W02-01 Advanced Psychopharmacology: practical strategies for rational polypharmacy in mood disorders

Patients with mood disorders frequently present with treatment resistant syndromes or develop tolerance to once effective first line medications. Refractory depressive, manic or mixed episodes challenge psychiatrists to find means of augmenting traditional therapies, despite the paucity of evidence based data that support this practice. The balance between risks and benefits in most cases seems acceptable, provided that the physician and the patients have a clear understanding of the possible adverse and therapeutic interactions and that treatment resistance is not the result of inadequate (dose/time) prescription of a first line monotherapy. The workshop will review the pharmacokinetic and pharmacodynamic interactions among the psychotropic drugs and the strategies to safely and successfully use a rational polypharmacy for the management of treatment resistant mood disorders

National Differences in the Prevalence of Depressive Symptoms in Mania: a Naturalistic Study Using the Dsm-5 'with Mixed Features' Specifier M.I.N.I. Module

Introduction In bipolar I disorder (BD1), manic episodes with depressive symptoms are generally more severe than pure manic episodes, but are not easily identified. The DSM-5 'With Mixed Features' specifier, and accompanying patient-rated Mini-International Neuropsychiatric Interview (M.I.N.I.) module, were designed to aid diagnosis. Objectives To examine patients with BD1 who have mania with depressive symptoms, across countries. Aims To improve the identification of depressive symptoms during a BD1 manic episode. Methods This naturalistic study surveyed psychiatrists and their patients with BD1 (manic episode within previous 3 months), in Germany, Italy, Spain, UK, Turkey, Australia, Brazil and Canada. Psychiatrists provided information on depressive symptoms (DSM-5 'With Mixed Features' specifier plus patient-rated M.I.N.I. module); anxiety, irritability, and agitation; suicide attempts; and treatment response. Results Of 1,035 bipolar patients, 34% had mania 'With Mixed Features'(≥05;3 depressive symptoms), and displayed more severe symptoms, and higher rates of attempted suicide than patients without mixed features. Across countries, severe anxiety occurred in 3.5–19.5% of patients; severe irritability in 4.3–17.0%; and severe agitation in 4.3–19.6%. The proportion of patients experiencing 'prominent dysphoria or depressed mood' was highest in Italy (64.2%). Recurrent suicidal ideation ranged from 8.0% (Germany) to 25.7% (Spain); lifetime rate of attempted suicide was highest in Canada (64.7%). Between-country differences were also reflected in the M.I.N.I. module outcomes. Conclusion Patients with BD1 'With Mixed Features', suffer from a greater burden of disease than patients with pure mania, and there is variation between countries – as detected by physician and patient evaluations

Long-Term Real-World Effectiveness of Aripiprazole Once-Monthly. Treatment Persistence and Its Correlates in the Italian and Spanish Clinical Practice: A Pooled Analysis

BackgroundOne of the most significant risk factors for relapse and hospitalization in schizophrenia is non-adherence to antipsychotic medications, very common in patients with schizophrenia. The aim of this analysis was to evaluate the treatment persistence to aripiprazole once-monthly (AOM) and the factors affecting it in the pooled population of two similar studies performed previously in two different European countries. MethodsPooled analysis of two non-interventional, retrospective, patient record-based studies: DOMINO and PROSIGO. Both analyzed treatment persistence after starting AOM treatment in the real-world setting. The primary variable was persistence with AOM treatment during the first 6 months after treatment initiation. A multivariate Cox regression model was used to evaluate the influence of several baseline characteristics on the persistence. ResultsThe study population comprised 352 patients included in the two studies, DOMINO (n = 261) and PROSIGO (n = 91). The overall persistence with AOM treatment at the end of the 6-month observation period was 82.4%. The multivariate analysis showed that patients with "secondary school" level of education present a 67.4% lower risk of discontinuation within 6 months after AOM initiation when compared with "no/compulsory education patients" (p = 0.024). In addition, patients with an occupation present a 62.7% lower risk of discontinuation when compared with unemployed patients (p = 0.023). Regarding clinical history, patients with a Clinical Global Impression-Severity scale (CGI-S) score <= 3 present a 78.1% lower risk of discontinuation when compared with patients with a CGI-S score >= 6 (p = 0.044), while patients with a time since schizophrenia diagnosis <= 8.4 years present a 52.9% lower risk of discontinuation when compared with the rest of patients (p = 0.039). ConclusionThe AOM persistence rate observed in this study was 82.4%, which was higher than that reported in clinical trials, aligned with other real-life studies and higher than reported for other long-acting injectable antipsychotics. The persistence rate was high in complex patients, although patients with higher level of education, active occupation, lower initial CGI-S score and shorter time since the diagnosis of schizophrenia appear to be more likely to remain persistent with AOM during the 6 months after initiation

Emotional blunting in patients with depression. Part III: relationship with psychological trauma

Background This international online survey investigated the experience and impact of emotional blunting in the acute and remission phases of depression from the perspective of patients and healthcare providers (HCPs). This paper presents data on the history and severity of psychological trauma and its potential impact on emotional blunting in major depressive disorder (MDD); differences between patient and HCP perceptions are explored. Methods Patient respondents (n = 752) were adults with a diagnosis of depression who were currently taking antidepressant therapy and reported emotional blunting during the past 6 weeks. HCPs provided details on two eligible patients: one in the acute phase of depression and one in remission from depression (n = 766). Trauma was assessed using questions based on the Childhood Trauma Questionnaire; emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ). Multivariate regression analyses were applied to examine the relationship between trauma and ODQ score. Results A history of any childhood or recent traumatic event was reported by 97% of patients in the self-assessed cohort and for 83% of those in the HCP-assessed cohort (difference, p < 0.01). Patients were more likely than HCPs to feel that this trauma had contributed to their/the patient's depression (58% vs 43%, respectively; p < 0.01) and that the depression was more severe because of trauma (70% vs 61%, respectively; p < 0.01). Emotional blunting was significantly worse in patients who reported severe trauma than in those who had not experienced severe trauma (mean total ODQ score, 90.1 vs 83.9, respectively; p < 0.01). In multivariate regression analyses, experiencing both severe childhood and recent trauma had a statistically significant impact on ODQ total score (p = 0.001). Conclusions A high proportion of patients with depression and emotional blunting self-reported exposure to childhood and/or recent traumatic events, and emotional blunting was more severe in patients who reported having experienced severe trauma. However, history of psychological trauma in patients with MDD appeared to be under-recognized by HCPs. Improved recognition of patients who have experienced psychological trauma and are experiencing emotional blunting may permit more targeted therapeutic interventions, potentially resulting in improved treatment outcomes

Emotional blunting in patients with depression. Part I: clinical characteristics

Background: Emotional blunting-inability to feel positive or negative emotions, detachment, or reduced emotional responsiveness-is common in people with depression. However, there is a paucity of studies comprehensively investigating this symptom and its functional impact. This study investigated the experience of emotional blunting, and its impact on overall functioning and quality of life, in the acute and remission phases of depression from the perspective of patients and healthcare providers. This paper presents data on the clinical presentation of emotional blunting in depression from the patient perspective. Methods: Cross-sectional, observational study conducted in Brazil, Canada, and Spain between April 15 and May 18, 2021. Data were collected via a self-completed online survey. Respondents were adults with depression (acute or remission phase), who were currently using a prescribed antidepressant, and who reported emotional blunting during the past 6 weeks. Emotional blunting was assessed using the Oxford Depression Questionnaire (ODQ; total score range 26-130, higher scores indicate greater emotional blunting). Results: In all, 752 patients completed the survey (62% female; mean age, 45 years). Overall, 44% of patients rated their emotional blunting as extremely severe (acute phase [n = 300], 72%; remission phase [n = 452], 25%; difference, p < 0.01). In all, 56% of patients considered their emotional blunting to be caused by their depression (acute phase, 62%; remission phase, 52%). Mean ODQ total score was 94.8 for patients in the acute phase of depression and 85.7 for those in remission (difference, p < 0.01). Mean score for the ODQ 'antidepressant as cause' domain (maximum possible score, 30) was 18.0 in patients in the acute phase and 17.6 in those in remission. Overall, 45% of patients believed that their antidepressant medication was blunting their emotions and 39% were considering stopping or had already stopped their antidepressant because of perceived emotion-related side effects. Conclusions: Almost three-quarters of patients in the acute phase of depression and one-quarter of those in remission reported severe emotional blunting. Approximately 56% of patients considered their emotional blunting to be caused by their depression, while 45% believed that their antidepressant medication was negatively affecting their emotions. Just over one-third of patients were considering stopping or had stopped their antidepressant as a result

Emotional blunting in patients with depression. Part II: relationship with functioning, well-being, and quality of life

Background Emotional blunting is a common symptom in people with depression and an important factor preventing full functional recovery. This international survey investigated the experience of emotional blunting in the acute and remission phases of depression from the perspective of patients and healthcare providers. This paper presents data on the impact of emotional blunting on overall functioning and health-related quality of life from the patient perspective. Methods Respondents were adults diagnosed with depression by a physician, currently prescribed an antidepressant, and reporting emotional blunting during the past 6 weeks. Assessments included the Oxford Depression Questionnaire (ODQ), the Functioning Assessment Short Test (FAST), and the World Health Organization-Five Well-being Index (WHO-5). Pearson correlation and multivariate regression analyses were applied to examine the relationship between ODQ and FAST scores. Results Data are available for 752 patients (62% female; mean age, 45 years). Mean ODQ total score was 94.8 in patients in the acute phase of depression (n = 300) and 85.7 in those in remission (n = 452; possible maximum, 130). Mean FAST total scores were 47.0 and 33.5, respectively (possible maximum, 72). Patients in the acute phase of depression had significantly greater impairment in functioning across all FAST domains than those in the remission phase (all differences, p < 0.01). Mean WHO-5 scores were 6.4 and 9.8 in the acute and remission phases, respectively (lower scores indicate poorer well-being). Overall, 65% of patients in the acute phase and 36% of those in remission reported that emotional blunting had a significant impact on their quality of life. Pearson correlation analysis showed a moderate positive correlation between ODQ and FAST total scores (r = 0.52) and a weak negative correlation between ODQ total score and WHO-5 score (r = - 0.26; both p < 0.01). In multivariate regression analysis, ODQ total score (in combination with other covariates) was the strongest significant predictor of poor patient functioning. Conclusions Emotional blunting has a substantial negative impact on patients' daily functioning, well-being, and quality of life in both the acute and remission phases of depression. These findings highlight the importance of recognizing and treating emotional blunting in patients with major depressive disorder in order to achieve full functional recovery

Emotional blunting in patients with depression. Part IV: differences between patient and physician perceptions

Background Emotional blunting is common in patients with depression. An online survey was undertaken to assess the experience of emotional blunting, and its impact on functioning and quality of life, in the acute and remission phases of depression from the perspective of patients and healthcare providers (HCPs). This paper presents data on the level of concordance between patient and HCP perspectives. Methods This was a cross-sectional, observational study. Patient respondents were adults with a diagnosis of depression, who were currently using a prescribed antidepressant, and who reported emotional blunting during the past 6 weeks. HCPs completed the survey for the last two eligible patients they had seen, one in each phase of depression. Assessments included the Oxford Depression Questionnaire (ODQ) 'antidepressant as cause' domain and the Functioning Assessment Short Test (FAST). Results Mean ODQ 'antidepressant as cause' domain scores were significantly higher in the patient-reported cohort (n = 752) than in the HCP-assessed cohort (n = 766) in both the acute (18.0 vs 12.5, respectively; p < 0.01) and remission phases (17.6 vs 12.6; p < 0.01). Overall, 45% of patients believed that their antidepressant medication was negatively affecting their emotions and 39% were considering stopping or had stopped their antidepressant because of perceived emotion-related side effects. In the HCP-assessed cohort, the antidepressant was considered responsible for emotional blunting in 30% of patients and only 18% of patients were believed to be considering stopping their medication due to emotional blunting. Patients reported a greater impact of emotional blunting on activities of daily living than HCPs. Mean FAST score was significantly higher in each phase of depression in the patient-reported cohort than in the HCP-assessed cohort (acute phase, 47.0 vs 39.1; remission phase, 33.5 vs 19.4; both p < 0.01). Conclusions Compared with previous studies, our results suggest that HCPs may underestimate the prevalence of emotional blunting in patients with depression. HCPs also appear to underestimate the severity and impact of emotional blunting on patient functioning and treatment adherence compared with patients' own perspectives. Differences between patient and HCP perspectives were most pronounced during the acute phase of the disease

Block-Based Models and Theorem Proving in Model-Based Development

This paper presents a methodology to integrate computer-assisted theorem proving into a standard workflow for model-based development that uses a block-based language as a modeling and simulation tool. The theorem prover provides confidence in the results of the analysis as it guides the developers towards a correct formalization of the system under developmen