Anxiety Disorders: Real Disease, Real Treatment

Pharmacists can emphasize to patients that anxiety is a real disease with effective treatments.

Anxiety is an umbrella term encompassing several psychiatric disorders (Table 1), the more common of which are phobias, social anxiety, and generalized anxiety disorder (GAD). Previously, obsessive-compulsive behaviors, acute stress, and posttraumatic stress disorders were grouped under anxiety disorders; however, in the most recent Diagnostic Statistical Manual-5 (DSM-5), these disorders were placed in other categories.^1,2

GAD is a chronic and highly prevalent debilitating disorder and is the most common anxiety disorder seen by practitioners. Patients suffering from GAD excessively worry about situations or objects in the absence of real danger. GAD is characterized by the following symptoms: increased motor tension (eg, fatigability, trembling, restlessness, muscle tension), autonomic hyperactivity (eg, shortness of breath, rapid heartbeat, high heart rate, dry mouth, cold hands, dizziness), and increased vigilance and scanning (eg, feeling keyed up, increased startling, impaired concentration). Men generally experience different symptoms from women. Men exhibit more psychologic symptoms, such as irritability and a sense of impending doom, whereas women develop more physical symptoms, such as chest pain, palpitations, and shortness of breath.^3,4

Diagnostic criteria stipulate that an individual must have 2 or more symptoms most days of the week for at least 6 months. Disease onset typically occurs early in life and quickly erodes quality of life, social relationships, job performance, and physical health.^5,6

Approximately 5% of people develop GAD over the course of their lifetime. In any given year, 3.1% of Americans suffer from GAD, which disproportionally affects women. Within a 6-month period, 6% of men and 13% of women suffer from anxiety.⁷ Long-term remission statistics are discouraging. Approximately 25% of adults will be in full remission after 2 years, and 38% will be in remission after 5 years.^3,4 Table 2 lists risk factors for GAD.

Several physical illnesses are associated with anxiety, including gastroesophageal reflux disease, heart disease, hypothyroidism, and hyperthyroidism. Overall, anxiety has high rates of comorbidity with depression as well as alcohol and drug abuse.^8,10 GAD may also worsen other mental and physical conditions, such as depression, insomnia, digestive or bowel problems, and headaches. Anxiety increases the risk for developing coronary heart disease and for mortality.⁴ Anxiety’s disease burden is comparable to that of other chronic illnesses, such as arthritis and diabetes.¹¹

Until recently, the pathophysiology of GAD remained elusive. Researchers postulate that anxiety is linked to dysregulation of neurotransmitters (ie, gamma-aminobutyric acid, serotonin, dopamine, and norepinephrine). The brain’s amygdala also appears key in modulating fear and anxiety. Patients with anxiety disorders often show heightened amygdala responses to anxiety cues.⁵

Treatment

Benzodiazepines, buspirone, hydroxyzine, antidepressants (eg, imipramine, paroxetine, sertraline, escitalopram, venlafaxine, opipramol), and pregabalin are effective in reducing anxiety symptoms. Benzodiazepines are generally used only for short-term relief of symptoms. When antidepressants are used, patient adherence may be problematic because of the agents’ adverse effects (eg, sedation, dizziness, falls, nausea, sexual dysfunction).² Second-generation antipsychotics (eg, quetiapine, risperidone, olanzapine, aripiprazole) are also effective, but given their side effects, they are reserved for people who have not responded to other agents. No drug class is considered superior to others.^12,13

Along with prescription agents, cognitive behavioral therapy (CBT) is extremely effective in treating anxiety. The hallmark features of CBT are intervention strategies derived from learning and cognitive theory principles. CBT interventions include cognitive restructuring (teaching specific skills to identify negative thoughts and behaviors and replace them with positive ones). CBT is generally short-term; positive results are often achieved with 8 sessions.^4,14

Herbal Remedies

Passionflower, valerian, St. John’s wort, and kava significantly reduce anxiety-related symptoms. While the FDA has not approved these agents for the treatment of anxiety, passionflower and kava are approved antianxiety agents in several countries.5 One small study, for example, demonstrated that passionflower was equally as effective as prescription benzodiazepine.⁵ Nutritional supplements such as L-lysine, L-arginine, vitamin B, and folic acid have also demonstrated effectiveness as alternatives to prescription agents. The use of these agents, however, has been associated with several adverse effects. Kava has been linked to hepatotoxicity, which prompted the FDA to issue warnings against its use. Additionally, St. John’s wort has significant negative clinical interactions with several classes of medications, such as anticancer agents, anti-HIV agents, anti-inflammatory agents, antimicrobial agents, cardiovascular drugs, proton pump inhibitors, and statins.^9,15,16

Counseling

Patients suffering from GAD often encounter ridicule, with friends telling them to “Just snap out of it.” Patients are relieved when someone takes their symptoms seriously. Because many prescription and nonprescription agents can induce anxiety, counseling begins with reviewing the patient’s medication profile to determine if anxiety may be medication induced. Online Table 3 highlights several counseling tips.

Table 3: Counseling for Generalized Anxiety Disorder

• Recommend a healthy diet and the avoidance of caffeine, alcohol, and illicit drug use.
• Explain how cognitive behavioral therapy can reduce anxiety, noting that only 8 sessions can reduce anxiety.
• Warn against abruptly discontinuing medication without physician approval. If patients complain about side effects, recommend alternatives to health care providers.
• Inform patients that antidepressants may take a few weeks to have an effect.
• Avoid clinical jargon because it may provoke more anxiety.
• Recommend daily exercise because it helps reduce anxiety. Exercise has minimal side effects with the added benefit of positively impacting other conditions, such as obesity and diabetes.
• Encourage patients to try relaxation exercises such as yoga or meditation.
• Warn patients that some herbal remedies have negative side effects. Patients should obtain physician approval prior to using such agents.
• Enlist the help of family members who can reinforce medication adherence.
• Recommend resources where patients and families can find useful information. The Anxiety and Depression Association of America (www.adaa.org) and the National Institute of Mental Health (www.nimh.nih.gov) both have useful and easy-to-understand information.

Adapted from references 4, 8, and 14.

Final Thought

When patients ask about a product that might “calm the nerves,” pharmacists should use this counseling opportunity to emphasize that anxiety is a real disease in which symptoms can be lessened or alleviated with treatment.

Dr. Zanni is a psychologist and health-system consultant based in Alexandria, Virginia.

References

• Recent updates to proposed revisions for DSM-5. American Psychiatric Association website. www.dsm5.org/Pages/RecentUpdates.aspx. Accessed January 27, 2014.
• Highlights of changes from DSM—IV-TR to DSM-5. American Psychiatric Association website. www.dsm5.org/Documents/changes%20from%20dsm-iv-tr%20to%20dsm-5.pdf. Accessed January 24, 2014.
• Gale CK, Millichamp J. Generalised anxiety disorder [published online October 27, 2011]. Clin Evid.
• Dryden-Ewards R. Generalized anxiety disorder. www.medicinenet.com/anxiety/article.htm. Accessed January 24, 2014.
• Lakhan SE, Vieira KF. Nutritional and herbal supplements for anxiety and anxiety-related disorders: systematic review. Nutr J. 2010;9:42.
• Gao K, Sheehan DV, Calabrese JR. Atypical antipsychotics in primary generalized anxiety disorder or comorbid with mood disorders. Expert Rev Neurother. 2009;9:1147-1158.
• Leon AC, Portera L, Weissman MM. The social costs of anxiety disorders. Br J Psychiatry Suppl. 1995;27:19-22.
• Generalized anxiety disorder. Mayo Clinic website. http://www.mayoclinic.org/diseases-conditions/generalized-anxiety-disorder/basics/definition/CON-20024562. Accessed January 23, 2014.
• Morgan AJ, Jorm AF. Outcomes of self-help efforts in anxiety disorders. Expert Rev Pharmacoecon Outcomes Res. 2009;9:445-459.
• Yates W. Anxiety disorders. http://emedicine.medscape.com/article/286227-overview. Accessed January 23, 2014.
• Shen BJ, Avivi YE, Todaro JF, et al. Anxiety characteristics independently and prospectively predict myocardial infarction in men the unique contribution of anxiety among psychologic factors. J Am Coll Cardiol. 2008;51:113-119.
• Koen N, Stein DJ. Pharmacotherapy of anxiety disorders: a critical review. Dialogues Clin Neurosci. 2011;13:423-437.
• Collins K, Mathew S. Current evidence in the treatment of generalized anxiety disorder. www.medscape.org/viewarticle/590285_2. Accessed January 31, 2014.
• Otte C. Cognitive behavioral therapy in anxiety disorders: current state of the evidence. Dialogues Clin Neurosci. 2011;13:413-421.
• Mental health medications. National Institute of Mental Health website. www.nimh.nih.gov/health/publications/mental-health-medications/complete-index.shtml. Accessed January 31, 2014.
• Herring MP, O’Connor PJ, Dishman RK. The effect of exercise training on anxiety symptoms among patients: a systematic review. Arch Intern Med. 2010;170:321-331.