Rudolf Hoehn-saric, MD

Generalized anxiety disorder (GAD) is characterized by excessive or unrealistic anxiety and worries about life circumstances. In the general population, the prevalence of GAD is 2% to 5%. It is the most frequent anxiety disorder seen in primary care, where 22% of patients complain of anxiety problems.

lists 6 somatic symptoms associated with GAD: restlessness, increased fatigability, difficulty in concentrating, irritability, muscle tension, and sleep disturbance. These symptoms may present with hyperarousal, hypervigilance, and heightened muscle tension; autonomic symptoms are milder than in other anxiety disorders and can be absent.

Patients with GAD do not form a homogeneous group. Cardiovascular or GI symptoms predominate in some patients. In one study, more than half of a surveyed population complained of palpitations and had had, at least once, a consultation with a cardiologist.

 In another study, results showed that patients with GAD who expressed high levels of cardiac complaints had higher levels of skin conductance, which measures sweat gland activity. They had greater cardiac variability during stress and required higher levels of benzodiazepines during treatment.

 more than 50% of patients with irritable bowel syndrome (IBS) also had GAD. In addition, GAD was found to have high comorbidity with other anxiety disorders and depression.

 In the presence of medical comorbidity, anxiety may crystallize around the physical state.

Treatment of GAD and its somatic symptoms 

 
Since excessive and often unrealistic worries are central to GAD, cognitive-behavioral therapy (CBT) is the preferred mode of psychological treatment. CBT teaches self-monitoring: patients learn to observe their anxious experiences and to correct faulty response patterns. In addition, various relaxation techniques help reduce the physiological expressions of hyperarousal and muscle tension.

Medications to control symptoms in GAD include benzodiazepines, SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), antipsychotics, and ß-blockers. The 

 presents an overview of the most frequent pharmacotherapies for treating GAD.

Treatment of GAD depends on the severity of the problem and the preferences of the individual patient and can consist of psychotherapy, pharmacotherapy, or both. Because each patient is unique, treatment plans have to be tailored to meet specific needs. The quality and severity of psychic symptoms need to be examined; the fears and worries, the level of arousal, the presenting somatic symptoms, and their behavioral consequences all need to be taken into account. This article will briefly review the various treatments available for GAD and its symptoms.

 
Many patients with GAD, particularly those with a family history, are concerned about having an illness and become preoccupied with their bodily state. Others experience cardiac or GI changes that may be harmless or may need medical attention. Patients worried about their physical state should undergo a thorough physical examination, and the results should be discussed with them to clarify which symptoms are due to anxiety and which symptoms to a potential physical illness.

One problem in assessing somatic symptoms is that patients show considerable discrepancies between perception of bodily states and actual changes of physiological states; they generally misperceive their bodily states.

 During acute stress, patients are fairly accurate in perceiving the direction of, but not the magnitude of, bodily changes. The relationship between bodily states and their perception is even more complex when changes are compared over longer periods.

The perception of bodily states depends to a large degree on the mood of a person and the attention paid to bodily states rather than on the actual physiological state.

 Therefore, improvement of anxiety lessens the perception of physical symptoms irrespective of the effect of medication on the bodily state. Treatment of physical symptoms without concomitant treatment of anxiety is usually insufficient but, when combined with a benzodiazepine or an anxiolytic such as buspirone, can help reduce the dose of the latter.

 
Few patients are anxious all the time, but some patients experience symptoms regularly (most of the day) while others only episodically (during demanding times). In the latter, only short-term use of benzodiazepines or antihistamines is needed. However, because of the potential for habituation, long-term use of benzodiazepines should be avoided.

Psychological treatments not only reduce psychic but also somatic symptoms; the latter diminish with reduction of worries irrespective of the patient's physical condition. Psychotherapy should be planned according to the needs and expectations of the patients. Milder cases may require only supportive therapy. More severely ill patients may need CBT with greater emphasis on relaxation when physical symptoms predominate and with more emphasis on cognitive aspects when strong psychic symptoms are present.

Antidepressants with serotonin- inhibiting properties have anxiolytic effects on psychic symptoms and are indicated in patients who have difficulties in coping with pathological fears and worries. The effect of antidepressants is not immediate, and medications must be taken regularly for several weeks. The choice of the antidepressant depends on how a patient tolerates adverse effects and on possible physical comorbidity. Generally, it is best to start with a low dose and titrate the dose until a therapeutic effect is achieved or until poor tolerance necessitates a change in medication.

Tolerance to the anxiolytic effects does not develop, and there is no abuse potential. Plasma levels are of little clinical help except to assess a lack of response caused by low levels or toxic effects produced by excessive levels. The duration of treatment has to be individualized; some patients improve within a few months and the dosage of the medication can be reduced and eventually stopped, while others have to take medication indefinitely.

 
Hyperarousal may manifest itself in tension lasting throughout the day and as insomnia at night. Patients may have difficulty in falling asleep or may wake up in the middle of the night, or both. Proper sleep hygiene and relaxation exercises help milder forms of insomnia. Alcohol in the evening should be avoided, because its sedative effect is brief and patients tend to wake up in the middle of the night. Antidepressants with sedative properties, such as mirtazapine or the sedating tricyclic antidepressants (TCAs) amitriptyline, doxepin, or clomipramine, may suffice. SSRIs have little or no sedative properties and additional sedative medication may have to be prescribed.

Benzodiazepines, zaleplon, zolpidem, eszopiclone, and sedating antihistamines such as diphenhydramine effectively induce sleep. Compared with benzodiazepines, zaleplon, zolpidem, and eszopiclone are less habit-forming; for instance, eszopiclone has been found effective for 12 months without causing tolerance.

 Patients who wake up at night need longer-acting sedatives. Trazodone and the long-acting benzodiazepine, flurazepam, induce long-lasting sleep; the former is not habit-forming but sometimes induces a hangover. To reduce daytime arousal, sedative antidepressants, benzodiazepines, and antihistamines are useful.	

 
Increased muscle tension is the most consistent physiological finding in anxious patients.

 However, many patients are unaware of increased muscle tension until they undergo relaxation exercises. While increased muscle tension affects the whole body, it can focus on specific groups of muscles, causing tension headache, writer's cramp, or globus hystericus. General muscle tension is a peripheral manifestation of central arousal; therefore, treatments that reduce hyperarousal also reduce general muscle tension. Spasms that affect specific muscle groups respond acutely to benzodiazepines but may need specific behavioral interventions.	

 
SSRIs and SNRIs have fewer cardiovascular adverse effects than TCAs and are better tolerated by older patients and patients with cardiovascular illnesses. Caution is necessary with venlafaxine because it can raise blood pressure.

SSRIs and SNRIs tend to stimulate the GI tract and can aggravate GI symptoms, particularly in patients with comorbid IBS. In such patients the anticholinergic effects of a tertiary TCA, such as doxepin, can reduce abdominal pain and improve bowel movements.	

 
The ultimate goal of treatment for somatic symptoms in patients with GAD is to help the patients become self-sufficient without the need for medication. However, a minority of patients who have GAD need continuous pharmacotherapy, including benzodiazepines. It would be shortsighted and insensitive to deny such patients medications that could improve their quality of life.

Wittchen HU. Generalized anxiety disorder: prevalence, burden and cost to society. 

. Cambridge UK: Cambridge University Press; 1998:37-85.


 Logue MB, Thomas AM, Barbee JG, et al. Generalized anxiety disorder patients seek evaluation for cardiological symptoms at the same frequency as patients with panic disorder. 

 Hoehn-Saric R, McLeod DR, Zimmerli WD. Symptoms and treatment responses of generalized anxiety disorder patients with high versus low levels of cardiovascular complaints. 

 Ballenger JC, Davidson JRT, Lecrubier Y, et al. Consensus statement on generalized anxiety disorder from the international consensus group on depression and anxiety. 

 McLeod DR, Hoehn-Saric R. Perception of physiological changes in normal and pathological anxiety. In: Hoehn-Saric R, McLeod DR, eds. 

. Washington, DC: American Psychiatric Press; 1993:223-243.


 Hoehn-Saric R, Borkovec TD, Nemiah JC. Generalized anxiety disorder. In: Gabbard GO, ed. 

 2nd ed. Washington, DC: American Psychiatric Press; 1995:1691-1722.


 Roth T, Walsh JK, Krystal A, et al. An evaluation of the efficacy and safety of eszopiclone over 12 months in patients with chronic primary insomnia. 

 Hoehn-Saric R, McLeod DR. Somatic manifestations of normal and pathological anxiety. In: Hoehn-Saric R, McLeod DR, eds. 

Washington, DC: American Psychiatric Press; 1993:77-222.

Articles

Generalized anxiety disorder (GAD) is characterized by excessive or unrealistic anxiety and worries about life circumstances. In the general population, the prevalence of GAD is 2% to 5%. It is the most frequent anxiety disorder seen in primary care, where 22% of patients complain of anxiety problems.1 DSM-IV lists 6 somatic symptoms associated with GAD: restlessness, increased fatigability, difficulty in concentrating, irritability, muscle tension, and sleep disturbance. These symptoms may present with hyperarousal, hypervigilance, and heightened muscle tension; autonomic symptoms are milder than in other anxiety disorders and can be absent.

Rudolf Hoehn-saric, MD

Articles

Treatment of Somatic Symptoms in Generalized Anxiety Disorder