Predictors of anxiety recurrence in the Coordinated Anxiety Learning and Management (CALM) trial

Highlights

• After anxiety remission, 33% of patients had symptoms recur within a year.

• Anxiety recurrence was lower in collaborative care (29%) than in usual care (41%).

• Collaborative care especially benefited depressed and low socioeconomic status patients.

• Post-treatment residual symptoms and anxiety sensitivity predicted recurrence.

• Benzodiazepine prescription, smoking, and being single predicted recurrence.

Abstract

Few studies have examined anxiety recurrence after symptom remission in the primary care setting. We examined anxiety recurrence in the Coordinated Anxiety Learning and Management (CALM) trial. From 2006 to 2009, CALM randomized adults with anxiety disorders (generalized anxiety disorder, panic disorder, social anxiety disorder, and post-traumatic stress disorder) in primary care clinics to usual care (UC) or a collaborative care (CC) intervention of pharmacotherapy and/or cognitive behavioral therapy. We examined 274 patients who met criteria for anxiety remission (Brief Symptom Inventory for anxiety and somatization (BSI-12) < 6) after 6 months of randomized treatment and completed a follow-up of 18 months. Logistic regression and receiver operating characteristics (ROC) were used to identify predictors of anxiety recurrence (BSI-12 ≥ 6 and 50% increase from 6-month ratings) during the year following remission. Recurrence was lower in CC (29%) compared to UC (41%) (p = 0.04). Patients with comorbid depression or lower self-perceived socioeconomic status particularly benefited (in terms of reduced recurrence) if assigned to CC instead of UC. In the multivariable logistic regression model, smoking, being single, Anxiety Sensitivity Index score, functional impairment at month 6 due to residual anxiety (measured with the Sheehan Disability Scale), and treatment with benzodiazepines were associated with subsequent anxiety recurrence. ROC identified prognostic subgroups based on the risk of recurrence. Our study was exploratory, and our findings require replication. Future studies should also examine the effectiveness of relapse prevention programs in patients at highest risk for recurrence.

Introduction

Although many trials have examined the efficacy of short-term treatments in anxiety disorders, few trials have examined how those treatment gains are maintained (Batelaan et al., 2010, Bruce et al., 2005, Calkins et al., 2009, Rodriguez et al., 2005, Scholten et al., 2013). Anxiety recurrence is the emergence of symptoms after remission has been achieved. A recent study found that 20% of patients with remitted anxiety will experience anxiety recurrence (Scholten et al., 2013). Identifying which patients have the highest risk for symptom recurrence is important so that relapse prevention resources can be directed to patients with the greatest need. Furthermore, identifying patient and treatment characteristics associated with increased recurrence risk may help in the development of new relapse prevention programs.

Previous research has found that baseline anxiety severity (Bruce et al., 2005, Scholten et al., 2013), anxiety sensitivity (fear that anxiety symptoms will be noticed by others or that the symptoms indicate serious illness) (Calkins et al., 2009, Mitchell et al., 2014, Scholten et al., 2013), and depression (Batelaan et al., 2010, Bruce et al., 2005, Rodriguez et al., 2005) are associated with anxiety recurrence. Higher rates of anxiety recurrence have been identified in patients with generalized anxiety disorder (GAD) and panic disorder (PD) compared to other anxiety disorders (Rodriguez et al., 2005). Still, little is known about predictors of anxiety recurrence in the primary care setting (Rodriguez et al., 2006), where most patients with anxiety receive treatment (Young et al., 2001). Moreover, prior studies examining risk factors for anxiety recurrence have 1) relied on lifetime anxiety diagnoses to retrospectively determine anxiety remission and recurrence making them vulnerable to recall bias (Batelaan et al., 2010, Calkins et al., 2009, Scholten et al., 2013) or 2) used observational designs instead of monitoring for recurrence after a course of treatment (Batelaan et al., 2010, Bruce et al., 2005, Calkins et al., 2009, Rodriguez et al., 2005, Scholten et al., 2013).

The Coordinated Anxiety Learning and Management (CALM) trial addressed the need for studies examining anxiety treatment in the primary care setting (Sullivan et al., 2007). In CALM, primary care patients with GAD, PD, generalized social anxiety disorder (SAD), and/or post-traumatic stress disorder (PTSD) were randomized to usual care (UC) or collaborative care (CC), which employed evidence-based pharmacotherapies and/or cognitive behavioral therapy (CBT) (Craske et al., 2011, Roy-Byrne et al., 2010). In contrast to prior anxiety recurrence studies, in CALM patients were assessed for symptom remission after a course of randomized treatment, and remitted patients were then prospectively monitored for recurrence.

We studied patients in the CALM trial whose anxiety and somatization symptoms had remitted after 6 months of randomized treatment, and we determined the recurrence rate of their symptoms over the subsequent year. We also examined several possible predictors of symptom recurrence. By identifying which patients are likely (and unlikely) to maintain treatment gains, this paper complements prior CALM data analyses which identified patient populations likely to improve with treatment (Kelly et al., 2015). To our knowledge, our study is the first to examine anxiety recurrence in the collaborative care model and the largest prospective study to examine recurrence in the primary care setting.