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Essentials of Primary Care 2008: Anxiety Disorders

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1 Essentials of Primary Care 2008: Anxiety Disorders
Descartes Li, M.D. Associate Clinical Professor University of California, San Francisco What are the emotions? Emotions not that easily defined Sad, mad, glad and scared Define anxiety: “Fight or Flight” Anxiety (also called solicitude) is a psychological and physiological state characterized by cognitive, somatic, emotional, and behavioral components[1]. These components combine to create the painful feelings that we typically recognize as anger, fear, apprehension, or worry. Anxiety is often accompanied by physical sensations such as heart palpitations, nausea, chest pain, shortness of breath, stomach aches, or headache. The cognitive component entails expectation of a diffuse and certain danger. Somatically the body prepares the organism to deal with threat (known as an emergency reaction): blood pressure and heart rate are increased, sweating is increased, bloodflow to the major muscle groups is increased, and immune and digestive system functions are inhibited (the 'fight or flight' response). Externally, somatic signs of anxiety may include pale skin, sweating, trembling, and pupillary dilation. Emotionally, anxiety causes a sense of dread or panic and physically causes nausea, diarrhea, and chills. Behaviorally, both voluntary and involuntary behaviors may arise directed at escaping or avoiding the source of anxiety and often maladaptive, being most extreme in anxiety disorders. However, anxiety is not always pathological or maladaptive: it is a common emotion along with fear, anger, sadness, and happiness, and it has a very important function in relation to survival. Neural circuitry involving the amygdala and hippocampus is thought to underlie anxiety[2]. When confronted with unpleasant and potentially harmful stimuli such as foul odors or tastes, PET-scans show increased bloodflow in the amygdala.[3][4] In these studies, the participants also reported moderate anxiety. This might indicate that anxiety is a protective mechanism designed to prevent the organism from engaging in potentially harmful behaviors.

2 Anxiety Disorders Epidemiology Assessment and Diagnosis
Review of Anxiety Disorders Treatments

3 Question What is the prevalence of panic disorder in patients with coronary artery disease? 2% 5% 10% 50% 75%

4 Question What is the prevalence of panic disorder in patients with coronary artery disease? Answer: % (choices 3 or 4) Fleet et al. Is panic disorder associated with coronary artery disease? A critical review of the literature. J Psychosom Res 2000 Apr-May;48(4-5):

5 Epidemiology Disorder Prevalence in primary care population (n=965)
Twelve-month prevalence estimates for anxiety in the general population: 18.1% (Arch Gen Psychiatry. 2005;62: ) Disorder Prevalence in primary care population (n=965) PTSD 8.6% (83) GAD 7.6% (73) Panic d/o 6.8% (66) Social phobia 6.2% (60) At least one d/o 19.5% (188) Kroenke K et al. Anxiety Disorders in Primary care: Prevalence, Impairment, Comorbidity, and Detection. Ann Intern Med. 2007;146:

6 Cardiac Presentations of Anxiety
GAD was the primary dx among 20% of patients with atypical chest pain (1). 55% of patients with chest pain and normal coronary arteries (2). 50% of patients seeking cardiac evaluation (3). Kane, F et al. Angina as a symptom of psychiatric illness. Southern Med J 1988;81: Wulsin LR et al. Axis I disorders in ER patients with atypical chest pain. Int J Psychiatry Med 1991;21:37-46 Logue MB et al. Generalized anxiety disorder patients seek evaluation for cardiological symptoms at the same frequency as patients with panic disorder. J Psychiatr Res 1993;27:55-59. We retrospectively studied all patients who had normal coronary angiograms at The Methodist Hospital during the year 1984 (8% of all angiograms). Patients were surveyed eight to 18 months after angiography. Of the 216 patients (83% of total sample), 130 were female and 86 male. Sixty-three percent of the women and 50% of the men satisfied the criteria for generalized anxiety disorder, and 20% satisfied the criteria for panic attacks. On the Brief Symptom Inventory (BSI) Somatization Scale, 64% had scores above the average reported for psychiatric outpatients. Eighty-one percent received only reassurance about the absence of heart disease, and 25% received continuing nitrate therapy in the absence of heart disease. A majority of these patients remain untreated functional "cardiac neurotics" with untreated anxiety symptoms. We make suggestions regarding a clinical profile to identify these patients and appropriate measures to avoid prolonged disability. To examine the contribution of psychopathology to emergency room (ER) visits for atypical chest pain, we administered two screening measures and the Structured Clinical Interview for DSM III-R (SCID) to thirty-five subjects within seventy-two hours of their ER visit. Follow-up SCID interviews were completed in thirty subjects at five to twelve months. Sixty percent of the sample had an initial Axis I diagnosis, predominately affective (34%) and anxiety (46%) disorders. Forty percent had multiple diagnoses initially. The most common diagnoses were panic disorder (31%) and major depression (23%). At follow-up 47 percent had Axis I diagnoses, 30 percent had multiple diagnoses, with only slightly decreases rates for panic disorder (27%) and major depression (17%). Many subjects had lost, gained, or switched diagnoses by follow-up, in spite of one consistent rater and a few subjects seeking treatment. ER physicians often do not recognize these psychiatric disorders in chest pain patients. The high risk of suicide in panic disorder and depression, and the high cost of disability in recurrent chest pain make it essential that ER physicians include these disorders in the differential of atypical chest pain. Although panic disorder (PD) and generalized anxiety disorder (GAD) have similar somatic symptoms, panic attacks with chest pain and/or palpitations may seem more likely to be mistaken for heart attacks because of their acute onset. One would therefore expect that PD patients are more likely than GAD patients to seek cardiological consultations. In a survey of 146 PD and 154 GAD patients entering a multi-site drug trial, we found virtually identical rates of such consults. Approximately 50% of each patient group sought medical evaluation for cardiac symptoms. Furthermore, 40% of each group had standard treadmill evaluations and 33% reported having an echocardiogram. This study suggests that future epidemiological studies in cardiology populations should include probes for generalized anxiety disorder.

7 GI Presentations of Anxiety: Irritable Bowel Syndrome
Study Lifetime prevalence of GAD Current rate of GAD 1. Walker et al. (n=47) 58% 25% 2. Lydiard et al. (n=35) 28% 13% Walker EA et al. Psychiatric illness and irritable bowel syndrome: a comparison with inflammatory bowel disease . Am J Psychiatry 1990;147: Structured psychiatric interviews and psychological self-report measures were administered to 28 patients with irritable bowel syndrome and 19 patients with inflammatory bowel disease. Significantly more of the patients with irritable bowel syndrome had lifetime diagnoses of major depression, somatization disorder, generalized anxiety disorder, panic disorder, and phobic disorder. They had significantly more medically unexplained somatic symptoms, and most had suffered from psychiatric disorders, particularly anxiety disorders, before the onset of their irritable bowel symptoms. 2. Lydiard RB et al. Prevalence of psychiatric disorders in patients with irritable bowel syndrome. Psychhosomatics 1993;34: Thirty-five patients with irritable bowel syndrome were referred from the gastroenterology service and underwent structured psychiatric interviews to assess the prevalence of psychiatric illness. Thirty-three (94%) of 35 patients were found to have a lifetime prevalence of any Axis I disorder; the predominant diagnoses were mood and anxiety disorders. Theoretical and practical implications of these findings are discussed. 1. Walker EA et al. Psychiatric illness and irritable bowel syndrome: a comparison with inflammatory bowel disease . Am J Pyshciatry 1990;147: 2. Lydiard RB et al. Prevalence of psychiatric disroders in patients with irritable bowel syndrome. Psychhosomatics 1993;34:

8 Anxiety Disorders Epidemiology Assessment and Diagnosis
Review of Anxiety Disorders Treatments

9 Case Vignette A 27-year-old woman has dissociative (feelings of unreality) symptoms accompanied by nightmares, hypervigilance, and anger that continue 6 weeks after being a victim of an armed robbery and assault. What diagnosis, if any, should she receive? Acute Stress Disorder Post-Traumatic Stress Disorder Generalized anxiety disorder Obsessive-Compulsive Disorder Anxiety Disorder, not other specified

10 Case Vignette Answer Post-Traumatic Stress Disorder
Acute Stress Disorder lasts for less than 4 weeks, whereas PTSD lasts more than 4 weeks. PTSD also generally emphasizes avoidance symptoms, but these can overlap with dissociative symptomatology.

11 The Three S’s of the Psychiatric Interview
S – Stressors/triggers S – Suicidality S – Substance Abuse

12 Screening Questions “Over the last two weeks, how often have you been bothered by the following problems?” Feeling nervous, anxious, or on edge Not being able to stop or control worrying 0-not at all, 1-several days, 2-more than half the days, 3-nearly every day Score of 2 or greater, has sensitivity of 0.86, and specificity of 0.70 for any anxiety disorder Kroenke K et al. Anxiety Disorders in Primary care: Prevalence, Impairment, Comorbidity, and Detection. Ann Intern Med. 2007;146:

13 Key Questions Is there an underlying medical disorder or substance abuse? Is the anxiety triggered (cued) or not? Are there panic attacks?

14 Is the anxiety cued or uncued?
Anxiety disorders Is the anxiety cued or uncued? No cues Cued (or triggered) Panic attacks? Specific object or situation  specific phobia Social situation  social phobia yes no Reminder of traumatic event  PTSD closed in spaces (no help)  agoraphobia OCD, GAD or Anx d/o nos Panic disorder

15 Anxiety Disorders Epidemiology Assessment and Diagnosis
Review of Anxiety Disorders Treatments

16 Anxiety disorders Panic Disorder Agoraphobia
Social Phobia (Social Anxiety Syndrome) Specific Phobia Obsessive-Compulsive Disorder Post-Traumatic Stress Disorder Acute Stress Disorder Generalized anxiety disorder Adjustment disorder, with anxious features Anxiety Disorder, not other specified

17 Panic Disorder Key Diagnostic Points
Panic attacks can occur in a number of Anxiety Disorders in addition to Panic Disorder The diagnosis of Panic Disorder requires the presence of recurrent unexpected (uncued) panic attacks. The uncued panic attacks of Panic Disorder can progress, over time to the cured attacks of Specific Phobia or Social Phobia (and vice versa).

18 Panic Attacks: A Syndrome
Not specific to Panic Disorder Occurs in social phobia, specific phobia, PTSD and OCD May herald depression May be secondary to: underlying medical condition medication side effect illicit drug use

19 Panic Attack Episodes have a sudden onset and peak rapidly (usually in 10 minutes or less) Often accompanied by a sense of imminent danger or doom and an urge to escape Frequently presents to ER with fear of catastrophic medical event (e.g., MI or stroke)

20 Panic Attack Discrete period of intense fear or discomfort accompanied by four or more of following: Palpitations Sweating Trembling Choking Chest pain Dizzy, faint Derealization Numbness Chills or hot flashes Fear of losing control, going crazy Fear of dying, passing out

21 Panic Disorder Recurrent unexpected panic attacks
Followed by one or more of the following: Anticipation of additional attacks Worry about implications of attacks Change in behavior With or without Agoraphobia

22 Agoraphobia Anxiety about being in situations from which escape might be difficult Usually secondary to panic attacks Avoided situations include: driving, bridges, tunnels, elevators, airplanes, malls, long lines, sitting in middle of row, etc.

23 Post-Traumatic Stress Disorder
Requires history of trauma Three clusters of symptoms Re-experiencing (flashbacks, nm’s) Avoidance and numbing Arousal (insomnia, hypervigilance) Duration of more than one month

24 Obsessive-compulsive disorder
Patient usually has obsessions and compulsions: Obsessions are recurrent and persistent thoughts, impulses, or images that are experienced, at some time during the disturbance, as intrusive and inappropriate and that cause marked anxiety or distress. The person recognizes that the obsessional thoughts, impulses, or images are a product of his or her own mind. Compulsions are repetitive behaviors or mental acts that the person feels driven to perform in response to an obsession, or according to rules that must be applied rigidly. Generally, they are not connected in a realistic way with what they are designed to neutralize or prevent, or are clearly excessive.

25 Obsessive-compulsive disorder
Treatments include: SSRI’s: usually high dose, take longer for effect Clomipramine (Anafranil) Behavior Therapy: Exposure-Response Prevention 4) Psychosurgery for treatment-refractory cases response prevention exposure Increased anxiety obsessions compulsions desensitization Decreased anxiety

26 Obsessive-compulsive disorder
Typical obsessions: Typical compulsions Contamination: Fear of dirt or germs, bodily waste or fluids (a feeling of dirtiness) Repeated washing/cleaning, ritual behavior or thinking Ordering: Concern with order, symmetry (balance) and exactness Concern with order, symmetry (balance) and exactness Perfectionism: Worry that a task has been done poorly, or a mistake has been made Checking drawers, door locks and appliances to be sure they are shut, locked or turned off (see also hypochondriasis) Intrusive thoughts: blasphemous, sexual, violent Ritual behavior or “superstitious thinking” “I might use it later.” hoarding

27 Specific Phobia, Social Phobia, Acute Stress Disorder Anxiety Disorder, NOS
Social Phobia (often overlaps with Avoidant Personality Disorder) Common, but often difficult to treat Specific Phobia Usually best treated with desensitization, but medication augmentation occasionally indicated

28 Generalized Anxiety Disorder
Excessive worries for at least six months about real life problems such as school and work performance. Accompanied by anxiety symptoms 3 or more of the following: Restlessness or feeling keyed-up or on edge Easy fatigability Trouble concentrating Irritability Muscle tension Sleep disturbance

29 Case vignette For the past three months, a 38yo depressed man has been obsessed with thoughts that he is evil and guilty of being insensitive to others. He has intrusive thoughts that he should kneel down in front of his co-workers in the weekly staff meeting and ask their forgiveness. He tries to ignore these thoughts and suppress them by repeatedly counting the number of ceiling tiles in the room when the thoughts occur. He periodically recognizes that the concerns are excessive but he cannot control them.

30 Case vignette Which ONE of following diagnoses is most likely?
Post-traumatic stress disorder Generalized anxiety disorder Obsessive-compulsive disorder Obsessive-compulsive personality disorder Major depressive disorder

31 Case vignette (answer)
Which ONE of following diagnoses is most likely? Answer: e) Major depressive disorder Guilty ruminations may be part of a depressive syndrome and MDD takes precedence over OCD in this case. However, mood-incongruent obsessions (eg, sexual obsessions) might lead one to MDD co-morbid with OCD. OCD is different from OCPD.

32 Anxiety Disorders Epidemiology Assessment and Diagnosis
Review of Anxiety Disorders Treatments

33 Case Vignette A 77yo male, widowed Chinese retired accountant, who is healthy except for mild hypertension and a history of chronic multiple somatic complaints, now complains of a “heavy head”, as well as ongoing complaints of anxiety, decreased energy and insomnia for the past several months or years (hx is vague). Screening neuro exam is unremarkable. Routine labs done two months ago are also noncontributory.

34 Case Vignette Question
Which of the following is the MOST appropriate in the management of this patient? The goal should be complete remission of symptoms. Initiate citalopram 20mg daily. Avoid discussing social issues with patient. Instruct patient to return to clinic for follow-up “as needed”. Instruct patient to go to Emergency Department “as needed”.

35 Case Vignette Answers Discussed
“Curing the patient” should not be the goal in this situation Antidepressants can be helpful for subclinical anxious syndromes. Focus on social issues Regular visits decreases inadvertent reinforcement of symptom production. As above.

36 Health Anxiety and Hypochondriasis
Fear or belief of potential of serious illness Misinterpretation of bodily sensations Persists despite appropriate medical reassurance Lasts for at least six months Variant of OCD? (Fallon BA, Qureshi, AI, Laje G, Klein B: Hypochondriasis and its relationship to obsessive-compulsive disorder. Psychiatr Clin North Am 2000; 23: ) Variant of OCD? Differs in two important ways Ocd suffers think thoughts, obsessions are senseless and/or irrational and try to suppress them Also, therefore tend to keep disorder private

37 Hypochondriasis and Health Anxiety
From the Greek hypochondrium Affected individuals frequently investigate symptoms through reading or the Internet (cyberchondria) “Every physical symptom must have an explanation.”

38 Hypochondriasis and Health Anxiety
Reassurance may reinforce fear, particularly if it reduce anxiety temporarily “Sick role” may reinforce behaviors Physical de-conditioning may increase somatic sensations Social isolation (eg, staying home from work) may worsen somatic preoccupation.

39 Hypochondriasis: Treatment
Possible treatment modalities include: SSRI’s Cognitive-behavioral therapy (CBT) Education about health beliefs Greeven A, et al: Cognitive behavior therapy and paroxetine in the treatment of hypochondriasis: a randomized controlled trial. Am J Psychiatry 2007; 164:91-99 Treating Health Anxiety: A Cognitive-Behavioral Approach, by Taylor and Asmundson, Guilford Publications, 2004

40 Anxiety Disorders Epidemiology Assessment and Diagnosis
Review of Anxiety Disorders Treatments

41 Anxiety Disorder Treatments
Psychotherapy Psychopharmacological Effectiveness = [efficacy of treatment] X [degree to which the patient is engaged in treatment]* Robustness = difficulty in administering a particular treatment (eg, pharmacotherapy more robust than psychotherapy) * I will turn to this issue in the workshop

42 Psychotherapy of Anxiety Disorders
Behavior Therapy Anxiety disorders are conceptualized as arising from avoidance behaviors. Therefore, treatment is directed at having the individual desensitize to avoided stimuli through exposure and other behavioral interventions. Internal mental states are relatively unimportant. Cognitive Therapy Anxiety disorders are conceptualized as arising from cognitive distortions. Thus, treatment is directed at changing unproductive or intrusive thought patterns. The individual examines his or her feelings and learns to separate realistic from unrealistic thoughts. Cognitive-Behavioral Therapy (CBT) Combination of cognitive and behavior therapies. Relaxation Techniques Relaxation techniques help individuals develop the ability to cope more effectively with the stresses and physical symptoms contributing to anxiety (eg,breathing retraining and exercise).

43 Self-Help Books for Anxiety Disorders
Anxiety and Phobia Workbook, by E. Bourne Stop Obsessing, by E. Foa van Boeijen et al. Efficacy of self-help manuals for anxiety disorders in primary care: a systematic review. Fam. Pract. 22: , 2005. Bower P et al. The clinical and cost-effectiveness of self-help treatments for anxiety and depressive disorders in primary care: a systematic review. Br J Gen Pract 2001; 51: 838–845. Newman et al. Self-help and minimal-contact therapies for anxiety disorders: is human contact necessary for therapeutic efficacy? J Clin Psychol 2003; 59: 251–274.

44 Websites Anxiety Disorders Association of America
The Anxiety and Phobia Internet Resouce (TAPIR)

45 Anxiety Disorder Treatments
Psychopharmacological selective serotonin reuptake inhibitors other antidepressants anxiolytics

46 Antidepressants SSRI’s (selective serotonin reuptake inhibitors)– first line (fairly safe in OD), recommend 9m minimum duration of treatment side effects: a) “long term”: weight gain (moderate), sexual side effects (in around 35%) b) “short term”:nausea, diarrhea, headache, rash, insomnia, sweating c) “serotonin syndrome” – usually in combo with two or more serotonergic agents: restlessness confusion, flushing, tremor progressing to hyperthermia, hypertonicity, rhabdomyolysis, death Fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro)

47 Antidepressants Other antidepressants
Mirtazapine (Remeron): sedation and weight gain Venlafaxine (Effexor): Mixed NE and 5HT activity, increases BP, similar side effect profile to ssri’s Duloxetine (Cymbalta): Also mixed NE and 5HT activity Buproprion (Wellbutrin): low rate of sexual side effects or weight gain, associated with increase rate of seizures, not for use in patients with eating disorders, prior seizure d/o Nefazodone (Serzone)5-HT2 blocker, often recommended for anxious depression, black box warning for liver failure, low rate of sexual se’s Trazodone (Desyrel) – usually prescribed as a hypnotic (ie, sleep aid)

48 Anxiolytics Buspirone – partial agonist of 5HT1a
5-20mg tid, takes 2-6 weeks no w/d sx, easy to use, may be preferred in elderly Benzo’s


50 Anxiety Disorders Benzos
Anxiolytics– benzodiazepines (BDZ) All share same mechanism of action Vary by speed of onset, metabolism and duration of action Shorter-acting usually means faster speed of onset: eg, alprazolam (Xanax) triazolam (Halcion) Longer-acting: diazepam (Valium), clonazepam (Klonopin), lorazepam (Ativan)


52 Anxiety Disorders Benzos
Anxiolytics– benzodiazepines Main side effects include: sedation, ataxia, amnesia, potential for abuse Generally useful for short-term anti-anxiety, tolerance frequently develops within 1-2 weeks Should not be discontinued abruptly (esp. shorter acting bdz’s): taper over 1-3 weeks

53 BDZ’s and the geriatric patient: It’s not just about addition
Benzodiazepines associated with: Sleep disturbance Cognitive difficulty Impairment in activities of daily living Motor vehicle accidents Gait disturbance (with concomitant increased risk of hip fractures) [references next slide]

54 References 1. Hemmelgarn B, Suissa S, Huang A, Boivin JF, Pinard G. Benzodiazepine use and the risk of motor vehicle crash in the elderly. JAMA. 1997;278:27–31. 2. Pomara N, Tun H, DaSilva D, Hernando R, Deptula D, Greenblatt DJ. The acute and chronic performance effects of alprazolam and lorazepam in the elderly: relationship to duration of treatment and self-rated sedation. Psychopharmacol Bull. 1998;34:139–53. 3. Ried LD, Johnson RE, Gettman DA. Benzodiazepine exposure and functional status in older people. J Am Geriatr Soc. 1998;46:71–6. 4. Wang PS, Bohn RL, Glynn RJ, Mogun H, Avorn J. Hazardous benzodiazepine regimens in the elderly: effects of half-life, dosage, and duration on risk of hip fracture. Am J Psychiatry. 2001;158:892–8. 5. Glass J, Lanctot KL, Herrmann N, Sproule BA, Busto UE. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005;331:1169–73. 6. Stewart S. The effects of benzodiazepines on cognition. J Clin Psychiatry. 2005;66 (suppl 2):9–13.

55 Clinician Attitudes Geriatric patients have low rate of addiction.
“If it works and she doesn’t abuse it, who cares?” Continuation is compassionate; discontinuation is harsh. “In the greater scheme of things I have a feeling there are other problems that are much, much worse.” Geriatric patients will be resistant to even discussing it. Tapering off benzodiazepines will require a lot of time.

56 Getting patients off Benzo’s
Does abruptly stopping a BDZ cause problems? 180 chronically anxious patients rx’d for 6 weeks with diazepam (avg dose 25mg/d), then: a) switched to placebo b) continued on diazepam for 8 more weeks, then switched to placebo c) continued on diazepam for 16 more weeks , then switched to placebo Rickels, K K. Long-term diazepam therapy and clinical outcome. JAMA. Vol:250, no:6, page:767-71 1983.

57 Getting patients off Benzo’s
Results: only 2/61 (3%) in first group experienced withdrawal Other groups had 18% withdrawal rate Main predictive factor: duration of previous BDZ treatment >8 months If >8m, withdrawal rate = 43% if <8m, withdrawal rate = 5% Rickels, K K. Long-term diazepam therapy and clinical outcome. JAMA. Vol:250, no:6, page:767-71 1983.

58 Getting patients off Benzo’s
Take home message: Short term usage (<6 weeks) unlikely to lead to significant problems with withdrawal. Patients who have been on BDZ’s for more than one year will need more careful tapering. Rickels, K K. Long-term diazepam therapy and clinical outcome. JAMA. Vol:250, no:6, page:767-71 1983.

59 Summary Anxiety Disorders are common in primary care and are frequently associated with somatic complaints. Screening for anxiety disorders can be done by two questions: “Over the last two weeks, how often have you been bothered by the following problems?” Feeling nervous, anxious, or on edge? Not being able to stop or control worrying?

60 Summary There are a finite number of anxiety disorders (seven) and an accurate diagnosis leads to appropriate treatment. There are multiple efficacious treatments for anxiety disorders, both pharmacological and psychosocial. Patient engagement is a key factor is improving effectiveness.

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