generalized anxiety disorder in the elderly

GENERALIZED ANXIETY DISORDER 0193-953X/Ol $15.00 + .OO

GENERALIZED ANXIETY DISORDER IN THE ELDERLY

Farooq Dada, MD, Sanjiv Sethi, MD, and George T. Grossberg, MD

The thought of getting old is anxiety provoking because of associated loss of health, financial security, relationships, and mental faculties. As with depression in the elderly, geriatric anxiety is commonly dis- guised and presents with varied symptoms, particularly physical ones. In geriatric patients, anxiety disorders may present with cognitive (e.g., worry or fear), behavioral (e.g., hyperkinesis or phobias), and physiologic symptoms, including:

Anorexia Body aches Diaphoresis Diarrhea Dizziness Dyspnea Headache

Flushing Frequent urination Light-headedness Nausea Palpitation Sweating Vomiting

Geriatric anxiety disorders most commonly begin in early adult- hood, tend to be chronic and interspersed with remissions and relapses of varying degrees, and usually continue into old age. Although uncom- mon, late onset of anxiety disorders occurs. Anxiety may be a symptom of an underlying psychiatric disturbance; secondary to a general medical condition; or induced by dietary substances, substances of abuse (e.g., alcohol), or medications, including:

From the Division of Geriatric Psychiatry, Department of Psychiatry, St. Louis University School of Medicine, St. Louis, Missouri

THE PSYCHIATRIC CLINICS OF NORTH AMERICA

VOLUME 24 NUMBER 1 * MARCH 2001 155

156 D A D A e t a l

Anticholinergics Antidepressants (e.g., selective serotonin reuptake inhibitors) Antihypertensives (e.g, hydralazine) Antipsychotics Bronchodilators (e.g., albuterol or terbutaline) CNS stimulants (e.g., caffeine) Digitalis preparations Steroids

Anxiety also may be caused by withdrawal from some agents, including:

Alcohol Barbiturates

Narcotics Nicotine

Regardless of the cause, anxiety disorders require intervention when they interfere with social, occupational, or recreational functioning. Inter- vention must be preceded by an adequate diagnostic assessment. This article outlines the clinical, diagnostic, and therapeutic issues that are pertinent to generalized anxiety disorder (GAD) in geriatric patients.

DEFINITION AND CLINICAL FEATURES

GAD is manifested by excessive anxiety or worry on most days for 6 months or longer. The worry is pervasive and interferes with daily life activities2 The duration requirement for the disorder was increased from 1 month or longer in the DSM-I11 to at least 6 months in the DSM-III-R.2

EPIDEMIOLOGY

Anxiety disorders as a group are the most common psychiatric conditions in the elderly, although the overall prevalence seems to be somewhat lower than in younger adults7 The prevalence of GAD in the elderly has not been estimated but is probably more than that of any other individual anxiety disorder in the elderly. The National Survey of Psychotherapeutic Drug Use showed anxiety disorders as a group to be more prevalent among patients aged 65 years or more (10.2%) compared with other age groups (9.9y0).~~

There are conflicting data regarding the prevalence of GAD in the elderly. For example, the National Survey of Psychotherapeutic Drug Use in the United States67 estimates the annual incidence of geriatric GAD to be 7.1%, whereas Blazer et a17 estimate the 6-month incidence to be 1.9%. Studies investigating the longitudinal course of this illness are nonexistent. The disorder has low diagnostic reliability4 and often is comorbid with depression.61 The evaluation of geriatric GAD is further complicated because many medical illnesses cause the symptoms of anxiety, which may be indistinguishable from GAD.57 GAD tends to be

GENERALIZED ANXIETY DISORDER IN THE ELDERLY 157

more frequently diagnosed in women, unmarried people, racial and ethnic minorities, and people of low socioeconomic status.8, lo, 68

NEUROBIOLOGY

The pathophysiology of anxiety disorders is complex, and none of the anxiety disorders emerges from a single pathologic state. Instead, the growing biochemical data and brain imaging studies support the idea of pathologic anxiety states being associated with a disruption of multiple neurotransmitter systems and multiple brain structures. GAD has many features in common with panic disorder, including autonomic hyperactivity. Although some studies have demonstrated abnormally decreased peripheral a,adrenergic receptor sensitivity12, 14, l7 or increased levels of norepinephrine and its metabolites,44* 58 these findings have not been replicated.', 14, 45, 49 Studies using adrenergic antagonists also have not demonstrated significant abnormalities in noradrenergic function among patients with GAD.1, 14, 43, 49 Some studies have reported abnormal growth hormone release but normal physiologic and subjective response to clonidine challenge.39

TREATMENT

In the treatment of anxiety disorders, psychosocial stressors and underlying medical conditions must be addressed. Patients should be monitored for side effects of medications. After the potential causes and contributors have been addressed, pharmacologic intervention may be necessary.

Nonpharmacologic Treatment

Psychotherapeutic interventions for anxiety disorders are much better defined for younger populations than for older ones.65 Because of their reluctance to acknowledge psychological problems, many elderly persons are more accepting of medical treatments than nonpharmacologic ones. To this end, education about the biological basis of anxiety may increase compliance. Elderly patients with concomitant physical illnesses often are sensitive to the side effects of drugs. Also, many patients also have psychosocial issues requiring attention. To date, no systematic data support the idea of anyone being too old for psychological change. Most experts agree that, as long as cognitive functions are intact, elderly patients respond well to psychotherapeutic interventions. Data indicate that cognitive-behavioral therapy (CBT) may be as effective in the elderly population as in younger patients.62 This therapy includes deep-breathing and muscle-relaxation techniques, cognitive interventions, and therapist-assisted exposure. The best results may be achieved

158 DADAetal

by combining medication with therapy3, 45* 51 Cognitive therapy is likely to be more effective than psychodynamic psychotherapy with chronically anxious patients.z3 Data show that patients require approximately 8 to 10 sessions.23 Behavioral methods, although effective, have been found to be significantly unde ru~ed .~~ The outcome predictors in a clinical trial of psychological therapies for GAD were marital status, marital tension, and comorbidity with an Axis I disorder.24 The effectiveness of group CBT has been found to be greatest for cognitive symptoms of anxiety, but the impact of treatment is less for patients with significant comorbid medical problems and those with chronic anxiety.53

Regarding electroconvulsive therapy (ECT), Finkz6 suggested that anxiety is a contraindication for ECT use in 1982. Since then, studies have advocated ECT for treatment-resistant obsessive-compulsive disorder? 13,

22, 32, 33, 36, 37, 42, 46, 64 but none has advocated it for GAD. Long-term use of benzodiazepines (discussed later) seems to interfere with ECT.l6

Pharmacologic Treatment

Benzodiazepines

Benzodiazepines are commonly prescribed for the treatment of anxiety disorders in the elderl~,2~, 63 but epidemiologic data suggest overuse of benzodiazepines in the elderly pop~la t ion .~~ Long-term benzodiazepine use is common in nursing homes, with one study reporting that 80% of institutionalized sedative-hypnotic users received these drugs regularly.6 Efficacy of benzodiazepines in older patients is similar to that in younger patients.63 Benzodiazepines differ from one another in pharmacokinetic profile and metabolism. The relative rate of absorption, half-life, presence of active metabolites, and recommended daily dosage differ among older patients and are summarized in Table 1. Lorazepam, oxazepam, and alprazolam have no pharmacologically active metabo- l i t e ~ . * ~ , ~ ~ Lorazepam and oxazepam are conjugated in the liver, a mechanism that is not significantly affected by agh1g.4~ Lorazepam is the only benzodiazepine that is reliably absorbed after intramuscular injection.60

Unfortunately, benzodiazepines may produce several adverse side effects in the elderly, including cognitive impairment, sedation, drowsi- ness, slow and poor coordination, decreased mental acuity and increased risk for falls and hip fractures caused by ataxia.41 Consequently, this

Table 1. COMMONLY PRESCRIBED BENZODIAZEPINES

Dosage Range Active Agent (mgld) Half-Life Metabolites

Alprazolam 0.375-2.0 Oxazepam 15-30

Lorazepam 0.5-2.0 Clonazepam 0.52.0

12

34 15

8-1 0 Minor No Yes No


class of drugs must be used cautiously in the elderly. Liver damage, blood dyscrasias, and other end-organ toxic effects are rare.27 In general, low hepatic extraction compounds metabolized by conjugation (e.g., temazepam, oxazepam, or lorazepam) tend not to contribute to pharmacokinetic drug interactions and are preferred for elderly patients, but chronic use of lorazepam in the elderly may be associated with undesir- able amnesia as a side effect. Benzodiazepines should be prescribed for a limited time, with precautions taken relative to abrupt discontinuation, and with short half-life agents, interdose withdrawal. The long-acting benzodiazepine clonazepam may induce liver enzyme abnormalities but produces fewer withdrawal-related problems.28, 34 Among benzodiazepines with a short half-life, high-potency compounds (e.g., lorazepam and alprazolam) may be more toxic and cause more dependence, re- bound symptoms, and memory impairment than low-potency benzodiazepines (e.g., oxa~eparn) . '~ ,~~

Despite their disadvantages, benzodiazepines are commonly used and are efficacious in the acute and subacute treatment of many anxiety disorders in the elderly. These patients should be monitored closely, and benzodiazepine therapy should be used in conjunction with psychological treatments.

Buspirone

The anxiolytic buspirone belongs to a chemical subgroup known as azapirones and has postsynaptic 5-HTlA partial agonist and presynaptic 5-HTlA full agonist properties. Its mechanism of action is probably related to reducing or modulating serotonergic activity by binding to the 5-HTlA receptor. Its other actions include enhancing dopaminergic and noradrenergic activity. It has demonstrated efficacy in younger patients with GAD.% In a controlled, double-blind study of 40 anxious patients aged 65 years or older, buspirone was significantly more effective than pla~ebo.~ Buspirone does not have sedative, muscle-relaxing, or anticon- vulsant properties. One study demonstrated improvement in psychomo- tor impairment with its use.48 In one open, multicenter trial, older and younger groups achieved similar improvement of anxiety symptoms during a 4-week It is a safe, well-tolerated medication with no significant drug-drug interactions. Side effects include light-headedness, headache, and nausea.21, 50 In replacing benzodiazepines, buspirone therapy may be started benzodiazepines are slowly tapered.40 In a large studyz0 clinical improvement with buspirone was similar to that of benzodiazepines in groups receiving no prior benzodiazepine treatment or remote benzodiazepine treatment but less than that in another benzodiazepine-treated group. In the elderly, 15 to 30 mg/d is often an effective dosage. A disadvantage of buspirone is its slow onset. Maxi- mum therapeutic effect may not occur for 6 weeks. Another disadvantage is a lack of efficacy in treating panic and anxiety.

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Antidepressants Data from controlled trials of antidepressant medications for treat-

ing GAD are limited. Clinical experience and conclusions favor antidepressants with relative sedative and anxiolytic effects.

Tertiary tricyclic antidepressants with dual serotonergic-noradrenergic effects, such as imipramine and amitriptyline, seem consistently effective across the anxiety disorders. Although tricyclic antidepressants and hetero- cyclic agents (e.g., trazodone) have sedative properties, their usefulness is limited in the elderly because of associated anticholinergic properties or orthostasis.

Monoamine oxidase inhibitors have been found to be effective in treating depression, panic disorder, and social phobia, but their effectiveness in treating GAD has not been studied. In a study of elderly outpatients, phenelzine was demonstrated to be approximately as well tolerated as n~rtriptyline.~~ Additional research on the effectiveness of newer, reversible inhibitors of MAO-A in the elderly are needed.

Although selective serotonin reuptake inhibitors have much safer pharmacologic profiles than do tricyclic antidepressants and monoamine oxidase inhibitors and have well-proven effectiveness for panic disorder and phobias, they have not been found effective in treating GAD. Anxi- ety and agitation may be exacerbated with these agents. Also, their slow onset of action is a disadvantage.

Several studies of younger subjects have shown venlafaxine to be an effective pharmacotherapeutic treatment option for GAD. 11, 29* 55* 59

One study demonstrated venlafaxine to be significantly superior to buspirone as measured with the Hamilton Anxiety Scale.ls Venlafaxine is an effective, relatively well-tolerated medication in elderly, depressed patients, but the data regarding its use in geriatric patients with GAD are limited. It may be an effective pharmacotherapeutic treatment for elderly people with GAD, however. A limitation with venlafaxine is the need to monitor for drug-induced blood pressure elevation.

Newer antidepressants, such as mirtazepine, nefazodone, and citalo- pram, may provide some benefits across the broad spectrum of anxiety disorders with the safety and tolerability that are the hallmarks of third- generation antidepressant^.^^

Barbiturates and Meprobamate Barbiturates and meprobamate have been used in the past for their

nonspecific sedative properties, but they are relatively dangerous medications with a low toxicity ratio and a high tolerance potential and the risk for life-threatening withdrawal symptoms, seizures, and CNS and respiratory depression. Their use should be avoided in the elderly population.

Antipsychotic Agents Typical (e.g., haloperidol) and atypical (e.g., risperidone or olanzep-

ine) antipsychotics have been used for acute anxiety, which may trigger


agitation in patients with dementia. These agents have potential side effects, such as lethargy, risk for falls, extrapyramidal side effects. Even with short-term (12-36 months) use of typicals, there is a risk for tardive dyskinesia in the elderly. Because of these limitations, antipsychotics are not recommend for the treatment of primary anxiety symptoms or disorders. They may, however, be useful to treat psychotic symptoms, which may trigger anxiety in the elderly.

p -Adrenergic blockers

Although p-adrenergic blockers have demonstrated effectiveness for suppressing somatic autonomic symptoms over the short term in young patients, they have distinct limitations for use in the elderly because of their potential to cause and exacerbate pulmonary disease, heart failure, cardiac conduction deficits, diabetes, renal disease, hypotension, cognitive impairment, and delirium.

Gabapentin

Gabapentin has been tried as a therapy for GAD. The authors’ preliminary observations suggest a role for gabapentin as monotherapy or for adjunctive use in patients with panic disorder or GAD.15, 52 Other treatment options that are still being investigated include partial benzodiazepine receptor agonists, such as alpidem and bretazanil; neurostero- ids; various 5-HT antagonists; and neuropeptide receptor agonists and antagonist^.^^

General guidelines for the treatment of anxiety in the elderly include:

A comprehensive physical examination and psychiatric evaluation A thorough review of prescribed and over-the-counter drugs that may

Education of patients and their families regarding the illness Choice of an appropriate medication (”start low and go slow”) Consideration of nonpharmacologic intervention, such as CBT, which

be contributing to anxiety

may reduce anxiolytic dependence

SUMMARY

Anxiety disorders, especially GAD, are among the most prevalent psychiatric illnesses in the elderly. Unfortunately, research relative to late-onset anxiety syndromes and longitudinal studies of early-onset anxiety syndromes are sparse. Nonetheless, clinicians can properly as- sess and treat older adults with anxiety disorders and improve their quality of life. Additional research is needed to better elucidate the various presentations of GAD in the elderly and in developing safe, effective, nonpharmacologic and pharmacologic treatment approaches.

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pp 1301-1310

4:9-20, 1994

Address reprint requests to Farooq Dada, MD

Division of Geriatric Psychiatry Department of Psychiatry

St. Louis University School of Medicine St. Louis University Health Sciences Center

1221 South Grand Boulevard St. Louis, MO 63104

generalized anxiety disorder in the elderly

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