Agitated “unipolar” depression re-conceptualized as a depressive mixed state: implications for the antidepressant-suicide controversy

• Published in: Journal of affective disorders 2005-04, Vol.85 (3), p.245-258
• Main Authors: Akiskal, Hagop S., Benazzi, Franco, Perugi, Giulio, Rihmer, Zoltán
• Format: Article
• Language: English
• Subjects: Adult; Agitated depression; Ambulatory Care; Antidepressants; Antidepressive Agents - adverse effects; Antidepressive Agents - therapeutic use; Arousal; Biological and medical sciences; Bipolar Disorder - drug therapy; Bipolar Disorder - epidemiology; Bipolar II; Comorbidity; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - epidemiology; Diagnosis, Differential; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Logistic Models; Major depressive disorder; Male; Medical sciences; Mixed state; Nosology. Terminology. Diagnostic criteria; Personality Assessment - statistics & numerical data; Private Practice; Psychology. Psychoanalysis. Psychiatry; Psychometrics - statistics & numerical data; Psychomotor Agitation - drug therapy; Psychomotor Agitation - epidemiology; Psychopathology. Psychiatry; Reproducibility of Results; Risk; Statistics as Topic; Suicide; Suicide - psychology; Suicide - statistics & numerical data; Techniques and methods
• ISSN: 0165-0327; 1573-2517
• DOI: 10.1016/j.jad.2004.12.004

The nosologic status of agitated depression is unresolved. Are they unipolar (UP) or bipolar (BP)? Are they mixed states? Even more controversial is the notion that antidepressants might play some role in the suicidality of such patients ( Akiskal and Mallya, 1987) [Akiskal, H.S., Mallya, G., 1987. Criteria for the “soft” bipolar spectrum: treatment implications. Psychopharmacol Bull. 23, 68–73]. After excluding all patients with history of hypomanic episodes occurring outside the frame of a major depressive episode (MDE), even those with a shorter duration of hypomanic symptoms than stipulated in DSM-IV, the remaining consecutive 254 unipolar major depressive disorder (MDD) private adult (>21 years old) outpatients were interviewed (off psychoactive drugs for 2 weeks) with the Structured Clinical Interview for DSM-IV (SCID-CV), the Hypomania Interview Guide (HIGH-C), and the Family History Screen. Intra-MDE hypomanic symptoms were systematically assessed, with ≥3 such symptoms required for a diagnosis of depressive mixed state (DMX). Agitated depression was defined as an MDE with HIGH-C psychomotor agitation score ≥2. Logistic regression was used to study associations and control for confounding variables. In this strictly defined unipolar sample, agitated depression was present in 19.7%. Compared with its non-agitated counterpart, it had significantly fewer recurrences, less chronicity, higher rate of family history for bipolar disorder, and DMX; and, among the intra-depressive non-euphoric hypomanic symptoms (in decreasing order of frequency), distractibility, racing/crowded thoughts, irritable mood, talkativeness, and risky behavior. The most striking finding was the robust association between agitated depression and DMX (OR=36.9). Furthermore, patients with psychomotor agitation had significantly higher rate of weight loss and suicidal ideation. Of DMX symptoms, we found an association between suicidal ideation, psychomotor activation, and racing thoughts. Agitated depression was tested by forward stepwise logistic regression versus all variables significantly different in the pairwise comparisons, yielding DMX, talkativeness, and suicidal ideation as the independent significant positive predictors. No suicidal ideation scale was used. Agitated depression emerges as a distinct affective syndrome with weight loss, pressure of speech, racing thoughts and suicidal ideation. Psychomotor activation and racing thoughts during MDD independently predicted sui