Elsevier

Psychiatry Research

Volume 141, Issue 1, 30 January 2006, Pages 81-88
Psychiatry Research

Psychometric delineation of the most discriminant symptoms of depressive mixed states

https://doi.org/10.1016/j.psychres.2005.07.024Get rights and content

Abstract

Recent studies have shown that depressive mixed state (DMX), i.e., a major depressive episode (MDE) plus 3 or more intra-MDE hypomanic symptoms, is prevalent in bipolar-II disorder (BP-II) and not uncommon in major depressive disorder (MDD) outpatients. The main aim of the present analyses was to find the most discriminant intra-MDE hypomanic signs and symptoms predicting depressive mixed state. Consecutive 602 MDE outpatients (348 BP-II, 254 MDD) were interviewed with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen, by a senior psychiatrist in a private practice. Sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of individual intra-MDE hypomanic signs and symptoms for depressive mixed state showed that irritability had a balanced combination of SE, SP, PPV, NPV, and that psychomotor agitation and greater talkativeness had the highest SP and PPV, but lower SE. By virtue of reducing misdiagnoses, SP and PPV are the most important of these tests for clinicians. On the basis of SP and PPV, our results suggest that, though not the most prevalent, irritability (50.3%) and psychomotor agitation (27.7%) represent the most discriminant features of depressive mixed state. Presence of these features should serve as a “red flag” to help clinicians probe more skillfully for the diagnosis of depressive mixed state. Beyond its diagnostic significance, the foregoing signs and symptoms are among the clinical features the FDA lists as presaging “suicidality” on antidepressant monotherapy.

Introduction

Rate of DSM-IV-TR bipolar-II disorder (BP-II) versus major depressive disorder (MDD) (American Psychiatric Association, 2000) has recently been found to be around 50% in clinical settings (Akiskal and Mallya, 1987, Hantouche et al., 1998, Akiskal and Pinto, 1999, Manning et al., 1999, Angst et al., 2003, Benazzi, 2005, Rybakowski et al., 2005, Smith et al., 2005, Akiskal and Benazzi, 2005). Lifetime community prevalence of BP-II, once believed to be 0.5% (Weissman et al., 1988, Kessler et al., 1994, American Psychiatric Association, 2000), has recently been reported to be between 5% and 11% (Angst et al., 2003, Judd and Akiskal, 2003, Angst and Zihmer, 2005). The new rates reflect shortening of hypomania threshold to ≥ 2 days, and improved assessment methods to detect BP-II.

Unlike BP-II, where hypomanic episodes occur outside the time frame of an MDE, in depressive mixed states (DMX) hypomanic features intrude into an MDE, i.e. they occur during the depressive episode. DMX continues to be underdiagnosed, as this category is not present in the current diagnostic systems, ICD-10 and DSM-IV-TR (World Health Organization, 1992, American Psychiatric Association, 2000).

DMX was systematically described by Kraepelin (1921) (1913, English translation by Barclay, 1921) as inpatient depressions with concurrent hypomanic/manic symptoms. Hecker, studying outpatients (1898, English translation by Koukopoulos, 2003), reported that DMX was frequent in the depressed phase of “cyclothymia” (corresponding to BP-II), and that it was a marker of this disorder. A recent series of studies has found that DMX is common in BP-II and not uncommon in MDD (Akiskal and Pinto, 1999, Akiskal and Benazzi, 2003, Sato et al., 2003, Bottlender et al., 2004, Ducrey et al., 2004, Mantere et al., 2004, Benazzi, 2005, Serretti and Olgiati, 2005, Biondi et al., 2005, Bauer et al., 2005). The most frequent DSM-IV-TR hypomanic symptoms of DMX were irritability, distractibility, racing/crowded thoughts, psychomotor agitation, and greater talkativeness. DMX, defined as a major depressive episode (MDE) plus 3 or more intra-MDE hypomanic symptoms (DMX3), was shown to have clinical, family history, and psychometric diagnostic validity and utility, stronger than that of several dimensional and categorical alternative definitions of DMX (Akiskal and Benazzi, 2003, Benazzi and Akiskal, 2003a, Benazzi, 2005). DMX3 was more common in BP-II versus MDD (around 60% versus 30%). Factor analysis of intra-MDE hypomanic symptoms found a “motor activation” factor including psychomotor agitation and greater talkativeness (corresponding to Kraepelin's “excited depression” mixed state), and a “mental activation” factor including racing/crowded thoughts (corresponding to Kraepelin's “depression with flight of ideas” mixed state). Interestingly, these factors corresponded to those found in hypomania outside the MDE, supporting the hypomanic nature of these intra-MDE symptoms (Benazzi, 2004).

DMX3 was significantly associated with variables distinguishing bipolar from unipolar MDD (younger age at onset, higher recurrences, atypical depressions, and bipolar family history). “Unipolar” DMX3 (MDE with hypomanic features solely intra-episodically) was not significantly different from BP-II MDE on age at onset, atypical features, and bipolar family history, supporting its bipolar nature (a finding replicated by Sato et al. (2003) and by Biondi et al. (2005). Factor analysis of concurrent MDE and intra-MDE hypomanic symptoms found a “hypomanic” factor, a finding replicated by Sato et al. (2005) and Biondi et al. (2005). Multivariate analysis of MDE symptoms was also used to validate the category of atypical depression (Kendler et al., 1996).

The aim of the present analyses was to find the most discriminant hypomanic signs and symptoms of DMX3, which could be useful to point to this diagnosis in clinical practice.

Section snippets

Methods

Greater details on study methods can be found in previous reports (Akiskal and Benazzi, 2003, Akiskal and Benazzi, 2005, Benazzi and Akiskal, 2003b, Benazzi, 2003a). We provide here details necessary to understand the methodology of the present analyses.

Results

Sample features are presented in Table 1. BP-II had significantly younger age at onset, higher recurrences, atypical depressions, bipolar family history, DMX3, and individual intra-MDE hypomanic signs and symptoms (mainly distractibility, racing/crowded thoughts, irritability, psychomotor agitation, greater talkativeness). DMX3 was present in 62.3% of BP-II (95% CI 57.2% to 67.3%), and in 33.4% of MDD (95% CI 27.9% to 39.5%).

Table 2 shows the SE, SP, PPV, and NPV of individual intra-MDE

Main findings

In this much larger sample than in previous work from this center (Akiskal and Benazzi, 2003), DMX3 was again shown to be more common in BP-II versus MDD, and not uncommon in MDD. The same is true for the high rate of BP-II versus MDD (Akiskal et al., 2005).

With respect to the main objective of the present analyses, among the hypomanic symptoms of DMX3, irritability had the best combination of SE, SP, PPV and NPV for DMX3, and psychomotor agitation (and increased talkativeness) had the highest

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