Help For Generalized Anxiety Disorder

Although few controlled studies support the long-term use of benzodiazepines, GAD is a chronic disorder, and some patients will require benzodiazepine therapy for months to years. Generally, patients who present with acute anxiety or those with chronic anxiety who undergo a new stressor ("double anxiety") should receive benzodiazepine therapy for several weeks. Patients may be less tolerant of anxiety that recurs when the benzodiazepine is discontinued and, if necessary, it may have to be resumed indefinitely. Patients who use benzodiazepines chronically tend to be elderly, to be in psychologic distress and to have multiple medical problems.

Other Medications. Buspirone (BuSpar) is the drug often used in patients with severe anxiety and those who relapse after a course of benzodiazepine therapy. It is also the initial treatment for anxious patients with a previous history of substance abuse. Buspirone appears to be as effective as the benzodiazepines in the treatment of patients with GAD, and its use does not result in physical dependence or tolerance.

Unlike the immediate relief of symptoms that occurs with benzodiazepine therapy, buspirone's onset of action takes two to three weeks. Therefore, patients should be informed of the expected delay in relief of symptoms. Buspirone has an opposite effect of the benzodiazepines in that it treats the worry associated with GAD rather than the somatic symptoms. However, buspirone may not be as effective in patients who have been treated with a benzodiazepine during the previous 30 days.

The initial dosage of buspirone is 5 mg three times daily with a gradual dose titration until symptoms remit or the maximum dosage of 20 mg three times daily is reached. If the dosage is titrated too quickly, headaches or dizziness may occur. In patients who are taking benzodiazepines at the time of the initiation of buspirone, tapering the benzodiazepine should not begin until the patient reaches a daily dosage of 20 to 40 mg of buspirone.

In addition to the GABA/BZ complex, research has shown that GAD involves several neurotransmitter systems, including that of norepinephrine and serotonin. Pharmacologic agents that affect these neurotransmitters, such as the tricyclic antidepressants and the SSRIs, have been studied in patients with GAD who do not respond to the benzodiazepine therapy or buspirone. Imipramine (Tofranil) has been shown to be effective in controlling the worrying that is associated with GAD, but whether it is as effective as benzodiazepines or buspirone in those patients who have anxiety without depressive symptoms has not been determined. Imipramine also has anticholinergic and antiadrenergic side effects that limit its use. Desipramine (Norpramin) and nortriptyline (Pamelor) can be used as alternatives.

Trazodone (Desyrel) is a serotonergic agent, but because of its side effects (sedation and, in men, priapism), it is not an ideal first-line agent.Daily dosages of 200 to 400 mg are reported to be helpful in patients who have not responded to other agents. Nefazodone (Serzone) has a similar pharmacologic profile to trazodone, but it is better tolerated and is a good alternative. Paroxetine (Paxil), an SSRI, has also been studied as a treatment for patients with GAD, but the trial was small, as has been the case with most of the antidepressants under investigation. Venlafaxine SR (Effexor) is the first medication to be labeled by the U.S. Food and Drug Administration as an anxiolytic and as an antidepressant; thus, it can be used for the treatment of patients with major depression or GAD, or when they occur comorbidly.

Antihistamines are not potent anxiolytics. Although some antipsychotic drugs have sedating properties, they should rarely be used as therapy for patients with GAD. Beta-adrenergic agents are useful for the treatment of patients with performance anxiety (a type of social phobia) because they lower heart rate and decrease tremulousness; they do not however, decrease the worrying or other somatic symptoms associated with GAD.

Two herbal remedies that are often used for the treatment of anxiety are Valeriana officinalis (valerian), a root extract, and a beverage made from the root of Piper methysticum (kava-kava). Both have sedating properties, but kava has worrisome side effects that include synergy with alcohol and benzodiazepines, dyskinesias and dystonia, and dermopathy. Valerian root has been reported to cause delirium and cardiac failure if abruptly discontinued. Further studies are needed before these herbal products can be recommended as therapeutic agents for persons with GAD.

Consultation with a psychiatrist should be considered if a patient with GAD does not respond to an appropriate course of benzodiazepine or buspirone therapy. A psychiatrist can help clarify the diagnosis, determine if a comorbid psychiatric disorder is present and determine which comorbid disorder should be treated as the primary disorder. A psychiatrist can also make recommendations about therapy, including the addition of psychotherapy and changes in medications.