Mixed states vs. pure mania in the french sample of the EMBLEM study: results at baseline and 24 months – European mania in bipolar longitudinal evaluation of medication

Abstract

BackgroundTo describe the clinical course and treatment patterns over 24 months of patients experiencing an acute manic/mixed episode within the standard course of care.MethodsEMBLEM was a 2-year European prospective, observational study on outcomes of patients experiencing a manic/mixed episode. Adults with bipolar disorder were enrolled within the standard course of care as in/outpatients if they initiated or changed oral medication for treatment of acute mania. After completing 12 weeks of acute phase, patients were assessed every 3–6 months during the maintenance phase. We present the 24 month results, with subgroup analysis for mixed states (MS) and pure mania (PM). These subgroup analyses are driven by the high proportion of antidepressants prescribed in this cohort.ResultsIn France, 771 patients were eligible for the maintenance phase. 69% of patients completed the follow up over 24 months. The mean age was 45.5 years (sd = 13.6) with 57% of women. 504 (66%) patients were experiencing a PM and 262 (34%) a MS at baseline. The main significant differences in MS vs. PM at baseline were: a higher rate of women, and in the previous 12 months, a higher frequency of episodes (manic/mixed and depressive), more suicide attempts, more rapid cycling, fewer social activities and more work impairment. Over the 24 months of follow-up the MS group had a significantly lower recovery than PM (36% vs. 46%, p = 0.006). Overall, 42% of all patients were started on monotherapy and 58% on combination therapy; of those 35% and 30% respectively remained on their initial medication throughout the 24 months. At baseline, 36% were treated with an antidepressant, this proportion remains high throughout the follow-up period, with a significantly higher rate for MS vs. PM at 24 months (55% vs. 27%, p < 0.001).ConclusionIn this large sample, MS occur frequently (34%), they are more severe at baseline and have a worse functional prognosis than PM. Although antidepressants are not recommended in MS and PM, they were frequently prescribed at baseline and are maintained during the 24 months of follow-up.

The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders

“…Predictors of continuing antidepressants for up to 24 months of follow-up were mixed states, more previous depressive episodes, rapid cycling, and higher rates of depressive and anxiety symptoms at baseline (47, 48). …”

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013

“…In a sub-analysis of 771 patients in the two-year EMBLEM study, approximately one in three presented with a mixed episode, which was associated with a lower likelihood of recovery and greater use of antidepressant therapy compared to a pure manic state during follow-up (14). The Systematic Treatment Optimization Program for Early Mania (STOP-EM) project followed 53 patients presenting with a first episode of mania, and found that more than half experienced recurrence of a mood episode during the one-year follow-up, with a mean time to event of 7.9 months (15).…”

Dissimilar morbidity following initial mania versus mixed-states in type-I bipolar disorder

“…There is growing evidence that early BPD mixed-states may be followed by particularly severe later morbidity that includes a great deal of dysphoria, depression and suicide-risk; moreover, their optimal treatment remains much less studied than mania or bipolar depression (Berk et al, 2005; Vieta et al, 2005; González-Pinto et al, 2007). There is some evidence that the nature of initial episodes, including mixed-states versus mania, can predict similar and greater morbidity during later follow-up (Azorin et al, 2009; Forty et al, 2009; Swan et al, 2009), usually based on retrospective or mid-course studies, rather than with systematic, prospective assessment of psychopathology in detail from onset (Baldessarini et al, 2010a). …”