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Elevated cortisol in older adults with generalized anxiety disorder is reduced by treatment: a placebo-controlled evaluation of escitalopram.

ABSTRACT: Generalized anxiety disorder (GAD) is a common disorder in older adults, which has been linked to hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in this age group. The authors examined whether treatment of GAD in older adults with a selective serotonin reuptake inhibitor (SSRI) corrects this HPA axis hyperactivity.The authors examined adults aged 60 years and older with GAD in a 12-week randomized controlled trial comparing the SSRI escitalopram with placebo. The authors collected salivary cortisol at six daily time points for 2 consecutive days to assess peak and total (area under the curve) cortisol, both at baseline and posttreatment.Compared with placebo-treated patients, SSRI-treated patients had a significantly greater reduction in both peak and total cortisol. This reduction in cortisol was limited to patients with elevated (above the median) baseline cortisol, in whom SSRI-treated patients showed substantially greater reduction in cortisol than did placebo-treated patients. Reductions in cortisol were associated with improvements in anxiety. Additionally, genetic variability at the serotonin transporter promoter predicted cortisol changes.SSRI treatment of GAD in older adults reduces HPA axis hyperactivity. Further research should determine whether these treatment-attributable changes are sustained and beneficial.

SUBMITTER: Lenze EJ

PROVIDER: S-EPMC3424606 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Elevated cortisol in older adults with generalized anxiety disorder is reduced by treatment: a placebo-controlled evaluation of escitalopram.

Lenze Eric J EJ Mantella Rose C RC Shi Peichang P Goate Alison M AM Nowotny Petra P Butters Meryl A MA Andreescu Carmen C Thompson Paul A PA Rollman Bruce L BL

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20110501 5

<h4>Background</h4>Generalized anxiety disorder (GAD) is a common disorder in older adults, which has been linked to hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in this age group. The authors examined whether treatment of GAD in older adults with a selective serotonin reuptake inhibitor (SSRI) corrects this HPA axis hyperactivity.<h4>Methods</h4>The authors examined adults aged 60 years and older with GAD in a 12-week randomized controlled trial comparing the SSRI escitalopram ...[more]

PMID: 20808146

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Project description:ContextGeneralized anxiety disorder (GAD) is one of the most common psychiatric disorders in older adults; however, few data exist to guide clinicians in efficacious and safe treatment. Selective serotonin reuptake inhibitors (SSRIs) are efficacious for younger adults with GAD, but benefits and risks may be different in older adults.ObjectiveTo examine the efficacy, safety, and tolerability of the SSRI escitalopram in older adults with GAD.Design, setting, and participantsA randomized controlled trial in primary care practices and related specialty clinics in Pittsburgh, Pennsylvania, of 177 participants aged 60 years or older with a principal diagnosis of GAD randomized to receive either escitalopram or placebo and conducted between January 2005 and January 2008.InterventionsTwelve weeks of 10 to 20 mg/d of escitalopram (n = 85) or matching placebo (n = 92).Main outcome measuresCumulative response defined by Clinical Global Impressions-Improvement score of much or very much improved; time to response; and anxiety and role functioning changes measured by the Clinical Global Impressions-Improvement scale, Hamilton Anxiety Rating Scale, Penn State Worry Questionnaire, Late-Life Function and Disability Instrument activity limitations subscale, and the role-emotional impairment and social function subscales of the Medical Outcome Survey 36-item Short Form.ResultsIn the primary analytic strategy in which participants (n = 33) were censored at the time of dropout, mean cumulative response rate for escitalopram was 69% (95% confidence interval [CI], 58%-80%) vs 51% (95% CI, 40%-62%) for placebo (P = .03). A conservative intention-to-treat analysis showed no difference in mean cumulative response rate between escitalopram and placebo (57%; 95% CI, 46%-67%; vs 45%; 95% CI, 35%-55%; P = .11). Participants treated with escitalopram showed greater improvement than with placebo in anxiety symptoms and role functioning (Clinical Global Impressions-Improvement scale: effect size, 0.93; 95% CI, 0.50-1.36; P < .001; Penn State Worry Questionnaire: 0.30; 95% CI, 0.23-0.48; P = .01; activity limitations: 0.32; 95% CI, 0.01-0.63; P = .04; and the role-emotional impairment and social function: 0.96; 95% CI, 0.03-1.90; P = .04). Adverse effects of escitalopram (P < .05 vs placebo) were fatigue or somnolence (35 patients [41.1%]), sleep disturbance (12 [14.1%]), and urinary symptoms (8 [9.4%]).ConclusionsOlder adults with GAD randomized to escitalopram had a higher cumulative response rate for improvement vs placebo over 12 weeks; however, response rates were not significantly different using an intention-to-treat analysis. Further study is required to assess efficacy and safety over longer treatment durations.Trial registrationclinicaltrials.gov Identifier: NCT00105586.

Project description:Cognitive behavior therapy (CBT) can be effective for late-life generalized anxiety disorder (GAD), but only pilot studies have been conducted in primary care, where older adults most often seek treatment.To examine effects of CBT relative to enhanced usual care (EUC) in older adults with GAD in primary care.Randomized clinical trial recruiting 134 older adults (mean age, 66.9 years) from March 2004 to August 2006 in 2 primary care settings. Treatment was provided for 3 months; assessments were conducted at baseline, posttreatment (3 months), and over 12 months of follow-up, with assessments at 6, 9, 12, and 15 months.Cognitive behavior therapy (n = 70) conducted in the primary care clinics. Treatment included education and awareness, motivational interviewing, relaxation training, cognitive therapy, exposure, problem-solving skills training, and behavioral sleep management. Patients assigned to receive EUC (n = 64) received biweekly telephone calls to ensure patient safety and provide minimal support.Primary outcomes included worry severity (Penn State Worry Questionnaire) and GAD severity (GAD Severity Scale). Secondary outcomes included anxiety ratings (Hamilton Anxiety Rating Scale, Beck Anxiety Inventory), coexistent depressive symptoms (Beck Depression Inventory II), and physical/mental health quality of life (12-Item Short Form Health Survey).Cognitive behavior therapy compared with EUC significantly improved worry severity (45.6 [95% confidence interval {CI}, 43.4-47.8] vs 54.4 [95% CI, 51.4-57.3], respectively; P < .001), depressive symptoms (10.2 [95% CI, 8.5-11.9] vs 12.8 [95% CI, 10.5-15.1], P = .02), and general mental health (49.6 [95% CI, 47.4-51.8] vs 45.3 [95% CI, 42.6-47.9], P = .008). There was no difference in GAD severity in patients receiving CBT vs those receiving EUC (8.6 [95% CI, 7.7-9.5] vs 9.9 [95% CI, 8.7-11.1], P = .19). In intention-to-treat analyses, response rates defined according to worry severity were higher following CBT compared with EUC at 3 months (40.0% [28/70] vs 21.9% [14/64], P = .02).Compared with EUC, CBT resulted in greater improvement in worry severity, depressive symptoms, and general mental health for older patients with GAD in primary care. However, a measure of GAD severity did not indicate greater improvement with CBT.clinicaltrials.gov Identifier: NCT00308724.

Dataset Information

Elevated cortisol in older adults with generalized anxiety disorder is reduced by treatment: a placebo-controlled evaluation of escitalopram.

Publications

Elevated cortisol in older adults with generalized anxiety disorder is reduced by treatment: a placebo-controlled evaluation of escitalopram.

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