Jordan Bertsch

Suicidal attempts in bipolar disorder: results from an observational study (EMBLEM)

Bellivier F, Yon L, Luquiens A, Azorin J‐M, Bertsch J, Gerard S, Reed C, Lukasiewicz M. Suicidal attempts in bipolar disorder: results from an observational study (EMBLEM).
Bipolar Disord 2011: 13: 377–386.

Incidence of extrapyramidal symptoms and tardive dyskinesia in schizophrenia: thirty-six-month results from the European schizophrenia outpatient health outcomes study.

The incidence of treatment-emergent extrapyramidal symptoms (EPSs) and tardive dyskinesia (TD) in schizophrenic patients, and the clinical characteristics associated with an increased risk of developing EPSs and TD were examined. Patients (N = 7728) in the 3-year, prospective, observational Schizophrenia Outpatient Health Outcomes study were examined according to baseline antipsychotic drug exposure. At baseline, 4893 patients (63.3%) had no EPS, and 6921 (89.6%) had no TD. Extrapyramidal symptoms and TD were assessed separately during follow-up: frequency and time to appearance from Kaplan-Meier survival curves and factors associated with time to appearance using Cox proportional hazard regression models. The cumulative incidence of EPS ranged from 7.7% (olanzapine) to 32.8% (depot typical drugs). Compared with olanzapine, patients taking depot typical drugs, oral typical drugs, risperidone, and amisulpride had a significantly higher risk of developing EPS. Differences from clozapine were marginally significant. High baseline clinical severity was associated with a significantly higher risk of developing EPS. The incidence of TD ranged from 2.8% (olanzapine) to 11.1% (depot typical agent). Compared with olanzapine, patients taking depot typical agents, oral typical agents, and risperidone had a significantly higher risk of developing TD. Baseline factors associated with a significantly higher risk of developing TD were age, EPS, a higher negative Clinical Global Impression score, and presence of gynecomastia. In summary, patients treated with typical antipsychotic agents (oral and depot) and risperidone had a higher risk of developing EPS and TD than patients treated with olanzapine. Higher baseline clinical severity was associated with EPS development, whereas age, presence of EPS, a higher negative Clinical Global Impression score, and presence of gynecomastia were associated with TD development.

2-year course of bipolar disorder type I patients in outpatient care: Factors associated with remission and functional recovery

EMBLEM is a 2-year, prospective, observational study that enrolled patients initiating/changing oral treatment for an acute manic/mixed episode. This paper analysed remission and functional recovery in 1656 patients who entered the 2-year long-term phase. Cox models identified variables significantly associated with achieving remission and functional recovery at 2years. Of these patients, 64% achieved remission and 34% achieved functional recovery. Patients with a higher CGI-BP overall score at baseline, who had depressive episodes in the year before inclusion and who had poor social functioning (work or social impairment, not living independently or without a spouse/partner) were less likely to achieve remission or recovery. Prescription of typical antipsychotics and prescription of antidepressants at the first visit of the long-term treatment phase (12weeks) were independent predictors of lower remission and recovery rates. In conclusion, functional recovery occurred in approximately half of those who achieved remission. Impairment of work and social functioning was consistently associated with lower remission and recovery rates.

Why do clinicians maintain antidepressants in some patients with acute mania? Hints from the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM), a large naturalistic study.

OBJECTIVE Antidepressants are supposed to be withdrawn during a manic episode. The aim of this study was to analyze the characteristics of manic patients who received antidepressants during a manic phase in a large, naturalistic study. METHOD The European Mania in Bipolar Longitudinal Evaluation of Medication was a 2-year prospective observational study of inpatients and outpatients with acute mania/mixed mania (DSM-IV or ICD-10 criteria) conducted in 14 European countries. Of 2,416 manic patients who continued into the maintenance phase of the study, 345 (14%) were taking an antidepressant and 2,071 (86%) were not taking an antidepressant at baseline, week 1, and/or week 2 postbaseline. Demographic and clinical variables were collected at baseline and each study visit up to 24 months. Outcome measures included the Clinical Global Impressions-Bipolar Disorder scale (CGI-BP overall, mania, and depression scores) at 12 weeks and 24 months, the 5-item Hamilton Depression Rating Scale (HDRS-5), and the Young Mania Rating Scale (YMRS) at 12 weeks only. The present study was conducted from December 2002 to June 2004. RESULTS More antidepressant maintenance use was seen in patients with mixed episodes (P < .001), rapid cyclers (P < .02), patients with more previous depressive episodes (P < .001), and patients with higher mean HDRS-5 score at baseline (P < .001)-specifically patients with anxiety (P = .013). Patients in the antidepressant group had significantly higher CGI-BP depression scores (P < .001) and a significantly higher rate of depression relapse (P < .001) at both 12 weeks and 24 months. CONCLUSIONS Patients with mania receiving antidepressants are more likely to be outpatients with mixed episodes, anxiety, or rapid cycling and have a higher risk of depression relapse during follow-up.

Rapid-cycling bipolar I disorder: Course and treatment outcome of a large sample across Europe

OBJECTIVES To evaluate the baseline characteristics and follow-up outcomes of rapid-cycling (RC) bipolar I patients in a large, prospective, observational study. METHODS EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) is a long-term prospective observational study of in- and outpatients with an acute mania/mixed episode conducted in 14 European countries. Demographic and clinical variables were collected at baseline, including the presence or absence of DSM-IV rapid-cycling during the past year. Outcome measures included the 5-item Hamilton Depression Rating Scale (HAMD-5) and Young Mania Rating Scale (YMRS) over 12 weeks, as well as the Clinical Global Impressions-Bipolar Disorder Scale (CGI-BP overall, mania and depression) over 12 months. RESULTS Of 3684 patients enrolled, 3089 patients provided reliable data to qualify for either RC (N=535, 17.3%) or non-RC (NRC, N=2554), according to DSM-IV. RC prevalence varied across countries (p<0.001). Baseline and 12 week outcomes on the YMRS and HAMD-5, 12 month ratings on the CGI-BP subscales and work impairment at 12 months were significantly different (p<0.001) between groups, being worse in RC. RC patients were more likely to receive antidepressants and lamotrigine (p<0.001). Using logistic regression, RC was associated to country (p<0.001), female sex (p=0.029), outpatients (p=0.035), more history of attempted suicide (p<0.001) and alcohol abuse (p<0.001). CONCLUSIONS The EMBLEM results suggest that in naturalistic settings, patients with mania and RC differ from NRC in socio-demographic characteristics, treatment prescriptions and clinical outcome measures with a consistently worse occupational outcome and comorbidities. RC represents a longitudinally severe form of bipolar disorder, with poorly evidence-based diagnostic and therapeutic tools.

Assessment of Medication Adherence in a Cohort of Patients with Bipolar Disorder

INTRODUCTION This study aimed to identify factors associated with medication adherence in bipolar disorder (BPD) patients. METHODS EMBLEM is a 2-year, prospective, observational study on the outcomes of BPD patients initiating or changing treatment for a manic/mixed episode. Data were collected at baseline, during the first 12 weeks of treatment (acute phase) and up to 24 months of follow-up (maintenance phase). Adherence was assessed by investigators at every visit. Repeated measures logistic regression analyses identified variables associated with adherence. RESULTS Of 1,831 patients included in the analysis, 76.6% were adherent and 23.4% were non-adherent with their BPD medication during the maintenance phase. Patients were more likely to be adherent if they had insight into their illness at week 12. Patients were less likely to be adherent if they had cannabis abuse/dependence during the acute phase, work impairment or higher CGI hallucinations/delusions at baseline DISCUSSION Psychotic symptoms, poor insight, cannabis abuse/dependence and work impairment are negatively related to medication adherence during maintenance therapy of bipolar disorder. Patients with these characteristics may need a different therapeutic approach.

Factor structure, internal consistency and construct validity of the Sheehan Disability Scale in a Spanish primary care sample

RATIONALE, AIMS AND OBJECTIVES The Sheehan Disability Scale (SDS) is a three-item instrument that measures disability in three inter-related domains: work, family life/home responsibilities and social/leisure activities. The main objective of the present study was to examine the factor structure, reliability and construct validity of the SDS in a wide Spanish sample of primary care (PC) patients. METHODS One phase cross-sectional survey. A total of 3815 patients, aged 18 years or older attending PC for a medical visit, were interviewed between October 2005 and March 2006. The interviews included the Structured Clinical Interview for DSM-IV Axis I Disorders for depressive and anxiety disorders, the Mini-International Neuropsychiatric Interview for the rest of mental disorders, a medical conditions checklist, the 2.0 version of the 12-item Short-Form Health Survey (SF-12) for measuring quality of life and the SDS. RESULTS The principal component analysis and the subsequent confirmatory factor analysis indicated that the SDS is one-dimensional (normed fit index = 0.990, non-normed fit index = 0.987, comparative fit index = 0.991, goodness-of-fit index = 0.993, standardized root mean-square residual = 0.037, root mean-square error of approximation = 0.053). The internal consistency of the scale was good (α = 0.83) and it was significantly associated with the physical and mental component of the SF-12. Concerning discriminative validity, patients with major depression or panic disorder scored higher on the SDS than patients with chronic medical conditions or with no chronic pathology. We also found that a cut-off point of 8 in the SDS adequately discriminated between patients with and without depression (area under the curve = 0.814, sensitivity = 81.60%, specificity = 70.60%). CONCLUSIONS The SDS seems a reliable, valid and useful clinical tool for measuring disability in Spanish PC patients.

Validity and reliability of the Hamilton depression rating scale (5 items) for manic and mixed bipolar disorders.

Depressive symptoms during mania have prognostic value in bipolar disorder. For depressive symptoms, it has been proposed that shorter scales should be cost-effective and practical. To determine the usefulness of 5-item Hamilton Depression Rating Scale (HAMD-5) in manic and mixed bipolar disorder, we used a four-week follow-up prospective, observational study. Convergent and discriminant validity, internal consistency, and reliability were analyzed and compared with HAMD-21, HAMD-5, and HAMD-21 cut-off points were calculated versus CGI-BP. A total of 173 manic and mixed patients were evaluated. HAMD-5 showed appropriate convergent validity, discriminant validity, internal consistency, and test-retest reliability. Discriminant validity was higher for HAMD-5 than HAMD-21. Best cut-off point of remission was: HAMD-21 ≤5 and HAMD-5 ≤1. HAMD-5 presents appropriate validity and reliability estimates. It is comparable to HAMD-21 and focuses more specifically on depressive symptoms.

Symptomatic remission and patient quality of life in an observational study of schizophrenia: Is there a relationship?

This analysis aimed to examine the association between remission and quality of life (QOL) in schizophrenia. In post-hoc analyses of the 3-year, prospective, observational Schizophrenia Outpatients Health Outcomes (SOHO) study, we compared the QOL of patients who achieved symptomatic and clinical remission with those who did not, and the factors associated. Symptomatic remission was defined as achieving a score of ≤3 on the Clinical Global Impression-Schizophrenia (CGI-SCH) scale, maintained for 6 months and without hospitalization. QOL was patient self-rated using the European-QOL. Of the 6516 patients analyzed, 38% were in symptomatic remission 12 months post-baseline and 52% at 36 months. Functional remission remained fairly constant from 12 months to 36 months (22.4% at both time points). At all visits from 12 to 36 months, patient QOL and social functioning were significantly higher for patients in symptomatic remission. QOL was higher in patients in functional remission. Patients with maintained symptomatic remission over the 3-year follow-up had a much greater improvement in QOL than patients with no symptomatic remission or symptomatic remission for part of the period. Factors associated with a better QOL also included paid employment, socially active, a higher CGI-SCH cognitive score, good compliance, and a better baseline QOL.

Observational study designs for bipolar disorder — What can they tell us about treatment in acute mania?

Randomised controlled trials may have generalisability limitations when applied to the complex treatment of patients with bipolar disorder. Observational study designs can inform us about the diversity of bipolar disorder treatment in naturalistic settings. The aim of this paper was to describe the treatments prescribed for acute mania in a large prospective observational study of bipolar disorder. Patients with a manic/mixed episode were enrolled in EMBLEM (European Mania in Bipolar Longitudinal Evaluation of Medication) if they initiated or changed oral medication with antipsychotics, lithium and/or anticonvulsants. The use of monotherapy or combination therapy for treatment of acute mania, concomitant medications and rate of treatment switching during the 12-week acute treatment phase were assessed. Of the 3459 patients, 36% were treated with one drug and 64% with combination therapy. 55% of patients initiating combination therapy started on an atypical antipsychotic plus lithium or an anticonvulsant. Patients prescribed combination therapy at baseline were more clinically severe, were more often treated as inpatients and had more manic episodes in the previous year compared with the monotherapy group. Treatment switching occurred in 54.4% of patients over the 12-week acute phase. Many patients were taking at least one concomitant medication at baseline (69.4%) and week 12 (50.5%). The results of this observational study show that treatment for mania is complex with multiple combinations of treatment and frequent switching during an acute episode.