A pragmatic approach to the diagnosis and treatment of mixed features in adults with mood disorders

CNS Spectrums ◽  
2016 ◽  
Vol 21 (S1) ◽  
pp. 25-33 ◽  
Author(s):  
Roger S. McIntyre ◽  
Yena Lee ◽  
Rodrigo B. Mansur
Keyword(s):  
Depressive Episode ◽  
Ecological Validity ◽  
Age At Onset ◽  
Mood Stabilizers ◽  
Mixed States ◽  
Major Depressive ◽  
Mixed Features ◽  
Episode Frequency ◽  
Nosological Entity ◽  
Hypomanic Episode

Mixed features specifier (MFS) is a new nosological entity defined and operationalized in the Diagnostic and Statistical Manual of Mental Disorders (DSM), 5th Edition. The impetus to introduce the MFS and supplant mixed states was protean, including the lack of ecological validity, high rates of misdiagnosis, and guideline discordant treatment for mixed states. Mixed features specifier identifies a phenotype in psychiatry with greater illness burden, as evidenced by earlier age at onset, higher episode frequency and chronicity, psychiatric and medical comorbidity, suicidality, and suboptimal response to conventional antidepressants. Mixed features in psychiatry have historical, conceptual, and nosological relevance; MFS according to DSM-5, is inherently neo-Kraepelinian insofar as individuals with either Major Depressive Disorder (MDD) or Bipolar Disorder (BD) may be affected by MFS. Clinicians are encouraged to screen all patients presenting with a major depressive episode (or hypomanic episode) for MFS. Although “overlapping symptoms” were excluded from the diagnostic criteria (eg, agitation, anxiety, irritability, insomnia), clinicians are encouraged to probe for these nonspecific symptoms as a possible proxy of co-existing MFS. In addition to conventional antidepressants, second generation antipsychotics and/or conventional mood stabilizers (eg, lithium) may be considered as first-line therapies for individuals with a depressive episode as part of MDD or BD with mixed features.

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.

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

CNS Spectrums ◽  
2017 ◽  
Vol 22 (2) ◽  
pp. 196-202 ◽  
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.

Mixed Features in Patients With a Major Depressive Episode

2015 ◽  
Vol 76 (03) ◽  
pp. e351-e358 ◽  
Author(s):  
Giulio Perugi ◽  
Jules Angst ◽  
Jean-Michel Azorin ◽  
Charles L. Bowden ◽  
Sergey Mosolov ◽  
...  
Keyword(s):  
Depressive Episode ◽  
Major Depressive Episode ◽  
Major Depressive ◽  
Mixed Features

scholarly journals Antidepressant-Resistant Depression and Antidepressant-Associated Suicidal Behaviour: The Role of Underlying Bipolarity

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Zoltan Rihmer ◽  
Xenia Gonda
Keyword(s):  
Depressive Episode ◽  
Suicidal Behaviour ◽  
Major Depressive Episode ◽  
Age At Onset ◽  
Early Age ◽  
Bipolar Spectrum ◽  
Clinical Markers ◽  
Major Depressive ◽  
Resistant Depression

The complex relationship between the use of antidepressants and suicidal behaviour is one of the hottest topics of our contemporary psychiatry. Based on the literature, this paper summarizes the author's view on antidepressant-resistant depression and antidepressant-associated suicidal behaviour. Antidepressant-resistance, antidepressant-induced worsening of depression, antidepressant-associated (hypo)manic switches, mixed depressive episode, and antidepressant-associated suicidality among depressed patients are relatively most frequent in bipolar/bipolar spectrum depression and in children and adolescents. As early age at onset of major depressive episode and mixed depression are powerful clinical markers of bipolarity and the manic component of bipolar disorder (and possible its biological background) shows a declining tendency with age antidepressant-resistance/worsening, antidepressant-induced (hypo)manic switches and “suicide-inducing” potential of antidepressants seem to be related to the underlying bipolarity.

Pharmacologic Mood Destabilization: Case Vignettes

CNS Spectrums ◽  
2009 ◽  
Vol 14 (S11) ◽  
pp. 9-11
Author(s):  
Alan C. Swann
Keyword(s):  
Bipolar Disorder ◽  
Depressive Episode ◽  
Depressive Illness ◽  
First Episode ◽  
Major Depressive ◽  
Mood Instability ◽  
Case Vignettes ◽  
Disorder Treatment ◽  
Hypomanic Episode

Bipolar disorder is an illness characterized by inherent mood instability that produces a predisposition to depressive, hypomanic, or manic episodes. This predisposition to affective episodes, rather than the episodes themselves (which can have many causes), is arguably the hallmark of bipolar disorder.Most episodes of bipolar disorder, including the first episode, are depressive. This exposes an inherent flaw in our nosological system, which requires a manic or hypomanic episode for diagnosis of bipolar disorder. Treatment of a depressive episode in undiagnosed bipolar disorder can entail the use of medications that were developed to treat a different disorder (major depressive illness) and that may have mood-destabilizing or activating properties.

Proposed DSM-5 mixed features are associated with greater likelihood of remission in out-patients with major depressive disorder

2012 ◽  
Vol 44 (7) ◽  
pp. 1361-1367 ◽  
Author(s):  
R. H. Perlis ◽  
C. Cusin ◽  
M. Fava
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Depressive Episode ◽  
Major Depressive Episode ◽  
Antidepressant Treatment ◽  
Adverse Outcomes ◽  
Self Report ◽  
Major Depressive ◽  
Dsm 5 ◽  
Mixed Features

BackgroundDraft DSM-5 criteria for a mixed major depressive episode have been proposed, but their predictive validity has not yet been established. We hypothesized that such symptoms would be associated with poorer antidepressant treatment outcomes.MethodWe examined outcomes among individuals with major depressive disorder participating in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, an effectiveness study conducted at primary and specialty care centers in the USA. Mixed features were derived from the six self-report items of the mania subscale of the Psychiatric Diagnosis Screening Questionnaire. Primary analyses examined the association between the presence of at least two of these in the 6 months before study entry, and remission across up to four sequential treatment trials, as well as adverse outcomes.ResultsOf the 2397 subjects with a major depressive episode of at least 6 months' duration, 449 (18.7%) reported at least two mixed symptoms. The presence of such symptoms was associated with a greater likelihood of remission across up to four sequential treatments, which persisted after adjustment for potential confounding clinical and demographic variables (adjusted hazard ratio 1.16, 95% confidence interval 1.03–1.28). Two individual items, expansive mood and cheerfulness, were strongly associated with a greater likelihood of remission.ConclusionsProposed DSM-5 mixed state features were associated with a greater rather than a lesser likelihood of remission. While unexpected, this result suggests the potential utility of further investigation of depressive mixed states in major depression.

The need to consider mood disorders, and especially chronic mania, in cases of Diogenes syndrome (squalor syndrome)

2010 ◽  
Vol 23 (3) ◽  
pp. 505-507 ◽  
Author(s):  
G. Fond ◽  
F. Jollant ◽  
M. Abbar
Keyword(s):  
Mood Disorders ◽  
Female Patient ◽  
Depressive Episode ◽  
Social Withdrawal ◽  
Manic Episode ◽  
Personal History ◽  
Mood Stabilizers ◽  
Diogenes Syndrome ◽  
Hypomanic Episode

ABSTRACTWe report the case of a 69 year-old female patient who was hospitalized for Diogenes syndrome, defined by marked self-neglect, social withdrawal and excessive hoarding, leading to squalor. Somatic causes were eliminated. Her personal history showed an eight-year depressive episode followed by a 20-year hypomanic episode without remission, followed by a persistent manic episode associated with Diogenes syndrome for four years. The Diogenes syndrome was successfully treated with mood stabilizers. Mood disorders – in particular chronic mania (i.e. a manic episode lasting more than two years) – should be considered in cases of Diogenes syndrome and in current classifications.

Treatment resistance in bipolar disorder

2011 ◽  
Vol 26 (S2) ◽  
pp. 2025-2025
Author(s):  
Z. Rihmer
Keyword(s):  
Bipolar Disorder ◽  
Major Depression ◽  
Depressive Episode ◽  
Depressive Disorders ◽  
Major Depressive Episode ◽  
Treatment Resistance ◽  
Mood Stabilizers ◽  
Common Source ◽  
Major Depressive ◽  
Unipolar Major Depression

Antidepressant-resistant major depression (AD-RD) is a great challenge for the treating clinician. The most widely accepted definition of AD-RD refers that the depressed patient does not show a clinically significant response after at least two adequate trials of different classes of antidepressants. In spite of the fact that there are several causes of AD-RD in general, there is increasing evidence that one of the most common sources of it is the unrecognized bipolar nature of the “unipolar” major depressive episode, when the patients receive antidepressant monotherapy - unprotected by mood stabilizers/atypical antipsychotics. While it is well documented that the optimal clinical response to antidepressants is much rare in bipolar I and II than in unipolar major depression, only the most recent clinical studies have focused on the boundaries between treatment-resistant unipolar major depressive disorder and bipolar disorder. The most widely noted conclusion of the prior studies on AD-RD is that if noncompliance, hypothyreosis, use of “depressiogenic” drugs and pharmacokinetic causes etc, can be excluded, antidepressant-resistance reflects the heterogeneity of depressive disorders and different subgroups of depressed patients respond (or do not respond) to different drugs. However, current psychopathological research on the complex relationship between unipolar depression and bipolar disorders show that the most common source of antidepressant-resistance in DSM-IV diagnosed unipolar major depression is the result of the subthreshold or unrecognized bipolar nature of the depressive episode and antidepressant-induced (hypo)manic switches, antidepressant-resistance and “suicide-inducing” potential of antidepressants seem to be related to the underlying bipolarity of the major depressive episode.

scholarly journals Guidelines for the recognition and management of mixed depression

CNS Spectrums ◽  
2017 ◽  
Vol 22 (2) ◽  
pp. 203-219 ◽  
Author(s):  
Stephen M. Stahl ◽  
Debbi A. Morrissette ◽  
Gianni Faedda ◽  
Maurizio Fava ◽  
Joseph F. Goldberg ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Threshold Level ◽  
Current Treatment ◽  
Mixed States ◽  
Manic Symptoms ◽  
Mixed Features ◽  
Nosological Entity ◽  
Dsm Iv ◽  
Definition Of ◽  
Threshold Criteria

A significant minority of people presenting with a major depressive episode (MDE) experience co-occurring subsyndromal hypo/manic symptoms. As this presentation may have important prognostic and treatment implications, the DSM–5 codified a new nosological entity, the “mixed features specifier,” referring to individuals meeting threshold criteria for an MDE and subthreshold symptoms of (hypo)mania or to individuals with syndromal mania and subthreshold depressive symptoms. The mixed features specifier adds to a growing list of monikers that have been put forward to describe phenotypes characterized by the admixture of depressive and hypomanic symptoms (e.g., mixed depression, depression with mixed features, or depressive mixed states [DMX]). Current treatment guidelines, regulatory approvals, as well the current evidentiary base provide insufficient decision support to practitioners who provide care to individuals presenting with an MDE with mixed features. In addition, all existing psychotropic agents evaluated in mixed patients have largely been confined to patient populations meeting the DSM–IV definition of “mixed states” wherein the co-occurrence of threshold-level mania and threshold-level MDE was required. Toward the aim of assisting clinicians providing care to adults with MDE and mixed features, we have assembled a panel of experts on mood disorders to develop these guidelines on the recognition and treatment of mixed depression, based on the few studies that have focused specifically on DMX as well as decades of cumulated clinical experience.

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