No abstract

No abstract

Background Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need. Structure The H2020-funded Response to Lithium Network (R-LiNK; http://www.r-link.eu.com/) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants’ response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence. Conclusions The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.

Objective Mood instability in patients with bipolar disorder has been associated with impaired functioning and risk of relapse. The present study aimed to investigate whether increased mood instability is associated with increased perceived stress and impaired quality of life and functioning in patients with bipolar disorder. Methods A total of 84 patients with bipolar disorder used a smartphone‐based self‐monitoring system on a daily basis for 9 months. Data on perceived stress, quality of life, and clinically rated functioning were collected at five fixed time points for each patient during follow‐up. A group of 37 healthy individuals served as a control comparison of perceived stress, quality of life, and psychosocial functioning. Results The majority of patients presented in full or partial remission. As hypothesized, mood instability was significantly associated with increased perceived stress (B: 10.52, 95% CI: 5.25; 15.77, P < 0.0001) and decreased quality of life (B: −12.17, 95% CI. −19.54; −4.79, P < 0.0001) and functioning (B: −12.04, 95% CI: −19.08; −4.99, P < 0.0001) in patients with bipolar disorder. There were no differences in mood instability according to prescribed psychopharmacological treatment. Compared with healthy individuals, patients reported substantially increased perceived stress and experienced decreased quality of life and decreased functioning based on researcher‐blinded evaluation. Conclusion Mood instability in bipolar disorder is associated with increased perceived stress and decreased quality of life and functioning even during full or partial remission. There is a need to monitor and identify subsyndromal inter‐episodic symptoms. Future studies investigating the effect of treatment on mood instability are highly warranted.

IntroductionThere is a lack of objective methods for continuous monitoring of illness activity in bipolar disorder. Smartphones offer novel and unique opportunities for monitoring of symptoms and collection of real-time data.ObjectiveTo test the hypothesis that automatically generated objective data and self-monitored correlate with clinically rated depressive and manic symptoms in patients with bipolar disorder.MethodsSoftware for smartphones (the MONARCA system) was developed by our group. This system allows for continuous collection of automatically generated objective data and self-monitored data. A total of 61 patients with bipolar disorder aged 18-60 years used the MONARCA system for a six months period. Patients were rated, by a researcher blinded to smartphone data, once a month for six months using Hamilton Depression Rating Scale 17-item (HDRS-17) and Young Mania Rating Scale (YMRS).ResultsData showed significant correlations between automatically generated objective data (the number of incoming and outgoing phone calls/ day, the duration of incoming and outgoing phone calls/ day, and the number of outgoing text messages/ day) and depressive and manic symptoms according to HDRS-17 and YMRS, respectively. Data showed significant correlations between self-monitored data (mood, sleep, activity level and stress level) and depressive and manic symptoms according to HDRS-17 and YMRS, respectively.ConclusionsAutomatically generated objective data and self-monitored data collected using the MONARCA system correlate with clinically rated depressive and manic symptoms in patients with bipolar disorder. Smartphone apps reflect an easy and objective way to continuously monitor illness activity with real-time data.

No abstract

No abstract

Objective To evaluate the development and implementation of clinical practice guidelines for the management of depression globally. Methods We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries. Findings We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence. Conclusion Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost–effectiveness and impact on health outcomes.