The importance of irritability as a symptom of major depressive disorder: results from the National Comorbidity Survey Replication

Abstract

Irritability is a diagnostic symptom of child-adolescent but not adult major depressive disorder (MDD) in both the DSM-IV and ICD-10 systems. We explore the importance of irritability for sub-typing adult DSM-IV MDD in the National Comorbidity Survey Replication (NCS-R), a national US adult household survey. The WHO Composite International Diagnostic Interview (CIDI) was used to assess prevalence of many DSM-IV disorders in the lifetime and in the year before interview (12-month prevalence). MDD was assessed conventionally (i.e., requiring either persistent sadness or loss of interest), but with irritability included as one of the Criterion A symptoms. We also considered the possibility that irritability might be a diagnostic symptom of adult MDD (i.e., detect cases who had neither sad mood nor loss of interest). Twelve-month MDD symptom severity was assessed with the Quick Inventory of Depressive Symptomatology and role impairment with the Sheehan Disability Scale. After excluding bipolar spectrum disorders, irritability during depressive episodes was reported by roughly half of respondents with lifetime DSM-IV MDD. Irritability in the absence of either sad mood or loss of interest, in comparison, was rare. Irritability in MDD was associated with early age-of-onset, lifetime persistence, comorbidity with anxiety and impulse-control disorders, fatigue and self-reproach during episodes, and disability. Irritability was especially common in MDD among respondents in the age range 18–44 and students. Further investigation is warranted of distinct family aggregation, risk factors, and treatment response. Consideration should also be given to including irritability as a non-diagnostic symptom of adult MDD in DSM-V and ICD-11.

Lurasidone for major depressive disorder with mixed features and irritability: a post-hoc analysis

“…6,11,13,14 It is not clear why the magnitude of the lurasidone treatment effect observed in the current study was larger among patients with irritable features. Larger MADRS effect sizes appeared to be attributable, in part, to reduced improvement on placebo among patients with (vs. without) irritability (MADRS change = -9.5 vs. -13.8, respectively), while improvement on lurasidone was somewhat higher among patients with (vs. without) irritability (MADRS change = -22.6 vs. -19.9, respectively).…”

“…8,17,20,21,34,35 The presence of irritability complicates the clinical picture of MDD with mixed features and may further increase treatment resistance to standard antidepressants. 6,[11][12][13][14][15] In the first prospective placebo-controlled trial in MDD with subthreshold hypomania (mixed features), lurasidone demonstrated significant efficacy in improving the symptoms of depression and subthreshold hypomanic symptoms. 29 The post-hoc analysis reported here now extends these results by finding lurasidone to have significant efficacy in MDD with mixed features patients who also presented with irritability (defined by the attainment of threshold scores on two irritability-related YMRS items).…”

“…[1][2][3][4][5][6][7] As noted in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-5), 8 many individuals with a diagnosis of MDD report or exhibit irritability.…”

“…2,3,[5][6][7]9 Some 3,10 but not all 6,7 studies of MDD have identified irritability as a risk factor for the development of a bipolar or bipolar mixed diagnosis.…”

“…The presence of irritable features-as part of a spectrum that may include anger, hostility, agitation, and aggressive behavior-has been found to be associated with a significantly delayed or reduced response to standard antidepressants in both unipolar MDD 6,[11][12][13] and bipolar depression. 14,15 MDD with mixed features is a common and often severe subtype of major depression that is recognized by the mixed-features specifier in DSM-5.…”