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Dr. Vande Griend is an assistant professor in the Department of Clinical Pharmacy at the University of Colorado Denver School of Pharmacy, Aurora, Colorado.
Anxiety is the body?s natural response to real or perceived danger. When kept in check, anxiety can be very useful by allowing individuals to enhance their perception of external stimuli and potentially improve performance. For example, anxiety from fear of failure may force a pharmacy student to increase the amount of time spent studying and may improve his or her mental acuity, resulting in better grades and retention of knowledge. Likewise, anxiety concerning inaccurately dispensing a prescription may result in a pharmacist double-checking his or her work or setting up safeguards within the pharmacy to prevent filling errors.
The natural response of anxiety becomes a disorder when it is excessive and difficult to control and when it leads to significant distress and impairment. For instance, excessive anxiety over an upcoming examination may cause a pharmacy student physical symptoms (eg, abdominal pain, diarrhea, nausea) and prevent the student from being able to focus on studying the material, resulting in poor performance.
Anxiety disorders come in 5 forms: social anxiety disorder, an irrational persistent fear of being negatively evaluated and embarrassed by peers1,2; posttraumatic stress disorder, characterized by exposure to a traumatic event, resulting in flashbacks and avoidance of event remembrance1,3; panic disorder, characterized by spontaneous attacks involving intense fear, with physical symptoms (eg, palpitations, sweating, and shortness of breath); obsessive? compulsive disorder, resulting in recurrent and persistent intrusive thoughts causing fear and anxiety that lead to obsessions which can include repetitive behaviors (eg, cleaning, washing, counting)1,4; and generalized anxiety disorder (GAD), characterized by excessive anxiety and worry that is not necessarily specific to any one concern.1,5
Treatment of anxiety varies, depending upon the specific type of disorder, but generally includes both pharmacologic and nonpharmacologic approaches. According to a recent review, the point prevalence of GAD is 8% in primary care, suggesting that GAD is the most common anxiety disorder seen by physicians in this setting.6,7 In addition, medication therapy is the primary method for treating this disorder in the outpatient setting. Full diagnostic criteria for GAD, adapted from the Diagnostic and Statistical Manual of Mental Disorders, are listed in Table 1.
The pharmacologic treatment of GAD involves the use of antidepressants, benzodiazepines, and buspirone. Depending on the severity of the anxiety, as well as the response to individual medications, a patient may receive 1 or more of these treatment options.
Antidepressants include selective serotonin reuptake inhibitors (SSRIs; eg, paroxetine, escitalopram, citalopram, fluoxetine, sertraline), serotonin and norepinephrine reuptake inhibitors (SNRIs; eg, venlafaxine, duloxetine), and tricyclic antidepressants (eg, amitriptyline, nortriptyline, imipramine). Antidepressants are first-line treatment for GAD, because they treat the underlying cause, which may be an abnormality in serotonin.5,8,9 SSRIs or SNRIs are considered equally effective.7 Choice of therapy is dependent upon cost and tolerability. Because of their side-effect profile, tricyclic antidepressants are rarely used.
When initiating an antidepressant, it is important to start at a low dose and increase the dose as necessary. Upon initiation, side effects of antidepressants include restlessness, jitteriness, insomnia, and agitation. These symptoms mimic anxiety, and may cause a patient to discontinue therapy. Patients should expect at least 4 weeks before some improvement has been seen and up to 16 weeks for full effect.5
Commonly used benzodiazepines include alprazolam (short half-life and duration of action), lorazepam and clonazepam (intermediate half-life and duration of action), and diazepam (long half-life and duration of action). Benzodiazepines rapidly relieve the symptoms of anxiety, and are also useful for intermittent and episodic flares in anxiety symptoms. They are not appropriate for use as firstline or monotherapy treatment of GAD, because they do not treat the underlying cause of the anxiety, but rather only mask the symptoms. They are best used for acute relief of anxiety symptoms while a long-term treatment is initiated and begins to provide relief. In addition, benzodiazepines have many side effects, some of which are associated with longterm treatment.9
Buspirone is indicated for the treatment of GAD, but not other anxiety disorders. It does not have activity against depression, a common comorbid condition associated with anxiety; therefore, it is not considered first-line treatment.5,9 It does not cause sedation, physical dependency, and has not been shown to lead to withdrawal, however.5 Because of this, it may have benefits over benzodiazepines and possibly over antidepressants. Similar to antidepressants, it may take 4 to 6 weeks or longer for benefit to be realized; treatment of acute anxiety symptoms is likely needed when using buspirone for initial treatment.5
The use of benzodiazepines will make a patient feel very relaxed, and anxiety symptoms will disappear very quickly. Because of this, it can be easy for patients to overuse them and possibly develop side effects and addictive behaviors over time. Educating patients about appropriate use may prevent long-term problems. In addition, patients must be aware that antidepressants can cause increased anxiety when first initiated. Patients discontinue therapy too frequently due to lack of knowledge concerning side effects and therapy expectations. Important medication-specific counseling points for patients with anxiety are described in Table 2.