Treatment of mixed features in bipolar disorder

CNS Spectrums ◽  
2016 ◽  
Vol 22 (2) ◽  
pp. 141-146 ◽  
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.

scholarly journals Mixed features in bipolar disorder

CNS Spectrums ◽  
2016 ◽  
Vol 22 (2) ◽  
pp. 134-140 ◽  
Author(s):  
Eva Solé ◽  
Marina Garriga ◽  
Marc Valentí ◽  
Eduard Vieta
Keyword(s):  
Bipolar Disorder ◽  
Diagnostic Category ◽  
Specific Treatment ◽  
Unipolar Depression ◽  
Manic Symptoms ◽  
Dsm 5 ◽  
Increased Risk ◽  
Mixed Features ◽  
Major Depressive Episodes ◽  
Depressive Episodes

Mixed affective states, defined as the coexistence of depressive and manic symptoms, are complex presentations of manic-depressive illness that represent a challenge for clinicians at the levels of diagnosis, classification, and pharmacological treatment. The evidence shows that patients with bipolar disorder who have manic/hypomanic or depressive episodes with mixed features tend to have a more severe form of bipolar disorder along with a worse course of illness and higher rates of comorbid conditions than those with non-mixed presentations. In the updated Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM–5), the definition of “mixed episode” has been removed, and subthreshold nonoverlapping symptoms of the opposite pole are captured using a “with mixed features” specifier applied to manic, hypomanic, and major depressive episodes. However, the list of symptoms proposed in the DSM–5 specifier has been widely criticized, because it includes typical manic symptoms (such as elevated mood and grandiosity) that are rare among patients with mixed depression, while excluding symptoms (such as irritability, psychomotor agitation, and distractibility) that are frequently reported in these patients. With the new classification, mixed depressive episodes are three times more common in bipolar II compared with unipolar depression, which partly contributes to the increased risk of suicide observed in bipolar depression compared to unipolar depression. Therefore, a specific diagnostic category would imply an increased diagnostic sensitivity, would help to foster early identification of symptoms and ensure specific treatment, as well as play a role in suicide prevention in this population.

scholarly journals Cariprazine in the Treatment of Bipolar Disorder: Within and Beyond Clinical Trials

2021 ◽  
Vol 12 ◽  
Author(s):  
André Do ◽  
Kamyar Keramatian ◽  
Ayal Schaffer ◽  
Lakshmi Yatham
Keyword(s):  
Bipolar Disorder ◽  
Clinical Trials ◽  
Psychosocial Functioning ◽  
Bipolar Depression ◽  
Partial Agonist ◽  
Current Evidence ◽  
Tolerability Profile ◽  
Significant Impairment ◽  
Post Hoc ◽  
Depressive Episodes

Bipolar disorder (BD) is chronic psychiatric disorder associated with significant impairment in psychosocial functioning and quality of life. Although current pharmacological treatments for BD have improved its clinical management, many patients do not achieve remission, particularly those suffering from bipolar depression. In addition, available treatments are associated with a myriad of potential adverse effects, which highlights the need for novel therapeutic agents that can be effective for both phases of the illness with a reduced side effect burden. Cariprazine is a novel antipsychotic that is a dopamine D2/D3 partial agonist with a preference for D3 receptors. In this review, we examine the pharmacological properties, clinical efficacy and tolerability profile of cariprazine in patients with BD, taking into account the latest clinical trials data. We also review post hoc analyses addressing clinically relevant subgroups and symptom domains in BD. Current evidence suggests efficacy for cariprazine 3–12 mg/day in the treatment of acute manic and mixed episodes; for bipolar depression, the efficacy of cariprazine appears to be dose-related, with doses of 1.5–3 mg/day beneficial as monotherapy. Cariprazine is overall well-tolerated by patients in both manic and depressive episodes. Its most common side effects relative to placebo include akathisia, extrapyramidal symptoms and nausea. There are no metabolic concerns reported with cariprazine use. In summary, the latest evidence suggests that cariprazine is an effective and safe treatment option for BD.

Bipolar Disorder

Depression ◽  
2019 ◽  
pp. 102-117
Author(s):  
Sabrina C. da Costa ◽  
Marsal Sanches ◽  
Jair C. Soares
Keyword(s):  
Bipolar Disorder ◽  
Bipolar Depression ◽  
Treatment Resistance ◽  
Subsequent Treatment ◽  
Average Delay ◽  
Course Of Illness ◽  
Therapeutic Implications ◽  
At Risk Populations ◽  
Diagnosis Accuracy ◽  
Long Term Prognosis

Bipolar disorder (BD) is a complex and severe mental illness, associated with substantial morbidity and increased mortality. Depressive symptoms frequently prevail in the course of illness, and significant morbidity arises from acute affective episodes and subacute states. Phenotypically, unipolar and bipolar depression seem to share several clinical features, which leads to an average delay of 10 years between initial symptoms and the diagnosis of BD. Multidimensional approaches have been proposed to better predict BD in at-risk populations; however, the differential diagnosis between these two entities remains a clinical challenge. Similarly to other chronic conditions, it has been proposed that BD is also a progressive disorder, where multiple affective episodes may result in structural, functional, and neurobiological brain abnormalities that accelerate illness progression, with subsequent treatment resistance and reduction in interepisode interval. Therefore, strategies to improve diagnosis accuracy are pivotal to improve clinical outcomes and long-term prognosis in the course of BD. In this chapter, we aim to provide a critical overview of psychopathological, sociodemographic, and neurobiological features to help clinicians properly distinguish unipolar and bipolar depression. Pathological and therapeutic implications of misdiagnosing BD are briefly discussed.

scholarly journals Mania and bipolar depression: complementing not opposing poles—a post-hoc analysis of mixed features in manic and hypomanic episodes

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Christoph Born ◽  
Heinz Grunze ◽  
Robert M. Post ◽  
Lori L. Altshuler ◽  
Ralph Kupka ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Bipolar Depression ◽  
Correlation Coefficients ◽  
Post Hoc Analysis ◽  
Dsm 5 ◽  
Mixed Features ◽  
Symptom Load ◽  
Patient Groups ◽  
Sum Scores ◽  
Post Hoc

Abstract Background Depending on the classification system used, 5–40% of manic subjects present with concomitant depressive symptoms. This post-hoc analysis evaluates the hypothesis that (hypo)manic subjects have a higher burden of depression than non-(hypo)manic subjects. Methods Data from 806 Bipolar I or II participants of the Stanley Foundation Bipolar Network (SFBN) were analyzed, comprising 17,937 visits. A split data approach was used to separate evaluation and verification in independent samples. For verification of our hypotheses, we compared mean IDS-C scores ratings of non-manic, hypomanic and manic patients. Data were stored on an SQL-server and extracted using standard SQL functions. Linear correlation coefficients and pivotal tables were used to characterize patient groups. Results Mean age of participants was 40 ± 12 years (range 18–81). 460 patients (57.1%) were female and 624 were diagnosed as having bipolar I disorder (77.4%) and 182 with bipolar II (22.6%). Data of 17,937 visits were available for analyses, split into odd and even patient numbers and stratified into three groups by YMRS-scores: not manic < 12, hypomanic < 21, manic < 30. Average IDS-C sum scores in manic or hypomanic states were significantly higher (p < .001) than for non-manic states. (Hypo)manic female patients were likely to show more depressive symptoms than males (p < .001). Similar results were obtained when only the core items of the YMRS or only the number of depressive symptoms were considered. Analyzing the frequency of (hypo)manic mixed states applying a proxy of the DSM-5 mixed features specifier extracted from the IDS-C, we found that almost 50% of the (hypo)manic group visits fulfilled DSM-5 mixed features specifier criteria. Conclusion Subjects with a higher manic symptom load are also significantly more likely to experience a higher number of depressive symptoms. Mania and depression are not opposing poles of bipolarity but complement each other.

scholarly journals Comorbid Premenstrual Dysphoric Disorder and Bipolar Disorder: A Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Anastasiya Slyepchenko ◽  
Luciano Minuzzi ◽  
Benicio N. Frey
Keyword(s):  
Bipolar Disorder ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Clinical Presentation ◽  
Premenstrual Dysphoric Disorder ◽  
Severe Form ◽  
Course Of Illness ◽  
Manic Symptoms ◽  
Mixed Features ◽  
Depressive Episodes ◽  
Degrees Of Severity

Bipolar disorder (BD) differs in its clinical presentation in females compared to males. A number of clinical characteristics have been associated with BD in females: more rapid cycling and mixed features; higher number of depressive episodes; and a higher prevalence of BD type II. There is a strong link between BD and risk for postpartum mood episodes, and a substantial percentage of females with BD experience premenstrual mood worsening of varying degrees of severity. Females with premenstrual dysphoric disorder (PMDD)—the most severe form of premenstrual disturbances—comorbid with BD appear to have a more complex course of illness, including increased psychiatric comorbidities, earlier onset of BD, and greater number of mood episodes. Importantly, there may be a link between puberty and the onset of BD in females with comorbid PMDD and BD, marked by a shortened gap between the onset of BD and menarche. In terms of neurobiology, comorbid BD and PMDD may have unique structural and functional neural correlates. Treatment of BD comorbid with PMDD poses challenges, as the first line treatment of PMDD in the general population is selective serotonin reuptake inhibitors, which produce risk of treatment-emergent manic symptoms. Here, we review current literature concerning the clinical presentation, illness burden, and unique neurobiology of BD comorbid with PMDD. We additionally discuss obstacles faced in symptom tracking, and management of these comorbid disorders.

scholarly journals Bipolar depression: trial-based insights to guide patient care

2008 ◽  
Vol 10 (2) ◽  
pp. 181-192 ◽  
Keyword(s):  
Bipolar Disorder ◽  
Bipolar Depression ◽  
Unmet Need ◽  
Mood Stabilizers ◽  
Number Needed To Treat ◽  
Clinical Approach ◽  
Clinical Trial Results ◽  
Major Depressive Episodes ◽  
Depressive Episodes ◽  
Illness Phase

For the majority of patients with bipolar disorder, major depressive episodes represent the most debilitating and difficult-to-treat illness dimension. Patients spend significantly more time depressed than manic or hypomanic, and attempt suicide more frequently during this illness phase, yet the availability of treatments remains limited. The discovery of more effective therapeutics for managing depressive episodes is arguably the greatest unmet need in bipolar disorder. This article provides an evidence-based summary of pharmacological treatments for the acute and longitudinal management of bipolar depression. Clinical trial results are reviewed for a diverse array of compounds, inclusive of traditional mood stabilizers (eg, lithium and divalproex), atypical antipsychotics, unimodal antidepressants, and modafinil. Where applicable, differences in efficacy across compounds are examined through discussion of number needed to treat and effect size determinations. A pragmatic clinical approach is presented for management of the depressed phase of bipolar disorder.

Factors related to suicidal behavior in korean patients with bipolar disorder: The effect of mixed features on suicidality

2016 ◽  
Vol 33 (S1) ◽  
pp. s270-s271
Author(s):  
H.J. Seo ◽  
H.R. Wang ◽  
Y.S. Woo ◽  
H.C. Kim ◽  
W.M. Bahk ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bipolar Disorder ◽  
Suicidal Behavior ◽  
Significant Risk ◽  
Suicidal Behaviors ◽  
Korean Patients ◽  
Dsm 5 ◽  
Mixed Features ◽  
Bipolar Patients ◽  
Depressive Episodes

IntroductionThe aim of the present study was to investigate various risk factors of suicidal behaviors, including the mixed features specifier, in Korean patients with bipolar disorder.MethodsWe retrospectively reviewed medical charts from 2005 to 2014. A total of 334 patients diagnosed with bipolar disorder using the DSM-IV TR were enrolled. Subjects were categorized into two groups according to their history of suicidal behavior and the demographic and clinical characteristics of the groups were compared, including the mixed features specifier. We re-evaluated the index episode using DSM-5 criteria and classified subjects into an index episode with mixed features group and an index episode without mixed features group. Logistic regression was performed to evaluate significant risk factors associated with suicidal behavior.ResultsSuicidal behavior had an independent relationship with mixed features at the index episode using DSM-5 criteria (OR = 3.39; 95% CI: 1.57–7.34) and number of previous depressive episodes (OR = 1.62; 95% CI: 1.34–1.95) in Korean bipolar patients. The mixed feature specifier was the strongest risk factor for suicidal behavior in the present study. Limitations: this was a retrospective study and structured psychiatric interviews were not conducted.ConclusionsThis study may help clinicians understand potential risk factors and manage bipolar disorders with suicidal behaviors. Clinicians should carefully monitor patients with bipolar disorder who exhibit numerous depressive episodes or mixed features for suicidal behavior.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Treating mixed mania/hypomania: a review and synthesis of the evidence

CNS Spectrums ◽  
2016 ◽  
Vol 22 (2) ◽  
pp. 177-185 ◽  
Author(s):  
Minoru Takeshima
Keyword(s):  
Depressive Symptoms ◽  
Acute Phase ◽  
Opposite Polarity ◽  
Mood Stabilizers ◽  
Current Evidence ◽  
Mixed States ◽  
Mixed Features ◽  
Broad Concept ◽  
Major Depressive Episodes ◽  
Depressive Episodes

The DSM–5 incorporates a broad concept of mixed states and captured ≥3 nonoverlapping symptoms of the opposite polarity using a “with mixed features” specifier to be applied to manic/hypomanic and major depressive episodes. Pharmacotherapy of mixed states is challenging because of the necessity to treat both manic/hypomanic and depressive symptoms concurrently. High-potency antipsychotics used to treat manic symptoms and antidepressants can potentially deteriorate symptoms of the opposite polarity. This review aimed to provide a synthesis of the current evidence for pharmacotherapy of mixed states with an emphasis on mixed mania/hypomania. A PubMed search was conducted for randomized controlled trials (RCTs) that were at least moderately sized, included a placebo arm, and contained information on acute-phase and maintenance treatments of adult patients with mixed episodes or mania/hypomania with significant depressive symptoms. Most studies were post-hoc subgroup and pooled analyses of the data from RCTs for acute manic and mixed episodes of bipolar I disorder; only two prospectively examined efficacy for mixed mania/hypomania specifically. Aripiprazole, asenapine, carbamazepine, olanzapine, and ziprasidone showed the strongest evidence of efficacy in acute-phase treatment. Quetiapine and divalproex/valproate were also efficacious. Combination therapies with these atypical antipsychotics and mood stabilizers can be considered in severe cases. Olanzapine and quetiapine (alone or in combination with lithium/divalproex) showed the strongest evidence of efficacy in maintenance treatment. Lithium and lamotrigine may be beneficial given their preventive effects on suicide and depressive relapse. Further prospective studies primarily focusing on mixed states are needed.

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