Is it possible to diagnose therapeutic adherence in mild cognitive impairment and dementia patients in clinical practice?

Background: Non-adherence is common and contributes to adverse health outcomes, reduced quality of life, and increased healthcare expenditure. The objective of this study was to assess the diagnostic validity to estimate the prevalence of non-adherence in patients with mild cognitive impairment (MCI) and dementia using two self-reported methods (SRMs) that are useful and easy in clinical practice, considering the pill count as a reference method (RM). Methods: The cohort study was nested in a multicenter randomized controlled trial NCT03325699. A total of 387 patients from 8 health centers were selected using a non-probabilistic consecutive sampling method. Inclusion criteria were as follows: a score of 20-28 points on the Mini-Mental State Examination (MMSE); older than 55 years; taking prescribed medication; and are in charge of their own medication use. Participants were followed up for 18 months after the baseline visit, i.e., 6, 12, and 18 months. Variables related with treatment adherences were measured in all visits. The variables included age, sex, treatment, comorbidities, and the MMSE test. Adherences included pill counts and Morisky-Green test (MGT) and Batalla test (BT) as SRMs. Statistical analysis included descriptive analysis and 95% confidence intervals (CIs). The diagnostic validity included the following: 1) open comparison statistical association between SRMs and RMs and 2) hierarchy comparison: the RM as the best method to assess non-adherence, kappa value (k), sensitivity (S), specificity (Sp), and likelihood ratio (PPV/PPN). Results: A total of 387 patients were recruited with an average age of 73.29 years (95% CI, 72.54-74.04), of which 59.5% were female. Comorbidities were 54.4% HTA, 35.9% osteoarticular pathology, and 24.5% DM. The MMSE mean score was 25.57 (95% CI, 25.34-25.8). The treatment adherence for the RM oscillates between 22.5% in the baseline and 26.3%, 14.8%, and 17.9% in the follow-up visits. For SRMs, the treatment adherence oscillates between 43.5% in the baseline and 32.4%, 21.9%, and 20.3% in the follow-up visits. The kappa value was statistically significant in all the comparison in all visits with a score between 0.16 and 035. Regarding the diagnostic validity, for the MGT, the sensibility oscillated between 0.4 and 0.58, and the specificity oscillated between 0.68 and 0.87; for the BT, the sensibility oscillated between 0.4 and 0.7, and the specificity oscillated between 0.66 and 0.9; and when both tests were used together, the sensibility oscillated between 0.22 and 0.4, and the specificity oscillated between 0.85 and 0.96. Conclusion: SRMs classify non-adherent subjects correctly. They are very easy to use and yield quick results in clinical practice, so SRMs would be used for the non-adherence diagnosis in patients with MCI and mild dementia.

Economic Evaluation of a Web Application Implemented in Primary Care for the Treatment of Depression in Patients With Type 2 Diabetes Mellitus: Multicenter Randomized Controlled Trial.

BACKGROUND: Depressive disorder and type 2 diabetes mellitus (T2DM) are prevalent in primary care (PC). Pharmacological treatment, despite controversy, is commonly chosen due to resource limitations and difficulties in accessing face-to-face interventions. Depression significantly impacts various aspects of a person's life, affecting adherence to medical prescriptions and glycemic control and leading to future complications and increased health care costs. To address these challenges, information and communication technologies (eg, eHealth) have been introduced, showing promise in improving treatment continuity and accessibility. However, while eHealth programs have demonstrated effectiveness in alleviating depressive symptoms, evidence regarding glycemic control remains inconclusive. This randomized controlled trial aimed to test the efficacy of a low-intensity psychological intervention via a web app for mild-moderate depressive symptoms in individuals with T2DM compared with treatment as usual (TAU) in PC. OBJECTIVE: This study aimed to analyze the cost-effectiveness and cost-utility of a web-based psychological intervention to treat depressive symptomatology in people with T2DM compared with TAU in a PC setting. METHODS: A multicenter randomized controlled trial was conducted with 49 patients with T2DM, depressive symptoms of moderate severity, and glycosylated hemoglobin (HbA1c) of 7.47% in PC settings. Patients were randomized to TAU (n=27) or a web-based psychological treatment group (n=22). This web-based treatment consisted of cognitive behavioral therapy, improvement of diabetes self-care behaviors, and mindfulness. Cost-effectiveness analysis for the improvement of depressive symptomatology was conducted based on reductions in 3, 5, or 50 points on the Patient Health Questionnaire-9 (PHQ-9). The efficacy of diabetes control was estimated based on a 0.5% reduction in HbA1c levels. Follow-up was performed at 3 and 6 months. The cost-utility analysis was performed based on quality-adjusted life years. RESULTS: Efficacy analysis showed that the web-based treatment program was more effective in improving depressive symptoms than TAU but showed only a slight improvement in HbA1c. Incremental cost-effectiveness ratios of 186.76 for a 3-point reduction in PHQ-9 and 206.31 for reductions of 5 and 50 percentage points were obtained. In contrast, the incremental cost-effectiveness ratio for improving HbA1c levels amounted to €1510.90 (€1=US $1.18 in 2018) per participant. The incremental cost-utility ratio resulted in €4119.33 per quality-adjusted life year gained. CONCLUSIONS: The intervention, using web-based modules incorporating cognitive behavioral therapy tools, diabetes self-care promotion, and mindfulness, effectively reduced depressive symptoms and enhanced glycemic control in patients with T2DM. Notably, it demonstrated clinical efficacy and economic efficiency. This supports the idea that eHealth interventions not only benefit patients clinically but also offer cost-effectiveness for health care systems. The study emphasizes the importance of including specific modules to enhance diabetes self-care behaviors in future web-based psychological interventions, emphasizing personalization and adaptation for this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT03426709; https://clinicaltrials.gov/study/NCT03426709. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/S12888-019-2037-3.

Pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in bipolar disorder: A systematic review.

BACKGROUND: The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD. METHODS: PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected. RESULTS: Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1ß, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients. CONCLUSION: Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.

Efficacy of clozapine versus standard treatment in adult individuals with intellectual disability and treatment-resistant psychosis (CLOZAID): study protocol of a multicenter randomized clinical trial.

Background: Intellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field. Methods: A Phase IIB, open-label, randomized, multicenter clinical trial (NCT04529226) is currently ongoing to assess the efficacy of oral clozapine in individuals diagnosed with ID and suffering from treatment-resistant psychosis. We aim to recruit one-hundred and fourteen individuals (N=114) with ID and resistant psychosis, who will be randomized to TAU (treatment as usual) and treatment-with-clozapine conditions. As secondary outcomes, changes in other clinical scales (PANSS and SANS) and the improvement in functionality, assessed through changes in the Euro-QoL-5D-5L were assessed. The main outcome variables will be analyzed using generalized linear mixed models (GLMM), assessing the effects of status variable (TAU vs. Clozapine), time, and the interaction between them. Discussion: The treatment of resistant psychosis among ID individuals must be directed by empirically supported research. CLOZAID clinical trial may provide relevant information about clinical guidelines to optimally treat adults with ID and treatment-resistant psychosis and the benefits and risks of an early use of clozapine in this underrepresented population in clinical trials. Trial registration: Clinicaltrials.gov: NCT04529226. EudraCT: 2020-000091-37.

Impulsivity, decision-making, and risk behavior in bipolar disorder and major depression from bipolar multiplex families.

OBJECTIVES: Bipolar disorder (BD) and major depressive disorder (MDD) are characterized by specific alterations of mood. In both disorders, alterations in cognitive domains such as impulsivity, decision-making, and risk-taking have been reported. Identification of similarities and differences of these domains in BD and MDD could give further insight into their etiology. The present study assessed impulsivity, decision-making, and risk-taking behavior in BD and MDD patients from bipolar multiplex families. METHODS: Eighty-two participants (BD type I, n = 25; MDD, n = 26; healthy relatives (HR), n = 17; and healthy controls (HC), n = 14) underwent diagnostic interviews and selected tests of a cognitive battery assessing neurocognitive performance across multiple subdomains including impulsivity (response inhibition and delay aversion), decision-making, and risk behavior. Generalized estimating equations (GEEs) were used to analyze whether the groups differed in the respective cognitive domains. RESULTS: Participants with BD and MDD showed higher impulsivity levels compared to HC; this difference was more pronounced in BD participants. BD participants also showed lower inhibitory control than MDD participants. Overall, suboptimal decision-making was associated with both mood disorders (BD and MDD). In risk-taking behavior, no significant impairment was found in any group. LIMITATIONS: As sample size was limited, it is possible that differences between BD and MDD may have escaped detection due to lack of statistical power. CONCLUSIONS: Our findings show that alterations of cognitive domains-while present in both disorders-are differently associated with BD and MDD. This underscores the importance of assessing such domains in addition to mere diagnosis of mood disorders.