Tranxene

Anxiety is a common symptom in family practice, with approximately 15 percent of patients meeting research criteria for any anxiety disorder.(1,2) The medical literature often suggests that anxiety and depression are underdiagnosed and undertreated in the primary care setting, and that patient outcomes will inevitably improve if family physicians simply learn to better recognize and treat standard psychiatric syndromes with therapies derived from the psychiatric practice.(3)

The time has come for family physicians and psychiatrists to acknowledge that this approach is at best misleading and may simply be wrong. It distracts family physicians from a nuanced understanding of how patients present with psychiatric disorders and how they are best treated in the family medicine setting. Recommendations derived from psychiatric populations have limited application to patients seen by family physicians.(4,5)

In this issue of American Family Physician, Gliatto(6) provides a useful review of generalized anxiety disorder (GAD). However, family physicians should temper their understanding of GAD by keeping in mind several issues that are especially pertinent to the care of patients seen in a family physician's office.

The first issue is that studies suggesting a high prevalence and underrecognition of psychiatric conditions in primary care may significantly overestimate the prevalence of these disorders. These studies often rely on screening instruments that result in high false-positive rates. For example, results from the PRIME-MD 1,000 study(1) revealed that 7 percent of patients met the criteria for GAD, but in-depth clinician interviews confirmed the diagnosis in only about one third of these patients.

The second issue, noted by Gliatto,(6) is that anxiety, even an apparently rather specific disorder such as GAD, is seldom a discrete illness. Rather, a common "mixed" depression and anxiety syndrome has been epidemiologically confirmed.(7) Not only are mixed syndromes the norm, but depression and GAD may not be separate syndromes at all.(8) Treatment of patients with medications such as benzodiazepines may worsen their depression.(9) Therefore, the family physician might rationally err on the side of treating the patient who has comorbid anxiety and depression with antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants that are known to be effective in this circumstance.

Family physicians understand that personality disorders, substance abuse and somatization disorders are common in the primary care setting and that anxiety often coexists. Moreover, family physicians are always balancing priorities, not just among coexisting and overlapping psychiatric syndromes, but between these and other acute and chronic disorders faced by patients.(10) In primary care, the patient with GAD as the highest priority disorder is unusual if not rare. The third issue is that the spectrum of illness is different in family medicine than in psychiatric practice, even within a single diagnostic category. Treatment of patients for the milder illnesses that are typical in a family practice setting may not lead to better patient outcomes. Family physicians tend to detect more severe than mild psychiatric disorders and, at least for depression, undetected patient outcomes do not differ from those whose mild depression is detected.(4)

While less research has been completed on "pure" GAD in the primary care setting than on depression, preliminary European research suggests that detection of anxiety may be associated with improved outcome.(11) However, patients in this study had more severe illnesses. Also, symptom severity may better predict the impact of psychiatric distress on patients' quality of life than does the diagnosis.(12) Family physicians may thus appropriately base decisions to initiate treatment more on symptom severity and functional status than on the mere presence of a disorder that meets the diagnostic criteria as outlined in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV).

The fourth issue is consistently and appropriately managing patients with GAD. The physician and patient should set treatment goals at the beginning of therapy and regularly monitor progress. For example, if the patient has one target symptom (e.g., a feeling of restlessness), then the physician should inquire about this symptom at each visit and document its resolution with treatment. If the patient's symptom fails to resolve, then the treatment regimen should be changed or discontinued.

Appropriate treatment requires rethinking the use of benzodiazepines. Their extensive use in the treatment of patients with GAD does not mean that they are necessarily the safest or most effective agents for this disorder. Most studies of benzodiazepines were conducted in the 1970s and 1980s using different diagnostic criteria than those now in use. Furthermore, few data are available on the treatment of patients with anxiety with benzodiazepines for longer than six months.

The use of benzodiazepines in the elderly poses special problems. It is important to recognize that while alprazolam (Xanax) and clorazepate (Tranxene) are short- or intermediate-duration agents in younger adults, they may function as "long-acting" agents in elderly persons because of age-related changes in cytochrome P450 metabolism and/or metabolism to active metabolites. Lorazepam (Ativan), oxazepam (Serax) and temazepam (Restoril) are the only benzodiazepines that are exclusively metabolized via conjugation to inactive metabolites. The ability to metabolize medications via conjugation is unaffected by age. If elderly patients require treatment with a benzodiazepine, therapeutic doses should begin at the lowest available dose of one of these three agents and increase slowly as target symptoms are addressed.

Gliatto(6) points out that benzodiazepines effectively relieve the somatic but not the psychic symptoms associated with anxiety. The search for agents, particularly antidepressants, to address the "worry" symptoms associated with GAD is in progress. One study(13) demonstrated superior efficacy in relieving the symptoms of GAD with the use of venlafaxine (Effexor) as compared with buspirone (BuSpar) and placebo. Other antidepressants under investigation for the treatment of patients with GAD include mirtazapine (Remeron) and nefazodone (Serzone).(14,15)

Buspirone, while similar to the benzodiazepines in effectively relieving the symptoms associated with GAD, may be used less often because of its delayed onset of action and the concern of efficacy in patients who have previously taken benzodiazepines. Buspirone may still be effective in treating patients with GAD, provided patients and physicians are informed about its time to onset and the initial adverse effects.(16)

In the family practice setting, venlafaxine and buspirone are acceptable first-line agents in the treatment of patients with GAD. Benzodiazepine therapy should be reserved primarily for patients with GAD who exhibit significant somatic symptoms of anxiety. If a benzodiazepine is prescribed, it should be used as short-term therapy (four to six weeks), and the patient should be followed carefully for successful resolution of target symptoms.

REFERENCES

(1.) Spitzer RL, Williams JB, Kroenke K, Linzer M, deGruy FV 3rd, Hahn SR, et al. Utility of a new procedure for diagnosing mental disorders in primary care. The PRIME-MD 1000 study. JAMA 1994;272: 1749-56.

(2.) Nisenson LG, Pepper CM, Schwenk TL, Coyne JC. The nature and prevalence of anxiety disorders in primary care. Gen Hosp Psychiatry 1998;20:21-8.

(3.) Tylee A. Depression in the community: physician and patient perspective. J Clin Psychiatry 1999;60 (suppl 7):12-6.

(4.) Schwenk TL, Klinkman MS, Coyne JC. Depression in the family physician's office: what the psychiatrist needs to know: the Michigan Depression Project. J Clin Psychiatry 1998;59(suppl 20):94-100.

(5.) Heath I. Commentary: there must be limits to the medicalisation of human distress. BMJ 1999;318: 439-40.

(6.) Gliatto M. Generalized anxiety disorder. Am Fam Physician 2000;62:000-000.

(7.) Blazer D, Swarz M, Woodbury M, Manton KG, Hughes D, George LK. Depressive symptoms and depressive diagnoses in a community population. Use of a new procedure for analysis of psychiatric classification. Arch Gen Psychiatry 1988;45:1078-84.

(8.) Liebowitz MR, Hollander E, Schneier F, Campeas R, Fallon B, Welkowitz L, et al. Anxiety and depression: discrete diagnostic entities? J Clin Psychopharmacol 1990;10(suppl 3):61S-6S.

(9.) Lydiard RB, Laraia MT, Ballenger JC, Howell EF. Emergence of depressive symptoms in patients receiving alprazolam for panic disorder. Am J Psychiatry 1987;144:664-5.

(10.) Schwenk TL. Competing priorities and comorbidities. So much to do and so little time. Arch Fam Med 1997;6:238-9.

(11.) Ormel J, Koeter MW, van den Brink W, van de Willige G. Recognition, management, and course of anxiety and depression in general practice. Arch Gen Psychiatry 1991;48:700-6.

(12.) Nease DE Jr, Volk RJ, Cass AR. Investigation of a severity-based classification of mood and anxiety symptoms in primary care patients. J Am Board of Fam Pract 1999;12:21-31.

(13.) Davidson JR, DuPont RL, Hedges D, Haskins JT. Efficacy, safety, and tolerability of venlafaxine extended release and buspirone in outpatients with generalized anxiety disorders. J Clin Psychiatry 1999;60:528-35.

(14.) Sitsen JM, Moors J. Mirtazapine, a novel antidepressant, in the treatment of anxiety symptoms. Results from a placebo controlled trial. Drug Investigation (New Zealand) 1994;86:339-44.

(15.) Hedges DW, Reimherr FW, Strong RE, Halls CH, Rust C. An open trial of nefazodone in adult patients with generalized anxiety disorder. Psychopharmacol Bull 1996;32:671-6.

(16.) Feighner JP. Overview of antidepressants currently used to treat anxiety disorders. J Clin Psychiatry 1999;60(suppl 22):18-22.

Dr. Magill is professor and chair in the Department of Family and Preventive Medicine, University of Utah School of Medicine, Salt Lake City. Dr. Gunning is assistant professor, Department of Pharmacy Practice, University of Utah College of Pharmacy, Salt Lake City.

Address correspondence to Michael K. Magill, M.D., Department of Family and Preventive Medicine, University of Utah School of Medicine, 50 North Medical Dr.--1C26SOM, Salt Lake City, UT 84132 (e-mail: mmagill@dfpm.utah.edu).

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