P.2.d.013 Evaluating depressive symptoms in mania study using a structured diagnostic tool, the DSM-5 “with mixed features” specifier MINI module

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.

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

CNS Spectrums ◽

10.1017/s1092852916000845 ◽

2016 ◽

Vol 22 (2) ◽

pp. 177-185 ◽

Cited By ~ 13

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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Measures of the DSM–5 mixed-features specifier of major depressive disorder

CNS Spectrums ◽

10.1017/s1092852916000857 ◽

2017 ◽

Vol 22 (2) ◽

pp. 196-202 ◽

Cited By ~ 4

Author(s):

Mark Zimmerman

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Antidepressant Medication ◽

Reliability And Validity ◽

Mixed States ◽

Major Depressive ◽

Manic Symptoms ◽

Dsm 5 ◽

Depressed Patients ◽

Mixed Features

During the past two decades, a number of studies have found that depressed patients frequently have manic symptoms intermixed with depressive symptoms. While the frequency of mixed syndromes are more common in bipolar than in unipolar depressives, mixed states are also common in patients with major depressive disorder. The admixture of symptoms may be evident when depressed patients present for treatment, or they may emerge during ongoing treatment. In some patients, treatment with antidepressant medication might precipitate the emergence of mixed states. It would therefore be useful to systematically inquire into the presence of manic/hypomanic symptoms in depressed patients. We can anticipate that increased attention will likely be given to mixed depression because of changes in the DSM–5. In the present article, I review instruments that have been utilized to assess the presence and severity of manic symptoms and therefore could be potentially used to identify the DSM–5 mixed-features specifier in depressed patients and to evaluate the course and outcome of treatment. In choosing which measure to use, clinicians and researchers should consider whether the measure assesses both depression and mania/hypomania, assesses all or only some of the DSM–5 criteria for the mixed-features specifier, or assesses manic/hypomanic symptoms that are not part of the DSM–5 definition. Feasibility, more so than reliability and validity, will likely determine whether these measures are incorporated into routine clinical practice.

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Rethinking the spectrum of mood disorders: implications for diagnosis and management – Proceedings of a symposium presented at the 30th Annual European College of Neuropsychopharmacology Congress, 4 September 2017, Paris, France

Therapeutic Advances in Psychopharmacology ◽

10.1177/2045125318762911 ◽

2018 ◽

Vol 8 (1_suppl) ◽

pp. 1-16 ◽

Cited By ~ 4

Author(s):

Roger S. McIntyre ◽

Allan H. Young ◽

Peter M. Haddad

Keyword(s):

Controlled Trial ◽

Treatment Options ◽

Current Evidence ◽

Simultaneous Occurrence ◽

Affective States ◽

Mixed States ◽

Course Of Illness ◽

Dsm 5 ◽

Opposite Pole ◽

Mixed Features

The simultaneous occurrence of manic and depressive features has been recognized since classical times, but the term ‘mixed state’ was first used by Kraepelin at the end of the 19th century. From the 1980s, until the advent of the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), psychiatric disorders were classified using a categorical approach. However, it was recognized that such an approach was too rigid to encompass the range of symptomatology encountered in clinical practice. Therefore, a dimensional approach was adopted in DSM-5, in which affective states are considered to be distributed across a continuum ranging from pure mania to pure depression. In addition, the copresence of symptoms of the opposite pole are captured using a ‘with mixed features’ specifier, applied when three or more nonoverlapping subthreshold symptoms of the opposite pole are present. Mixed features are common in patients with mood episodes, complicating the course of illness, reducing treatment response and worsening outcomes. However, research in this area is scarce and treatment options are limited. Current evidence indicates that antidepressants should be avoided for the treatment of bipolar mixed states. Evidence for bipolar mixed states supports the use of several second-generation antipsychotics, valproate and electroconvulsive therapy. One randomized controlled trial has demonstrated the efficacy of lurasidone, compared with placebo, in patients with major depressive disorder with mixed features, and there is limited evidence supporting the use of ziprasidone in such patients. Further research is required to determine whether other antipsychotic agents, or additional therapeutic approaches, might also be effective in this setting.

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Dysphoric mania, mixed states, and mania with mixed features specifier: are we mixing things up?

CNS Spectrums ◽

10.1017/s1092852916000717 ◽

2016 ◽

Vol 22 (2) ◽

pp. 170-176 ◽

Cited By ~ 2

Author(s):

Susan L. McElroy ◽

Paul E. Keck

Keyword(s):

Depressive Symptoms ◽

Mixed State ◽

Mixed States ◽

Mixed Features

Various terms have been used to describe mania when it is accompanied by depressive symptoms. In this article, we attempt to define and discuss 3 of these terms: dysphoric mania, mixed state, and mania with mixed features specifier. We conclude that whatever term is used, it is important to be aware that mania is more often unpleasant than pleasant, and that the unpleasantness is not limited to depression.

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