Meeting the challenge of generalized anxiety disorder

Robin N. Hunter Buskey, MPAS, PA-C

Ms. Hunter Buskey is Health Service Officer in the Federal Bureau of Prisons in Butner, NC. The author has indicated no relationships to disclose relating to the content of this article. The views expressed in this article are those of the author and do not reflect the official policy of her employer.

Worry, tension, and nervousness are the hallmarks of GAD, whose sufferers often stretch the boundaries of the primary care office visit.

 

Earn Category I CME credit by reading this article and "Chronic pancreatitis Debilitating for the patient, frustrating to manage" and then successfully completing the post-test. Successful completion is defined as a cumulative score of at least 70% correct. This material has been reviewed and is approved for 1 hour of clinical Category I (Preapproved) CME credit by the AAPA. The term of approval is for 1 year from the publication date of December 2004.

Learning objectives Review the symptoms of and common somatic complaints associated with generalized anxiety disorder (GAD), and list the organic and psychiatric disorders that can cause symptoms of GAD List the tools that can be used to screen for GAD Describe when the judicious use of expensive tests may be appropriate in GAD Describe how to select the appropriate treatment

Generalized anxiety disorder (GAD) is an important clinical condition characterized by excessive anxiety and worry that can be difficult to recognize, even as it interferes with the daily lives of more than 27.4 million Americans.¹ Patients with GAD, the most prevalent anxiety disorder in primary care, worry incessantly. Some are aware of their uncontrolled worry, while others notice it only when a family member or friend points it out. The worry is usually associated with everyday events, but it can be more global, such as worry that something catastrophic will happen to themselves or family members.

Patients are likely to appear restless and keyed up. Associated symptoms are similar to those seen in depressive disorders, including fatigue, difficulty concentrating, irritability, muscle tension, and sleep disturbances. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), criteria for GAD include apprehensive expectation on more days than not for at least 6 months, along with three or more of the symptoms of restlessness, easy fatigue, poor concentration, irritability, muscle tension, and sleep disturbance.²

Anxiety is defined as painful or apprehensive uneasiness of mind, an abnormal and overwhelming sense of apprehension and fear often marked by sweating, tension, and increased heart rate.³ Worry is defined as a mental distress or agitation that results from concern.³ Sigmund Freud was the first physician to document an association between symptoms of anxiety and underlying problems and termed the disorder anxiety neurosis. Before Freud's work, anxiety was considered a physical rather than mental disorder. Under the current definition, patients with GAD exhibit significant distress and impairment in functioning. "I worry all the time" is a common complaint.

The disorder affects daily interaction with family, friends, and colleagues and performance at work or school, all of which can exacerbate the patient's problems and fears. A feature that differentiates GAD from other anxiety disorders such as panic attacks, phobias, or obsessive-compulsive disorder (OCD) is diffuse anxiety without a specific focus. The most severe loss of functioning has been found in patients who have both GAD and depression.⁴

Some experts have proposed that GAD has subtypes.^5-8 These include acute anxiety, which is described as a reaction to situational stress that lasts for several days, and subacute anxiety, a reaction to stress that can last several weeks. Symptoms of anxiety that persist for at least 6 months characterize so-called chronic or double anxiety.

The disorder affects approximately 5.1% of Americans aged 15 to 45 years,⁹ often appearing before or during young adulthood and continuing through life. GAD may also be the most common anxiety disorder in patients aged 65 years and older. Spontaneous remission is rare, so it is particularly important that providers be able to recognize and treat the disorder.^9,10 Major depressive disorder (MDD) and panic disorder are the most common comorbid conditions seen with GAD.¹¹ A higher incidence of GAD has been found in women, single persons, minorities, and those of low socioeconomic status.¹

The clinical face of GAD

Patients who have GAD tend to use health care resources frequently, often to investigate somatic complaints.¹⁰ As many as one third of patients with GAD present to primary care providers for help,^1,12 and typically they complain of one symptom. Symptoms and signs associated with GAD generally include increased autonomic function, motor tension, fearful expectations, and hypervigilance (see Table 1). A patient may describe the anxiety and nervousness in terms of neurologic, musculoskeletal, or GI complaints.^13,14

 

TABLE 1 Symptoms of generalized anxiety disorder
Type	Manifestation
Motor tension	Trembling, twitching, shakiness; muscle tension, aches, or soreness; restlessness; easy fatigue
Autonomic hyperactivity	Shortness of breath or smothering sensations; hyperventilation; palpitations or rapid heart rate; chest pain; sweating or cold clammy hands; dry mouth; dizziness or lightheadedness; headache; nausea, diarrhea, or other abdominal distress; flushes or chills; frequent urination; dysphagia
Autonomic vigilance and scanning	Feeling keyed up or on edge; exaggerated startle response; fear; difficulty concentrating; disordered sleep; irritability

Mental distress or excessive worry that impairs the patient's ability to function is a cardinal feature of GAD, and so excessive worry over minor matters and inability to control the worry warrant probing after organic or physiologic causes of these symptoms have been ruled out by a thorough history and a physical examination. Medical problems to consider include GI, musculoskeletal, cardiovascular, respiratory, and thyroid disorders. Psychiatric problems including personality disorders and depression must also be ruled out.^13-15 Symptoms of anxiety can also be caused by anticholinergics, bronchodilators, steroids, oral contraceptives, antihypertensives, neuroleptics, and some OTC products such as cough and cold remedies, herbal therapies, and diet drugs.² Alcohol or illicit drug use should also be asked about, along with caffeine use. Increased agitation and restlessness in the elderly warrant suspicion of GAD, along with nutritional deficiencies, delirium, tumors, and dementia.⁸

Some complaints associated with GAD—such as symptoms of myocardial infarction (MI), ulcer, asthma, or irritable bowel syndrome (IBS)—may require extensive evaluation, often with diagnostic tests such as colonoscopy and imaging studies (see Table 2). The reassuring effect that normal results may have on the patient may justify the expense of these tests. Once physical problems have been excluded as a cause of the symptoms, the patient may accept the diagnosis of GAD. Some patients, however, may resist the diagnosis and continue to seek medical help for their unresolved physical complaints.

 

TABLE 2 Pursue generalized anxiety disorder only after ruling out these disorders
System	Disorders
Cardiac	Angina, arrhythmias, mitral valve prolapse
Endocrine	Cushing's disease, hyperparathyroidism, hyperthyroidism, pheochromocytoma
Gastrointestinal	Irritable bowel syndrome
Musculoskeletal	Arthritis, injury
Neurologic	Seizure disorder, vestibular dysfunction
Psychiatric	Acute stress disorder, depression, panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder
Respiratory	Asthma, pulmonary embolismAsthma, pulmonary embolismAsthma, pulmonary embolism

Making the diagnosis

An efficient approach to symptoms of GAD is important, particularly among primary care clinicians having to evaluate physical and somatic complaints within the time limits of a typical office visit.¹² Several screening tools may be useful.^16,17 These include the 15-question Anxiety Screening Questionnaire (ASQ-15), which can identify GAD consistent with the DSM-IV-TR criteria;¹⁸ a shortened version of the Primary Care Evaluation of Mental Disorders (PRIME-MD); the Hamilton Scale for Anxiety (HAM-A); the Center for Epidemiological Studies Depression Scale; the Hospital Anxiety and Depression Scale; and the Beck Depression Inventory.¹⁸ Many of these tools are available on the Web.

A simple approach to assessing for GAD involves asking the following two questions:

• During the past 4 weeks, have you been bothered by feeling worried, tense, or anxious most of the time?
• Are you frequently tense, irritable, and having trouble sleeping?⁷

An answer of yes to either question or both warrants further investigation.

If further questioning appears to be appropriate, ask about the age when worry began and about any treatment, whether the worry is perceived as a problem, and if the patient's work or school performance has been affected. Ask about current stressors and about important issues that need immediate attention. Listen for urgency.

Often, patients can recall symptoms associated with anxiety during their teenage years, and they may be able to provide examples of how anxiety has impaired social and occupational functioning. Severe childhood trauma, including sexual and physical abuse, can be a persistent stressor.¹⁹ The patient's past or current use of alcohol, diet drugs, stimulants, and anabolic steroids may provide clues to comorbid conditions that require further evaluation. These factors are important when deciding on a treatment plan, particularly counseling.

Developing a treatment plan

Effective treatments for anxiety disorders include psychosocial therapies to address the psychic symptoms of GAD and pharmacotherapy, which generally targets somatic symptoms; together, these may have longer lasting therapeutic effects than either therapy alone.^4,10,20 Once the diagnosis of GAD has been made and accepted by the patient, it is essential that the patient understand the importance of adherence to the treatment plan and feel that the provider takes the somatic complaints seriously. Discuss with the patient the risks for treatment failure, such as concomitant use of substances like alcohol; also mention potential drug interactions and the side effects of the agents selected for treatment.

Pharmacotherapeutic options

Antidepressants A selective serotonin reuptake inhibitor (SSRI) is an appropriate initial treatment for GAD.^7,21-23 Drugs in this class generally have few side effects, are not addictive, and can address comorbid problems such as depression.⁷ Paroxetine (Paxil) is the only SSRI to be FDA approved for GAD. Other SSRIs, including fluoxetine (Prozac), sertraline (Zoloft), citalopram (Celexa), and fluvoxamine (Luvox), have indications for panic disorder, OCD, posttraumatic stress disorder (PTSD), and phobias. The adverse effects associated with the use of SSRIs are usually dosage dependent and include nausea, decreased libido, abnormal ejaculation, agitation, sedation, sweating, and tremor.^24,25 It is not known how long SSRI therapy should continue, but since GAD is a chronic condition, it is reasonable to continue treatment with a goal of remission if a response is seen.²⁶ The lowest effective dosage should be used, with periodic reassessment.²⁶

Venlafaxine (Effexor), a serotonin-norepinephrine reuptake inhibitor (SNRI), is FDA approved for GAD.²⁷ Side effects include GI complaints, sexual dysfunction, visual disturbances, sweating, somnolence, dry mouth, and dizziness; venlafaxine can also increase BP and cause weight changes.^21,23,27 A therapeutic response may take 3 to 8 weeks. Like the SSRIs, this agent is useful for comorbid depression.

Research has suggested that the tricyclic antidepressant (TCA) imipramine (Tofranil) is an effective long-term treatment for GAD.^10,14,24 Imipramine has a greater effect on symptoms of psychic anxiety such as tension, apprehension, and worry, whereas the benzodiazepine alprazolam (Xanax) is more effective against hyperarousal and somatic symptoms such as palpitations, nausea, and feeling on edge. A therapeutic response to imipramine may not be noted for several weeks.¹⁴

TCAs are not often used in GAD because they cause anticholinergic side effects such as dry mouth, blurred vision, constipation, orthostatic hypotension, and sexual dysfunction.²⁵ Imipramine must be used with caution in patients with a history of urinary retention, cardiovascular disease, and narrow-angle glaucoma.²² Drug-drug interactions can be a problem,²⁵ as can weight gain.

Benzodiazepines Although their addictiveness prevents many primary care providers from prescribing drugs from this class, these drugs are often appropriate first-line pharmacotherapy for anxiety disorders including GAD, and they are particularly useful in acute anxiety. Benzodiazepines include alprazolam, chlordiazepoxide (Librium), clorazepate (Tranxene), diazepam (Valium), and oxazepam (Serax). With the exception of alprazolam, the recommended dosage of most drugs in this class is usually sufficient in treating the symptoms of GAD, although careful titration is important.^13,24 The risk of dependence may increase with dosage and duration of use, and the short half-life of most benzodiazepines requires frequent dosing to prevent symptoms from recurring between doses.

Although appropriate use of these agents does not impair functioning in most patients, the drugs can cause dosage-related problems that range from mild impairment in task performance to psychomotor or memory impairment to sedation and a near hypnotic state.²⁵ Abrupt cessation of these agents once tolerance has developed can cause symptoms of withdrawal, including increased anxiety, irritability, insomnia, and seizure.²³ Although its indication is panic disorder, clonazepam (Klonopin) may also be useful in GAD. The drug has a longer half-life than others in its class and requires less frequent dosing.^6,22 Possible side effects include sedation and depression.

Anxiolytics A popular alternative to benzodiazepines is buspirone (BuSpar), a partial 5 HT_1A receptor agonist. This non-sedating drug lacks the addictive potential associated with benzodiazepines, and a therapeutic response usually occurs within 4 weeks of initiating treatment.²⁴ Although it does not relieve physical symptoms such as muscle tension, buspirone promotes relaxation by reducing overall anxiety symptoms. It is generally well tolerated and causes no rebound anxiety or withdrawal symptoms on cessation. The dosage should be titrated slowly to minimize the potential for appetite disturbances and dizziness. Although evidence shows that buspirone is less effective when used with a benzodiazepine,²² carefully coordinated therapy may include a titrated dosage of a benzodiazepine to address acute symptoms together with buspirone for long-term control.^18,24

Other agents Although not as well studied as the drugs previously described, the atypical antidepressants nefazodone (Serzone) and trazodone (Desyrel) have been used for some of the symptoms of GAD. Worrisome possible side effects, however, limit their use, and these agents are currently not recommended. Mirtazapine (Remeron) has been under investigation for GAD since it was found to reduce anxiety in patients with depression.^24,28

Psychotherapy

Cognitive behavior therapy (CBT) can be effective in GAD²⁹ when the patient is willing to participate in therapy and understands the goals of modifying behavior and emotions by reframing thinking.^25,26 The techniques used in behavior modification include identifying anxiety triggers; cognitive rehearsal; biofeedback; deep, slow, rhythmic breathing; and learning coping skills.^12,14,25,26 Treatment lasts 3 to 6 months, and therapeutic response depends on the patient's participation in regular sessions and a good rapport with the therapist. The long-term effect of CBT in GAD is currently under study.²⁹

Although patients with comorbid depression may also benefit from CBT, those with personality disorders or chronic stressors and those who expect little benefit from therapy generally do not respond well to CBT.¹⁴ Regular counseling sessions can address occupational and family tensions and financial problems that exacerbate worry and physical tension.

Treatment failure may be caused by concomitant alcohol or substance abuse or by comorbidities such as depression, panic disorder, a personality disorder, or an organic problem. A poor response to pharmacotherapy may be due to inadequate duration of treatment, underdosing, adverse effects, or patient nonadherence.^14,24 Patients may fear becoming drug dependent or the stigma of therapy. Treatment failure generally warrants a psychiatric referral.

Patients who abuse alcohol or drugs may have symptoms that are difficult to differentiate from those of GAD, and the treatment of GAD in these patients is a challenge perhaps best met with a psychiatric consultation.⁸ Patients with a history of psychiatric admissions, detoxification episodes, or suicide attempts should be referred to a psychiatrist.

KEY POINTS in this article Patients with generalized anxiety disorder (GAD) worry constantly and may have symptoms similar to those seen in depressive disorders. No reliable demographic or medical profiles exist for GAD, which is often difficult to differentiate from other anxiety disorders. The patient's description of vague somatic complaints suggests that GAD is the cause of the symptoms. GAD is generally a diagnosis of exclusion after other medical and psychiatric conditions have been ruled out; symptoms must be unrelated to another disorder, and neither organic, related to substance abuse or medications, nor associated with other mood disorders. Effective treatment options include psychotherapy and pharmacotherapy, either alone or together.

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Robin Hunter Buskey. Meeting the challenge of generalized anxiety disorder. JAAPA December 2004;17:19-24.

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