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Major Depressive Disorder (MDD) is prevalent, often chronic, and requires ongoing monitoring of symptoms to track response to treatment and identify early indicators of relapse. Remote Measurement Technologies (RMT) provide an exciting opportunity to transform the measurement and management of MDD, via data collected from inbuilt smartphone sensors and wearable devices alongside app-based questionnaires and tasks.
To describe the amount of data collected during a multimodal longitudinal RMT study, in an MDD population.
RADAR-MDD is a multi-centre, prospective observational cohort study. People with a history of MDD were provided with a wrist-worn wearable, and several apps designed to: a) collect data from smartphone sensors; and b) deliver questionnaires, speech tasks and cognitive assessments and followed-up for a maximum of 2 years.
A total of 623 individuals with a history of MDD were enrolled in the study with 80% completion rates for primary outcome assessments across all timepoints. 79.8% of people participated for the maximum amount of time available and 20.2% withdrew prematurely. Data availability across all RMT data types varied depending on the source of data and the participant-burden for each data type. We found no evidence of an association between the severity of depression symptoms at baseline and the availability of data. 110 participants had > 50% data available across all data types, and thus able to contribute to multiparametric analyses.
RADAR-MDD is the largest multimodal RMT study in the field of mental health. Here, we have shown that collecting RMT data from a clinical population is feasible.
Bipolar disorder (BD) is a psychiatric disorder characterized by alternating episodes of high mood and low mood similar to depression. To differentiate BD patients from unipolar (UN) depressed patients remains a challenge and the clinical scales available failed to distinguish these 2 populations. ALCEDIAG developed EDIT-B, the first blood test able to make a differential diagnosis of BD. Based on RNA editing modifications measurement and AI, the test requires a simple blood draw and equipment available in most central laboratories. A first study on 160 UN and 95 BD patients allowed a differential diagnosis with an AUC of 0.935 and high specificity (Sp=84.6%) and sensitivity (Se=90.9%). A multicentric clinical study has been set up to validate these performances.
The objective of this project is to run a multicentric clinical study in Europe and assess the performances of the test.
The EDIT-B project, led by Alcediag, is supported by EIT-Health grant (European institute of Innovation and Technology) and gathers 4 clinical centers in 3 countries (France, Spain, Danemark), a CRO for the clinical study management (Aixial), a CRO for the development of a diagnostic kit (Veracyte), a diagnostic lab for molecular biology analyses (Synlab), and a regulatory company (PLG).
At the end of the study, the EDIT-B performance will be confirmed and the test will be CE-marked.
This test will address the needs of millions of patients suffering from misdiagnosis and therefore allow them to receive the correct treatment.
To identify factors associated with suicide attempts using data from a large, 3-year, multinational follow-up study of schizophrenia (SOHO study).
All baseline characteristics of 8,871 adult patients with schizophrenia collected in patients included in the SOHO study were included in a GEE logistic regression post-hoc analysis comparing patients who attempted suicide during the study with those who did not.
A total of 384 (4.3%) patients attempted or committed suicide. The risk factors that resulted statistically associated with suicide attempt were a lifetime history of suicide attempts (OR 3.6 [95% CI 2.8, 4.6; p< 0.0001]), suicide attempts in the last 6 months (OR 2.5 [95% CI 1.8, 3.4; p< 0.0001]), prolactin-related side effects (OR 2.0 [95%CI 1.4, 2.9; p=0.0002]), CGI depression (OR 1.2 [95% CI 1.1, 1.3; p=0.0004]) and history of hospitalization for schizophrenia (OR 1.4 [95% CI 1.1, 1.8; p=0.009]).
In view of the observational design of the study and the post-hoc nature of the analysis, the identified risk factors should be confirmed by ad-hoc specifically designed studies.
To estimate costs associated with medication non-adherence over a 3-year follow-up period in the treatment of schizophrenia in routine clinical practice in Europe.
SOHO is a 3-year, prospective, observational study of 10972 outpatient participants across 10 European countries. Data were collected at baseline and at 6-month intervals up to 36 months. Medication adherence was assessed at each visit by participating psychiatrists during 4 weeks prior to the visit as: (1) not prescribed medication; (2) always adherent; (3) partially adherent; and (4) never adherent. In this post-hoc analysis, multivariate analyses were performed to compare the costs of resource use (inpatient stay, day care, psychiatrist visits and medication) in patients who were adherent, partially adherent, and non-adherent, using a log-link function. Adherence status was included as a time-varying variable, and other baseline patient characteristics were adjusted for. UK unit costs were applied to resource use.
Out of 5364 patients who were prescribed medication prior to baseline, 5.9% were non-adherent while 77.1% and 17.0% were adherent and partially adherent, respectively, at baseline. The average 6-month cost incurred by non-adherent patients was £2505 while that for adherent and partially adherent patients was £2029 and £2130 respectively. This difference was mainly due to inpatient costs. The inpatient costs incurred by non-adherent patients (£987) were almost double those for adherent patients (£475).
Non-adherence in schizophrenia was likely to incur more inpatient services, which may indicate poorer clinical prognosis. A study limitation is that adherence was assessed by investigators using a single-item measure.
To assess the psychometric properties of the Spanish version of the SWN scale, an instrument which evaluates the subjective experience of psychotic patients towards neuroleptic treatment.
A validation study (feasibility, reliability, and validity) was conducted in 20 psychiatric centers. Patients were evaluated with the PANSS, the CGI severity scale and the SWN-20. A re-test was conducted one week after baseline. The study included clinically stabilized outpatients diagnosed with schizophrenia (DSM-IV-TR criteria) who were on treatment as usual. The SWN used in this study consists of 20 questions answered on a 6-point Likert scale. The total score ranges from 20 to 120 points (higher scores indicating better well-being). The original version was back-translated and a focus group was conducted to improve the comprehension of the items.
97 patients were included. Seventy-two percent of them (70) were male. Mean age was 35 years (SD = 10.0). Mean SWN total score: 83.5 (SD = 14.0). Internal homogeneity: 0.86. Test-retest in clinically stable patients was 0.89. SWN correlated significantly with the PANSS, but not with the DAI-10. Patients with none-mild clinical affectation had higher SWN scores, indicating a better subjective well-being, and vice versa.
The subjective experience of psychotic patients towards treatment is a key factor in therapeutic adherence, quality of life, and clinical outcome. The Spanish version of the SWN scale showed good psychometric properties in a sample of schizophrenic stabilized outpatients. SWN scale constitutes a valuable addition to evaluate patients’ subjective well-being.
To compare CATIE, a randomized double blind study, and SOHO, a 3-year prospective non-randomized observational European study of outpatients with schizophrenia, on the Number Needed to Treat (NNT) for all-cause medication discontinuation. NNTs place data into a clinically meaningful context - the number of patients needed to be treated with one antipsychotic instead of another to prevent one negative outcome, defined here as one additional medication discontinuation for any cause.
Rate of medication discontinuation for any cause during the 18 months post initiation was calculated for patients newly initiated on olanzapine (N=4247), risperidone (N=1549), quetiapine (N=583), amisulpride (N=256), clozapine (N=274), oral typicals (N=471) or depot typicals (N=348). Cox models were employed to adjust for treatment group differences at baseline. NNTs with their 95% confidence intervals were calculated and compared with published NNTs for CATIE (Phase 1).
The NNTs for all-cause discontinuation of olanzapine vs. each studied atypical antipsychotic during the 18 month following medication initiation in SOHO were comparable to CATIE: 4.3(95% CI: 3.6–5.3) for olanzapine vs. quetiapine (5.5 in CATIE); 16.1(11.0–28.1) for olanzapine vs. risperidone (10.1 in CATIE); 6.9(5.2–10.1) for olanzapine vs. oral typicals (9.0 in CATIE for olanzapine vs. perphenazine).
The NNTs for all-cause medication discontinuation based on CATIE appeared comparable to NNTs based on SOHO. The NNTs for olanzapine therapy were consistently better when compared to each studied atypical antipsychotic (except clozapine) and when compared to typical antipsychotics. Results should be interpreted conservatively, due to the observational design of SOHO.
To complete missing information on the influence of spiritual and religious advisors as informal providers for mental health problems in Europe.
Recourse to religious practice or belief when coping with mental health problems was evaluated using data from the ESEMED survey. This was a stratified, multistage, clustered-area probability sample survey of mental health carried out in six European countries which included 8796 subjects. Between countries differences in sociodemographic characteristics, religious affiliation, and prevalence of mental disorders and management of mental disorders were evaluated.
Religion appears to play a limited role in coping with mental health problems in Europe. Only 7.9% of individuals seeking help for such problems turned to a religious advisor. This proportion differed between countries from 13% in Italy, 12.5% in Germany, 10.5% in the Netherlands, 5.8% in France, 4.7% in Belgium to 4% in Spain. In addition, seeking help exclusively from religion was reported by only 1.3% of subjects. Practicing religion at least once a week and considering religion as important in daily life were predictors of using religion versus conventional health care only. Use of religion was not influenced by gender and age. Non-Christian respondents and individuals with alcohol disorders were more likely to use religion. In Spain, the use of religion is much lower than average.
Unlike the situation in the United States, organised religion does not provide alternative informal mental health care in Europe. At best, it could be considered as an adjunct to conventional care.
Antidepressants are recommended to be withdrawn during a manic episode. This analysis explored the characteristics of patients receiving antidepressants during an acute manic episode in the context of a large, observational study.
EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a 2-year prospective observational study of acute mania/mixed mania. Of 2416 patients, 345 (14%) were taking an antidepressant (AD) and 2071 (86%) were not (NAD) during acute mania. Demographic and clinical variables were collected at baseline and at outpatient visits up to 2 years. Illness severity was measured using Clinical Global Impressions–Bipolar Disorder (CGI-BP), 5-item Hamilton Depression Rating Scale (HAM-D-5), and Young Mania Rating Scale (YMRS). Logistic regression analysis was used to identify variables associated with AD use.
AD use varied across countries (p<0.05), more use with mixed episodes (p<0.001), rapid cyclers (p=0.02), more previous depressive episodes (p<0.001) and higher HAM-D-5 severity at baseline (p<0.001) but less use with higher education (p=0.029), YMRS (p=0.022), CGI-BP overall (p=0.006) severity and inpatients at baseline (p<0.001). There were no differences in alcohol abuse or suicide attempts. Depression recurrence rates were significantly higher with AD (p<0.001).
The EMBLEM study suggests that patients with mania receiving antidepressants are more likely to be outpatients with mixed mania or rapid cycling, and have a higher risk of depressive recurrence during follow-up. Clinicians seem to maintain antidepressants in manic patients to address depressive features during mania and prevent further depressive episodes.
To compare the relative effectiveness and tolerability profile, in terms of Number Needed to Treat (NNT) for all causes of medication discontinuation and Number Needed to Harm (NNH) for 7% of increased of body weight of olanzapine, risperidone, typical (oral and depot) and other atypical antipsychotic medications (quetiapine and amisulpride) in previously untreated outpatients with schizophrenia during 36-month follow-up.
NNTs (NNHs) mean the number of patients needed to be treated with one antipsychotic instead of another to prevent (produce) one negative outcome.
Previously untreated patients with schizophrenia were defined as patients who i) had never received antipsychotic treatment for schizophrenia and ii) had not received antipsychotic treatment in the 6 months prior to study inclusion. Rate of medication discontinuation for any cause during the 36 months post initiation was calculated for olanzapine (28.9%), risperidone (36.2%), typicals (44.5%) and other aypicals) (34.7%). Cox and logistic regression models were employed to adjust for treatment group differences at baseline and NNTs and NNHs with their 95% confidence intervals were calculated.
The NNTs for all-cause discontinuation of olanzapine were: 12.2.(95% CI: 5.8; 229.7) for olanzapine vs. risperidone, and 6.2 (3.1 ; 37.8) for olanzapine vs. typicals. The NNH for 7% weight gain was -3.7 (-2.6 ; -9.5) for olanzapine vs. typicals.
Treatment effectiveness and tolerability varied among medications. The NNTs for olanzapine therapy were consistently better when compared to other treatment cohorts. The weight-gain NNHs for olanzapine treatment were less favourable when compared to other antipsychotic medications.
To explore factors associated with work impairment at 2 years following an acute episode.
European Mania in Bipolar disorder Longitudinal Evaluation of Medication (EMBLEM) is a prospective, observational study on the outcomes of patients with a manic/mixed episode. Work impairment was measured using a Longitudinal Interval Follow-up Evaluation (slice of LIFE) item and patients were categorised with either low or high work impairment at each observation. Baseline factors associated with work impairment at 2 years were assessed using multivariate modelling.
At baseline (n = 2289), 69% of patients had high work impairment. At 2 years (n = 1393), high impairment reduced to 41%. Modelling identified rapid cycling as the strongest disease-related factor associated with high work impairment at 2 years, although high work impairment at baseline had the strongest association overall. Lower levels of education, recent admissions, CGI-BP overall severity in the 12 months prior to baseline and CGI-BP mania at baseline all predicted higher work impairment. Living together in a relationship and independent housing were both significantly associated with having low work impairment at 2 years.
Work impairment in bipolar disorder is maintained over long periods, and is strongly associated with relationship status, living conditions and various disease-related factors.
To contrast the outcomes of olanzapine- and valproate-treated patients in an observational study of acute mania with the results of a RCT assessing the same treatments (Tohen et al., 2002).
EMBLEM (European Mania in Bipolar Evaluation of Medication) was a 2-year, prospective, observational study of health outcomes associated with treatment of mania. Severity of mania and depression was assessed at baseline and 6 weeks using the YMRS and 5-item version of the HAMD, respectively. The RCT was a 3-week, randomised, double-blind comparison of olanzapine (n=125) and divalproate-treated (n=123) patients hospitalised for acute manic or mixed episodes. The YMRS and HAMD were used to quantify manic and depressive symptoms, respectively.
621 EMBLEM patients were analysed (n=107 valproate, n=514 olanzapine). Both observed groups improved from baseline to 6 weeks in mean YMRS and HAMD-5 total scores, with significantly greater mean improvements in the olanzapine compared with the valproate group using linear regression to adjust for baseline differences. The RCT reported significantly greater mean YMRS improvement (but not HAMD) in the olanzapine-treated group. EMBLEM patients treated with olanzapine experienced significantly greater weight gain than patients treated with valproate, similar to RCT results. There was a significantly greater incidence of treatment-emergent gastrointestinal adverse events in EMBLEM patients treated with valproate.
The EMBLEM results support those of the RCT, which suggest that olanzapine monotherapy may be more effective than valproate monotherapy in the treatment of acute mania. Contrasting observational and RCT results present methodological challenges but can provide important complementary information.
To assess frequency and baseline factors associated with adherence with antipsychotic medication during long-term treatment in outpatients with schizophrenia.
SOHO is a 3-year, prospective, observational study that included 10 972 patients changing or starting a new antipsychotic medication Treatment adherence during 4 weeks prior to the visit was assessed at each visit by participating psychiatrists as:
• the patient has not been prescribed medication;
• the patient almost always adheres;
• the patient adheres half of the time; and
• the patient never adheres to antipsychotic medication.
Logistic regression models were fitted to analyze the baseline factors associated to compliance during follow-up.
6731 patients with at most one missing visit were analysed. Data from the missing visit were imputed from the previous visit; 71.2% were considered to be adherent and 28.8% non-adherent over the 3-year follow-up period. the strongest predictor of medication adherence during follow-up was adherence at baseline (OR = 4.01, 95% CI: 3.46-4.64). other baseline predictors of adherence included not using antipsychotics in the previous 4 weeks, receiving treatment for first time, being socially active, and a higher body mass index. Baseline predictors of non-adherence were alcohol dependence, substance abuse, hospitalisation in previous 6 months, living independently housing and having hostile behaviours.
Alcohol dependence, substance abuse and living independently were associated with non-adherence. Previous adherence, being socially active and receiving medication for the first time was associated with better adherence. Limitation: medication adherence was assessed by the psychiatrist through a single item question.
Paranoid Schizophrenia (PS), yet included within the same nosological category than Non-Paranoid Schizophrenia (NPS), may in fact constitute a different disorder. In this study, the above both schizophrenia subtypes are compared with Delusional Disorder (DD). We hypothesized that, phenomenologically PS could either be a half-way category between DD and NPS or part of a phenomenological continuum of psychotic and cognitive symptoms between these three psychotic categories.
102 patients fulfilling DSM-IV-TR criteria of schizophrenia (with 56 PS and 46 with NPS) and 80 DD patients were included in this study (n=182). We compared outcome groups (DD vs. PS vs. NPS) on clinical dimensions, global functioning and sociodemographics. Clinical dimensions were extracted from the PANSS and neuropsychological scales using Principal-Component-Analysis and, subsequently, cluster analysis to assign subjects to empirically emerging clinical groups. The associations between such groups and DSM-IV-TR groups were explored using polynomial regression.
We found lineal associations demonstrating empirically that, from the psychopathological, neuropsychological and functioning perspectives, it is reasonable to consider PS as an intermediate and independent category right in between DD and NPS. Thus, the distribution of subjects assigned to three empirically emerging clinical groups (Paranoid-Affective, Paranoid-Hostile and Negative) associated, significantly and preferentially, with DSM-IV categories along the following fashion: The proportion of paranoid-hostile and, particularly, paranoid-affective subjects decreased progressively along DD, PS and NPS categories; On the contrary, the proportion of negative subjects increased lineally along those categories (Mante-Haenszel-X2= 18.02;p=0.0001). Our results question, on the bases of an empirical study, the current categorical division of paranoid psychoses.
Stigma and social exclusion related to mental health are of substantial public health importance for Europe. As part of ROAMER (ROAdmap for MEntal health Research in Europe), we used systematic mapping techniques to describe the current state of research on stigma and social exclusion across Europe. Findings demonstrate growing interest in this field between 2007 and 2012. Most studies were descriptive (60%), focused on adults of working age (60%) and were performed in Northwest Europe—primarily in the UK (32%), Finland (8%), Sweden (8%) and Germany (7%). In terms of mental health characteristics, the largest proportion of studies investigated general mental health (20%), common mental disorders (16%), schizophrenia (16%) or depression (14%). There is a paucity of research looking at mechanisms to reduce stigma and promote social inclusion, or at factors that might promote resilience or protect against stigma/social exclusion across the life course. Evidence is also limited in relation to evaluations of interventions. Increasing incentives for cross-country research collaborations, especially with new EU Member States and collaboration across European professional organizations and disciplines, could improve understanding of the range of underpinning social and cultural factors which promote inclusion or contribute toward lower levels of stigma, especially during times of hardship.
Verbal working memory span is decreased in patients with schizophrenia, and this might contribute to impairment in higher cognitive functions as well as to the formation of certain clinical symptoms. Processing speed has been identified as a crucial factor in cognitive efficiency in this population. We tested the hypothesis that decreased processing speed underlies the verbal working memory deficit in patients and mediates the associations between working memory span and clinical symptoms.
Forty-nine schizophrenia inpatients recruited from units for chronic and acute patients, and forty-five healthy participants, were involved in the study. Verbal working memory span was assessed by means of the letter-number span. The Digit Copy test was used to assess motor speed, and the Digit Symbol Substitution Test to assess cognitive speed.
The working memory span was significantly impaired in patients (F(1,90) = 4.6, P < 0.05). However, the group difference was eliminated when either the motor or the cognitive speed measure was controlled (F(1,89) = 0.03, P = 0.86, and F(1,89) = 0.03, P = 0.88). In the patient group, working memory span was significantly correlated with negative symptoms (r = –0.52, P < 0.0001) and thought disorganisation (r = –0.34, P < 0.025) scores. Regression analyses showed that the association with negative symptoms was no longer significant when the motor speed measure was controlled (β = –0.12, P = 0.20), while the association with thought disorganisation was no longer significant when the cognitive speed measure was controlled (β = –0.10, P = 0.26).
Decrement in motor and cognitive speed plays a significant role in both the verbal working memory impairment observed in patients and the associations between verbal working memory impairment and clinical symptoms.
Medication non-compliance is common in the treatment of depression, particularly in Asia.
1) To describe the frequency and factors associated with medication non-compliance. 2) To study the influence of non-compliance on treatment outcomes.
Nine hundred and nine in- and out-patients from Asia presenting with a new or first episode of major depressive disorder were enrolled in a 3-month prospective observational study. Clinical severity and quality of life were assessed, using Hamilton Depression Scale (HAMD-17), Clinical Global Impression Severity (CGI-S), and EuroQoL measures (EQ-5D and EQ-VAS). Medication compliance was also assessed by the investigator and patient. Linear and logistic multiple regression models were used to analyze the consequences of non-compliance.
The proportion of non-compliant patients as assessed by the investigator was 16%. Sociodemographic factors and clinical severity were not associated with compliance at baseline. Regression models showed that medication non-compliance was associated with worse depression severity (difference in HAMD-17 -3.98; 95% CI -5.10, -2.87) and overall clinical severity (CGI-S difference -0.46; 95%CI -0.68, -0.24) at three months. Medication non-compliance was also associated with lower quality of life at three months (EQ-VAS difference -7.47; 95%CI -11.13, - 3.82) and EQ-5D score difference -0.08; 95%CI -0.1, -0.04)). Compliant patients had higher odds of response (odds ratio (OR) 3.18; 95% CI 1.98, 5.10) and remission (OR 3.94; 95% CI 2.42, 6.43) compared with non-compliant patients.
Patients non-compliant with medication had worse 3-month outcomes in terms of depression severity, quality of life, and response and remission rates, compared with compliant patients.
The European Commission funded the ROAMER project, which was launched in October 2011, to develop a roadmap to promote and integrate research on the biological, epidemiological, social and public health aspects of mental health. ROAMER has established six scientific domains (i.e. infrastructures and capacity building; biomedicine; psychological treatments and processes; social and economic aspects; public health; and wellbeing) that are being addressed in parallel. This process is developed in three different phases devoted to conducting an initial state-of-the-art analysis, enumerating gaps in current knowledge, and defining advances needed in research in each field. The project includes the participation of researchers, professionals, service users, families and other stakeholders.
The project is funded by the coordination and support action under the Seventh Framework Programme (FP7). This funding instrument is oriented towards non-research initiatives which require a wide participation of European institutions.
In the session, we will describe the role of coordinators and project managers in European Projects, as well as the current status of funding programs in the EC, the steps to apply to their calls, and the daily issues you should deal with when managing European projects profiting our ROAMER experience.
[ROAMER has received funding from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement n° 282586]