Practice Guidelines and Principles: Guidelines and principles are intended to be flexible. They serve as reference points or recommendations, not rigid criteria. Guidelines and principles should be followed in most cases, but there is an understanding that, depending on the patient, the setting, the circumstances, or other factors, care can and should be tailored to fit individual needs. Purpose: Patients that have Generalized Anxiety Disorder (GAD) are more often treated by their primary care physician than by a psychiatrist. These patients are difficult to diagnose as they tend to have multiple, unexplained somatic symptoms coupled with frequent office visits or telephone calls. Early diagnosis of GAD can improve the patients overall sense of wellbeing and can eliminate the multiple symptom complaints. Other anxiety disorders such as; panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, and phobias are not the focus of this guideline. Key Messages: More than 19 million American adults are affected by an anxiety disorder. Of this population, 4 million have GAD during the course of a given year. (Grade A) Among PCP patients, GAD has a 8% prevalence. This is the most prevalent anxiety disorder in the primary care environment. (Grade B) Research shows that GAD often coexists with depression, substance abuse, or other anxiety disorders. Other conditions associated with stress, such as irritable bowel syndrome, often accompany GAD. (Grade A) Anxiety disorders are highly treatable, yet only about one-third of those suffering from an anxiety disorder receive treatment. (Grade A) Treatments for GAD include medications and cognitive-behavioral therapy. (Grade A) High Risk Populations/Disparities GAD is more prevalent in women then men with a median onset in the early 20s. Some research suggests that GAD may run in families, and it may also grow worse during stress. GAD usually begins at an earlier age and symptoms may manifest themselves more slowly than in most other anxiety disorders. Geriatric patients tend to have an altered drug metabolism and multiple medical diagnoses. When medication is needed, smaller doses are usually required and side effects can be greater than in the nongeriatric patients. Benzodiazepines should be used with caution in geriatric patients. Distributed to: Primary Care Physicians, including Internists, General Practice and Family Practice Physicians, Developed by: Eugene Schneider, MD, Excellus BlueCross Blue Shield (chair); Mona Chitre, PharmD, Ann Griepp, MD, Excellus BCBS; Susan McDaniel, PhD, Psychology; John McIntyre, MD, Psychiatry; Michael Privitera, MD, Psychiatry; Timothy Sheehan, CSW, Thomas Campbell, MD, Family Medicine. Approved by: The Rochester Health Commission s Community-wide Clinical Guidelines Steering Committee on October 17, 2005. Next scheduled update to be completed by October, 2007. Page 1 of 8
ROCHESTER COMMUNITY-WIDE GUIDELINES GRADING SYSTEM STRENGTH OF RECOMMENDATIONS: The Rochester Community-wide Clinical Guidelines Steering Committee (CWGSC) grades its recommendations according to one of five classifications (A, B, C, D, I) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms). A CWGSC strongly recommends that clinicians provide [the service] to eligible patients. There is good evidence that [the service] improves important health outcomes to conclude that benefits substantially outweigh harms. B CWGSC recommends that clinicians provide [this service] to eligible patients. There is at least fair evidence that [the service] improves important health outcomes to conclude that benefits outweigh harms. C CWGSC makes no recommendation for or against routine provision of [the service]. There is at least fair evidence that [the service] can improve health outcomes to conclude that the balance of benefits and harms is too close to justify a general recommendation. D CWGSC recommends against routinely providing [the service] to asymptomatic patients. There is at least fair evidence that [the service] is ineffective or that harms outweigh benefits. I CWGSC concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that the [service] is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined. QUALITY OF EVIDENCE: The quality of the overall evidence for a service is on a 3-point scale (good, fair, poor). Good Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes. Fair Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies, generalizability to routine practice, or indirect nature of the evidence on health outcomes. Poor Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes. Adapted from the USPSTF grading system. Approved 05.16.05 Page 2 of 8
Symptoms of Generalized Anxiety Disorder (GAD) DSM-IV Criteria The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) is a guide to the diagnosis of mental disorders in the United States. The following are a list of the criteria for Generalized Anxiety Disorder. Please note: although these criteria are designed to provide a guideline to diagnosis they cannot substitute a visit to a doctor or mental health practitioner. These guidelines are provided for information purposes only. Diagnostic Criteria for Generalized Anxiety Disorder (GAD) A. Excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance). B. The person finds it difficult to control the worry. C. The anxiety and worry are associated with three (or more) of the following six symptoms (with at least some symptoms present for more days than not for the past 6 months). Note: Only one item is required in children. restlessness or feeling keyed up or on edge being easily fatigued difficulty concentrating or mind going blank irritability muscle tension, sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep) D. The focus of the anxiety and worry is not confined to features of another anxiety disorder. For example: the anxiety or worry is not about having a Panic Attack (as in a Panic Disorder), being embarrassed in public (as in Social Phobia), being contaminated (as in Obsessive-Compulsive Disorder), being away from home or close relatives (as in Separation Anxiety Disorder), gaining weight (as in Anorexia Nervosa), having multiple physical complaints (as in Somatization Disorder), or having a serious illness (as in Hypochondriasis), and the anxiety and worry do not occur exclusively during Posttraumatic Stress Disorder. E. The anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. F. The disturbance is not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hyperthyroidism) and does not occur exclusively during a Mood Disorder, a Psychotic Disorder, or a Pervasive Developmental Other factors that can be associated with GAD: Family history of an anxiety disorder or alcoholism High utilization and urgent care needs Repeated office visits or ER visits with negative work-ups Diagnosis of an anxiety disorder that include: atypical chest pain, hyperventilation, and irritable bowel syndrome October 17, 2005. Next scheduled update by October, 2007. Page 3 of 8
Treatment of Generalized Anxiety Disorder in the Primary Care Setting Patient presenting with excessive worry and anxiety occurring on more days than not for at least six months Evaluate: any medical reason for symptoms medication usage history of substance/alcohol abuse rule out any other anxiety and mood disorder family history other psychosocial factors previous history of counseling, medication therapy (note if successful or failed treatment) Assess Suicide/Homicidal Risk Factors Does patient have: suicidal thoughts plan means intent High Risk Implement Crisis Options Call 911 Contact local services Call local Poison Control if Overdose Suspected Contact emergency room Non Pharmacological Treatment: relaxation techniques lifestyle changes: regular exercise, adequate sleep, avoid caffeine / alcohol consider referral to behavioral health specialist Low Risk Pharmacological Treatment indicated for those patients that anxiety results in significant distress or the inability to perform daily functions ( See GAD Medication Algorithm) consider a referral to mental health services anywhere along that medication guideline. Monitoring the Treatment Progress Consider utilizing attached GAD Self Test Monitor monthly to bimonthly via office visits for symptom improvement Patient documentation of symptom frequency and duration, situational triggers, and coping mechanisms utilized Refer to and Collaborate with a Psychiatrist or Mental Health Provider Patient is not able to obtain/maintain recovery Patient does not respond to behavioral therapy and pharmacological treatment Co-morbidity suspected, such as depression October 17, 2005. Next scheduled update by October, 2007. Page 4 of 8
Generalized Anxiety Disorder Medication Algorithm *Caution in substance abuse patients Benzodiazepines for 4-6 wks* Lorazepam (Ativan) Clonazepam(Klonopin) Diazepam (Valium) Alprazolam (Xanax) Oxazepam (Serax) TE: Needs to be used with extreme caution for long term use. Evaluate need on a case by case basis. Long Term Therapy needed? General Anxiety Disorder Diagnosis Acute Relief Needed? Start Selective Serotonin Reuptake Iinhibitor**, 4-6 weeks Paroxetine (Paxil), Citalopram(Celexa), Sertraline (Zoloft) Venlafaxine (Effexor) or Buspirone (BuSpar): Adequate Response? Switch to Selective Serotonin Reuptake Inhibitor**, 4-6 weeks Paroxetine (Paxil), Citalopram (Celexa), Sertraline (Zoloft) Venalfaxine (Effexor) or Buspirone (BuSpar) Monitor Treatment Progress (monthly to Bimonthly) Adequate Response? Switch to one of the following: 4-6 weeks Tricyclic Antidepressant: Imipramine (Tofranil) or Nortriptyline (Pamelor) Atypical antidepressants: Mirtazepine (Remeron) Antihistamine: Hydroxyzine (Atarax, Vistaril) **Choice of Selective Serotonin Reuptake Inhibitor depends on many factors Adequate Response? Adjunct therapy options: Benzodiazepine (prn basis) Propanolol (Inderal) October 17, 2005. Next scheduled update by October, 2007. Page 5 of 8
Generalized Anxiety Disorder Dosing Drug Class Initial Dose mg/d Dose Range mg/d Selective Serotonin Reuptake Inhibitors Citalopram (Celexa) 10 20-60 Fluoxetine (Prozac) 5-10 10-80 Fluvoxamine 25 25-300 Paroxetine* (Paxil) 10 10-50 Sertraline (Zoloft) 25 25-200 Serotonin Norepinephrine Reuptake Inhibitor Venlafaxine* (Effexor) 25-37.5 50-75 TID Venlafaxine XR* (Effexor XR) 37.5 75-225 Tricyclic Antidepressants Azapirone Buspirone* (BuSpar) 10-15 10-60 Clomipramine (Anafranil) 25-75 (qhs) 100-250 Desipramine(Norpramin) 10-75 (qhs) 150-300 Imipramine(Tofranil) 10-75 (qhs) 50-300 Nortriptyline(Pamelor) 10-50 (qhs) 50-150 Benzodiazepines Alprazolam*(Xanax) 0.25-0.5 2-10 TID Chlordiazepoxide(Librium) 5-25 15-100 TID/QID Clonazepam(Klonopin) 0.25 BID 0.5-2 Diazepam*(Valium) 4 4-40 Lorazepam*(Ativan) 0.5 BID 2-4 Oxazepam(Serax) 10-30 TID/QID 30-120 Atypical Antidepressants Mirtazapine (Remeron) 15 15-45 Antihistamine Hydroxyzine (Atarax, Vistaril) Varies Varies Beta-Blocker Propranolol(Inderal) Varies Varies * FDA indication for GAD October 17, 2005. Next scheduled update by October, 2007. Page 6 of 8
Generalized Anxiety Disorder: Consideration Points ** Choice of SSRI depends on many factors: Patient past response Patient opinion Pharmacokinetics Drug interactions Adverse effects Cost Benzodiazepines: High addiction, abuse and overdose potential Primary symptom (Worry) not relieved Patients (>33->50%) do not reach remission Higher recurrence rate with this class verses other anxiolytic classes No antidepressant properties Problematic side effects Buspirone: No antidepressant properties Compliance with TID dosing Long term efficacy not well studied SNRI: Venlafaxine Significant risk of hypertension with doses >300 mg/d Careful monitoring of blood pressure is indicated in these patients October 17, 2005. Next scheduled update by October, 2007. Page 7 of 8
References 1) American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4 th Ed, text revision (DSM-IV-TR). Washington, American Psychiatric Association, 2000:472-476. 2) Anxiety Disorders Association of America. Improving the Diagnosis and Treatment of Generalized Anxiety Disorder: A Dialogue Between Mental Health Professionals and Primary Care Physicians. Anxiety Disorders Association of America, 2004. Website: http://www.adaa.org/bookstore/adaapublications.asp (accessed 7/25/05) 3) Anxiety Disorders. In Dipiro s, et al. Pharmacotherapy: A Pathophysiological Approach. 5 th ed. McGraw Hill. 2002; Chapter 71:1291-1301. 4) Fricchione, Gregory. Generalized Anxiety Disorder. N Engl J Med. 2004 Aug; 12:675-682. 5) Gale, Christopher. Generalized Anxiety Disorder. American Family Physician. 2003 Jan; 1:135-138. 6) Gliatto, M. Generalized Anxiety Disorder. American Family Physician. 2000; 62 (7): 1591-1600, 1602. 7) Goodman, Wayne K. Selecting Pharmacotherapy for Generalized Anxiety Disorder. J Clin Psychiatry. 2004; 65 (suppl. 13): 8-13. 8) Hales, R., Hilty, D. and Wise, M. A Treatment Algorithm for the Management of Anxiety in Primary Care Practice. Journal of Clinical Psychiatry. 1997; 58 (suppl 3): 76 80. 9) Lacy, Charles. Drug Information Handbook. 13 th ed, Hudson, Ohio. Lexi-Comp: 2005. 10) Mitte, Kristin. A Meta-analytic Review of the Efficacy of Drug Treatment in Generalized Anxiety Disorder. J Clin Psychopharmacol. 2005; 25: 141-150. 11) National Institute of Mental Health. Facts about Anxiety Disorders. Publication No. OM-99 4152. January 1999. 12) Schweizer, E. and Rickels, K. Strategies for Treatment of Generalized Anxiety in the Primary Care Setting. Journal of Clinical Psychiatry. 1997; 58 (suppl 3): 27 31. 13) Screening for Mental Health. Depression and Generalized Anxiety Disorder: A Guide for Health Care Clinicians. National Depression Screening Day 2004. 14) Thompson, P. Generalized Anxiety Disorder Treatment Algorithm. Psychiatric Annals. 1996; 26 (4): 227-232. 15) www.adaa.org accessed 07-19-05. 16) www.nami.org accessed 07-20-05. October 17, 2005. Next scheduled update by October, 2007. Page 8 of 8