Evaluating the influence of nonproblematic alcohol intake on the outcome of major depression.

The effect of light or moderate alcohol intake on the outcome of patients with major depression taking antidepressants is a question that remains unanswered. The main objective of this study was to assess the association between light or moderate alcohol consumption and the acute response (efficacy and tolerability) to pharmacological treatment in unipolar major depression. Efficacy and tolerability analyses compared 8-week outcomes between three subgroups, abstainers, light drinkers and moderate drinkers, of patients with major depression using a prospective naturalistic single-blind design. The treatment strategy was adapted from a local clinical guideline. Antidepressants prescribed were escitalopram, venlafaxine extended-release and imipramine; benzodiazepines and antipsychotics could be prescribed as needed. The final sample consisted of 614 severe unipolar major depressive inpatients and outpatients aged 18 years or older. Notably, no significant differences in efficacy or tolerability (including all subscores assessed) were found between the abstainer and nonproblematic drinker subgroups. Without ever forgetting the serious implicit risks associated with the inappropriate use of alcohol, in conclusion, our results suggest that nonproblematic alcohol consumption does not influence the outcome of patients diagnosed with an acute severe major depressive episode.

Vickybot, a Chatbot for Anxiety-Depressive Symptoms and Work-Related Burnout in Primary Care and Health Care Professionals: Development, Feasibility, and Potential Effectiveness Studies.

BACKGROUND: Many people attending primary care (PC) have anxiety-depressive symptoms and work-related burnout compounded by a lack of resources to meet their needs. The COVID-19 pandemic has exacerbated this problem, and digital tools have been proposed as a solution. OBJECTIVE: We aimed to present the development, feasibility, and potential effectiveness of Vickybot, a chatbot aimed at screening, monitoring, and reducing anxiety-depressive symptoms and work-related burnout, and detecting suicide risk in patients from PC and health care workers. METHODS: Healthy controls (HCs) tested Vickybot for reliability. For the simulation study, HCs used Vickybot for 2 weeks to simulate different clinical situations. For feasibility and effectiveness study, people consulting PC or health care workers with mental health problems used Vickybot for 1 month. Self-assessments for anxiety (Generalized Anxiety Disorder 7-item) and depression (Patient Health Questionnaire-9) symptoms and work-related burnout (based on the Maslach Burnout Inventory) were administered at baseline and every 2 weeks. Feasibility was determined from both subjective and objective user-engagement indicators (UEIs). Potential effectiveness was measured using paired 2-tailed t tests or Wilcoxon signed-rank test for changes in self-assessment scores. RESULTS: Overall, 40 HCs tested Vickybot simultaneously, and the data were reliably transmitted and registered. For simulation, 17 HCs (n=13, 76% female; mean age 36.5, SD 9.7 years) received 98.8% of the expected modules. Suicidal alerts were received correctly. For the feasibility and potential effectiveness study, 34 patients (15 from PC and 19 health care workers; 76% [26/34] female; mean age 35.3, SD 10.1 years) completed the first self-assessments, with 100% (34/34) presenting anxiety symptoms, 94% (32/34) depressive symptoms, and 65% (22/34) work-related burnout. In addition, 27% (9/34) of patients completed the second self-assessment after 2 weeks of use. No significant differences were found between the first and second self-assessments for anxiety (t8=1.000; P=.34) or depressive (t8=0.40; P=.70) symptoms. However, work-related burnout scores were moderately reduced (z=-2.07, P=.04, r=0.32). There was a nonsignificant trend toward a greater reduction in anxiety-depressive symptoms and work-related burnout with greater use of the chatbot. Furthermore, 9% (3/34) of patients activated the suicide alert, and the research team promptly intervened with successful outcomes. Vickybot showed high subjective UEI (acceptability, usability, and satisfaction), but low objective UEI (completion, adherence, compliance, and engagement). Vickybot was moderately feasible. CONCLUSIONS: The chatbot was useful in screening for the presence and severity of anxiety and depressive symptoms, and for detecting suicidal risk. Potential effectiveness was shown to reduce work-related burnout but not anxiety or depressive symptoms. Subjective perceptions of use contrasted with low objective-use metrics. Our results are promising but suggest the need to adapt and enhance the smartphone-based solution to improve engagement. A consensus on how to report UEIs and validate digital solutions, particularly for chatbots, is required.

Lithium Augmentation Versus Citalopram Combination in Imipramine-Resistant Major Depression: A 10-Week Randomized Open-Label Study.

PURPOSE/BACKGROUND: According to available international clinical guides, tricyclic antidepressants are our first- or second-line treatment of choice for severe unipolar major depression. However, the therapeutic option after an unsuccessful response to a tricyclic antidepressant drug in unipolar major depression is still unclear. METHODS/PROCEDURES: This 10-week randomized open-label study assessed the effectiveness of add-on lithium (adjusted to plasma levels) compared with add-on citalopram (30 mg/d) in 104 severe unipolar major depressive patients after a 10-week unsuccessful imipramine (adjusted to plasma level). Efficacy analyses examined changes in the severity of depression symptoms from baseline visit to endpoint and the comparative remission rate between treatment subgroups. FINDINGS/RESULTS: The randomized sample consisted of 104 imipramine-resistant severe unipolar major depressed patients. Both, the percentage of remitters (40.4% vs 21.1%, P = 0.034) and the mean reduction of the Hamilton Depression Rating Scale score (58.8% vs 42.5%, P = 0.005) were significantly greater in the add-on citalopram subgroup at endpoint visit. IMPLICATIONS/CONCLUSIONS: Although we should be cautious about generalizing these results to patients with a less severe unipolar major episode, results from the present study suggest that add-on citalopram is a very effective treatment option in unipolar major depressive episodes after an unsuccessful imipramine regimen.

Switching to Imipramine Versus Add-on Mirtazapine in Venlafaxine-Resistant Major Depression: A 10-Week Randomized Open Study.

PURPOSE/BACKGROUND: Newer-generation antidepressants used in monotherapy or in combination with other newer-generation antidepressants or other psychotropic drugs are usually preferred as first- or second-step treatment options in resistant depression. According to our clinical experience, tricyclic antidepressants still are one of our preferred first choices in treatment-resistant moderate to severe unipolar major depressive episodes. METHODS: This 10-week open-design randomized study assessed the effectiveness of switching to imipramine (adjusted to plasma levels) compared with add-on mirtazapine (30 mg/d) for treatment of moderate to severe unipolar major depressive episodes after a 10-week unsuccessful venlafaxine regimen (225-300 mg/d). Efficacy analyses examined the change in depressive symptoms severity from baseline visit to endpoint and the comparative remission rate between treatment subgroups. FINDINGS/RESULTS: The randomized sample consisted of 112 venlafaxine-resistant moderate to severe unipolar major depressed patients. Both the percentage of remitters (71.43% vs 39.28%) and the mean reduction of the Hamilton Depression Rating Scale score (76.94% vs 50.72%) were significantly larger in the imipramine subgroup. IMPLICATIONS/CONCLUSIONS: Even though we should be cautious about generalizing these results to patients with a less severe unipolar major episodes, our study suggest that switching to imipramine is a very effective treatment option in unipolar major depressive episodes after an unsuccessful venlafaxine regimen.

Dominios cognitivos en la depresión unipolar. Teorías multimodales y nuevas perspectivas terapéuticas / Cognitive domains in unipolar depression. Multimodal theories and new therapeutic perspectives

El trastorno depresivo mayor (TDM) se considera el prototipo de alteración del grupo heterogéneo de trastornos depresivos (DSM-5). El TDM es una patología pleomórfica, poligénica y multisistémica que emerge de los diferentes niveles de interacción entre genes y factores ambientales. Por desgracia el aumento del costo de la depresión y de los trastornos afectivos relacionados no ha ido acompañado de mejoras en la eficacia del tratamiento antidepresivo. Los retos actuales se centran en la búsqueda de dianas terapéuticas capaces de modular diferentes niveles fisiopatológicos desde el genoma, variables metabólicas sistémicas, hasta los mecanismos cognitivos de orden superior (p.ej. funciones ejecutivas). Esta breve revisión tiene como objetivo analizar los términos neuropsicológicos que consideramos necesarios en la evaluación clínica de los pacientes afectos de un TDM así como ciertos mecanismos neurobiológicos y nuevos antidepresivos que pretender superar las limitaciones clínicas actuales (AU)

Major depressive disorder (MDD) is considered the prototype of pathology heterogeneous group of Depressive Disorders (DSM-5). The MDD is a pleomorphic pathology and multisystem polygenic disorder emerging from different levels of interacting genes and environmental factors. Unfortunately, the increasing cost of depression and related affective disorders has not been paralleled by improvements in the efficacy of antidepressant treatment. Current challenges are focused on finding therapeutic targets capable of modulating different pathophysiological levels from the genome (eg. histone deacetylase inhibitors), and systemic metabolic variables (eg. drugs that interact at the level of oxidative and inflammatory phenomena), to higher order cognitive mechanisms (eg. executive functions). This brief review aims to analyze the neuropsychological terms we considered necessary in the clinical assessment of patients with MDD and the pathophysiological mechanisms and new therapeutic seeking to overcome current limitations (AU)

Treatment and outcome of antidepressant treatment-associated hypomania in unipolar major depression: a 3-year follow-up study.

BACKGROUND: The main aim of this study was to propose a standardized acute and maintenance/continuation treatment protocol for acute antidepressant treatment-associated hypomania (AAH) in major unipolar depression. The second objective was to describe outcomes at three-year follow-up in a cohort of patients with AAH who had been included in this standardized therapeutic protocol. METHODS: The study consisted of two distinct prospective phases: a 1-year follow-up first phase in which all consecutive patients with a diagnosis of moderate/severe unipolar depressive disorder received acute and continuation/maintenance antidepressant treatment; and a second phase, in which patients who had suffered AAH during the first phase were admitted to a 3-year follow-up with the authors-designed standardized acute and continuation/maintenance treatment protocol. RESULTS: In our patient sample, the reintroduction of antidepressant treatment according to the proposed protocol was not accompanied by new AAH episodes following 11-36 months of pharmacological antidepressant treatment. The second notable result was that no subject presented manic episodes or spontaneous hypomania (once antidepressant maintenance treatment had finished) during three years of follow-up. LIMITATIONS: We should be cautious when generalizing these results to patients with mild major depressive episode or other type of unipolar affective disorder. CONCLUSIONS: Based on these results, we should not refuse the prescription of antidepressant drugs to patients with unipolar depression and subsequent AAH. The treatment protocol which we describe in this study can serve as a basis for future studies and, in anticipation of future consensus, as a practical proposal for clinical psychiatrists.

Association between symptomatic profile and remission following antidepressant treatment in unipolar major depression.

BACKGROUND: To evaluate, in patients affected by an acute major depressive episode, what predictive value certain baseline psychopathological characteristics have with regard to expected therapeutic remission following biological antidepressant treatment (pharmacological/electroconvulsive; non-psychological). METHODS: Six predefined psychopathological characteristics in acute major depressive episode were evaluated using a logistic regression model through a protocolised antidepressant treatment to assess their predictive value with regard to expected remission rate. RESULTS: The final study sample consisted of 129 subjects affected by an acute major depressive episode. From the baseline evaluation of the anguish/restlessness, reduced emotional reactivity, reduced attention, reduced motor response, feeling of worthlessness, and mood characteristics items, it was possible to correctly classify 88.1% of the sample as remitter/non-remitter with sensitivity of 0.77 and specificity of 0.96. Addition of the 17-item HRSD baseline variable to the regression model increased the capacity for correct classification of the baseline sample by only 0.09%. LIMITATIONS: Protocolised antidepressant treatment was used. The results of this study may not be generalisable to pharmacological treatments not included in this protocol. CONCLUSIONS: The results of this study suggest that certain baseline psychopathological characteristics (and perhaps other clinical variables too) of the acute major depressive episode may be of great use in establishing patient subgroups according to expected clinical remission to the administration of biological antidepressant treatment. This could have considerable consequences for individualised therapeutic decision-making and for future researches (clinical trials included).

Executive function needs to be targeted to improve social functioning with Cognitive Remediation Therapy (CRT) in schizophrenia.

While the role of impaired cognition in accounting for functional outcome in schizophrenia is generally established, the relationship between cognitive and functional change in the context of treatments is far from clear. The current paper tries to identify which cognitive changes lead to improvements in daily functioning among persons with chronic schizophrenia who had current negative symptoms and evidenced neuropsychological impairments. In a previous work, Cognitive Remediation Therapy (CRT) was compared with a control therapy, involving similar length of therapist contact but different targets. At the end of treatment, CRT conferred a benefit to people with schizophrenia in cognition and functioning [Schizophrenia Research, 87 (2006) 323-331]. Subsequently, analyses of covariance (ANCOVA) were conducted with baseline and cognitive change scores as covariates to test whether cognitive change predicted change in functioning. Additionally, statistical tests to establish the mediation path with significant variables were performed. Although verbal memory, but not executive functioning, was associated with functioning at baseline, it was the improvement in executive functioning that predicted improved daily functioning. Verbal memory played a mediator role in the change process. Consequently, in order to improve daily functioning with CRT, executive function still needs to be targeted in despite of multiple cognitive impairments being present.

Continuation/maintenance treatment with nortriptyline versus combined nortriptyline and ECT in late-life psychotic depression: a two-year randomized study.

OBJECTIVE: The identification of effective continuation and maintenance strategies for elderly patients with psychotic depression is a critical issue that has not been fully explored. The aim of this study was to assess the tolerability and efficacy of continuation/maintenance electroconvulsive therapy (ECT) in elderly patients with psychotic depression after acute ECT remission. METHODS: The authors used a longitudinal, randomized, single-blind design to compare by survival analysis the 2-year outcome of two subgroups of elderly patients with psychotic unipolar depression who were ECT (plus nortriptyline) remitters. One group was treated with a continuation/maintenance nortriptyline regimen (N = 17) and the other with combined continuation/maintenance ECT plus nortriptyline (N = 16). RESULTS: Over 2 years of treatment in elderly, psychotic, unipolar depressed ECT (plus nortriptyline) remitters, the mean survival time was significantly longer in the combined ECT plus nortriptyline subgroup than in the nortriptyline subgroup. No differences were observed between treatments with regard to tolerability. CONCLUSIONS: This study supports the judicious use of combined continuation/maintenance ECT and antidepressant treatment in elderly patients with psychotic unipolar depression who are ECT remitters.

Clustering and switching in semantic fluency: predictors of the development of Alzheimer's disease.

OBJECTIVE: The aims of the study are twofold: (1) to compare semantic fluency, clustering and switching performance among subjects with memory complaints, patients with Alzheimer Disease (AD), and healthy controls; and (2) to examine the clinical utility of the clustering/switching scoring system in the prediction of incident AD in subjects with memory complaints. METHODS: A semantic fluency task was used to compare thirty eight subjects with memory complaints, forty two AD patients and twenty five healthy controls on the total number of words generated, clustering and switching performance. Subjects with memory complaints were followed-up for a maximum period of two years and re-evaluated. They remained in the memory complaints group (twenty eight subjects) or were defined as probable AD (ten subjects). RESULTS: AD patients generated fewer correct words (p < 0.001) and showed a reduction in clustering (p = 0.008) and switching (p < 0.001). Subjects with memory complaints showed a significant reduction in correct words (p < 0.001) and clustering performance (p = 0.008) compare to controls. In the first evaluation, the subgroup of patients who converted to AD at follow up produced less correct words (p < 0.01) and smaller clusters (p = 0.007) than the subgroup who did not become demented. There were no differences in switching between these two subgroups. AD development was better predicted by cluster size than by the total number of words generated or by switching. CONCLUSIONS: Subjects with memory complaints and AD patients have an alteration in both qualitative and quantitative aspects of semantic fluency. A clustering analysis could enhance the reliability of early AD diagnosis.

Cognitive remediation therapy for outpatients with chronic schizophrenia: a controlled and randomized study.

Cognitive Remediation Therapy (CRT) is a novel rehabilitation approach designed to improve neurocognitive abilities such as attention, memory and executive functioning. The aim of the present study is to evaluate the effect of CRT on neurocognition, and secondarily on symptomatology and psychosocial functioning. Cognitive Behavioural Therapy (CBT) was used as a control condition because it aims to improve emotional problems and positive symptoms, focusing on modification of maladaptive beliefs and schemas, but neurocognition is not targeted. A total of 40 chronic patients with DSM-IV schizophrenia disorder were randomly assigned for 4 months to one of two treatment groups: CRT or CBT. Repeated assessments were conducted before and after the treatments and at the end of a follow-up period of 6 months. Additionally, a method to establish reliable change was calculated from a separate sample of 20 schizophrenic patients who were under standard medication without any kind of psychological treatment. Results showed that CRT produced an overall improvement on neurocognition (Mean effect size=0.5), particularly in verbal and nonverbal memory, and executive function. CBT showed the expected treatment effect on general psychopathology (anxiety and depression) but produced only a slight non-specific improvement in neurocognition (Working Memory). Furthermore, patients receiving CRT showed improvement in social functioning, demonstrating that cognitive improvements are clinically meaningful. These gains were still present at the 6 month follow-up.

Influencia de la comorbilidad trastorno distímico-trastorno de la personalidad en el tratamiento cognitivo-conductual en grupo para el trastorno distímico / Influence of comorbidity of dysthymia and personality disorders on cognitive-behavioural group therapy for dysthymia

Objetivo: En el presente estudio pretendemos analizar la influencia de la asociación trastorno distímico y trastorno de la personalidad en los resultados de la intervención cognitivo-conductual en grupo para el trastorno distímico. Metodología: La muestra consta de 71 pacientes. Se evalúa el estado clínico y la personalidad de estos mediante los siguientes tests psicométricos: PDQ-4, BDI, STAI-E, STAI-R y Mini-Mult. Se divide la muestra en dos grupos: presencia o no de trastorno de personalidad y se analizan las diferencias respecto la severidad incial de psicopatología presentada y respecto al cambio clínico tras el tratamiento psicológico entre estos dos grupos. Resultados: Respecto a la severidad inicial del trastorno distímico se encuentran diferencias estadísticamente significativas entre los dos grupos en las variables STAI-R, en las escalas de validez del Mini-Mult (f y K) y en las clínicas: desviación psicopática, paranoia, esquizofrenia y manía. No se encuentran diferencias en el nivel de severidad previo al tratamiento de la sintomatología depresiva, ni a través del BDI ni en la escala de depresión del Mini-Mult. No se detecta un efecto del tratamiento psicológico diferenciado para ambos grupos y no se obtienen diferencias pre y post tratamiento estadísticamente significativas para ninguna de las variables de estado psicopatológico, con excepción de la escala manía, en la que el grupo con trastorno de la personalidad aumenta la puntuación respecto el nivel inicial. Conclusión: En función de nuestros datos parece que los pacientes con trastorno de la personalidad presentan más psicopatología previa al tratamiento, pero no parece que la asociación trastorno distímico-trastorno de la personalidad tenga ninguna influencia específica en el beneficio clínico obtenido para el tratamiento psicológico en comparación con los sujetos sin trastorno de la personalidad asociado. Es decir, que el tratamiento psicológico es igual de efectivo para ambos grupos (AU)

Variables predictorias del resultado terapéutico en el tratamiento cognitivo-conductual de la fobia social / Predictive variables of the therapeutic outcome in the cognitive-behavioral treatment of the social phobia

La fobia social es uno de los trastornos psiquiátricos más frecuentes en la población general. Distintos estudios señalan la terapia cognitiva y la exposición como las intervenciones más efectivas para este trastorno. En los últimos años se han realizado diversos estudios con la finalidad de averiguar qué factores pueden incidir en los resultados terapéuticos del tratamiento psicológico de la fobia social. En el presente trabajo, se analizan el nivel académico, la edad y la presencia de otros trastornos comórbidos como posibles variables intervinientes en los resultados terapéuticos obtenidos en 10 de pacientes a los que se les ha aplicado un programa de terapia cognitivo-conductual en grupo para la fobia social. La edad no interfiere en los resultados del tratamiento. El nivel académico predice los resultados en la mayoría de las medidas. Hay relación estadísticamente significativa entre comorbilidad y el cambio al miedo a la evaluación negativa (AU)