Daily electronic monitoring of subjective and objective measures of illness activity in bipolar disorder using smartphones--the MONARCA II trial protocol: a randomized controlled single-blind parallel-group trial

BACKGROUND: Patients with bipolar disorder often show decreased adherence with mood stabilizers and frequently interventions on prodromal depressive and manic symptoms are delayed. Recently, the MONARCA I randomized controlled trial investigated the effect of electronic self-monitoring using smartphones on depressive and manic symptoms. The findings suggested that patients using the MONARCA system had more sustained depressive symptoms than patients using a smartphone for normal communicative purposes, but had fewer manic symptoms during the trial. It is likely that the ability of these self-monitored measures to detect prodromal symptoms of depression and mania may be insufficient compared to automatically generated objective data on measures of illness activity such as phone usage, social activity, physical activity, and mobility. The Monsenso system, for smartphones integrating subjective and objective measures of illness activity was developed and will be tested in the present trial. METHODS: The MONARCA II trial uses a randomized controlled single-blind parallel-group design. Patients with bipolar disorder according to ICD-10 who previously have been treated at the Copenhagen Clinic for Affective Disorder, Denmark are included and randomized to either daily use of the Monsenso system including an feedback loop between patients and clinicians (the intervention group) or to the use of a smartphone for normal communicative purposes (the control group) for a 9-month trial period. The trial was started in September 2014 and recruitment is ongoing. The outcomes are: differences in depressive and manic symptoms; rate of depressive and manic episodes (primary); automatically generated objective data on measures of illness activity; number of days hospitalized; psychosocial functioning (secondary); perceived stress; quality of life; self-rated depressive symptoms; self-rated manic symptoms; recovery; empowerment and adherence to medication (tertiary) between the intervention group and the control group during the trial. Ethical permission has been obtained. Positive, neutral and negative findings will be published. DISCUSSION: If the system is effective in reducing depressive and/or manic symptoms (and other symptoms of bipolar disorder) and the rate of episodes, there will be basis for extending the use to the treatment of bipolar disorder in general and in larger scale. TRIAL REGISTRATION: ClinicalTrials.gov NCT02221336. Registered 26(th) of September 2014

Lithium and bipolar depression

Kelly1 has recently disputed the recommendations of several international guidelines on the use of lithium in bipolar depression. In his scrutiny, the author points to three main errors that seem to have affected systematically ten international guidelines, namely the Woozle effect (evidence by citation), reference inflation (inappropriate citation of pivotal, generally old, studies) and belief perseverance (inability to modify evidence‐based recommendations despite the presence of contrary data). We concur with the author that the evidence supporting the effectiveness of lithium in acute bipolar depression, and to a lesser degree also in major depressive episodes, remains inadequate.2, 3 A different matter is, in our opinion, to label guidelines recommendations as inaccurate or biased, even if, as the author stated, no deceptive intentions were present

Metabolic profile in patients with newly diagnosed bipolar disorder and their unaffected first-degree relatives

Abstract Objective The prevalence of metabolic syndrome and insulin resistance is twice as high in patients with bipolar disorder compared with the general population, and possibly associated with a disabling illness trajectory of bipolar disorder, an increased risk of cardiovascular disease and premature death. Despite these detrimental effects, the prevalence of metabolic syndrome and insulin resistance in patients newly diagnosed with bipolar disorder and their unaffected first-degree relatives is largely unknown. Methods In a cross-sectional study of 206 patients with newly diagnosed bipolar disorder, 50 of their unaffected first-degree relatives and 109 healthy age- and sex-matched individuals, we compared the prevalence of metabolic syndrome and insulin resistance (HOMA-IR). In patients with bipolar disorder, we further investigated illness and medication variables associated with the metabolic syndrome and insulin resistance. Results Higher rates of metabolic syndrome (odds ratio = 3.529, 95% CI 1.378–9.041, P = 0.009) and levels of insulin resistance (B = 1.203, 95% CI 1.059–1.367, P = 0.005) were found in patients newly diagnosed with bipolar disorder, but not in their unaffected first-degree relatives compared with matched healthy individuals (data adjusted for sex and age). Most patients with bipolar disorder (94.7%) were diagnosed within the preceding 2 years, and the average illness duration, defined as time from first mood episode, was 10 years. Conclusion Our findings of elevated prevalence of metabolic syndrome and insulin resistance in patients with newly diagnosed bipolar disorder highlight the importance of screening for these conditions at an early stage to employ adequate and early care reducing the risk of cardiovascular disease and premature death

Lithium in drinking water and incidence of suicide:A nationwide individual-level cohort study with 22 years of follow-up

Suicide is a major public health concern. High-dose lithium is used to stabilize mood and prevent suicide in patients with affective disorders. Lithium occurs naturally in drinking water worldwide in much lower doses, but with large geographical variation. Several studies conducted at an aggregate level have suggested an association between lithium in drinking water and a reduced risk of suicide; however, a causal relation is uncertain. Individual-level register-based data on the entire Danish adult population (3.7 million individuals) from 1991 to 2012 were linked with a moving five-year time-weighted average (TWA) lithium exposure level from drinking water hypothesizing an inverse relationship. The mean lithium level was 11.6 μg/L ranging from 0.6 to 30.7 μg/L. The suicide rate decreased from 29.7 per 100,000 person-years at risk in 1991 to 18.4 per 100,000 person-years in 2012. We found no significant indication of an association between increasing five-year TWA lithium exposure level and decreasing suicide rate. The comprehensiveness of using individual-level data and spatial analyses with 22 years of follow-up makes a pronounced contribution to previous findings. Our findings demonstrate that there does not seem to be a protective effect of exposure to lithium on the incidence of suicide with levels below 31 μg/L in drinking water

Out-of-Hospital Cardiac Arrest in Patients With Psychiatric Disorders - Characteristics and Outcomes

Aims To investigate whether the recent improvements in pre-hospital cardiac arrest-management and survival following out-of-hospital cardiac arrest (OHCA) also apply to OHCA patients with psychiatric disorders. Methods We identified all adult Danish patients with OHCA of presumed cardiac cause, 2001–2015. Psychiatric disorders were defined by hospital diagnoses up to 10 years before OHCA and analyzed as one group as well as divided into five subgroups (schizophrenia-spectrum disorders, bipolar disorder, depression, substance-induced mental disorders, other psychiatric disorders). Association between psychiatric disorders and pre-hospital OHCA-characteristics and 30-day survival were assessed by multiple logistic regression. Results Of 27,523 OHCA-patients, 4772 (17.3%) had a psychiatric diagnosis. Patients with psychiatric disorders had lower odds of 30-day survival (0.37 95% confidence interval 0.32–0.43) compared with other OHCA-patients. Likewise, they had lower odds of witnessed status (0.75 CI 0.70–0.80), bystander cardiopulmonary resuscitation (CPR) (0.77 CI 0.72–0.83), shockable heart rhythm (0.37 95% CI, 0.33–0.40), and return of spontaneous circulation (ROSC) at hospital arrival (0.66 CI 0.59–0.72). Similar results were seen in all five psychiatric subgroups. The difference in 30-day survival between patients with and without psychiatric disorders increased in recent years: from 8.4% (CI 7.0–10.0%) in 2006 to 13.9% (CI 12.4–15.4%) in 2015 and from 7.0% (4.3–10.8%) in 2006 to 7.0% (CI 4.5–9.7%) in 2015, respectively. Conclusion Patients with psychiatric disorders have lower survival following OHCA compared to non-psychiatric patients and the gap between the two groups has widened over time

The Center for Integrated Molecular Brain Imaging (Cimbi) database

AbstractWe here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes.The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies.The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank