Predictors of anxiety recurrence in the Coordinated Anxiety Learning and Management (CALM) trial☆
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.
Section snippets
Methods
The CALM methodology and anxiety remission outcomes have been detailed previously (Roy-Byrne et al., 2010, Sullivan et al., 2007). Data analyses were done using the NIMH-supported CALM public access database, Version 1. CALM was conducted in primary care settings in four U.S. cities (Little Rock, Seattle, Los Angeles, and San Diego) from 2006 to 2009. The research was approved by Institutional Review Boards at each site and the RAND Survey Research Group (Santa Monica, California). Written
Anxiety recurrence rates
In the year following 6 months of randomized CC or UC treatment, recurrence was lower in CC (29%) compared to UC (41%) (number needed to treat = 9, p = 0.04). Recurrence rates were similar across anxiety disorders (Table 2). PTSD had the highest recurrence rate (39%, 95% CI 22%–59%), while GAD had the lowest recurrence rate (33%, 26%–39%).
Interactions between patient characteristics and treatment group
Fig. 1 displays the significant interactions between patient characteristics and treatment modality in logistic regression models estimating recurrence.
Discussion
In the CALM study, 36% of patients with anxiety achieved remission after 6 months of treatment in the primary care setting (Roy-Byrne et al., 2010). However, we found that symptom recurrence during the year after remission was common (33% overall). Recurrence was lower in CC (29%) than in UC (41%) (number needed to treat = 9). Recurrence rates were similar across anxiety disorders (GAD, PD, SAD, or PTSD). Patients with lower self-perceived SES or comorbid MDD particularly benefited (in terms of
Role of the funding source
Funders did not participate in study design, data analysis, or writing of the article.
Contributors
All authors contributed to data interpretation and writing the report. Dr. Bloch came up with the idea for the paper. Dr. Taylor and Mr. Jakubovski analyzed the data. All authors approved the final manuscript.
Conflict of interest
None.
Acknowledgments
The authors acknowledge the support of the National Institutes of Health 1K23MH091240 (MHB), NARSAD (MHB), the Rembrandt Foundation (MHB), Patterson Trust (MHB and JHT), UL1 RR024139 from the National Center for Research Resources, a component of the National Institutes of Health, and NIH roadmap for Medical Research (MHB), 5T32MH18268 NIMH Sponsored Institutional Research Training Grant in Childhood Neuropsychiatric Disorders (JHT), American Psychiatric Association/Substance Abuse and Mental
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ClinicalTrials.gov Identifier: NCT00347269. The CALM database is available from the NIMH upon request. Information on available limited access datasets can be found at http://www.nimh.nih.gov/funding/clinical-trials-for-researchers/datasets/nimh-procedures-for-requesting-data-sets.shtml.