Sleep-wake variations of electrodermal activity in bipolar disorder.

BACKGROUND: Affective states influence the sympathetic nervous system, inducing variations in electrodermal activity (EDA), however, EDA association with bipolar disorder (BD) remains uncertain in real-world settings due to confounders like physical activity and temperature. We analysed EDA separately during sleep and wakefulness due to varying confounders and potential differences in mood state discrimination capacities. METHODS: We monitored EDA from 102 participants with BD including 35 manic, 29 depressive, 38 euthymic patients, and 38 healthy controls (HC), for 48 h. Fifteen EDA features were inferred by mixed-effect models for repeated measures considering sleep state, group and covariates. RESULTS: Thirteen EDA feature models were significantly influenced by sleep state, notably including phasic peaks (p < 0.001). During wakefulness, phasic peaks showed different values for mania (M [SD] = 6.49 [5.74, 7.23]), euthymia (5.89 [4.83, 6.94]), HC (3.04 [1.65, 4.42]), and depression (3.00 [2.07, 3.92]). Four phasic features during wakefulness better discriminated between HC and mania or euthymia, and between depression and euthymia or mania, compared to sleep. Mixed symptoms, average skin temperature, and anticholinergic medication affected the models, while sex and age did not. CONCLUSION: EDA measured from awake recordings better distinguished between BD states than sleep recordings, when controlled by confounders.

Emotion dysregulation in bipolar disorder compared to other mental illnesses: a systematic review and meta-analysis.

People with bipolar disorder (BD) often present emotion dysregulation (ED), a pattern of emotional expression interfering with goal-directed behavior. ED is a transdiagnostic construct, and it is unclear whether it manifests itself similarly in other conditions, such as major depressive disorder (MDD) or borderline personality disorder (BPD), or has specific features in BD. The present systematic review and meta-analysis explored ED and adopted emotion regulation (ER) strategies in BD compared with other psychiatric conditions. PubMed/MEDLINE, EMBASE, Scopus, and PsycINFO databases were systematically searched from inception to April 28th, 2022. Studies implementing validated instruments assessing ED or ER strategies in BD and other psychiatric disorders were reviewed, and meta-analyses were conducted. Twenty-nine studies yielding multiple comparisons were included. BD was compared to MDD in 20 studies (n = 2451), to BPD in six studies (n = 1001), to attention deficit hyperactivity disorder in three studies (n = 232), to anxiety disorders in two studies (n = 320), to schizophrenia in one study (n = 223), and to post-traumatic stress disorder in one study (n = 31). BD patients did not differ from MDD patients in adopting most adaptive and maladaptive ER strategies. However, small-to-moderate differences in positive rumination and risk-taking behaviors were observed. In contrast, patients with BPD presented an overall higher degree of ED and more maladaptive ER strategies. There were insufficient data for a meta-analytic comparison with other psychiatric disorders. The present report further supports the idea that ED is a transdiagnostic construct spanning a continuum across different psychiatric disorders, outlining specific clinical features that could represent potential therapeutic targets.

Correlation between emotion dysregulation and mood symptoms of bipolar disorder: A systematic review and meta-analysis.

BACKGROUND: Emotion dysregulation (ED) is a transdiagnostic construct characterized by difficulties regulating intense emotions. People with bipolar disorder (BD) are more likely to show ED and use maladaptive emotion regulation strategies than adaptive ones. However, little is known about whether ED in BD is a trait or it is rather an epiphenomenon of mood symptoms. METHODS: We conducted a systematic review and meta-analysis of the evidence across major literature databases reporting correlations between measures of emotion regulation (overall ED and different emotion regulation strategies) and measures of depressive and (hypo)manic symptoms in BD from inception until April 12th, 2022. RESULTS: Fourteen studies involving 1371 individuals with BD were included in the qualitative synthesis, of which 11 reported quantitative information and were included in the meta-analysis. ED and maladaptive strategies were significantly higher during periods with more severe mood symptoms, especially depressive ones, while adaptive strategies were lower. CONCLUSION: ED significantly correlates with BD symptomatology, and it mainly occurs during mood alterations. ED may be a target for specific psychotherapeutic and pharmacological treatments, according to precision psychiatry. However, further studies are needed, including patients with mood episodes and longitudinal design, to provide more robust evidence and explore the causal direction of the associations.

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.

Evaluating the Effect of a Telepsychiatry Educational Program on the Awareness, Knowledge, Attitude, and Skills of Telepsychiatry Among Spanish Psychiatrists during COVID-19 Pandemic.

Introduction: The COVID-19 pandemic has renewed the interest in telepsychiatry as a way to help psychiatrists care for their patients, but mental health providers' unfamiliarity and concerns may impede implementation of such services. This study aimed to determine the effect of an online educational intervention on awareness, knowledge, attitude, and skills (AKAS) of telepsychiatry among psychiatrists. Methods: The study used a pre-post-test design to compare AKAS of telepsychiatry among psychiatrists participating in an online course of practical telepsychiatry. The telemedicine AKAS questionnaire adapted to telepsychiatry was applied before and after the educational intervention, during the months of October to December 2020. Results: Responses from 213 participants were analyzed before the educational intervention and from 152 after it. The knowledge showed by Spanish psychiatrists before the educational intervention was good in 61% of participants, fair in 37%, and inadequate in 2%. With respect to attitudes toward telepsychiatry, 62% self-reported a high attitude, 33% moderate, and 5% low. With regard self-reported skills, 57% of the participating psychiatrists were highly skilled or experts, 22% moderately skilled, and 9% unskilled in handling telepsychiatry equipment. Despite the high baseline values, the educational intervention significantly improved psychiatrists' awareness, knowledge and attitudes toward telepsychiatry although not their skills. Conclusions: Online course of practical telepsychiatry was effective although future editions need to improve its focus on skills. This educational intervention represents an effort to promote the implementation of telepsychiatry as a health care alternative.

Smartphone-based interventions in bipolar disorder: Systematic review and meta-analyses of efficacy. A position paper from the International Society for Bipolar Disorders (ISBD) Big Data Task Force.

BACKGROUND: The clinical effects of smartphone-based interventions for bipolar disorder (BD) have yet to be established. OBJECTIVES: To examine the efficacy of smartphone-based interventions in BD and how the included studies reported user-engagement indicators. METHODS: We conducted a systematic search on January 24, 2022, in PubMed, Scopus, Embase, APA PsycINFO, and Web of Science. We used random-effects meta-analysis to calculate the standardized difference (Hedges' g) in pre-post change scores between smartphone intervention and control conditions. The study was pre-registered with PROSPERO (CRD42021226668). RESULTS: The literature search identified 6034 studies. Thirteen articles fulfilled the selection criteria. We included seven RCTs and performed meta-analyses comparing the pre-post change in depressive and (hypo)manic symptom severity, functioning, quality of life, and perceived stress between smartphone interventions and control conditions. There was significant heterogeneity among studies and no meta-analysis reached statistical significance. Results were also inconclusive regarding affective relapses and psychiatric readmissions. All studies reported positive user-engagement indicators. CONCLUSION: We did not find evidence to support that smartphone interventions may reduce the severity of depressive or manic symptoms in BD. The high heterogeneity of studies supports the need for expert consensus to establish ideally how studies should be designed and the use of more sensitive outcomes, such as affective relapses and psychiatric hospitalizations, as well as the quantification of mood instability. The ISBD Big Data Task Force provides preliminary recommendations to reduce the heterogeneity and achieve more valid evidence in the field.

Real-world Implementation of a Smartphone-Based Psychoeducation Program for Bipolar Disorder: Observational Ecological Study.

BACKGROUND: SIMPLe is an internet-delivered self-management mobile app for bipolar disorder (BD) designed to combine technology with evidence-based interventions and facilitate access to psychoeducational content. The SIMPLe app was launched to the real world to make it available worldwide within the context of BD treatment. OBJECTIVE: The main aims of this study are as follows: to describe app use, engagement, and retention rates based on server data; to identify patterns of user retention over the first 6-month follow-up of use; and to explore potential factors contributing to discontinuation of app use. METHODS: This was an observational ecological study in which we pooled available data from a real-world implementation of the SIMPLe app. Participation was open on the project website, and the data-collection sources were a web-based questionnaire on clinical data and treatment history administered at inclusion and at 6 months, subjective data gathered through continuous app use, and the use patterns captured by the app server. Characteristics and engagement of regular users, occasional users, and no users were compared using 2-tailed t tests or analysis of variance or their nonparametric equivalent. Survival analysis and risk functions were applied to regular users' data to examine and compare use and user retention. In addition, a user evaluation analysis was performed based on satisfaction, perceived usefulness, and reasons to discontinue app use. RESULTS: We included 503 participants with data collected between 2016 and 2018, of whom 77.5% (n=390) used the app. Among the app users, 44.4% (173/390) completed the follow-up assessment, and data from these participants were used in our analyses. Engagement declined gradually over the first 6 months of use. The probability of retention of the regular users after 1 month of app use was 67.4% (263/390; 95% CI 62.7%-72.4%). Age (P=.002), time passed since illness onset (P<.001), and years since diagnosis of BD (P=.048) correlate with retention duration. In addition, participants who had been diagnosed with BD for longer used the app on more days (mean 97.73, SD 69.15 days; P=.002) than those who had had a more recent onset (mean 66.49, SD 66.18 days; P=.002) or those who had been diagnosed more recently (mean 73.45, SD 66 days; P=.01). CONCLUSIONS: The user retention rate of the app decreased rapidly after each month until reaching only one-third of the users at 6 months. There exists a strong association between age and app engagement of individuals with BD. Other variables such as years lived with BD, diagnosis of an anxiety disorder, and taking antipsychotics seem relevant as well. Understanding these associations can help in the definition of the most suitable user profiles for predicting trends of engagement, optimization of app prescription, and management.

Long-term treatment of bipolar disorder type I: A systematic and critical review of clinical guidelines with derived practice algorithms.

OBJECTIVES: This systematic review aimed at providing a critical, comprehensive synthesis of international guidelines' recommendations on the long-term treatment of bipolar disorder type I (BD-I). METHODS: MEDLINE/PubMed and EMBASE databases were searched from inception to January 15th, 2019 following PRISMA and PICAR rules. International guidelines providing recommendations for the long-term treatment of BD-I were included. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation-AGREE II. RESULTS: The final selection yielded five international guidelines, with overall good quality. The evaluation of applicability was the weakest aspect across the guidelines. Differences in their updating strategies and the rating of the evidence, particularly for meta-analyses, randomized clinical trials (RCTs) and observational studies, could be responsible of some level of heterogeneity among recommendations. Nonetheless, the guidelines recommended lithium as the 'gold standard' in the long-term treatment of BD-I. Quetiapine was another possible first-line option as well as aripiprazole (for the prevention of mania). Long-term treatment should contemplate monotherapy, at least initially. Clinicians should check regularly for efficacy and side effects and if necessary, switch to first-line alternatives (i.e. Valproate), combine first-line compounds with different mechanisms of action or switch to second-line options or combinations. CONCLUSIONS: The possibility to monitor improvements in long-term outcomes, namely relapse prevention and inter-episode subthreshold depressive symptoms, based on the application of their recommendations is an unmet need of clinical guidelines. In terms of evidence of clinical guidelines, there is a need for more efficacious treatment strategies for the prevention of bipolar depression.

Patient and physician perspectives of a smartphone application for depression: a qualitative study.

BACKGROUND: Despite an increasing number of smartphone apps, such therapeutic tools have not yet consistently demonstrated their efficacy and many suffer from low retention rates. To ensure the development of efficient apps associated with high adherence, we aimed to identify, through a user-centred design approach, patient and physician expectations of a hypothetical app dedicated to depression. METHODS: We conducted semi-structured interviews with physicians (psychiatrists and general practitioners) and patients who had experienced a major depressive episode during the last 12 months using the focus group method. The interviews were audio recorded, transcribed and analysed using qualitative content analysis to define codes, categories and emergent themes. RESULTS: A total of 26 physicians and 24 patients were included in the study. The focus groups showed balanced sex and age distributions. Most participants owned a smartphone (83.3% of patients, 96.1% of physicians) and were app users (79.2% of patients and 96.1% of physicians). The qualitative content analysis revealed 3 main themes: content, operating characteristics and barriers to the use of the app. Expected content included the data collected by the app, aiming to provide information about the patient, data provided by the app, gathering psychoeducation elements, therapeutic tools and functionalities to help with the management of daily life and features expected for this tool. The "operating characteristics" theme gathered aims considered for the app, its potential target users, considered modalities of use and considerations around its accessibility and security of use. Finally, barriers to the use of the app included concerns about potential app users, its accessibility, safety, side-effects, utility and functioning. All themes and categories were the same for patients and physicians. CONCLUSIONS: Physician and patient expectations of a hypothetical smartphone app dedicated to depression are high and confirmed the important role it could play in depression care. The key points expected by the users for such a tool are an easy and intuitive use and a personalised content. They are also waiting for an app that gives information about depression, offers a self-monitoring functionality and helps them in case of emergency.

Feasibility of mHealth interventions for depressive symptoms in Latin America: a systematic review.

Depression is a prevalent disorder and leading cause of disability in Latin America, where the mental health treatment gap is still above 50%. We sought to synthesise and assess the quality of the evidence on the feasibility of mHealth-based interventions for depression in Latin America. We conducted a literature search of studies published in 2007 and after using four electronic databases. We included peer-reviewed articles, in English, Spanish or Portuguese, that evaluated interventions for depressive symptoms. Two authors independently extracted data using forms developed a priori. We assessed appropriateness of reporting utilising the CONSORT checklist for feasibility trials. Eight manuscripts were included for full data extraction. Appropriate reporting varied greatly. Most (n = 6, 75%) of studies were conducted in primary care settings and sought to deliver psychoeducation or behaviour change interventions for depressive symptoms. We found great heterogeneity in the assessment of feasibility. Two studies used comparator conditions. mHealth research for depression in Latin America is scarce. Included studies showed some feasibility despite methodological inconsistencies. Given the dire need for evidence-based mental health interventions in this region, governments and stakeholders must continue promoting and funding research tailored to cultural and population characteristics with subsequent pragmatic clinical trials.

Association between naturally occurring lithium in drinking water and suicide rates: systematic review and meta-analysis of ecological studies.

BACKGROUND: The prevalence of mental health conditions and national suicide rates are increasing in many countries. Lithium is widely and effectively used in pharmacological doses for the treatment and prevention of manic/depressive episodes, stabilising mood and reducing the risk of suicide. Since the 1990s, several ecological studies have tested the hypothesis that trace doses of naturally occurring lithium in drinking water may have a protective effect against suicide in the general population. AIMS: To synthesise the global evidence on the association between lithium levels in drinking water and suicide mortality rates. METHOD: The MEDLINE, Embase, Web of Science and PsycINFO databases were searched to identify eligible ecological studies published between 1 January 1946 and 10 September 2018. Standardised regression coefficients for total (i.e. both genders combined), male and female suicide mortality rates were extracted and pooled using random-effects meta-analysis. The study was registered with PROSPERO (CRD42016041375). RESULTS: The literature search identified 415 articles; of these, 15 ecological studies were included in the synthesis. The random-effects meta-analysis showed a consistent protective (or inverse) association between lithium levels/concentration in publicly available drinking water and total (pooled ß = -0.27, 95% CI -0.47 to -0.08; P = 0.006, I2 = 83.3%), male (pooled ß = -0.26, 95% CI -0.56 to 0.03; P = 0.08, I2 = 91.9%) and female (pooled ß = -0.13, 95% CI -0.24 to -0.02; P = 0.03, I2 = 28.5%) suicide mortality rates. A similar protective association was observed in the six studies included in the narrative synthesis, and subgroup meta-analyses based on the higher/lower suicide mortality rates and lithium levels/concentration. CONCLUSIONS: This synthesis of ecological studies, which are subject to the ecological fallacy/bias, supports the hypothesis that there is a protective (or inverse) association between lithium intakes from public drinking water and suicide mortality at the population level. Naturally occurring lithium in drinking water may have the potential to reduce the risk of suicide and may possibly help in mood stabilisation, particularly in populations with relatively high suicide rates and geographical areas with a greater range of lithium concentration in the drinking water. All the available evidence suggests that randomised community trials of lithium supplementation of the water supply might be a means of testing the hypothesis, particularly in communities (or settings) with demonstrated high prevalence of mental health conditions, violent criminal behaviour, chronic substance misuse and risk of suicide.

Treatment-resistant and multi-therapy-resistant criteria for bipolar depression: consensus definition.

BACKGROUND: Most people with bipolar disorder spend a significant percentage of their lifetime experiencing either subsyndromal depressive symptoms or major depressive episodes, which contribute greatly to the high levels of disability and mortality associated with the disorder. Despite the importance of bipolar depression, there are only a small number of recognised treatment options available. Consecutive treatment failures can quickly exhaust these options leading to treatment-resistant bipolar depression (TRBD). Remarkably few studies have evaluated TRBD and those available lack a comprehensive definition of multi-therapy-resistant bipolar depression (MTRBD).AimsTo reach consensus regarding threshold definitions criteria for TRBD and MTRBD. METHOD: Based on the evidence of standard treatments available in the latest bipolar disorder treatment guidelines, TRBD and MTRBD criteria were agreed by a representative panel of bipolar disorder experts using a modified Delphi method. RESULTS: TRBD criteria in bipolar depression was defined as failure to reach sustained symptomatic remission for 8 consecutive weeks after two different treatment trials, at adequate therapeutic doses, with at least two recommended monotherapy treatments or at least one monotherapy treatment and another combination treatment. MTRBD included the same initial definition as TRBD, with the addition of failure of at least one trial with an antidepressant, a psychological treatment and a course of electroconvulsive therapy. CONCLUSIONS: The proposed TRBD and MTRBD criteria may provide an important signpost to help clinicians, researchers and stakeholders in judging how and when to consider new non-standard treatments. However, some challenging diagnostic and therapeutic issues were identified in the consensus process that need further evaluation and research.Declaration of interestIn the past 3 years, M.B. has received grant/research support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, MBF, NHMRC, Beyond Blue, Rotary Health, Geelong Medical Research Foundation, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Meat and Livestock Board, Organon, Novartis, Mayne Pharma, Servier, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Bristol Myers Squibb, Eli Lilly, Glaxo SmithKline, Janssen Cilag, Lundbeck, Merck, Pfizer, Sanofi Synthelabo, Servier, Solvay and Wyeth and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eli Lilly, Grunbiotics, Glaxo SmithKline, Janssen Cilag, LivaNova, Lundbeck, Merck, Mylan, Otsuka, Pfizer and Servier. A.C. has received fees for lecturing from pharmaceutical companies namely Lundbeck and Sunovion. A.J.C. has in the past 3 years received honoraria for speaking from Astra Zeneca and Lundbeck, honoraria for consulting from Allergan, Janssen, Lundbeck and LivaNova and research grant support from Lundbeck. G.M.G. holds shares in P1Vital and has served as consultant, advisor or CME speaker for Allergan, Angelini, Compass pathways, MSD, Lundbeck, Otsuka, Takeda, Medscape, Minervra, P1Vital, Pfizer, Servier, Shire and Sun Pharma. J.G. has received research funding from National Institute for Health Research, Medical Research Council, Stanley Medical Research Institute and Wellcome. H.G. received grants/research support, consulting fees or honoraria from Gedeon Richter, Genericon, Janssen Cilag, Lundbeck, Otsuka, Pfizer and Servier. R.H.M.-W. has received support for research, expenses to attend conferences and fees for lecturing and consultancy work (including attending advisory boards) from various pharmaceutical companies including Astra Zeneca, Cyberonics, Eli Lilly, Janssen, Liva Nova, Lundbeck, MyTomorrows, Otsuka, Pfizer, Roche, Servier, SPIMACO and Sunovion. R.M. has received research support from Big White Wall, Electromedical Products, Johnson and Johnson, Magstim and P1Vital. S.N. received honoraria from Lundbeck, Jensen and Otsuka. J.C.S. has received funds for research from Alkermes, Pfizer, Allergan, J&J, BMS and been a speaker or consultant for Astellas, Abbott, Sunovion, Sanofi. S.W has, within the past 3 years, attended advisory boards for Sunovion and LivaNova and has undertaken paid lectures for Lundbeck. D.J.S. has received honoraria from Lundbeck. T.S. has reported grants from Pathway Genomics, Stanley Medical Research Institute and Palo Alto Health Sciences; consulting fees from Sunovion Pharamaceuticals Inc.; honoraria from Medscape Education, Global Medical Education and CMEology; and royalties from Jones and Bartlett, UpToDate and Hogrefe Publishing. S.P. has served as a consultant or speaker for Janssen, and Sunovion. P.T. has received consultancy fees as an advisory board member from the following companies: Galen Limited, Sunovion Pharmaceuticals Europe Ltd, myTomorrows and LivaNova. E.V. received grants/ research support, consulting fees or honoraria from Abbott, AB-Biotics, Allergan, Angelini, Dainippon Sumitomo, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka and Sunovion. L.N.Y. has received grants/research support, consulting fees or honoraria from Allergan, Alkermes, Dainippon Sumitomo, Janssen, Lundbeck, Otsuka, Sanofi, Servier, Sunovion, Teva and Valeant. A.H.Y. has undertaken paid lectures and advisory boards for all major pharmaceutical companies with drugs used in affective and related disorders and LivaNova. He has also previously received funding for investigator-initiated studies from AstraZeneca, Eli Lilly, Lundbeck and Wyeth. P.R.A.S. has received research funding support from Corcept Therapeutics Inc. Corcept Therapeutics Inc fully funded attendance at their internal conference in California USA and all related expenses. He has received grant funding from the Medical Research Council UK for a collaborative study with Janssen Research and Development LLC. Janssen Research and Development LLC are providing non-financial contributions to support this study. P.R.A.S. has received a presentation fee from Indivior and an advisory board fee from LivaNova.

International multi-site survey on the use of online support groups in bipolar disorder.

BACKGROUND: Peer support is an established component of recovery from bipolar disorder, and online support groups may offer opportunities to expand the use of peer support at the patient's convenience. Prior research in bipolar disorder has reported value from online support groups. AIMS: To understand the use of online support groups by patients with bipolar disorder as part of a larger project about information seeking. METHODS: The results are based on a one-time, paper-based anonymous survey about information seeking by patients with bipolar disorder, which was translated into 12 languages. The survey was completed between March 2014 and January 2016 and included questions on the use of online support groups. All patients were diagnosed by a psychiatrist. Analysis included descriptive statistics and general estimating equations to account for correlated data. RESULTS AND CONCLUSIONS: The survey was completed by 1222 patients in 17 countries. The patients used the Internet at a percentage similar to the general public. Of the Internet users who looked online for information about bipolar disorder, only 21.0% read or participated in support groups, chats, or forums for bipolar disorder (12.8% of the total sample). Given the benefits reported in prior research, clarification of the role of online support groups in bipolar disorder is needed. With only a minority of patients using online support groups, there are analytical challenges for future studies.

Risk factors for rapid cycling in bipolar disorder.

OBJECTIVES: The aim of this study was to investigate the clinical factors associated with the development of rapid cycling, as well as to elucidate the role of antidepressants. METHODS: The present study (NCT01503489) is a prospective, naturalistic cohort study conducted in a sample of 289 patients diagnosed with bipolar disorder followed and treated for up to 14 years. The patients were divided into two groups on the basis of the development of a rapid cycling course (n = 48) or no development of such a course (n = 241), and compared regarding sociodemographic, clinical, and outcome variables. RESULTS: Among the 289 patients, 48 (16.6%) developed a rapid cycling course during the follow-up. Several differences were found between the two groups, but after performing Cox regression analysis, only atypical depressive symptoms (p = 0.001), age at onset (p = 0.015), and number of suicide attempts (p = 0.030) persisted as significantly associated with the development of a rapid cycling course. CONCLUSIONS: The development of rapid cycling during the course of bipolar disorder is associated with a tendency to chronicity, with a poorer outcome, and with atypical depressive symptomatology. Our study also suggests that the development of rapid cycling is associated with a higher use of antidepressants.

Self-monitoring and psychoeducation in bipolar patients with a smart-phone application (SIMPLe) project: design, development and studies protocols.

BACKGROUND: New technologies have recently been used for monitoring signs and symptoms of mental health illnesses and particularly have been tested to improve the outcomes in bipolar disorders. Web-based psychoeducational programs for bipolar disorders have also been implemented, yet to our knowledge, none of them have integrated both approaches in one single intervention. The aim of this project is to develop and validate a smartphone application to monitor symptoms and signs and empower the self-management of bipolar disorder, offering customized embedded psychoeducation contents, in order to identify early symptoms and prevent relapses and hospitalizations. METHODS/DESIGN: The project will be carried out in three complementary phases, which will include a feasibility study (first phase), a qualitative study (second phase) and a randomized controlled trial (third phase) comparing the smartphone application (SIMPLe) on top of treatment as usual with treatment as usual alone. During the first phase, feasibility and satisfaction will be assessed with the application usage log data and with an electronic survey. Focus groups will be conducted and technical improvements will be incorporated at the second phase. Finally, at the third phase, survival analysis with multivariate data analysis will be performed and relationships between socio-demographic, clinical variables and assessments scores with relapses in each group will be explored. DISCUSSION: This project could result in a highly available, user-friendly and not costly monitoring and psychoeducational intervention that could improve the outcome of people suffering from bipolar disorders in a practical and secure way. TRIAL REGISTRATION: Clinical Trials.gov: NCT02258711 (October 2014).

e-HCL-32: a useful, valid and user friendly tool in the screening of bipolar II disorder.

BACKGROUND AND OBJECTIVES: Bipolar type II (BDII) is a frequent disorder with high morbidity and mortality, characterized by depressive and hypomanic episodes. Early diagnosis can be effective in improving long-term prognosis. However, diagnosing BDII is challenging due to the difficulty in detecting past hypomanic episodes. The HCL-32 is a widely used and reliable screening instrument for the detection of past hypomanic episodes. Making this tool available to more patients could help diagnose and treat undetected cases of BDII earlier. New technologies such as the Internet have been previously used for this purpose with favorable outcomes. Accordingly, the objective of this study is to evaluate the acceptability, validity, reliability and equivalence of an online version of this questionnaire. METHODS: From May 2012 to March 2013, 52 participants attending an outpatient mental health clinic completed a paper version of the HCL-32 (HCL-32) and its online version (e-HCL-32) within two weeks. After its completion, they were asked to answer a brief satisfaction survey. RESULTS: No differences were found (HCL-32 mean total score=17.73 (SD=7.37), e-HCL-32 mean total score=18.28 (SD=7.09). T=-1.720, p=0.092, 95% CI=-1.21 to 0.09) between the results of the paper and pencil HCL-32 compared to its online version (e-HCL-32). The psychometric properties of the online version of the hypomania checklist (e-HCL-32) were good and comparable to the paper and pencil version. 80% of participants found online questionnaires to be easier to answer and more user-friendly. CONCLUSION: The results of this study support the use of an online screening tool for the detection of previous hypomanic episodes (necessary for BDII diagnosis) as it showed to have a similar validity and reliability to the traditional paper and pencil method.

Comorbid bipolar disorder and borderline personality disorder and substance use disorder.

Bipolar disorder (BD) and borderline personality disorder (BPD) are disabling and life-threatening conditions. Both disorders share relevant comorbidities, particularly the risk of having a lifetime substance use disorder (SUD). We tested the hypothesis that patients with both BD type I (BDI) or II (BDII) and BPD would have a higher rate of SUD than would patients with either disorder alone. A total of 3651 psychiatric patients were evaluated with semistructured diagnostic interviews for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, axis I and II disorders. A total of 63 patients were diagnosed with both BD and BPD, and these patients were significantly more likely to have a SUD compared with BDII patients without BPD (76% vs. 50%, χ = 9.69, p < 0.01). There were no differences when comparing the comorbid group with BPD patients without BD (76% vs. 71%, χ = 0.519, p = 0.4). The present study shows the importance of taking both BPD and BD into consideration insofar as the co-occurrence of the disorders increased the risk of having a SUD especially when compared with BDII alone.

Making sense of DSM-5 mania with depressive features.

OBJECTIVE: The assessment of the depressive component during mania has become critical for the accurate diagnosis of mixed states, which were defined very narrowly in the past classification systems before Diagnostic and Statistical Manual of Mental Disorders (5th ed.). The aim of this study was to compare socio-demographic, clinical and therapeutic characteristics, as well as clinical and functional outcomes, between manic patients with and without mixed features to validate the relevance of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.) mixed specifier. METHODS: This is a subanalysis of a multicentre naturalistic study MANía Aguda y COnsumo de Recursos (acute mania and health resource consumption [MANACOR]) on the burden of mania in bipolar patients from four hospitals in Catalonia (Spain). The sample consisted of 169 adult patients presenting a manic episode and systematically assessed during a 6-month period. RESULTS: A total of 27% (n = 46/169) of manic patients showed mixed features. Total number of episodes (p = 0.027), particularly depressive and mixed, was greater in manic patients with mixed features, as well as depressive onset (p = 0.018), suicide ideation (p = 0.036), rapid cycling (p = 0.035) and personality disorders (p = 0.071). In contrast, a higher percentage of pure manic subjects were inpatients (p = 0.035), started the illness with mania (p = 0.018) and showed family history of bipolar disorder (p = 0.037), congruent psychotic symptoms (p = 0.001) and cannabis use (p = 0.006). At baseline, pure manic patients received more risperidone (p = 0.028), while mixed patients received more valproate (p = 0.049) and antidepressants (p = 0.005). No differences were found in syndromic recovery at the end of the study. However, depressive change was higher in the mixed group (p = 0.010), while manic change was higher in the pure manic group (p = 0.029). At the end of follow-up, the group with mixed features showed a significant trend towards higher psychosocial dysfunction. CONCLUSION: A total of 27% of manic patients showed mixed features. Groups differed regarding clinical characteristics, course of illness, psychosocial functioning, prescribed treatment and symptom progress. Depressive symptoms in mania should be routinely assessed and considered to guide treatment.