Escitalopram May Benefit Older Adults With Anxiety Disorder

Marlene Busko

January 21, 2009

January 21, 2009 (Updated January 27, 2009) — The selective serotonin-reuptake inhibitor (SSRI) escitalopram (Lexapro, Forest Laboratories) may provide modest symptom improvement in older adults with generalized anxiety disorder (GAD), a clinical trial suggests.

In a more conservative intention-to-treat (ITT) analysis, which assumes that all subjects who dropped out were nonresponders, the treatment was not significantly better than placebo. Adverse events were common — particularly fatigue and sleepiness — but they tended to be short-lived, rarely led to study dropout, and were not severe.

"The study showed that escitalopram is efficacious in improving anxiety symptoms and related impairments in everyday social, occupational, and family functioning," principal investigator Eric J. Lenze, MD, from Washington University, in St. Louis, Missouri, told Medscape Psychiatry.

"Chronic, distressing anxiety is not normal at this age, but it can be treated," he added.

The study is published in the January 21 issue of the Journal of the American Medical Association.

Anxious Older Adults Not Well-Studied

GAD is one of the most common mental-health problems in older adults — affecting almost 1 in 10 individuals over the age of 60 years — yet treatments for GAD have not been well-studied in this age group, said Dr. Lenze.

"As a result, most older adults with an anxiety disorder, including GAD, receive either no treatment or a sedative such as diazepam or alprazolam," he said.

However, long-term use of sedatives in older adults is linked to risks for falls and cognitive impairment. SSRIs are thought to be safer, but few data exist about use of SSRIs in older adults with GAD.

To examine the efficacy, safety, and tolerability of the escitalopram in older adults with GAD, the researchers conducted a randomized, controlled trial of 177 participants over the age of 60 years recruited from primary care, mental-health practices, and the community.

The participants, who had a mean age of 72 years, were randomized to 12 weeks of placebo (n = 92) or escitalopram (n = 85). The drug dosage was 10 mg/day (1 pill), which could be increased to 20 mg/day after 4 weeks.

The primary study outcome was cumulative response to treatment, defined as a Clinical Global Impressions-Improvement score of much improved or very much improved.

Other outcome measures assessed functioning and health.

Modest Effect Size

After 12 weeks of treatment, 69% of participants who received escitalopram vs 51% of subjects who received placebo attained a cumulative response.

However, when the analysis included individuals who dropped out of the study, the mean cumulative response rate in the treatment group was not significantly greater than in the placebo group at 57% vs 45%, respectively.

Adverse effects tended to be benign and rarely led to study dropout.

The effect size for most outcomes was low to moderate, consistent with SSRI effect size for GAD in young adults.

"Because of this modest effect size, many older adults will fail to achieve adequate resolution of GAD-related symptoms and role impairments with SSRI monotherapy, so there is great need for augmentation or switch strategies in this condition and also for efficacious nonpharmacologic treatments." the authors write.

In addition, they emphasize the need for further study of long-term treatment.

Dr. Lenze is currently conducting a study to investigate the efficacy and safety of 56 weeks of SSRI treatment plus cognitive behavior therapy in older adults with GAD.

Well-Designed Study

Asked by Medscape Psychiatry to provide independent comment on the findings, Gary J. Kennedy, MD, from Montefiore Medical Center, in New York, described the study as "exceptionally well-designed," presenting the results "very conservatively."

"I worry that a superficial reading will lead some to discount the importance of the findings and the benefits of escitalopram.

"Escitalopram is an antidepressant that is also approved for treating GAD, and this study shows how effective it can be for older adults.

"Benzodiazepines work faster but are associated with falls, cognitive impairment, and dependence. Citalopram is generic drug comprising a mix of escitalopram and related molecules. Escitalopram is pure, still branded, and may have fewer side effects," he said.

A certain amount of anxiety is normal in everyday life, said Dr. Kennedy. However, when anxiety reaches disabling proportions, lasts for 6 months or more, interferes with functioning, and is associated with 3 or more symptoms such as restlessness, difficulty concentrating, irritability, sleep disturbance, or muscle tension, criteria for GAD are met, he said.

Unlike other types of anxiety such as phobia and obsessive-compulsive disorder that are provoked by a specific situation, the source of the perceived threat in GAD is generalized, he added.

The length of time that study participants had GAD — more than 300 months — means that it was quite chronic and therefore more difficult to treat, he noted.

In addition, the outcome measure — "much" or "very much improved" based on clinical impression — is a real-world, rather than academic, measure.

"It is quite remarkable that so many chronically anxious patients improved so much," he said.

This study should improve treatment of older GAD patients by helping clinicians avoid prescribing benzodiazepines, said Dr. Kennedy. The study also provides information about the delay in response (so that patients will know what to expect) and about timing for a dose increase with escitalopram.

Antidepressants Should be Considered

According to Dr. Lenze, antidepressant medications approved for GAD include escitalopram, paroxetine, duloxetine, and venlafaxine extended release.

Using benzodiazepines for GAD, said Dr. Lenze, can be problematic in that GAD is a chronic diagnosis and benzodiazepines are more appropriate for short-term anxiety.

In this study, participants were not receiving any type of psychotherapy, he said. While there is most evidence for the effectiveness of cognitive behavioral therapy for GAD, relaxation, meditation, and acceptance therapies may also be effective, said Dr. Lenze.

"Choosing among these treatment options will be up to patient preference and availability of providers experienced in treating anxiety disorders," he said.

"The take-home message from this study is that antidepressants are helpful for anxiety disorders in older adults and therefore should be considered," said Dr. Lenze. "The benefit is not specific to escitalopram but representative of antidepressants as a drug class."

Dr Lenze reports being a consultant for Fox Learning Systems and for the Veterans Medical Research Foundation. He currently receives research support from Forest Laboratories and has received research support from Pfizer, Novartis, and Ortho-McNeill Neurologics. He received a speaker's honorarium from Eli Lilly. The financial disclosures of the other authors are listed in the paper. The study was supported by the National Institutes of Health, the Center for Mental Health Services Research, the Advanced Center for Interventions and Services Research in Late-Life Mood Disorders, the John A. Hartford Center of Excellence in Geriatric Psychiatry, and the University of Pittsburgh Medical Center. Forest Laboratories, which holds the US patent for escitalopram, provided escitalopram and matching placebo for the study.Dr. Kennedy reports receiving unrestricted educational grants and research support from Forest Laboratories; he has not been involved in promotional or scientific work with Lexapro.

JAMA. 2009; 301:295-303.


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