Diagnosis, Epidemiology and Management of Mixed States in Bipolar Disorder

Abstract

Approximately 40% of patients with bipolar disorder experience mixed episodes, defined as a manic state with depressive features, or manic symptoms in a patient with bipolar depression. Compared with bipolar patients without mixed features, patients with bipolar mixed states generally have more severe symptomatology, more lifetime episodes of illness, worse clinical outcomes and higher rates of comorbidities, and thus present a significant clinical challenge. Most clinical trials have investigated second-generation neuroleptic monotherapy, monotherapy with anticonvulsants or lithium, combination therapy, and electroconvulsive therapy (ECT). Neuroleptic drugs are often used alone or in combination with anticonvulsants or lithium for preventive treatment, and ECT is an effective treatment for mixed manic episodes in situations where medication fails or cannot be used. Common antidepressants have been shown to worsen mania symptoms during mixed episodes without necessarily improving depressive symptoms; thus, they are not recommended during mixed episodes. A greater understanding of pathophysiological processes in bipolar disorder is now required to provide a more accurate diagnosis and new personalised treatment approaches. Targeted, specific treatments developed through a greater understanding of bipolar disorder pathophysiology, capable of affecting the underlying disease processes, could well prove to be more effective, faster acting, and better tolerated than existing therapies, therefore providing better outcomes for individuals affected by bipolar disorder. Until such time as targeted agents are available, second-generation neuroleptics are emerging as the treatment of choice in the management of mixed states in bipolar disorder.

Time Dilation and Acceleration in Depression

“…group. This is despite current evidence that up to 40% of bipolar patients experienced mixed episodes of mania with depressive symptoms or, more problematically, depressive episodes with manic symptoms (Fagiolini et al, 2015). Heterogeneous groups were identified as a confound by Bschor et al (2004) suggests that, in addition to clinically depressed people experiencing time as dilated in the experienced moment, when those moments are expanded to encompass larger intervals of WM, time becomes accelerated in medium-range (10 -120 s) interval production tasks.…”

Treatment of mixed features in bipolar disorder

“…Reference lists from included articles were also manually searched for additional pertinent references. Of note, primary studies assessing treatments of DSM-IV-TR-defined mixed episodes were not systematically retrieved or reviewed in the current article, as this has been done by numerous other authors previously 3,9,[24][25][26][27] and the focus of the current article is on studies specifically evaluating the treatment of DSM-5-defined "mixed features" rather than DSM-IV-TR-defined "mixed episodes. "…”

“…23 At the current time, inadequate evidence exists to adequately inform evidencebased treatment guidelines for mixed features in BD, as randomized controlled trials (RCTs) assessing the efficacy of various treatments specifically for BD mood episodes with mixed features have yet to be conducted. Numerous RCTs have assessed the efficacy of treatments of DSM-IV-defined mixed episodes 3,9,[24][25][26][27] ; however, the translational application of these results to the treatment of DSM-5-defined mixed features is speculative, as the DSM-IV overlaps but is distinctly different.…”

Treatment recommendations for DSM-5–defined mixed features

“…Conversely, mixed episode studies are likely less applicable to the treatment of depression with mixed features. Based on results from recent meta-analyses and several systematic reviews, second-generation antipsychotics (SGAs) and divalproex appear to be the most efficacious acute treatments of mixed episodes for simultaneously alleviating symptoms of depression and mania 16 35 – 37 Therefore, these treatments may be of benefit for mania with mixed features.…”