Reducing the Burden of Generalized Anxiety Disorder

Anxiety disorders are widely prevalent yet often go undiagnosed. Generalized anxiety disorder (GAD), in particular, is estimated to affect 7.8% of adults in the United States during their lifetime.¹ According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), GAD is characterized by presence of anxiety and worry related to several events/activities that is difficult to control along with 3 or more of the following 6 symptoms: restlessness or feeling keyed up or on edge; being easily fatigued; difficulty concentrating or mind going blanks; irritability; muscle tension; and sleep disturbances.² Patients with GAD have impairments across multiple domains of life which are compounded by the chronic nature of illness given that anxiety/worry must be present for at least 6 months to make the diagnosis. The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has further added to the burden as individuals with no prior history of mood or anxiety disorders are experiencing significant increase in levels of generalized anxiety.³ In fact, a recent study found that during the pandemic, 1 in 2 community-dwelling adults were experiencing generalized anxiety that was at least mildly severe.⁴ Therefore, urgent action is needed from mental health providers to reduce the public health burden of GAD.

Screening for GAD in medical settings can be an initial step that allows for rapid identification of undiagnosed cases. The United States Preventive Services Task Force (USPSTF) is currently researching about recommendations for screening of anxiety in adults⁵ and in children and adolescents⁶. The Women's Preventive Services Initiative, a national coalition of 21 health professional organizations and patient representatives that is supported by the US Department of Health and Human Services and led by the American College of Obstetricians and Gynecologists, recently recommended screening women and adolescent girls aged 13 years or older, including pregnant and postpartum women, for anxiety.⁷ Building up on these recommendations, the mental health community should advocate for broader screening of GAD, especially in primary care settings. With broader adoption of patient-facing portals in electronic health record systems, self-report questionnaires such as the 7-item Generalized Anxiety Disorder scale (GAD-7)⁸ can be administered on a regular basis, such as annual wellness visits. To follow-up on those who screen positive, mental health providers should work with primary care providers to enable diagnosis and management in primary care settings for most patients using approaches that were developed for depression.^9,10 Irrespective of the setting (primary care or psychiatric), principles of measurement-based care (MBC) can be utilized. Developed initially for depression,¹¹ the MBC approach utilizes frequent (every 2-3 weeks) systematic assessments of symptom severity, adherence, and side-effects along with step-wise algorithms to guide pharmacotherapy treatment decisions such as whether to continue current treatment (strong response with minimal side effect burden) or increase the dose (minimal side effects but inadequate improvement) or change the treatment (inadequate improvement despite prolonged treatment with maximally tolerated dose of medication). Routine use of the MBC approach will also allow for the identification of patients who did not respond to one or more evidence-based treatments (treatment-refractory GAD) and may benefit from combination or more specialized treatment approaches.

For the initial management of GAD, evidence-based psychotherapies such as cognitive behavioral therapy are considered as first-line treatments.¹² However, access is often a limiting factor. Broad adoption of telehealth platforms driven by the pandemic may remove some barriers such as living in a remote areas or limited access to transportation. Yet, the larger issue of inadequate number of trained mental health provider persists. A promising approach involves enlisting lay persons as health counselors who are supervised by mental health specialists in collaboration with primary care provider.¹³ The recent report by Kahlon and colleagues further supports this approach and extends it to a preventive approach that is targeted towards those who are considered at risk, such as homebound elderly adults who participated in a Meals on Wheels program.⁴ In a randomized controlled trial, they found that empathy-focused telephone calls by laypersons over a 4-week period was associated with marked improvement in depression, anxiety, and loneliness. Callers in this program were young adults who received brief training in empathetic conversations and supported a panel of 6 to 9 participants each. Participants received daily phone calls for the first week and had the option to go down to two calls per week for the remaining three weeks. Interestingly, majority of the participants elected to continue with daily phone calls. Authors found that percentage of participants with mild or greater severity of anxiety symptoms reduced significantly from pre (50%) to post (36%) intervention as compared to control arm [pre (49%) to post (50%)]. The effect size of improvement in generalized anxiety symptoms with this intervention was comparable in magnitude to the effect size of medications for GAD.¹⁴ Future research studies are needed to evaluate how this (or similar interventions) compare to more established psychotherapy and pharmacotherapy treatment options.

In fact, there is a great paucity of research in anxiety disorders including how pharmacotherapy options line up with psychotherapy ones in head-to-head comparison. An ongoing study promises to be one of the first ones to compare mindfulness-based stress reduction with escitalopram in patients with anxiety disorder. Other unmet areas of need include management approaches for patients with treatment-refractory anxiety disorders and pathophysiological mechanisms underlying anxiety disorders. Understanding these mechanisms will enable the research community to identify and develop novel therapeutics.

In conclusion, concerted efforts from psychiatric clinicians and researchers are needed to reduce the public burden of anxiety disorders in general and GAD specifically. Collaborations with primary care providers can help in identifying undiagnosed cases with screening and in initiating evidence-based first-line treatments in a timely fashion. Future research efforts may help in developing scalable interventions that enlist laypersons to help those with anxiety disorder and/or those at risk of developing these disorders.

References

1. Ruscio AM, Hallion LS, Lim CCW, et al. Cross-sectional comparison of the epidemiology of DSM-5 generalized anxiety disorder across the globe. JAMA Psychiatry. 2017;74(5):465-475.

2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Association; 2013.

3. Pan KY, Kok AAL, Eikelenboom M, et al. The mental health impact of the COVID-19 pandemic on people with and without depressive, anxiety, or obsessive-compulsive disorders: a longitudinal study of three Dutch case-control cohorts. The Lancet Psychiatry. 2021;8(2):121-129.

4. Kahlon MK, Aksan N, Aubrey R, et al. Effect of layperson-delivered, empathy-focused program of telephone calls on loneliness, depression, and anxiety among adults during the COVID-19 pandemic: a randomized clinical trial. JAMA Psychiatry. 2021 February 23;[Epub ahead of print].

5. Screening for depression, anxiety, and suicide risk in adults, including pregnant and postpartum persons. US Preventive Services Task Force. September 3, 2020. Accessed April 14, 2021.

6. Screening for depression, anxiety, and suicide risk in children and adolescents. US Preventive Services Task Force. August 13, 2020. Accessed April 14, 2021.

7. Gregory KD, Chelmow D, Nelson HD, et al. Screening for anxiety in adolescent and adult women: a recommendation from the Women's Preventive Services Initiative. Annals of Internal Medicine. 2020;173(1):48-56.

8. Kroenke K, Spitzer RL, Williams JBW, O’Manahan P, Löwe B. Anxiety disorders in primary care: prevalence, impairment, comorbidity, and detection. Annals of Internal Medicine. 2007;146(5):317-325.

9. Jha MK, Grannemann BD, Trombello JM, et al. A structured approach to detecting and treating depression in primary care: VitalSign6 project. Annals of Family Medicine. 2019;17(4):326-335.

10. Locke AB, Kirst N, Shultz CG. Diagnosis and management of generalized anxiety disorder and panic disorder in adults. American Family Physician. 2015;91(9):617-624.

11. Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. The American Journal of Psychiatry. 2006;163(1):28-40.

12. Stein MB, Sareen J. Generalized anxiety disorder. The New England Journal of Medicine. 2015;373:2059-2068.

13. Patel V, Weiss HA, Chowdhary N, et al. Effectiveness of an intervention led by lay health counsellors for depressive and anxiety disorders in primary care in Goa, India (MANAS): a cluster randomised controlled trial. The Lancet. 2010;376(9758):2086-2095.

14. Carl E, Witcraft SM, Kauffman BY, et al. Psychological and pharmacological treatments for generalized anxiety disorder (GAD): a meta-analysis of randomized controlled trials. Cognitive Behaviour Therapy. 2020;49(1):1-21.

Manish K. Jha, MBBS, is an Assistant Professor of Psychiatry and Neuroscience at the Icahn School of Medicine at Mount Sinai (ISMMS), New York, New York, with substantial expertise in conducting clinical trials and extensive clinical experience in providing care to patients with treatment-refractory psychiatric illnesses. He also serves as the Assistant Director of the Depression and Anxiety Center for Discovery and Treatment (DAC) at ISMMS, a comprehensive research facility and clinical program that aims to develop cutting-edge treatments by identifying factors that contribute to the onset, progression, and course of mood, anxiety and related disorders. His work has focused on often-ignored features of depression such as irritability and he has evaluated clinical and biological markers that can prognosticate clinical outcomes for individuals with mood, anxiety, and related disorders. His  program of research uses functional neuroimaging and affective neuroscience experiments to elucidate the neurocircuit mechanisms in order to develop the next generation of circuit-specific treatments for psychiatric disorders.