Why we need to pursue both universal and targeted prevention to reduce the incidence of affective and psychotic disorders: Systematic review and meta-analysis.

The effectiveness of universal preventive approaches in reducing the incidence of affective/psychotic disorders is unclear. We therefore aimed to synthesise the available evidence from randomised controlled trials. For studies reporting change in prevalence, we simulated all possible scenarios for the proportion of individuals with the disorder at baseline and at follow-up to exclude them. We then combined these data with studies directly measuring incidence and conducted random effects meta-analysis with relative risk (RR) to estimate the incidence in the intervention group compared to the control group. Eighteen studies (k=21 samples) were included investigating the universal prevention of depression in 66,625 individuals. No studies were available investigating universal prevention on the incidence of bipolar/psychotic disorders. 63 % of simulated scenarios showed a significant preventive effect on reducing the incidence of depression (k=9 - 19, RR=0.75-0.94, 95 %CIs=0.55-0.87,0.93-1.15, p=0.007-0.246) but did not survive sensitivity analyses. There is some limited evidence for the effectiveness of universal interventions for reducing the incidence of depression but not for bipolar/psychotic disorders.

Preventive interventions for individuals at risk of developing bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to explore whether early interventions can reduce affective symptoms and have long-term benefits among individuals at risk of bipolar disorder (BD). METHODS: The PubMed, Embase, and Web of Science databases were searched. The primary outcome was continuous symptom scores before and after treatment. Random effects meta-analyses were conducted for each outcome arm studied and pooled mean difference estimates were calculated. RESULTS: The search identified 10 controlled studies involving 425 participants and 6 single-arm studies involving 90 participants. For controlled trials, meta-analysis showed that the interventions led to greater reduction in clinical global score than placebo (standardized mean differences (SMD) = -0.96, 95 % CI:-1.32, -0.60), and supported a long-term longitudinal effect for pharmacotherapy (SMD = -0.42, 95 % CI: -0.79, -0.05). For single-arm trials, both pharmacotherapy and psychotherapy showed efficacy for depressive symptoms, while pharmacotherapy only showed efficacy for hypomania symptoms (effect size (ES) = -9.16, 95 % CI:-11.29, -7.04). Discontinuation of pharmacotherapy due to adverse effects did not show a difference. LIMITATIONS: The primary limitations are the small number of RCTs and the influence of medication dosage. CONCLUSIONS: Based on the limited available data, early interventions show efficacy for individuals at risk of BD. Psychological therapy might be more beneficial for depressive symptoms and have long-term benefits for hypomania. Pharmacotherapy may be appropriate in situations of severe hypomanic symptoms and the poor functioning. Large, well-designed, double-blind -controlled trials are needed to make solid conclusions about the efficacy of early interventions.

Psychosis prediction 2.0: why child and adolescent mental health services should be a key focus for schizophrenia and bipolar disorder prevention research.

Existing approaches to psychosis prediction capture only a small minority of future cases. Recent research shows that specialist child and adolescent mental health services (CAMHS) offer a (previously unrecognised) high-risk and high-capacity approach for psychosis early identification, prediction and, ultimately, prevention.

Preventive interventions for children of parents with depression, anxiety, or bipolar disorder: A quasi-experimental clinical trial.

AIM: To investigate the effectiveness of preventive interventions for 8-17-year-old children of patients diagnosed with depression, anxiety, or bipolar disorder. METHODS: Sixty-two families including 89 children received either the more extensive Family Talk Intervention (FTI; n = 35), the brief Let's Talk about Children (LTC; n = 16), or Interventions as Usual (IAU; n = 38) in routine care in adult psychiatry. Parent-rated questionnaire data were collected at baseline, after 6 and 12 months. We used growth curve models to investigate the effect of intervention on child mental health problems (SDQ-P Total Difficulties) and perceived parental control of child behaviour (PLOC-PPC). RESULTS: Parents in the FTI and LTC groups, versus the IAU group, reported more favourable development in terms of preventing increase in child mental health problems with standardised intervention effects of d = -0.86 and -0.88 respectively, by study end, and reported improved perceived parental control, d = 1.08 and 0.71, respectively, by study end. No significant differences in effect were found when FTI and LTC were compared. CONCLUSIONS: The results support continued use of FTI and LTC in adult psychiatry, and since LTC is a brief intervention, it might be useful as a minimum-level preventive intervention.

Promoting physical activity for mental health: an updated evidence review and practical guide.

PURPOSE OF REVIEW: The aim of this study was to provide psychiatrists with the knowledge, tools and guidance to support physical activity promotion in clinical practice. The review also aims to provide an up-to-date summary of the evidence regarding physical activity in the prevention and treatment of mental disorders in adults. RECENT FINDINGS: There is emerging evidence demonstrating that physical activity can protect against incident anxiety and depression. There is robust evidence showing that physical activity is an effective adjunct treatment strategy for depressive disorders and anxiety and stress-related disorders, with emerging evidence for schizophrenia and bipolar disorders. Translation of this evidence into practice is in general ad hoc, and large physical health disparities for people with mental disorders persist. The reasons for this are multifactorial, and include the intersection of social, economic and personal barriers to physical activity. Evidence-based approaches include regular screening of physical activity levels, staff culture change within mental health services and established referral pathways. SUMMARY: Translation of evidence regarding physical activity for mental health into routine programmes is critical. Efforts to move beyond solely targeting individual-level barriers to physical activity and address systemic barriers include lack of access to appropriate exercise services. This requires consideration of training needs, service structure and culture change.

Evidence-based treatment strategies for rapid cycling bipolar disorder, a systematic review.

OBJECTIVES: Rapid cycling is a phase of bipolar disorder with increased episode frequencies. It is a severe and disabling condition that often poses a major challenge to the clinician. The aim of this paper is to give an overview of the evidence-based treatment options for rapid cycling. METHODS: A systematic search on Pubmed, Embase and Cochrane databases from inception until December 2021 was conducted according to the PRISMA guidelines. An additional search on clinicaltrials.gov was done. References of retrieved papers and key reviews were hand-searched. Randomized controlled trials including at least 10 patients with bipolar disorder, rapid cycling, reporting an objective outcome measure were selected. RESULTS: Our search, initially revealing 1330 articles, resulted in 16 papers about treatment of an acute mood episode, relapse prevention or both. Lithium, anticonvulsants, second generation antipsychotics, antidepressants and thyroid hormone were assessed as treatment options in the presented data. Evidence supporting the use of aripiprazole, olanzapine, quetiapine, valproate and lamotrigine for treatment of rapid cycling bipolar disorder was found. LIMITATIONS: Small sample sizes, different index episodes and variety of outcome measures. CONCLUSION: Evidence regarding treatment of rapid cycling remains scarce. Evidence supports the use of aripiprazole, olanzapine, and valproate for acute manic or mixed episodes, quetiapine for acute depressive episodes and aripiprazole and lamotrigine for relapse prevention. Given the paucity of available evidence, and the burden that accompanies rapid cycling, future research is warranted.

Genetic polymorphisms influencing response to lithium in early-onset Bipolar disorder from south India.

OBJECTIVES: Early-onset Bipolar disorder (EOBD), has a more malignant course with high recurrence risk and there is a need for population-specific pharmaco-genomic study. METHODS: This study is a prospective and retrospective observational study. Both newly diagnosed patients and those on follow-up with a diagnosis of bipolar I disorder with onset before 18 years of age and on lithium prophylaxis as part of treatment-as-usual were recruited for the study. Response to treatment was assessed at the end of two years follow up using ALDA scale. Ten single nucleotide polymorphisms associated with treatment response based on previous studies were chosen for analysis. RESULTS: Of 162 who had EOBD, sixty-four fulfilled inclusion criteria and fifty-seven completed the study. TT and TG genotypes of rs75222709 on AL157359.3 gene were found to be significantly different between non-responders(N = 43) and healthy controls (N = 220). The frequency of the GA genotype of the single nucleotide polymorphism rs17204573 of the RORA (Retinoic Acid related orphan receptor alpha) gene was significantly lower among subjects (27.3%, N = 54) as compared to controls (42.9%, OR:0.5, CI: 0.26-0.96, p value 0.035). However, the significance of both disappeared after Bonferroni correction. Among clinical factors female gender was significantly associated with lithium non-response. CONCLUSION: Although conducting pharmaco-genomic studies with large sample size is a challenge for low and middle-income countries, future studies can help improve the long-term outcome of youth with EOBD.

Activation of SIRT-1 Signalling in the Prevention of Bipolar Disorder and Related Neurocomplications: Target Activators and Influences on Neurological Dysfunctions.

SIRT-1 (silent mating-type information regulation 2 homolog-1) is a protein found in neuronal nuclei, microglia, and astrocyte cells of the brain. It is sometimes referred to as NAD + -dependent deacetylase (nicotinamide adenine dinucleotide). The activation of sirtuins (SIRT-1-7) has been shown to protect against a wide range of disorders, including neurodegenerative and neuropsychiatric disorders. SIRT-1 has gained considerable interest from these families because of its early link to long-life expansion and calorie restriction involvement. SIRT-1 is necessary for gene silencing, cell cycle regulation, fat and glucose metabolism, oxidative stress, ageing, and memory formation. In this review, we investigate the role of SIRT-1 downregulation in the progression of bipolar disorder (BD) and neurological abnormalities, as well as related neurological alterations such as genetic dysfunction, neurotransmitter imbalance, oxidative stress-induced apoptosis, and mitochondrial dysfunction. BD is a psychiatric disease distinguished by extreme mood fluctuations that range from depressive lows to manic highs. BD is a complicated disorder with numerous clinical signs and neurocomplications that produce significant behavioural problems. SIRT-1 deficiency in the brain has been demonstrated to affect the activity of its transcription factors and molecular changes, including genetic defects. SIRT-1 is now being studied as a potential therapeutic target for a range of brain disorders. A recent study also found that activating SIRT-1 signalling performs a protective effect in avoiding depression and mania-like behaviours. Furthermore, this review investigates the potential mechanisms by which SIRT-1 regulates neuronal transmission and neurogenesis. As a result of our review, we revealed that SIRT-1 activators have neuroprotective potential in BD and related neurological dysfunctions.

Preventing new episodes of bipolar disorder in adults: Systematic review and meta-analysis of randomized controlled trials.

Uncertainty remains regarding the relative efficacy of maintenance pharmacotherapy for bipolar disorder (BD), and available data require updating. The present systematic review and meta-analysis aims to consolidate the evidence from the highest quality randomized controlled trials (RCTs) published up to July 2021, overcoming the limitations of earlier reviews. The PubMed and the Cochrane Central Register of Controlled Trials were searched for double-blind RCTs involving lithium, mood stabilizing anticonvulsants (MSAs), antipsychotics, antidepressants, and other treatments. Rates of new mood episodes with test vs. reference treatments (placebo or alternative active agent) were compared by random-effects meta-analysis. Polarity index was calculated for each treatment type. Eligible trials involved ≥6 months of maintenance follow up. Of 2,158 identified reports, 22 met study eligibility criteria, and involved 7,773 subjects stabilized for 1-12 weeks and followed-up for 24-104 weeks. Psychotropic monotherapy overall (including lithium, MSAs, and second generation antipsychotics (SGA) was more effective in preventing new BD episodes than placebo (odds ratio, OR=0.42; 95% confidence interval, CI 0.34-0.51, p<0.00001). Significantly lower risk of new BD episodes was observed with the following individual drugs: aripiprazole, asenapine, lithium, olanzapine, quetiapine, and risperidone long-acting (ORs varied 0.19-0.46). Adding aripiprazole, divalproex, quetiapine, or olanzapine/risperidone to lithium or an MSA was more effective compared with lithium or MSA monotherapy (OR=0.37; 95%CI 0.25-0.55, p<0.00001). Active treatment favored prevention of mania over depression. The key limitations were "responder-enriched" design in most trials and high outcomes heterogeneity. PROSPERO registration number is CRD42020162663.

Studies on candidate genes for lithium prophylaxis performed at the Poznan University of Medical Sciences. / Badania genów kandydujacych profilaktyki litem przeprowadzone na Uniwersytecie Medycznym w Poznaniu.

Lithium is a drug of choice as a mood-stabilizer for the maintenance treatment of bipolar disorder. The prophylactic efficacy of lithium can be determined by genetic factors, partially related to a predisposition to bipolar disorder. In the field of psychiatric genetics, the first decade of the 21st century was dominated by the "candidate gene" research. In this paper, the studies on candidate genes connected with lithium prophylaxis performed at the Poznan University of Medical Sciences in 2005-2018 are presented. During this time, the polymorphisms of multiple genes have been investigated, many of which are also connected with a predisposition to bipolar illness. The associations with lithium prophylactic efficacy were found for the polymorphisms in 5HTT, ACP1, ARNTL, BDNF, COMT, DRD1, FKBP5, FYN, GLCC, NR3C1, and TIM, genes, but not those in 5HT2A, 5HT2C, DRD2, DRD3, DRD4, GRIN2B, GSK-3ß, MMP-9, and NTRK2 genes. The polymorphism of the GSK-3ß gene was found to be associated with the kidney side-effects occurring during lithium therapy. Possible roles for these genes in both the mechanism of lithium prophylactic activity and pathogenesis of bipolar mood disorder were discussed.

Intentos de suicidio y trastornos mentales / Suicide attempts and mental disorders

Introducción: el suicidio es un grave problema de salud pública mundial, más de 800,000 personas se suicidan cada año y entre 10 y 20 millones lo intentan cada año. Ha sido considerado como una conducta prevenible y el intento es un predictor clínicamente relevante que está presente en un tercio de los suicidios consumados, así como padecer un trastorno mental es otro factor de riesgo para el suicido. Objetivo: determinar la relación entre los intentos de suicidio y los trastornos mentales. Material y Métodos: se realizó una búsqueda en las bases de datos; Dialnet, Redalyc, Scielo, Biblioteca Virtual en Salud (BVS), PubMed, Science Direct y Google Académico, en español e inglés y limitada a las publicaciones entre 01 de enero 2010 y 31 de diciembre de 2020. Desarrollo: la prevalencia de vida del intento de suicidio en pacientes con Trastorno Bipolar es del 33,9 por ciento, en pacientes con Trastorno Depresivo Mayor es del 31 por ciento, y en pacientes con Esquizofrenia es del 26,8 por ciento. Conclusiones: los pacientes con trastorno bipolar y trastorno depresivo mayor, presentan mayor porcentaje de intentos de suicidio. Aunado a una comorbilidad psiquiátrica (consumo de alcohol, consumo de tabaco y trastorno de la personalidad límite), más intentos de suicidio previos, aumenta el riesgo del comportamiento suicida(AU)

Introduction: Suicide is a serious global public health problem. More than 800,000 people commit suicide every year and between 10 and 20 million people attempt suicide annually. Suicide has been considered a preventable behavior and suicide attempt is a clinically relevant predictor which is present in one-third of consummated suicides. Besides, having a mental disorder is another risk factor for suicide. Objective: To determine the relationship between suicide attempts and mental disorders such as depressive and anxiety disorders, bipolar disorder, substance-related disorders, schizophrenia and other psychotic disorders, personality disorders, and eating disorders. Material and Methods: A search was performed in Dialnet, Redalyc, Scielo, Virtual Health Library (VHL), PubMed, Science Direct, and Google Scholar databases in Spanish and English. It was limited to publications between January 1, 2010 and December 31, 2020. Development: The lifetime prevalence of suicide attempt is 31 percent in patients with Bipolar Disorder; 33,9 percent in patients with Major Depressive Disorder and 26.8 percent in patients with Schizophrenia. Conclusions: Patients with bipolar disorder and major depressive disorder have higher rates of suicide attempts. Coupled with psychiatric comorbidity (alcohol consumption, smoking, borderline personality disorder), more previous suicide attempts increase the risk of suicidal behavior(AU)

Olanzapine and quetiapine in the prevention of a new mood episode in women with bipolar disorder during the postpartum period: a retrospective cohort study.

OBJECTIVE: To examine whether olanzapine and quetiapine are useful in the prevention of a new mood episode during the postpartum period. METHODS: Data on 23 patients (n=14 for olanzapine and n=9 for quetiapine) with bipolar disorder who met the criteria for this study were retrospectively gathered. The diagnosis of bipolar disorder was determined by means of the DSM-IV. RESULTS: The mean follow-up period was 33.95±12.07 weeks. Six (26.1%) of 23 patients experienced recurrent mood episodes during the postpartum period. Four of these six patients were taking olanzapine and two were taking quetiapine. Patients with recurrent mood episodes had a significantly stronger family history of bipolar disorder, higher number of past episodes, and earlier onset and longer duration of illness compared to patients without recurrent mood episodes. CONCLUSION: Monotherapy with olanzapine or quetiapine can be considered as an alternative to mood stabilizers in preventing the development of new mood episodes after childbirth.

Preventive effect of morning light exposure on relapse into depressive episode in bipolar disorder.

OBJECTIVE: Light therapy has been suggested to have a curative effect on bipolar depression; however, preventive effects of light exposure on depressive episodes remain unclear. This study evaluated whether daytime light exposure in real-life situations was associated with a preventive effect on relapse into depressive episodes in patients with bipolar disorder. METHODS: This prospective, naturalistic, observational study was conducted in Japan between August 2017 and June 2020. Outpatients with bipolar disorder were objectively evaluated for daytime light exposure over 7 consecutive days using an actigraph that could measure ambient light at baseline assessment and then assessed at 12-month follow-up for relapse into mood episodes. RESULTS: Of 202 participants, 198 (98%) completed follow-up at 12 months and 78 (38%) experienced relapse into depressive episodes during follow-up. In a Cox proportional hazards model adjusting for potential confounders, a longer time above 1000 lux at daytime was significantly associated with decrease in relapse into depressive episodes (per log min; hazard ratio, 0.66; 95% confidence interval, 0.50-0.91). In addition, a higher average illuminance and longer time above 1000 lux in the morning exhibited a significant decrease in relapse into depressive episodes (per log lux and per log min; hazard ratio, 0.65 and 0.61; 95% confidence interval, 0.49-0.86 and 0.47-0.78, respectively). The association between daytime light exposure and relapse into manic/hypomanic/mixed episodes was not significantly different. CONCLUSION: A significant association was observed between increased daytime light exposure, mainly in the morning, and decreased relapse into depressive episodes.

Citalopram for Acute and Preventive Efficacy in Bipolar Depression (CAPE-BD): A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To assess the efficacy and safety of citalopram in the acute and maintenance phases of bipolar depression in a randomized, double-blind, placebo-controlled trial. METHODS: Between 2007 and 2014, 119 subjects with acute major depressive episodes diagnosed with DSM-IV bipolar disorder, type I or type II, were randomized blindly to citalopram or placebo, added to standard mood stabilizers. They were followed for 6 weeks for acute efficacy (primary outcome) and up to 1 year for maintenance efficacy (secondary outcome) using scores on the Montgomery-Asberg Depression Rating Scale (MADRS) and the Mania Rating Scale of the Schedule for Affective Disorders and Schizophrenia (MRS-SADS). The study was powered for a clinically meaningful effect size. RESULTS: Mean ± SD MADRS scores changed from a baseline value of 27.4 ± 9.1 to 13.1 ± 8.4 at the end of the acute phase for citalopram versus a change from 27.4 ± 7.3 to 15.2 ± 9.9 for placebo, a clinically and statistically nonsignificant difference. Maintenance efficacy also was not better with citalopram than with placebo. Acute manic/hypomanic episodes were similar in both groups, and subjects with type II illness did not have better outcomes than subjects with type I illness. In maintenance treatment, MRS-SADS scores were greater overall, especially in subjects with a rapid-cycling illness course, with citalopram versus placebo. CONCLUSIONS: Citalopram, added to standard mood stabilizers, did not have clinically meaningful benefit versus placebo for either acute or maintenance treatment of bipolar depression. Acute mania did not worsen with citalopram, but maintenance treatment led to worsened manic symptoms, especially in subjects with a rapid-cycling course. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00562861.

Relapse prevention in ambulant mental health care tailored to patients with schizophrenia or bipolar disorder.

WHAT IS ALREADY KNOWN ON THE SUBJECT?: Understanding the need for psychoeducation and management strategies in relapse prevention, for individuals with schizophrenia or bipolar disorder. Interventions for individuals with severe mental illness, especially schizophrenia, often requires support from family or social network to successfully improve mental stability in the life of the mentally ill. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: To our knowledge, no previous review has provided an overview of state of the art intervention elements currently used in ambulant mental health care interventions and how these elements are combined in interventions tailored to individuals with schizophrenia or bipolar disorder. Moreover, this systematic review indicates the effect of the different intervention elements. This review reveals an apparent gab in knowledge regarding patient perceptions of and need for individualized relapse prevention interventions. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The review is a relevant tool for stakeholders and practitioners in community mental health service when planning future interventions. Considering the specific needs for intervention complexity of the target group is likely to improve not only treatment outcome, but also patient satisfaction and treatment adherence. ABSTRACT: Introduction In recent years, there has been a development in ambulant mental health care towards a more preventive approach, resulting in relapse prevention interventions. Interventions may be patient tailored, to a greater or lesser extent, in relation to the treatment elements included. Aim To create an overview of non-pharmacological intervention elements described in relapse prevention interventions for patients with schizophrenia or bipolar disorder based on a systematic review. Method Six scientific databases were systematically searched. The search strategy, identification and selection of literature complied with the PRISMA statement. Results Of 7.429 studies screened, 25 were included for analysis. Six treatment elements were identified: Pharmacological treatment, personalized action plan, patient education, patient skills, treatment adherence and family involvement. Discussion The varying degree of complexity of the interventions indicates that patients with bipolar disorder and schizophrenia have, respectively, different treatment needs. Patients with schizophrenia seem to benefit more from interventions that include support from social network or family than patients with bipolar disorder. More qualitative studies clarifying the patient's perspective on tailored relapse prevention are indicated. Implications for practice Optimally tailoring relapse prevention for patients with schizophrenia and bipolar disorder will improve treatment outcome, and probably also treatment satisfaction and adherence.