Current irritability associated with hastened depressive recurrence and delayed depressive recovery in bipolar disorder

International Journal of Bipolar Disorders, Jul 2016

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.

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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)


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Laura D. Yuen, Saloni Shah, Dennis Do, Shefali Miller, Po W. Wang, Farnaz Hooshmand, Terence A. Ketter. Current irritability associated with hastened depressive recurrence and delayed depressive recovery in bipolar disorder, International Journal of Bipolar Disorders, 2016, pp. 15, Volume 4, Issue 1, DOI: 10.1186/s40345-016-0056-2