Antidepressant-associated chronic irritable dysphoria (ACID) in STEP-BD patients

Mood Disorders Research Program, Department of Psychiatry and Behavioral Sciences, University of Louisville School of Medicine, 501 East Broadway, MedCenter One, Suite 340, Louisville, Kentucky 40202, United States.
Journal of Affective Disorders (Impact Factor: 3.71). 07/2008; 111(2-3):372-7. DOI: 10.1016/j.jad.2008.03.025
Source: PubMed

ABSTRACT It has been proposed that antidepressants can induce a chronic, dysphoric, irritable state in bipolar patients (called ACID for antidepressant-associated chronic irritable dysphoria). This phenomenon has only been described in case series format, and has not been prospectively validated.
Prospective data from the first 1500 patients (62.7% with bipolar I, 30.1% with bipolar II, and 7.2% with NOS) treated in the STEP-BD database were examined and those who were euthymic for at least one month at study entry, subsequently developed a depressive episode, and were then followed for one year were identified. Outcome of those who received an antidepressant for this depressive episode (n=27) was compared to those who did not (n=56), with particular attention given to the presence of the proposed symptom triad of ACID, namely dysphoria, irritability, and middle insomnia.
Patients treated with antidepressants were ten times more likely to develop ACID than those who were not (Hazard ratio=9.95, CI=1.103-89.717, P=0.04). However, the hazard ratio dropped to 1.05 (P=0.99) when corrected for significant covariates, notably past antidepressant-related manic switch and sex.
This study does not support the existence of ACID as an independent phenomenon. Rather, ACID appears to be part of a broader spectrum of antidepressant treatment-emergent affective switches.

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Available from: Michael E Thase, Aug 14, 2015
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    • "For example, elements of activation—anxiety, inner tension, psychomotor hyperactivity—during a depressive episode (i.e., a mixed depressive state) may hamper treatment response and lead to treatment resistance, thus negatively affecting outcome (Goldberg et al., 2007; Rihmer and Gonda, 2011; Rybakowski, 2012). Furthermore, antidepressant use in such states may even worsen depression (Goldberg et al., 2007; El-Mallakh et al., 2008; Koukopoulos et al., 2007), or increase suicidality (Pacchiarotti et al., 2011; Valentí et al., 2011; Balá zs et al., 2006; Goldberg et al., 2009; Algorta et al., 2011). Similarly, the presence of depressive features during a manic episode may lead to poor responses to lithium (Swann et al., 1997), or may increase the risk of antipsychotic-induced post-manic depression (Zarate et al., 2001; Vieta, 2005b). "
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    ABSTRACT: OBJECTIVE: The nature of mixed mood episodes is still a matter of controversy amongst experts. Currently, the approach to this syndrome is mainly categorical and very restrictive. The factor-structure of bipolar mood episodes has not been studied yet. We performed a dimensional analysis of the structure of bipolar episodes aimed at identifying a factor deconstructing mixed episodes; furthermore, we analyzed correlations of factors emerging from the factorial analysis of the Brief Psychiatric Rating Scale (BPRS) with Temperament Evaluation of Memphis-Pisa-Paris-San Diego (TEMPS-A) and predominant polarity. METHOD: 187 consecutive bipolar I inpatients hospitalized for DSM-IV-TR acute mood episodes (depressive, manic or mixed) underwent a standardized assessment, including the 24-item Brief Psychiatric Rating Scale (BPRS 4.0), the 21-item Hamilton Depression Rating Scale (HDRS-21), the Young Mania Rating Scale (YMRS) and the TEMPS-A. Principal factor analysis was performed on BPRS-24 items. RESULTS: This analysis revealed five factors corresponding to "psychosis", "euphoric mania", "mixity", "dysphoria" and "inhibited depression", capturing 71.89% of the rotated variance. The mixity factor was characterized by higher rates of suicidal ideation, more mixed episodes, higher frequencies of antidepressant (AD) use, depressive predominant polarity and anxious temperament. DISCUSSION: The factor-structure of the BPRS in inpatients with bipolar I disorder with an acute episode of any type is pentafactorial; one factor identified is the mixity factor, which is independent from other factors and characterized by anxiety and motor hyperactivity and by the absence of motor retardation. Our results should prompt reconsideration of proposals for DSM-5 diagnostic criteria for the mixed features specifier. Limitations of the study include the relative small sample, the absence of drug-naïve patients and the use of rating scales no specific for mixed states.
    Journal of Affective Disorders 02/2013; 149(1-3). DOI:10.1016/j.jad.2013.01.003 · 3.71 Impact Factor
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    • "Recently, data from the first 1500 subjects treated in the STEP-BD (Goldberg et al., 2007) study confirmed patients taking antidepressant medications being 10 times more likely to develop ACID than those not taking antidepressant drugs (HR; 9.95, 95% CI = 1.10–89.72) (El-Mallakh et al., 2008). El-Mallakh et al. (2011) have hypothesized that since multiple AD exposures have been related to the incidence of this symptoms, the ACID syndrome may be better explained as a part of a broader spectrum of antidepressant treatment emergent affective switches. "
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