Cost-utility analysis of the UPRIGHT intervention promoting resilience in adolescents.

BACKGROUND: As mental health in adulthood is related to mental status during adolescence, school-based interventions have been proposed to improve resilience. The objective of this study was to build a simulation model representing the natural history of mental disorders in childhood, adolescence and youth to estimate the cost-effectiveness of the UPRIGHT school-based intervention in promoting resilience and mental health in adolescence. METHODS: We built a discrete event simulation model fed with real-world data (cumulative incidence disaggregated into eight clusters) from the Basque Health Service database (609,381 individuals) to calculate utilities (quality-adjusted life years [QALYs]) and costs for the general population in two scenarios (base case and intervention). The model translated changes in the wellbeing of adolescents into different risks of mental illnesses for a time horizon of 30 years. RESULTS: The number of cases of anxiety was estimated to fall by 5,125 or 9,592 and those of depression by 1,269 and 2,165 if the effect of the intervention lasted 2 or 5 years respectively. From a healthcare system perspective, the intervention was cost-effective for all cases considered with incremental cost-utility ratios always lower than €10,000/QALY and dominant for some subgroups. The intervention was always dominant when including indirect and non-medical costs (societal perspective). CONCLUSIONS: Although the primary analysis of the trial did not did not detect significant differences, the UPRIGHT intervention promoting positive mental health was dominant in the economic evaluation from the societal perspective. Promoting resilience was more cost-effective in the most deprived group. Despite a lack of information about the spillover effect in some sectors, the economic evaluation framework developed principally for pharmacoeconomics can be applied to interventions to promote resilience in adolescents. As prevention of mental health disorders is even more necessary in the post-coronavirus disease-19 era, such evaluation is essential to assess whether investment in mental health promotion would be good value for money by avoiding costs for healthcare providers and other stakeholders.

Risk of suicide attempt repetition after an index attempt: A systematic review and meta-analysis.

OBJECTIVES: To estimate the risk of suicide attempt repetition among individuals with an index attempt. It also aims to study the role of risk factors and prevention programme in repetition. METHODS: This systematic review and meta-analysis was conducted in keeping with the PRISMA 2020 guidelines. Studies on attempt repetition (both cohort studies and intervention studies) were searched from inception to 2022. RESULTS: A total of 110 studies comprising 248,829 attempters was reviewed. The overall repetition rate was 0.20 (0.17, 0.22). Repetition risk linearly increased over time. A higher risk of attempt repetition was associated with female sex and index attempts in which self-cutting methods were used. Moreover, a mental disorder diagnosis was associated with an increasing repetition risk (OR = 2.02, p < .01). The delivery of a preventive programme reduced the repetition risk, OR = 0.76, p < .05; however, this effect was significant for psychotherapy interventions, OR = 0.38, p < .01. CONCLUSION: One in five suicide attempters will engage in a new suicide attempt. An elevated repetition risk is associated with being female, more severe index methods and psychiatric disorder diagnosis. Preventive programmes, particularly psychotherapy, may contribute to reducing repetition risk and eventually save lives.

Clinical predictors and psychosocial risk factors of suicide attempt severity.

BACKGROUND: Suicide attempts are an important predictor of completed suicide and may differ in terms of severity of medical consequences or medical lethality. There is little evidence on serious suicide attempt (SSA) and very few studies have compared SSA with non-SSA. OBJECTIVE: The aim of this multisite, coordinated, cohort study was to analyze the role of clinical variables and the sociodemographic and psychological risk factors of SSA. METHOD: In this multisite, coordinated, cohort study, 684 participants (222 for the mild suicide attempt group, 371 for the moderate suicide attempt group and 91 for the SSA group) were included in the study. Ordinal regression models were performed to analyze the predictor variables of SSA. RESULTS: Early physical abuse (OR=1.231) and impulsivity (OR=1.036) were predictors of SSA, while depressive symptoms were associated with a lower risk of SSA. CONCLUSION: Environmental and psychological factors as physical abuse and impulsivity are related with severe suicide severity. These findings will help to develop strategies to prevent suicide and may be considered for the treatment and management of suicide.

Inflammation biomarkers in suicide attempts and their relation to abuse, global functioning and cognition.

OBJECTIVES: To explore the link between cytokines and suicide attempts and their relationship with the psychological aspects of this complex multifactorial phenomenon. METHODS: 96 participants, including 20 patients with a recent suicide attempt and diagnosis of Major Depression Disorder (MDD), 33 MDD patients with a lifetime history of suicide attempt, 23 non-attempter MDD patients, and 20 healthy controls underwent an assessment on depressive symptoms, global functioning, aggressive behaviour, presence of abuse and attention performance. Additionally, all participants had a blood extraction for IL-2, IL2-R, IL-4, IL-6, and TNF-α plasma levels analysis. RESULTS: IL-6 levels were significantly different across groups (F(3,89)=3.690; p = 0.015), with higher concentrations in both recent (p = 0.04) and distant (p = 0.015) attempt in comparison to MDD non-attempters. IL-6 was associated with adult physical abuse (B = 2.591; p = 0.021), lower global functioning score (B = -0.512; p = 0.011), and poorer performance on attention (B = -0.897; p = 0.011). CONCLUSIONS: Recent and distant suicidal behaviour is associated with elevated IL-6 levels, which may be influenced by stressful and traumatic experiences. Elevated concentrations of IL-6 could have a negative impact on attention, increasing suicide risk. More research is needed to clarify the role of cytokines in suicide-related features to explore novel treatments and more effective preventive interventions.

Cognition in Recent Suicide Attempts: Altered Executive Function.

Background: Neuropsychological alterations can lead to inaccurate perception, interpretation, and response to environmental information, which could be a risk factor for suicide. Methods: Ninety-six subjects were recruited from the Psychiatry Department of the Araba University Hospital-Santiago, including 20 patients with a recent attempt and diagnosis of major depressive disorder (MDD) according to DSM-V, 33 MDD patients with history of attempted suicide, 23 non-attempter MDD patients, and 20 healthy controls. All participants underwent a clinical interview and neuropsychological assessment on the following cognitive domains: working memory, processing speed, decision-making, executive function, and attention. Backward multiple regressions were performed adjusting for significant confounding variables. For group comparisons, ANOVA and Bonferroni post-hoc tests were performed with a p < 0.05 significance level. Results: The patient groups did not differ regarding severity of depression and stressful events in the last 6 months. In comparison to healthy controls, depressed patients with lifetime suicide attempts had more general trauma (p = 0.003), emotional abuse (p = 0.003), emotional negligence (p = 0.006), and physical negligence (p = 0.009), and depressed patients with recent suicide attempts had experienced more child sexual abuse (p = 0.038). Regarding neuropsychological assessment, all patient groups performed significantly worse than did healthy controls in processing speed, decision-making, and attention. Comparisons between patient groups indicated that recent suicide attempters had poorer performance on executive function in comparison to both depressed lifetime attempters and depressed non-attempters (B = 0.296, p = 0.019, and B = 0.301, p = 0.028, respectively). Besides, women with recent attempts had slightly better scores on executive function than males. Regarding the rest of the cognitive domains, there were no significant differences between groups. Conclusion: Executive function performance is altered in recent suicide attempts. As impaired executive function can be risk factor for suicide, preventive interventions on suicide should focus on its assessment and rehabilitation.

A Multicentre, Randomised, Controlled Trial of a Combined Clinical Treatment for First-Episode Psychosis.

INTRODUCTION: There is evidence that early intervention contributes to improving the prognosis and course of first-episode psychosis (FEP). However, further randomised treatment clinical trials are needed. OBJECTIVES: The aim of this study was to compare the efficacy of a combined clinical treatment involving Cognitive Behavioural Therapy (CBT) as an adjunctive to treatment-as-usual (TAU) (CBT+TAU) versus TAU alone for FEP. PATIENTS AND METHODS: In this multicentre, single-blind, randomised controlled trial, 177 participants were randomly allocated to either CBT+TAU or TAU. The primary outcome was post-treatment patient functioning. RESULTS: The CBT+TAU group showed a greater improvement in functioning, which was measured using the Global Assessment Functioning (GAF) and Functioning Assessment Short Test (FAST), compared to the TAU group post-treatment. The CBT+TAU participants exhibited a greater decline in depressive, negative, and general psychotic symptoms; a better awareness of the disease and treatment adherence; and a greater increase in brain-derived neurotrophic factor levels than TAU participants. CONCLUSIONS: Early intervention based on a combined clinical treatment involving CBT as an adjunctive to standard treatment may improve clinical and functional outcomes in FEP.

Suicidal behaviour and cognition: A systematic review with special focus on prefrontal deficits.

BACKGROUND: Suicide is a major health concern worldwide, thus, identifying risk factors would enable a more comprehensive understanding and prevention of this behaviour. Neuropsychological alterations could lead to difficulties in interpreting and managing life events resulting in a higher risk of suicide. METHOD: A systematic literature search from 2000 to 2020 was performed in Medline (Pubmed), Web of Science, SciELO Citation Index, PsycInfo, PsycArticles and Cochrane Library databases regarding studies comparing cognition of attempters versus non-attempters that share same psychiatric diagnosis. RESULTS: 1.885 patients diagnosed with an Affective Disorder (n = 1512) and Schizophrenia/ Schizoaffective Disorder (n = 373) were included. In general comparison, attention was found to be clearly dysfunctional. Regarding diagnosis, patients with Schizophrenia and previous history of suicidal behaviour showed a poorer performance in executive function. Patients with current symptoms of an Affective Disorder and a previous history of suicidal attempt had poorer performance in attention and executive function. Similarly, euthymic affective patients with history of suicidal behaviour had worse decision-making, attention and executive function performance compared to euthymic non-attempters. LIMITATIONS: The number of papers included in this review is limited to the few studies using non-attempter clinically-matched control group and therefore results regarding diagnosis, symptomatology and time of the attempt are modest and contradictory. CONCLUSIONS: Patients who have attempted suicide have a poorer neuropsychological functioning than non-attempters with a similar psychiatric disorder in attention and executive function. These alterations increase vulnerability for suicide.

Deficits of entropy modulation of the EEG: A biomarker for altered function in schizophrenia and bipolar disorder?

Background: The synchronized activity of distributed neural assemblies ­ reflected in the electroencephalogram (EEG) ­ underpins mental function. In schizophrenia, modulation deficits of EEG spectral content during a P300 task have been replicated. The effects of treatment, chronicity and specificity in these deficits and their possible relationship with anatomic connectivity remain to be explored. Methods: We assessed spectral entropy modulation of the EEG during a P300 task in 79 patients with schizophrenia (of those, 31 werein their first episode), 29 patients with bipolar disorder and 48 healthy controls. Spectral entropy values summarize EEG characteristics by quantifying the irregularity of spectral content. In a subsample, we calculated the network architecture of structural connectivity using diffusion tensor imaging and graph-theory parameters. Results: We found significant spectral entropy modulation deficits with task performance in patients with chronic or first-episode schizophrenia and in patients with bipolar disorder, without significant pre-stimulus spectral entropy differences. The deficits were unrelated to treatment doses, and spectral entropy modulation did not differ between patients taking or not taking antipsychotics, lithium, benzodiazepines or antidepressants. Structural connectivity values were unrelated to spectral entropy modulation. In patients with schizophrenia, spectral entropy modulation was inversely related to negative symptoms and directly related to verbal memory. Limitations: All patients were taking medication. Patients with bipolar disorder were euthymic and chronic. The cross-sectional nature of this study prevented a more thorough analysis of state versus trait criteria for spectral entropy changes. Conclusion: Spectral entropy modulation with task performance is decreased in patients with schizophrenia and bipolar disorder. This deficit was not an effect of psychopharmacological treatment or structural connectivity and might reflect a deficit in the synchronization of the neural assemblies that underlie cognitive activity.

A systematic review of sex-based differences in effectiveness and adverse effects of clozapine.

Clozapine is one of the most widely used antipsychotics for treating psychiatric illnesses such as schizophrenia and bipolar disorder. This drug, however, is associated with adverse effects such as weight gain, metabolic syndrome, and blood dyscrasias. The manifestations of mental illness may differ between men and women. Yet, there is little evidence on the influence of sex on treatment response or the occurrence of AEs. To fill this gap of knowledge, we carried out a systematic review of the literature on sex differences in the effectiveness and adverse effects of clozapine. Scant evidence has been published on differences in effectiveness of clozapine between men and women. Indeed, to the best of our knowledge, this issue has only been addressed in a published study. Regarding adverse effects, males have been reported to be more likely to develop metabolic abnormalities such as cholesterol or triglycerides, hypertension, and cardiovascular risk, while females are at a higher risk for gaining weight, developing diabetes, and needing laxatives. Nevertheless, given the scarcity of sex-based studies on this drug, further studies are needed to explore sex-based differences, as the results obtained may be crucial to clinical practice and help improve the quality of life of patients.

Influencia del sexo en el tratamiento con olanzapina: una revisión sistemática / Gender differences in olanzapine treatment: A systematic review

La olanzapina es un antipsicótico comúnmente utilizado como tratamiento de enfermedades como la esquizofrenia y el trastorno bipolar. En ocasiones la manifestación de la enfermedad difiere entre sexos, pero poco se ha investigado sobre la influencia de esta diferencia biológica en la respuesta al tratamiento o en los efectos secundarios. En esta revisión sistemática analizamos estas diferencias de sexo en la efectividad y en los efectos adversos de la olanzapina. Aunque algunos estudios mostraron mayor efectividad en mujeres, este resultado es ambiguo al no encontrar diferencias en otros trabajos. Por otro lado, encontramos mayor tendencia de los hombres a la ganancia de peso y al parkinsonismo, mientras que más mujeres experimentaron mareos, mayor aumento del colesterol y del intervalo QT. Dado el amplio uso a nivel mundial de la olanzapina, es importante realizar futuros estudios analizando las diferencias observadas, ya que podrían ser cruciales para mejorar la calidad de vida de los pacientes

Olanzapine is an antipsychotic drug commonly used in the treatment of illnesses such as schizophrenia and bipolar disorder. Occasionally the manifestation of the illness differs between genders, but little has been investigated on the influence of this biological difference in the response to the treatment or the secondary effects. In this systematic review, an analysis is made of these gender differences on the effectiveness and adverse effects of olanzapine treatment. Although some studies showed a higher effectiveness in women, this was ambiguous due to not finding any differences in other works. On the other hand, there was a greater tendency for men to gain weight and suffer from Parkinson symptoms, while the women were more likely to suffer from dizzy spells, a greater increase in cholesterol, and in QT interval. Given the worldwide use of olanzapine, it is important that further studies should be performed to analyse these differences observed, since they could be crucial for improving the quality of life of the patients