P.0420 The efficacy of lumateperone in patients with bipolar depression with and without mixed features

AbstractObjectiveTo evaluate the efficacy and safety of lurasidone in the treatment of children and adolescents with bipolar depression presenting with mixed features.MethodsPatients 10 to 17 years of age, inclusive, with a DSM-IV-TR diagnosis of bipolar I depression, were randomized to 6 weeks of double-blind treatment with once-daily, flexible doses of lurasidone 20-80 mg or placebo. The presence of mixed features (subthreshold hypomanic symptoms) was defined as a YMRS score > 5 at study baseline. Efficacy analyses included change from baseline to week 6 in Children Depression Rating Scale, Revised (CDRS-R) score (the primary outcome), and Clinical Global Impressions, Bipolar Severity of Depression Score (CGI-BP-S), using mixed model for repeated measures (MMRM) analysis.ResultsAt baseline, mixed features were present in 54.2% of patients (lurasidone, n=97/173; placebo, n=89/170). Treatment with lurasidone (vs placebo) was associated with significantly greater reductions in CDRS-R scores at week 6 in the mixed features group (-21.5 vs -15.9; P<0.01; effect size, 0.45), and in the group without mixed features (-20.4 vs -14.8; P<0.01; effect size, 0.45). Likewise, lurasidone was associated with greater effect size (vs placebo) for reductions inCGI-BP-S scores at week 6 in the mixed features group (-1.6 vs -1.1; P<0.001; effect size 0.57), and in the group without mixed features (-1.3 vs -1.0; P=0.05; effect size 0.30). Rates of protocol-defined treatment-emergent hypomania or mania were similar for lurasidone and placebo in patients with mixed features(lurasidone 8.2% vs. placebo 9.0%) and without mixed features (lurasidone 1.3% vs. placebo 3.7%).ConclusionsIn this post-hoc analysis, lurasidone was found to be efficacious for treating child and adolescent patients with bipolar depression presenting with mixed features(assessed cross-sectionally at study baseline). There was no increased risk of treatment-emergent mania observed in patients with or without mixed features.Funding AcknowledgementsSunovion Pharmaceuticals Inc.

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Bipolar depression: a major unsolved challenge

International Journal of Bipolar Disorders ◽

10.1186/s40345-019-0160-1 ◽

2020 ◽

Vol 8 (1) ◽

Cited By ~ 15

Author(s):

Ross J. Baldessarini ◽

Gustavo H. Vázquez ◽

Leonardo Tondo

Keyword(s):

General Population ◽

Psychiatric Disorders ◽

Suicide Risk ◽

Bipolar Depression ◽

Unipolar Depression ◽

Short Term ◽

Term Efficacy ◽

Medical Disorders ◽

Mixed Features

AbstractDepression in bipolar disorder (BD) patients presents major clinical challenges. As the predominant psychopathology even in treated BD, depression is associated not only with excess morbidity, but also mortality from co-occurring general-medical disorders and high suicide risk. In BD, risks for medical disorders including diabetes or metabolic syndrome, and cardiovascular disorders, and associated mortality rates are several-times above those for the general population or with other psychiatric disorders. The SMR for suicide with BD reaches 20-times above general-population rates, and exceeds rates with other major psychiatric disorders. In BD, suicide is strongly associated with mixed (agitated-dysphoric) and depressive phases, time depressed, and hospitalization. Lithium may reduce suicide risk in BD; clozapine and ketamine require further testing. Treatment of bipolar depression is far less well investigated than unipolar depression, particularly for long-term prophylaxis. Short-term efficacy of antidepressants for bipolar depression remains controversial and they risk clinical worsening, especially in mixed states and with rapid-cycling. Evidence of efficacy of lithium and anticonvulsants for bipolar depression is very limited; lamotrigine has long-term benefit, but valproate and carbamazepine are inadequately tested and carry high teratogenic risks. Evidence is emerging of short-term efficacy of several modern antipsychotics (including cariprazine, lurasidone, olanzapine-fluoxetine, and quetiapine) for bipolar depression, including with mixed features, though they risk adverse metabolic and neurological effects.

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145 Improving Management of Mood Disorders Through an Online Interactive Patient Case Challenge

CNS Spectrums ◽

10.1017/s1092852918000408 ◽

2018 ◽

Vol 23 (1) ◽

pp. 90-91

Author(s):

Jovana Lubarda ◽

Piyali Chatterjee-Shin ◽

Joseph F. Goldberg

Keyword(s):

Mood Disorders ◽

Bipolar Depression ◽

Accurate Diagnosis ◽

Educational Activity ◽

List Type ◽

Type Number ◽

Data Set ◽

P Values ◽

Mixed Features ◽

Post Assessment

AbstractBackgroundTo determine if online continuing medical education (CME) could improve knowledge, competence, and confidence of psychiatrists and primary care physicians (PCPs) in managing patients with major depressive disorder (MDD) and co-occurring hypomanic/manic features.Methods∙Physicians participated in a 1-hour text-based, online CME activity composed of 2 patient cases with interactive questions related to diagnosis, assessment, and management of various presentations of MDD∙Evidence-based educational feedback was provided following each answer∙Effects of CME were assessed using a repeated-question pairs pre- to post-assessment study design where individual participants served as his/her own control∙The assessment included 3 multiple-choice knowledge/competence questions and 1 self-efficacy question that rated confidence in managing MDD with mixed features on a 5-point Likert Scale∙For all questions combined, McNemar’s chi-square test assessed the differences from pre- to post-assessment∙P values measured significance; P values <.05 were considered statistically significant∙Effect size was calculated using Cramer’s V by determining the change in proportion of participants who answered questions correctly from pre- to post- assessment∙Survey data were collected from December 8th, 2016, to January 24th, 2017.Results∙Data set included responses from 1454 psychiatrists and 488 PCPs who completed all assessment questions during the study period∙Psychiatrists: Knowledge/competence improved (P<.001; V=0.54; large educational effect) following participation in the CME activity:°While 5% answered all 3 questions correctly on pre-assessment, 70% answered them all correctly on post- assessment, with the largest increases on accurate differentiation between possible signs of mania and depression, accurate diagnosis of bipolar depression, and ability to select treatments for MDD with mixed features°20% reported being more confident in their ability to select treatments for various presentations of mood disorders∙PCPs: Knowledge/competence improved (P<.001; V=0.49; large educational effect) following participation in the CME activity:°While 2% answered all 3 questions correctly on pre-assessment, 48% answered them all correctly on post-assessment, with the largest increases on accurate differentiation between possible signs of mania and depression, accurate diagnosis of bipolar depression, and ability to select treatments for MDD with mixed features°24% reported being more confident in their ability to select treatments for various presentations of mood disordersConclusionsOnline CME in a clinically relevant interactive case-based format can improve knowledge, competence, and confidence in management of various presentations of mooddisorders and better equip physicians to recognize key features, accurately diagnose, and treat the complex spectrum of this patient population.Funding AcknowledgementsThe educational activity and outcomes measurement were funded through an independent educational grant from Sunovion Pharmaceuticals Inc.

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Treatment of mixed features in bipolar disorder

CNS Spectrums ◽

10.1017/s1092852916000547 ◽

2016 ◽

Vol 22 (2) ◽

pp. 141-146 ◽

Cited By ~ 9

Author(s):

Joshua D. Rosenblat ◽

Roger S. McIntyre

Keyword(s):

Bipolar Disorder ◽

Bipolar Depression ◽

Treatment Resistance ◽

Course Of Illness ◽

Stabilizing Agents ◽

Dsm 5 ◽

Mixed Features ◽

Post Hoc ◽

Major Depressive Episodes ◽

Depressive Episodes

Mood episodes with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)–defined mixed features are highly prevalent in bipolar disorder (BD), affecting ~40% of patients during the course of illness. Mixed states are associated with poorer clinical outcomes, greater treatment resistance, higher rates of comorbidity, more frequent mood episodes, and increased rates of suicide. The objectives of the current review are to identify, summarize, and synthesize studies assessing the efficacy of treatments specifically for BD I and II mood episodes (ie, including manic, hypomanic, and major depressive episodes) with DSM-5–defined mixed features. Two randomized controlled trials (RCTs) and 6 post-hoc analyses were identified, all of which assessed the efficacy of second-generation antipsychotics (SGAs) for the acute treatment of BD mood episodes with mixed features. Results from these studies provide preliminary support for SGAs as efficacious treatments for both mania with mixed features and bipolar depression with mixed features. However, there are inadequate data to definitively support or refute the clinical use of specific agents. Conventional mood stabilizing agents (eg, lithium and divalproex) have yet to have been adequately studied in DSM-5–defined mixed features. Further study is required to assess the efficacy, safety, and tolerability of treatments specifically for BD mood episodes with mixed features.

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Psychopharmacology of Bipolar II Depression and Bipolar Depression with Mixed Features

FOCUS The Journal of Lifelong Learning in Psychiatry ◽

10.1176/appi.focus.12.2.136 ◽

2014 ◽

Vol 12 (2) ◽

pp. 136-145

Author(s):

Honor Hsin ◽

Trisha Suppes

Keyword(s):

Bipolar Depression ◽

Bipolar Ii ◽

Mixed Features

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Efficacy of olanzapine monotherapy in the treatment of bipolar depression with mixed features

Journal of Affective Disorders ◽

10.1016/j.jad.2014.04.003 ◽

2014 ◽

Vol 164 ◽

pp. 57-62 ◽

Cited By ~ 24

Author(s):

Mauricio Tohen ◽

Shigenobu Kanba ◽

Roger S. McIntyre ◽

Shinji Fujikoshi ◽

Hideaki Katagiri

Keyword(s):

Bipolar Depression ◽

Mixed Features

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Pharmacological treatment of mixed states

CNS Spectrums ◽

10.1017/s1092852917000013 ◽

2017 ◽

Vol 22 (2) ◽

pp. 186-195 ◽

Cited By ~ 8

Author(s):

Alessandro Cuomo ◽

Viktoriya L. Nikolova ◽

Nefize Yalin ◽

Danilo Arnone ◽

Andrea Fagiolini ◽

...

Keyword(s):

Pharmacological Treatment ◽

Bipolar Depression ◽

Case Reports ◽

Case Series ◽

Cochrane Library ◽

Future Research ◽

Mixed States ◽

Double Blind ◽

Dsm 5 ◽

Mixed Features

Mixed states in bipolar disorder have been neglected, and the data concerning treatment of these conditions have been relatively obscure. To address this, we systematically reviewed published pharmacological treatment data for “mixed states/episodes” in mood disorders, including “with mixed features” in DSM–5. We searched PubMed, MEDLINE, The Cochrane Library, clinicaltrials.gov, and controlled-trials.com (with different combinations of the following keywords: “mixed states/features,” “bipolar,” “depressive symptoms/bipolar depression,” “manic symptoms,” “treatment,” “DSM–5”) through to October 2016. We applied a quality-of-evidence approach: first-degree evidence=randomized placebo-controlled studies of pharmacological interventions used as monotherapy; second-degree evidence=a similar design in the absence of a placebo or of a combination therapy as a comparative group; third-degree evidence=case reports, case series, and reviews of published studies. We found very few primary double-blind, placebo-controlled studies on the treatment of mixed states: the preponderance of available data derives from subgroup analysis performed on studies that originally involved manic patients. Future research should study the effects of treatments in mixed states defined using current criteria.

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