Transdiagnostic treatment of bipolar disorder and comorbid anxiety using the Unified Protocol for Emotional Disorders: A pilot feasibility and acceptability trial

Highlights

• Examines a transdiagnostic CBT approach to treating anxiety in bipolar disorder (UP).

• Treatment with the UP demonstrated feasibility and acceptability.

• The UP adjunctive to medication TAU resulted in greater reductions in anxiety.

• The UP adjunctive to TAU also resulted in greater reductions in depression.

• UP adjunctive to TAU was a viable approach to treating anxiety in bipolar disorder.

Abstract

Background

Comorbid anxiety in bipolar disorder (BD) is associated with greater illness severity, reduced treatment response, and greater impairment. Treating anxiety in the context of BD is crucial for improving illness course and outcomes. The current study examined the feasibility, acceptability and preliminary efficacy of the Unified Protocol (UP), a transdiagnostic cognitive behavioral therapy, as an adjunctive treatment to pharmacotherapy for BD and comorbid anxiety disorders.

Methods

Twenty-nine patients with BD and at least one comorbid anxiety disorder were randomized to pharmacotherapy treatment-as-usual (TAU) or TAU with 18 sessions of the UP (UP+TAU). All patients completed assessments every four weeks to track symptoms, functioning, emotion regulation and temperament. Linear mixed-model regressions were conducted to track symptom changes over time and to examine the relationship between emotion-related variables and treatment response.

Results

Satisfaction ratings were equivalent for both treatment groups. Patients in the UP+TAU group evidenced significantly greater reductions over time in anxiety and depression symptoms (Cohen's d's>0.80). Baseline levels of neuroticism, perceived affective control, and emotion regulation ability predicted magnitude of symptom change for the UP+TAU group only. Greater change in perceived control of emotions and emotion regulation skills predicted greater change in anxiety related symptoms.

Limitations

This was a pilot feasibility and acceptability trial; results should be interpreted with caution.

Conclusions

Treatment with the UP+TAU was rated high in patient satisfaction, and resulted in significantly greater improvement on indices of anxiety and depression relative to TAU. This suggests that the UP may be a feasible treatment approach for BD with comorbid anxiety.

Introduction

Bipolar disorders (BD), including bipolar I, bipolar II, cyclothymia, “other specified” and “unspecified” bipolar and related disorders, affect approximately 4% of the population in the U.S. (Kessler et al., 2005) and 2% of the population worldwide (Merikangas et al., 2011). BD is characterized by the occurrence of (hypo)manic episodes and depressive mood episodes. While the mean duration of discrete mood episodes is about 13 weeks (Solomon et al., 2010), the majority of patients also have persistent comorbid anxiety symptoms or anxiety disorders. Over 86% of patients with BD endorse a lifetime diagnosis of a comorbid anxiety disorder (Merikangas et al., 2007) with over a third of BD patients meeting diagnostic criteria for a current comorbid anxiety disorder that warrants treatment at any given time (Simon et al., 2004). The presence of comorbid anxiety has been identified as an independent marker of greater BD severity, and is associated with greater chronicity, reduced treatment response, and greater functional impairment (Deckersbach et al., 2014, Goldberg and Fawcett, 2012; Lee and Dunner, 2008; Otto et al., 2006). Thus, the reality of BD extends beyond traditionally emphasized discrete mood episodes and is often exacerbated by the presence of anxiety. This point is reinforced by the recent addition of an “anxious distress” specifier to BD in the revised Diagnostic and Statistical Manual, 5th Edition (DSM-5; APA, 2013). Anxiety in the context of BD therefore represents a crucial target for improving illness course and outcomes.

Existing treatments thus far do not adequately meet the need to address anxiety in the context of BD (Vazquez, Baldessarini and Tondo, 2014). Although pharmacotherapy is the front-line treatment for BD, pharmacotherapy for the treatment of comorbid anxiety in BD faces significant challenges. Specifically, both SSRIs and benzodiazepines, the first-line pharmacological treatments for anxiety, may be contraindicated in the context of BD (El-Mallakh and Hollifield, 2008, Freeman et al., 2002, Pacchiarotti et al., 2013, Sasson et al., 2003). Though the negative effects of SSRIs in BD are under debate, there is evidence that they interact with mood stabilizers, aggravate side effects of other medications, and may trigger mania onset (Allain et al., 2016, Post et al., 2006, Tondo et al., 2010). Benzodiazepines carry the risk of developing dependence, which is particularly problematic for BD patients who show high incidences of comorbid substance use disorders (Brunette et al., 2003). Cognitive-behavioral therapy (CBT), highly effective in the treatment of primary anxiety disorders, may offer a viable treatment alternative to pharmacotherapy for the treatment of anxiety in BD. Thus far, however, very few studies of CBT for anxiety in BD have been conducted, and those that do exist are limited to targeting a single specific anxiety disorder (Provencher et al., 2011; Stratford et el, 2015). This approach is problematic, as individuals with BD often present with multiple anxiety disorder diagnoses, begging the question of which specific anxiety disorder to target for treatment.

The current study aims to address the need for improved treatments for anxiety in the context of BD by testing the feasibility, acceptability and preliminary efficacy of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP; Barlow et al., 2010a; Barlow et al., 2010b) as an adjunctive treatment to psychopharmacological treatment-as-usual (TAU) for BD and comorbid anxiety disorders. The UP is a transdiagnostic CBT treatment developed to address common core processes that underlie the full range of anxiety and mood disorders. Specifically, evidence from genetics, cognitive and affective neuroscience, and behavioral and physiological data shows that individuals across these disorder spectrums demonstrate a biological and psychological vulnerability towards increased affective lability relative to healthy controls, and exhibit a tendency to experience affective states as aversive, uncontrollable and unpredictable (Barlow et al., 2014). These patterns are coupled with maladaptive and ineffective attempts to control, avoid or regulate emotional experiences. The UP specifically targets such deficits in emotion processing that are evident across mood and anxiety disorders including bipolar disorder.

The rationale for testing the UP for the treatment of BD and comorbid anxiety is twofold: First, given the high rates of comorbity in BD referenced above, an approach that accounts for transdiagnostic processes offers greater parsimony. In addition to addressing symptoms of anxiety in BD, this approach may benefit other co-occurring disorders, such as substance dependence. Second, the UP specifically targets deficits in emotion regulation and emphasizes the adoption of more adaptive emotion regulation skills both through skills training and emotion exposures. BD are disorders particularly characterized by both emotion lability and the inability to adaptively manage or regulate emotional experiences, which are further intensified by anxiety symptoms (Heissler et al., 2014). Chronic emotion dysregulation can permeate every domain of functioning for individuals struggling with BD, and is linked to impulsive, risky or self-destructive behaviors, interpersonal problems, disruptions in work productivity, and even suicidality (Kessler et al., 2006, Muhtadie et al., 2014, Samalin et al., 2016, Swann et al., 2009; Van Rheenen et al., 2015). BD patients report investing more time and effort in trying to regulate their emotions than healthy controls, and engage maladaptive emotion regulation strategies such as rumination and suppression more frequently (Gruber et al., 2012, Thomas et al., 2007; Van der Gucht et al., 2009; Van Rheenen et al., 2015; Wolkenstein et al., 2014). Further, emotion dysregulation in BD is associated with worsened neuropsychological deficits (e.g. behavioral slowing, poor working memory, impaired executive control), worse subjective psychosocial functioning (Hoertnagl et al., 2011), more frequent mood episodes, and worse course of illness (Kanske et al., 2013).^, It has been postulated that difficulties in regulating emotions underlie the chronic course of the illness (Phillips and Vieta, 2007, Wolkenstein et al., 2014). Thus, treatments that focus on targeting and improving emotion regulation skills may be particularly beneficial for individuals with BD.

Given the UP's focus on ameliorating emotion dysregulation using a transdiagnostic framework, we hypothesized that the UP may be particularly suited to address BD with comorbid anxiety. The UP has demonstrated efficacy in the treatment of a range of co-occurring anxiety and unipolar mood disorders (Barlow et al., submitted for publication; Ellard et al., 2010; Farchione et al., 2012), and preliminary data suggests efficacy for bipolar mood disorders as well (Ellard et al., 2012). The current study investigates the feasibility and acceptability of this approach as applied to the treatment of BD and comorbid anxiety disorders as an adjunctive treatment to standardized psychopharmacological treatment as usual (TAU). In addition, we evaluated the preliminary efficacy of this approach on improvement in bipolar mood and anxiety symptoms and psychosocial functioning, relative to pharmacological TAU alone.

Given the focus of the UP on targeting underlying emotion dysregulation as a transdiagnostic, trait-like factor affecting mood and anxiety symptoms, we additionally examined specific factors related to emotion regulation, perceptions of controllability of emotions, and temperamental variables related to neuroticism and affective behavioral styles as a secondary, exploratory aim of this study, in order to better clarify potential treatment-related mechanisms of action. Specifically, we conducted exploratory analyses to determine whether baseline characteristics related to these factors predicted treatment response across treatment groups. Similarly, in order to begin to understand potential mechanisms of treatment effects, we examined whether treatment-related changes on these trait-like variables differentially predicted symptom change across treatment groups.