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

Abstract

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.

Mixed states in bipolar and major depressive disorders: systematic review and quality appraisal of guidelines

“…A 'with mixed features' specifier (MFS) has been incorporated in the DSM-5 (7); this specifier may be applied to manic episodes in BDI, hypomanic episodes in BDI and BDII, and to major depressive episodes (MDE) experienced in BDI, BDII, BD not otherwise specified (BD-NOS) as well as in MDD (8). As a consequence, hypomanic symptoms could currently denote both MDD or BD and many individuals along the mood disorders spectrum that were previously 'orphans' of a diagnosis could be classified according to a 'mixedcategorical-dimensional' approach (8,9).…”

“…In fact, it has 100% specificity but only 5.1% sensitivity (5). Specificity at the expense of sensitivity suggests that up to 95% of patients presenting with the MFS according to the DSM-5 are wrongly diagnosed as having 'pure' affective episodes (i.e., without mixed features) (5,9). The DSM-5 workgroup excluded overlapping symptoms such as distractibility, irritability, and psychomotor agitation, arguing that they may lack the ability to differentiate between manic and depressive states (13), in the choice of a more 'specific' approach at the expenses of the 'sensitivity' of the classification (8,9).…”

Mixed Features in Depression

“…23 As a consequence, the choice of a more "specific" approach has been made at the expenses of the "sensitivity" of the classification. 25,26 In fact, DSM-5 MFS presented a 100% specificity but only 5.1% sensitivity, 27 as also highlighted in the recent cluster analysis of the BRIDGE-II-Mix group. 19 This means that up to 95% of patients presenting with mixed features according to the DSM-5 are wrongly diagnosed as having "pure" affective episodes with huge clinical and therapeutic implications.…”

“…19 This means that up to 95% of patients presenting with mixed features according to the DSM-5 are wrongly diagnosed as having "pure" affective episodes with huge clinical and therapeutic implications. 25,27 The speculative wish to avoid "overlapping" symptoms, such as psychomotor agitation, irritability, and mood lability, the most common features of mixed depression across the literature, is very restrictive, allowing the diagnosis of mixed depression only in 1 out of 4 cases. 18 Certainly, these symptoms may be nonspecific but to exclude them entirely may be not justified, in the absence of any evidence that the remaining criteria are sufficiently sensitive.…”

The Diagnosis and Management of Bipolar I and II Disorders: Clinical Practice Update

“…Although major depression with mixed features is not pathognomonic of bipolar disorders, it may alert the clinician to the possibility of a bipolar spectrum disorder, and the need to carefully assess the patient for a history of manic or hypomanic episodes. 39…”