Current irritability associated with hastened depressive recurrence and delayed depressive recovery in bipolar disorder
Yuen et al. Int J Bipolar Disord
Current irritability associated with hastened depressive recurrence and delayed depressive recovery in bipolar disorder
Laura D. Yuen 0
Saloni Shah 0
Dennis Do 0
Shefali Miller 0
Po W. Wang 0
Farnaz Hooshmand 0
Terence A. Ketter 0
0 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine , 401 Quarry Road, Stanford, CA 94305-5723 , USA
Background: Current irritability is associated with greater retrospective and current bipolar disorder (BD) illness severity; less is known about prospective longitudinal implications of current irritability. We examined relationships between current irritability and depressive recurrence and recovery in BD. Methods: Outpatients referred to the Stanford BD Clinic during 2000-2011 were assessed with the Systematic Treatment Enhancement Program for BD (STEP-BD) Affective Disorders Evaluation at baseline, and with the Clinical Monitoring Form during follow-up during up to 2 years of naturalistic treatment. Prevalence and clinical correlates of any current irritability in depressed and recovered (euthymic ≥8 weeks) BD patients were assessed. Kaplan-Meier analyses (Log-Rank tests) assessed relationships between current irritability and longitudinal depressive severity, with Cox Proportional Hazard analyses assessing potential mediators. Results: Recovered BD outpatients with vs. without current irritability had significantly higher rates of 13/19 (68.4 %) other baseline unfavorable illness characteristics/current mood symptoms and hastened depressive recurrence (Log-Rank p = 0.020), driven by lifetime history of anxiety disorder and prior year rapid cycling, and attenuated by history of psychosis. Depressed BD outpatients with vs. without current irritability had significantly higher rates of 7/19 (36.8 %) other unfavorable illness characteristics/current mood symptoms and delayed depressive recovery (Log-Rank p = 0.034), NOT mediated by any assessed parameter. Limitations: Limited generalizability beyond our predominately white, female, educated, insured American BD specialty clinic sample. Conclusions: Current irritability was associated with hastened depressive recurrence and delayed depressive recovery in BD. Treatment studies targeting irritability may yield strategies to mitigate increased longitudinal depressive burden.
Irritability; Bipolar disorder; Bipolar depression; Recurrence; Recovery; Longitudinal
Background
Bipolar disorder (BD) is a chronic illness associated with
high rates of recurrence and impaired functionality
(Ketter 2010; Solomon et al. 1995)
. Up to one-half of BD
patients have mood episode recurrence within 1 year of
recovery (Solomon et al. 1995), commonly with severe
consequences, including higher rates of non-response,
social morbidity, and impaired functioning
(Berk et al.
2011; Lish et al. 1994; Rosa et al. 2012)
. Although mood
elevation episodes define BD, bipolar depression is more
pervasive
(Judd et al. 2002, 2003)
, and has been
associated with functional impairment
(Goldberg and Harrow
2011; Gyulai et al. 2008)
and suicidality
(Dilsaver et al.
1997; Suttajit et al. 2013)
, with the latter present in almost
four fifths of depressed patients (Dilsaver et al. 1997).
Notably, even subsyndromal depressive symptoms can
undermine function
(Altshuler et al. 2006; Goldberg and
Harrow 2011)
. In addition, bipolar depression negatively
impacts BD illness course; with illness severity worsening
with recurrent episodes, independent of treatment (Maj
et al. 1992).
Previous studies have demonstrated current irritability
to be both highly prevalent and indicative of worse illness
severity in acute bipolar depression. Irritability is a core
symptom of depression in children and adolescents (but
not in adults)
(American Psychiatric Association 2013)
,
and is present in up to three quarters of depressed BD
patients
(Winokur et al. 1969)
. Current irritability has
been associated with multiple unfavorable illness
characteristics in bipolar depression, including earlier onset age
and higher rates of suicidal ideation, axis I comorbidity,
atypical depressive features, and depressive mixed states
(
Balázs et al. 2006
;
Benazzi and Akiskal 2005
;
Benazzi
et al. 2004
). Additionally, current irritability appears
closely related to current anxiety and lifetime history of
anxiety disorder in BD
(Yuen et al. 2016)
.
The negative longitudinal impact of current mood
symptoms is well established
(Maj et al. 2003; Perlis
et al. 2006)
. Residual affective symptoms (which may be
related to irritability) in recovered patients predicted
hastened episode recurrence (Perlis et al. 2006). Also,
among depressed bipolar I disorder patients, those with
agitation (over half of whom had irritability) compared
to those without agitation (only 15 % of whom had
irritability) had significantly delayed depressive recovery
(Maj
et al. 2003)
. However, the association between cur (...truncated)