By Erica Benedicto, PA-C, MPH, PYT

The Well Collective, Austin, TX

Mrs. Benedicto reports no financial relationship relevant to this field of study.

SYNOPSIS: Reductions in stress markers for patients with generalized anxiety disorder were found using mindfulness-based stress reduction intervention.

SOURCE: Hoge EA, Bui E, Palitz SA, et al. The effect of mindfulness meditation on biological acute stress responses in generalized anxiety disorder. Psychiatry Res 2018;262:328-332.

Generalized anxiety disorder (GAD) is a debilitating condition that is the most frequent anxiety disorder in primary care.¹ Patients with a GAD diagnosis often complain of repeated and chronic worry, sleeplessness, and irritability. Other symptoms include fatigue, muscle aches, nervousness, and difficulty concentrating. Mindfulness-based interventions increasingly are used in psychiatry, with the most benefits found with anxiety and depression.² Most studies have focused on subjective conclusions from participants, so more randomized and adequately controlled trials are needed.

Mindfulness-based stress reduction (MBSR) was developed at the University of Massachusetts Medical Center by Jon Kabat-Zinn in the 1970s. The practice involves eight weeks of mindfulness meditation, body scanning, and hatha yoga. MBSR is described as a group program that focuses on the progressive acquisition of mindful awareness.³

To educate patients properly, clinicians need to know more about mindfulness-based practices and how they can be used appropriately for GAD. Hoge et al studied a group of 70 participants with GAD who were randomized to either an eight-week MBSR group or to an attention control class, called stress management education (SME). Other researchers have looked at self-reported and subjective findings from participants. The authors of this study expanded on this prior work by measuring inflammatory biomarker and stress hormone changes from chronic or repeated stress in patients with GAD.

Inflammatory markers and stress hormones fluctuate with chronic or repeated stress. These same blood markers are associated with the risk of developing cardiovascular disease and metabolic syndrome.^4,5 Research showed that patients with GAD and other chronically stressed populations have an exaggerated neuroendocrine response to the Trier social stress test (TSST) compared to healthy controls.⁶ The TSST is a well-validated, widely used, lab-based model of psychological stress.⁷ Researchers hypothesized that MBSR would reduce this exaggerated response to acute stress observed in people with GAD as demonstrated by decreased biomarker levels. In a 2013 study, Hoge et al measured only self-reported and subjective changes in people with GAD. They took a subset of participants with GAD and tested changes in biomarkers using MBSR and SME in a randomized, controlled approach.⁸ Clinical anxiety ratings dropped with MBSR in most measures during the study from 2013.⁸ The researchers examined the laboratory results from a group of patients from this study for hormones and inflammatory marker changes. The hormones studied were cortisol and adrenocorticotropic hormone (ACTH) and markers of inflammation were tumor necrosis factor (TNF)-alpha and interleukin (IL)-6. In 2013, they hypothesized that decreasing biological stress responses may improve overall cardiovascular and metabolic health, although that was not measured for this study.

The initial 2013 study included individuals older than 18 years of age who were diagnosed with GAD using the DSM-IV. They were randomized to a modified MBSR or SME group. Prior to the start of the intervention groups, participants completed the TSST and all blood testing. After the eight-week intervention, they returned for the second TSST. The researchers took several measures for the second TSST, including new room and new administrators, to lower potential stress habituation and improve study rigor.

The MBSR intervention was shortened from the original protocol. Classes were shortened from 2.5 to two hours, the day-long retreat was only four hours, and homework was only 20 minutes instead of the usual 45 minutes.

Seventy-nine participants completed the original 2013 study; 72 were eligible for the blood tests and were not analyzed by intention-to-treat. Some data were missing because of plasma quality and catheter failure, so the final sample sizes with all three time points for each biomarker were: n = 67 for ACTH, n = 68 for cortisol, n = 65 for TNF-alpha, and n = 62 for IL-6.

Calculations were made from the biomarkers during stress pre- and post-treatment using an area under the curve (AUC) for ACTH, TNF-alpha, cortisol, and IL-6 with +5 as the baseline blood level. The AUC for hormone and inflammatory levels before and after eight weeks of treatment are shown in Table 1. There were no significant differences in gender, age, or race distribution. Of the 72 participants eligible for blood tests and who were not analyzed by intention-to-treat, three dropped out from the MBSR group and 11 dropped out from the SME group.

COMMENTARY

As Hoge et al stated, “The value of an intervention that can improve resilience to psychological stress in this population cannot be over-estimated.” According to the American Psychological Association, psychological resilience is the process of adapting well when faced with adversity, trauma, tragedy, threats, or significant sources of stress.⁹ These findings help elucidate the benefits of using MBSR to gain resilience in the face of chronic or repeated stress for patients with GAD.

According to the National Institutes of Mental Health, in 2007, 19.1% of U.S. adults had an anxiety disorder diagnosis. An estimated 31.1% of U.S. adults suffer from an anxiety disorder at some point in their lives.¹⁰ Although mindfulness-based programs are low-cost treatment interventions, practitioners and facilitators may not be readily available in a clinic setting. Also, since not covered by insurance, access may be limited for patients.

Hoge et al found MBSR beneficial to participants with GAD, but there were multiple limitations. First, the researchers used laboratory stress vs. real-life stress as the basis for the study. Although previous studies have shown improved laboratory stress coping directly linked to improved mental health outcomes, more studies with real-life stress would increase the scientific rigor of these outcomes.¹¹

The original study included self-reporting and subjective responses, which often can be unreliable. Previous researchers have found a correlation between stress hormones and subjective stress and self-reporting in only about 25% of studies.¹² Fortunately, this extension of the original study measured lab markers that allow for objective results.

The population was quite small, with a total of 70 individuals, so larger-scale studies would be welcomed. The exclusion criteria, which included a lifetime of psychotic disorder, intellectual disability, organic medical disorders, bipolar disorders, obsessive-compulsive disorder, post-traumatic stress disorder, current or past alcohol or substance abuse or dependence, suicidal behaviors, and those in psychotherapy for GAD, may have limited their generalizability of the outcomes.

Also, MBSR is an intensive program that requires eight weeks of continuous involvement, including two hours or more each day, plus a day of retreat, and additional yoga and meditation. Researchers shortened the amount of time that individuals would be required to participate, but it is still a long-time commitment for most patients seen in a typical clinical setting.

Allostatic load is the physiological wear-and-tear on the body from repeated and/or chronic stress.¹³ Studies have shown that positive social experiences are associated with lower allostatic load, but there is no discussion about the benefits of social support from individuals in the MBSR group. Community and social support affect biological systems that have played a part in positive health outcomes.¹⁴ The researchers controlled this non-specific effect of social support in the SME group.

Introducing a mindfulness-based practice to patients in most clinic settings often is met with uncertainty, sometimes on behalf of both the patient and the clinician. This study is promising, but difficult to replicate because of the extensive time commitment that MBSR requires. In an ideal clinical scenario, MBSR would be a continuous offering, available to patients with set cohorts and schedules to deliver the program. Virtually any intervention that decreases the acute stress response and increases the relaxation response is going to be valuable within this vulnerable
population. Future work should expand on the number of participants as well as integrate real-life stress as part of the research. Although presented as a hypothesis, more research and more thorough studies showing how MBSR is linked to improving cardiovascular and metabolic health outcomes would be beneficial. A more accessible, less time-consuming intervention that succeeds at decreasing inflammatory markers and stress hormones also would have value and would add to the emerging evidence surrounding mindfulness-based tools and anxiety.

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