, valproate, and lamotrigine. Antipsychotic agents, such as quetiapine, aripiprazole, asenapine, lurasidone, and cariprazine, are recommended, but some are associated with weight gain. Antidepressants are not recommended as monotherapy. More than 50% of patients with bipolar disorder are not adherent to treatment. Life expectancy is reduced by approximately 12 to 14 years in people with bipolar disorder, with a 1.6-fold to 2-fold increase in cardiovascular mortality occurring a mean of 17 years earlier compared with the general population. Prevalence rates of metabolic syndrome (37%), obesity (21%), cigarette smoking (45%), and type 2 diabetes (14%) are higher among people with bipolar disorder, contributing to the risk of early mortality. The annual suicide rate is approximately 0.9% among individuals with bipolar disorder, compared with 0.014% in the general population. Approximately 15% to 20% of people with bipolar disorder die by suicide. Conclusions and Relevance: Bipolar disorder affects approximately 8 million adults in the US. First-line therapy includes mood stabilizers, such as lithium, anticonvulsants, such as valproate and lamotrigine, and atypical antipsychotic drugs, such as quetiapine, aripiprazole, asenapine, lurasidone, and cariprazine.

Treatment-resistant depression: definition, prevalence, detection, management, and investigational interventions.

Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population.

Development of a model to predict antidepressant treatment response for depression among Veterans.

BACKGROUND: Only a limited number of patients with major depressive disorder (MDD) respond to a first course of antidepressant medication (ADM). We investigated the feasibility of creating a baseline model to determine which of these would be among patients beginning ADM treatment in the US Veterans Health Administration (VHA). METHODS: A 2018-2020 national sample of n = 660 VHA patients receiving ADM treatment for MDD completed an extensive baseline self-report assessment near the beginning of treatment and a 3-month self-report follow-up assessment. Using baseline self-report data along with administrative and geospatial data, an ensemble machine learning method was used to develop a model for 3-month treatment response defined by the Quick Inventory of Depression Symptomatology Self-Report and a modified Sheehan Disability Scale. The model was developed in a 70% training sample and tested in the remaining 30% test sample. RESULTS: In total, 35.7% of patients responded to treatment. The prediction model had an area under the ROC curve (s.e.) of 0.66 (0.04) in the test sample. A strong gradient in probability (s.e.) of treatment response was found across three subsamples of the test sample using training sample thresholds for high [45.6% (5.5)], intermediate [34.5% (7.6)], and low [11.1% (4.9)] probabilities of response. Baseline symptom severity, comorbidity, treatment characteristics (expectations, history, and aspects of current treatment), and protective/resilience factors were the most important predictors. CONCLUSIONS: Although these results are promising, parallel models to predict response to alternative treatments based on data collected before initiating treatment would be needed for such models to help guide treatment selection.

A New Treatment Program: Focused Integrated Team-based Treatment Program for Bipolar Disorder (FITT-BD).

OBJECTIVE: Bipolar disorder (BD) is complicated by a dynamic, chronic course along with multiple comorbid psychiatric and medical conditions, making it challenging for clinicians to treat and patients to thrive. To efficiently manage the complexity of BD and help patients recover, we developed a Focused Integrated Team-based Treatment Program for Bipolar Disorder (FITT-BD). The purpose of this paper is to describe how we developed this clinic and the lessons we learned. METHODS: We developed FITT-BD by integrating strategies from stepped care, collaborative care, and learning health care systems. We describe the rationale, details, and lessons learned in developing FITT-BD. RESULTS: By integrating stepped care, collaborative care, and a learning health care system approach, FITT-BD aims to reduce barriers to care, leverage the expertise of a multidisciplinary treatment team, ensure patient-centeredness, and use assessments to inform and continuously improve outcomes in real time. We learned that there are challenges in the creation of a web-based application that tracks the treatment of patients within a network of hospitals. CONCLUSIONS: The success of FITT-BD will be determined by the degree to which it can increase treatment access, improve treatment adherence, and help individuals with BD achieve their treatment goals. We expect that FITT-BD will improve outcomes in the context of ongoing clinical care. PUBLIC HEALTH SIGNIFICANCE: The treatment of BD is challenging and complex. We propose a new treatment model for BD: FITT-BD. We expect that this program will be a patient-centered approach that improves outcomes in the context of ongoing clinical care for patients with BD.

Trends, Patterns and Associated User Characteristics of Antidepressant Prescriptions in Older Adults: A Nationwide Descriptive Cohort Study in Denmark.

BACKGROUND AND OBJECTIVE: Antidepressant use in older adults (≥ 65 years) is understudied in large population-based samples, particularly in recent years and regarding user characteristics. We aimed to describe the trends, patterns, and associated user characteristics of all antidepressant prescriptions redeemed by older adults at community pharmacies in Denmark during 2015-2019. METHODS: This register-based study used a cross-sectional design to characterize antidepressant prescription trends and patterns, and a cohort design to describe user characteristics associated with antidepressant prescription initiation. We used descriptive statistics to characterize trends and patterns, and Poisson regression for analyzing user characteristics. RESULTS: During the years 2015-2019, 17.9% of 1.2 million older adults redeemed 4.84 million antidepressant prescriptions, where 48.5% were selective serotonin reuptake inhibitors, followed by noradrenergic and specific serotonergic antidepressants (26.2%), serotonin-norepinephrine reuptake inhibitors (12.7%), tricyclic antidepressants (11.2%), and others (1.4%). Amitriptyline and nortriptyline, considered potentially inappropriate medications, were among the 10 most frequently redeemed antidepressants. Only 60.5% of prescriptions had a treatment indication of depression. Prescription-proportion trends by drug classes and individual antidepressants remained consistent. A higher incidence rate ratio (IRR) and 95% confidence interval (CI) of initiating antidepressants was associated with female sex (IRR 1.20, 95% CI 1.07-1.34), older age (e.g., 81-85 years vs. 65-70 years: IRR 1.74, 95% CI 1.44-2.11), living in rural areas (North Denmark vs. Capital Region: IRR 1.31, 95% CI 1.09-1.58), and having somatic and psychiatric diagnoses (e.g., per one psychiatric diagnosis: IRR 1.10, 95% CI 1.05-1.15), while a lower ratio was associated with being non-Western (vs. Danish: IRR 0.50, 95% CI 0.28-0.89) and having hospital contacts for psychiatric treatment (per each contact: IRR 0.96, 95% CI 0.93-1.00). CONCLUSION: SSRIs were the most commonly redeemed antidepressants, with consistent trends in Danish older adults. Besides clinical conditions, sociodemographics, e.g., sex, age, ethnicity, and place of residence, may influence antidepressant use.

Concurrent use of polypharmacy and potentially inappropriate medications with antidepressants in older adults: A nationwide descriptive study in Denmark during 2015-2019.

OBJECTIVE: Concurrent polypharmacy and potentially-inappropriate-medication (PIMs) use with antidepressants in older adults is understudied. We investigated the prevalence and associated user characteristics of concurrent polypharmacy (≥5 drugs) and PIMs with antidepressants in all older adults (≥65 years) in Denmark based on prescriptions filled at community pharmacies during 2015-2019. METHOD: We applied a cross-sectional and cohort study design using socio-demographic and clinical data from Danish registers. RESULTS: A total of 261,479 older adults (mean age 76 years, females 63%) redeemed at least one prescription of antidepressants during 2015-2019. The prevalence of polypharmacy was 73%, and PIMs was 56%, with over 80% using at least one other nervous system drug or cardiovascular system drug concomitantly with antidepressants. Characteristics associated with higher concurrent use of polypharmacy and PIM with antidepressants were older age, marital status as widow/widower/separated/single, place of residence predominantly in the rural regions, non-western origin, and having somatic diagnoses. Some characteristics showed opposite directions of the associations with the two outcomes, including previous antidepressant use and psychiatric diagnoses being associated with higher use of polypharmacy but lower use of PIM. CONCLUSION: High polypharmacy and PIM use with antidepressants underline the importance of regularly reviewing pharmacological treatments in older adults with depression.

Pharmacological treatment of bipolar disorder and risk of diabetes mellitus: A nationwide study of 30,451 patients.

OBJECTIVE: While treatment with antipsychotics and antiepileptics have been associated with an increased risk of diabetes mellitus (DM), lithium may have the opposite effect via inhibition of glycogen synthase kinase-3. The aim of this study was to investigate whether treatment of bipolar disorder with lithium, antipsychotics, or antiepileptics is associated with the risk of DM in a real-world clinical setting. METHODS: Using nationwide registers, we identified all patients diagnosed with bipolar disorder in Danish Psychiatric Services from January 1, 1996, to January 1, 2019 (N = 30,451). The risk of developing DM was operationalized via hospital diagnoses and redeemed prescriptions for glucose-lowering drugs. For lithium, antipsychotics, valproate, and lamotrigine, we calculated hazard rate ratios (HRR) for developing DM via adjusted Cox proportional hazards models. Potential cumulative dose-response-like associations were examined using the log-rank test. RESULTS: During follow-up (245,181 person-years), 2107 (6.9%) patients developed DM. Compared with non-users of the respective drugs, we found no clinically or statistically significant difference in the risk of developing DM among patients receiving lithium (n = 11,690; incidence rate of DM/1000 person-years (IR) = 8.87, 95% CI: 8.02-9.90; HRR = 0.94, 95% CI: 0.84-1.06) or lamotrigine (n = 11,785; IR = 7.58, 95% CI: 6.69-8.59; HRR = 0.89, 95% CI: 0.77-1.02), respectively. Conversely, for patients receiving valproate (n = 5171; IR = 12.68, 95% CI: 10.87-14.80; HRR = 1.34, 95% CI: 1.14-1.58) and antipsychotics (n = 22,719; IR = 12.00, 95% CI: 11.14-12.94; HRR = 1.65, 95% CI: 1.45-1.88), respectively, there was increased risk of developing DM. For antipsychotics, we observed a clear cumulative dose-response-like association with the risk of DM. CONCLUSIONS: Treatment with valproate and antipsychotics-but not with lithium and lamotrigine-was associated with increased risk of DM in a real-world cohort of patients with bipolar disorder.

Safety and feasibility of faecal microbiota transplant for major depressive disorder: study protocol for a pilot randomised controlled trial.

BACKGROUND: Mental disorders, including major depressive disorder (MDD), are a leading cause of non-fatal burden of disease globally. Current conventional treatments for depression have significant limitations, and there have been few new treatments in decades. The microbiota-gut-brain-axis is now recognised as playing a role in mental and brain health, and promising preclinical and clinical data suggest Faecal Microbiota Transplants (FMT) may be efficacious for treating a range of mental illnesses. However, there are no existing published studies in humans evaluating the efficacy of FMT for MDD. METHODS AND DESIGN: This protocol describes an 8-week, triple-blind, 2:1 parallel group, randomised controlled pilot trial (n = 15), of enema-delivered FMT treatment (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. There will be a further 26-week follow-up to monitor longer-term safety. Participants will receive four FMT or placebo enemas over four consecutive days. The primary aims of the study are to evaluate feasibility and safety of FMT as an adjunctive treatment for MDD in adults. Changes in gut microbiota will be assessed as a secondary outcome. Other data will be collected, including changes in depression and anxiety symptoms, and safety parameters. DISCUSSION: Modification of the microbiota-gut-brain axis via FMT is a promising potential treatment for MDD, but there are no published rigorous clinical trials evaluating its use. If this study finds that our FMT strategy is safe and feasible, a larger fully powered RCT is planned. Further high-quality research in this field is urgently needed to address unmet need. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12621000932864.

Coverage Parity And Racial And Ethnic Disparities In Mental Health And Substance Use Care Among Medicare Beneficiaries.

Many older Americans do not receive needed care for mental health and substance use disorders (MHSUD), and there are substantial racial and ethnic disparities in receipt of this care across the lifespan. Medicare introduced cost-sharing parity for outpatient MHSUD care during the period 2010-14, reducing beneficiaries' out-of-pocket share of MHSUD spending from 50 percent to 20 percent. Among traditional Medicare beneficiaries ages sixty-five and older, we examined changes in MHSUD use and spending during the period 2008-18 for low-income beneficiaries with the cost-sharing reduction versus a control group of beneficiaries with free care throughout the study period among Black, Hispanic, Asian, and American Indian/Alaska Native versus White beneficiaries. Among older Medicare beneficiaries, overall use of MHSUD services increased during this period. For White beneficiaries, MHSUD cost-sharing parity was associated with an increased likelihood of having specialty MHSUD visits and medication use and a reduced likelihood of having unmonitored MHSUD medication use and MHSUD emergency department visits and hospitalizations. However, cost-sharing parity was associated with smaller or no gains in MHSUD services use for racial and ethnic minority beneficiaries compared with White beneficiaries, thus widening racial and ethnic disparities in MHSUD care.

Development of a model to predict combined antidepressant medication and psychotherapy treatment response for depression among veterans.

BACKGROUND: Although research shows that more depressed patients respond to combined antidepressants (ADM) and psychotherapy than either alone, many patients do not respond even to combined treatment. A reliable prediction model for this could help treatment decision-making. We attempted to create such a model using machine learning methods among patients in the US Veterans Health Administration (VHA). METHODS: A 2018-2020 national sample of VHA patients beginning combined depression treatment completed self-report assessments at baseline and 3 months (n = 658). A learning model was developed using baseline self-report, administrative, and geospatial data to predict 3-month treatment response defined by reductions in the Quick Inventory of Depression Symptomatology Self-Report and/or in the Sheehan Disability Scale. The model was developed in a 70 % training sample and tested in the remaining 30 % test sample. RESULTS: 30.0 % of patients responded to treatment. The prediction model had a test sample AUC-ROC of 0.657. A strong gradient was found in probability of treatment response from 52.7 % in the highest predicted quintile to 14.4 % in the lowest predicted quintile. The most important predictors were episode characteristics (symptoms, comorbidities, history), personality/psychological resilience, recent stressors, and treatment characteristics. LIMITATIONS: Restrictions in sample definition, a low recruitment rate, and reliance on patient self-report rather than clinician assessments to determine treatment response limited the generalizability of results. CONCLUSIONS: A machine learning model could help depressed patients and providers predict likely response to combined ADM-psychotherapy. Parallel information about potential harms and costs of alternative treatments would be needed, though, to inform optimal treatment selection.

Feasibility, Acceptability, and Safety of Faecal Microbiota Transplantation in the Treatment of Major Depressive Disorder: A Pilot Randomized Controlled Trial.

OBJECTIVES: Perturbations of the intestinal microbiota have been associated with mental health disorders, including major depressive disorder (MDD). Therefore, faecal microbiota transplantation (FMT) holds promise as a microbiota-modulating treatment for MDD. Yet, to date, there are no published controlled studies evaluating the use of FMT for MDD. This study aimed to address this gap by evaluating the feasibility, acceptability, and safety of FMT for MDD. METHODS: The study was an 8-week, double-blind, 2:1 parallel group, randomized controlled pilot trial (n = 15) of enema-delivered FMT (n = 10) compared with a placebo enema (n = 5) in adults with moderate-to-severe MDD. RESULTS: Recruitment was completed within 2 months, with 0% attrition and 100% attendance at key study appointments. There were no major protocol deviations. The placebo and blinding strategies were considered successful; nurses and participants correctly guessing their treatment allocation at a rate similar to that anticipated by chance. No serious or severe adverse events were reported in either group, and there were no significant differences in mild-to-moderate adverse events between groups (median of 2 adverse events per participant reported in both groups). Furthermore, the 12/15 participants who completed the Week 2 participant satisfaction survey agreed or strongly agreed that the enema delivery was tolerable and that they would have the treatment again if required. Whilst the study was not designed to measure clinical outcomes, exploratory data also suggested that the active FMT treatment may lead to improvements in gastrointestinal symptoms and quality of life in this population, noting that irritable bowel syndrome is commonly comorbid with MDD. CONCLUSIONS: All feasibility targets were met or exceeded. This study found that enema-delivered FMT is feasible, acceptable, well-tolerated, and safe in patients with MDD. The findings of this study support further research to evaluate clinical efficacy, and the use of this protocol is supported.

Lithium plus antipsychotics or anticonvulsants for bipolar disorder: Comparing clinical response and metabolic changes.

OBJECTIVE: Patients with bipolar disorder treated with lithium often require additional antipsychotics or anticonvulsants. However, the comparative effectiveness and safety of these agents as add-on to lithium has not been studied. METHODS: This secondary analysis combined two similar 24-week trials on outpatients with bipolar disorder randomized to lithium (target serum level 0.4-0.6 mEq/L). Guideline-based adjunctive antipsychotics (Li+AP) and anticonvulsants (Li+AC) could be used if clinically indicated and was assessed at every study visit. Response was measured on the Clinical Global Impression scale and we performed adjusted mixed effects linear regression analyses. Analysis of variance tests compared metabolic measures including a binary diagnosis of metabolic syndrome before and after 24 weeks of treatment. RESULTS: Among 379 outpatients (57% female, mean age 38 years, mean Clinical Global Impression 4.4), users of Li+AP (N = 50, primarily quetiapine and aripiprazole) improved to a similar degree (mean Clinical Global Impression improvement = 1.6, standard deviation = 1.5) as those using lithium-only (i.e. without adjunctive antipsychotics or anticonvulsants, N = 149, mean Clinical Global Impression improvement = 1.7, standard deviation = 1.4) (p = 0.59). Users of Li+AC (N = 107, primarily lamotrigine and valproate, mean Clinical Global Impression improvement = 1.2, standard deviation = 1.3) and users of Li+AP+AC (N = 73, mean Clinical Global Impression improvement = 1.1, standard deviation = 1.3) showed worse response compared to lithium-only users (all p < 0.01). When comparing Li+AP to Li+AC, users of Li+AP improved slightly better on general (p = 0.05) and manic symptoms (p = 0.01), but showed a worse development of glucose, triglycerides, and metabolic syndrome. CONCLUSION: Despite treatment-by-indication confounding, these findings are relevant for real-world treatment settings and emphasize the need for randomized trials on this clinically important topic.