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Eric Lenze, M.D. Associate Professor of Psychiatry Washington University School of Medicine

Detecting and treating anxiety disorders in the elderly: clinical applications of new research findings. Eric Lenze, M.D. Associate Professor of Psychiatry Washington University School of Medicine October 2007. Goals of this lecture.

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Eric Lenze, M.D. Associate Professor of Psychiatry Washington University School of Medicine

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  1. Detecting and treating anxiety disorders in the elderly: clinical applications of new research findings Eric Lenze, M.D. Associate Professor of Psychiatry Washington University School of Medicine October 2007

  2. Goals of this lecture • Describe research in pharmacologic and psychotherapeutic treatment of late-life anxiety disorders and anxious depression. • Describe detection and management strategies for these disorders.

  3. Self-Assessment Question 1Which of the following should be considered in the differential diagnosis of anxiety symptoms in elderly patients? A. Cardiopulmonary and other medical conditions B. Medication side effects C. Sedative hypnotic withdrawal D. All of the above E. None of the above

  4. Self-Assessment Question 2What risks are associated with chronic benzodiazepine use in elderly? A. Delirium B. Cognitive impairment C. Falls D. Fractures E. All of the above

  5. Self-Assessment Question 3Which of the following may contribute to the low estimate of prevalence of anxiety disorders in the elderly? A. Age-related brain changes B. Selective increase in mortality among anxiety disorder patients C. Epidemiologic studies do not necessarily capture anxiety as it presents in older adults D. All of the above E. None of the above

  6. Self-Assessment Question 4Which of the following contribute to the importance of identifying and treating Generalized Anxiety Disorder in the elderly? A. Its prevalence may be as high as 7% B. It is unlikely to remit without treatment C. Effective pharmacotherapeutic treatment has been demonstrated. D. All of the above E. None of the above

  7. Self-Assessment Question 5Which of the following is true of late-life depression with comorbid anxiety as compared to “pure” depression? A. Severity of the illness is no different. B. Antidepressant treatment response is better when comorbid anxiety is present. C. Comorbid anxiety is associated with greater long-term cognitive decline. D. All of the above E. None of the above

  8. How fear works Arousal Acute anxiety Panic attack Amygdala Larson et al, 2006

  9. How fear works Arousal Acute anxiety Panic attack Amygdala Worry Escape Avoidance Frontal cortex Larson et al, 2006

  10. How fear works Control Arousal Acute anxiety Panic attack Amygdala Worry Escape Avoidance Frontal cortex Larson et al, 2006

  11. Worry “What if…?” Hoehn-Saric et al, 2004

  12. Worry Frontal cortex Worry +/- Avoidance Control Hoehn-Saric et al, 2004

  13. Anxiety disorders have distinct clinical features

  14. Anxiety disorders have distinct clinical features

  15. What do psychiatrists ask about late-life anxiety? • How important is it? • Who sees these cases? • Is there something unique about treating this?

  16. Prevalence of anxiety disorders in older adults Beekman et al., 1995, 1998

  17. GAD: chronic, difficult-to-control worry • “I can’t turn my mind off” • “I’m a worrier” • Associated symptoms of GAD • Sleep disturbance • Fatigue • Irritability • Keyed up/on edge • Muscle tension • Difficulty concentrating (elderly may describe as memory)

  18. Early vs. late-onset GAD Le Roux, Gatz, & Wetherell, 2005

  19. Aging: increased vulnerability to sequelae of anxiety 50 60 70 80 age

  20. Aging: increased vulnerability to sequelae of anxiety Declining homeostasis/reserve 50 60 70 80

  21. Aging: increased vulnerability to sequelae of anxiety Declining homeostasis/reserve childhood adulthood late life very-late life 1. HPA axis functioning

  22. Aging: increased vulnerability to sequelae of anxiety Declining homeostasis/reserve childhood adulthood late life very-late life 1. HPA axis functioning 2. Cognitive reserve, brain volumes

  23. Aging: increased vulnerability to sequelae of anxiety Declining homeostasis/reserve childhood adulthood late life very-late life 1. HPA axis functioning 2. Cognitive reserve, brain volumes 3. Functional ability, physical performance

  24. Aging: increased vulnerability to sequelae of anxiety Declining homeostasis/reserve childhood adulthood late life very-late life 1. HPA axis functioning 2. Cognitive reserve, brain volumes 3. Functional ability, physical performance 4. Systemic functions (cardiac, renal, etc)

  25. Aging: increased vulnerability to sequelae of anxiety Anxiety Declining homeostasis/reserve 50 60 70 80

  26. Aging: increased vulnerability to sequelae of anxiety Anxiety Declining homeostasis/reserve HPA axis hyperactivity 50 60 70 80

  27. HPA Axis in Late-Life GAD Mantella et al, in press

  28. Aging: increased vulnerability to sequelae of anxiety Anxiety Declining homeostasis/reserve HPA axis hyperactivity Neuronal atrophy 50 60 70 80

  29. Aging: increased vulnerability to sequelae of anxiety Anxiety HPA axis hyperactivity Neuronal atrophy Sympathetic tone Declining homeostasis/reserve 50 60 70 80

  30. Aging: increased vulnerability to sequelae of anxiety Anxiety HPA axis hyperactivity Neuronal atrophy Sympathetic tone Cerebrovascular changes Declining homeostasis/reserve 50 60 70 80

  31. Aging: increased vulnerability to sequelae of anxiety HPA axis hyperactivity Neuronal atrophy Sympathetic tone Cerebrovascular changes ?Pro-inflammatory cytokine cascade Anxiety Declining homeostasis/reserve 50 60 70 80

  32. Aging: increased vulnerability to sequelae of anxiety HPA axis hyperactivity Neuronal atrophy Sympathetic tone Cerebrovascular changes ?Pro-inflammatory cytokine cascade ?Decreased neurogenesis Anxiety Declining homeostasis/reserve 50 60 70 80

  33. Aging: increased vulnerability to sequelae of anxiety HPA axis hyperactivity Neuronal atrophy Sympathetic tone Cerebrovascular changes ?Pro-inflammatory cytokine cascade ?Decreased neurogenesis Anxiety Declining homeostasis/reserve Treatment-resistance Comorbidity 50 60 70 80

  34. Aging: increased vulnerability to sequelae of anxiety HPA axis hyperactivity Neuronal atrophy Sympathetic tone Cerebrovascular changes ?Pro-inflammatory cytokine cascade ?Decreased neurogenesis Anxiety Treatment-resistance Comorbidity Cognitive decline Alzheimers Dz Declining homeostasis/reserve 50 60 70 80 Depression

  35. Aging: increased vulnerability to sequelae of anxiety HPA axis hyperactivity Neuronal atrophy Sympathetic tone Cerebrovascular changes ?Pro-inflammatory cytokine cascade ?Decreased neurogenesis Anxiety Treatment-resistance Comorbidity Cognitive decline Alzheimers Dz Disability Declining homeostasis/reserve 50 60 70 80 Depression

  36. Aging: increased vulnerability to sequelae of anxiety HPA axis hyperactivity Neuronal atrophy Sympathetic tone Cerebrovascular changes ?Pro-inflammatory cytokine cascade ?Decreased neurogenesis Anxiety Treatment-resistance Comorbidity Cognitive decline Alzheimers Dz Disability Mortality Declining homeostasis/reserve 50 60 70 80 Depression

  37. Comorbidity in late-life depression and anxiety Beekman et al., 2000 (LASA)

  38. Anxiety comorbidity and acute treatment response in LLD 0.9 0.8 No Baseline GAD 0.7 0.6 0.5 % Remitted 0.4 0.3 Baseline GAD 0.2 0.1 0.0 0 100 200 300 400 500 600 700 800 Days To Remission Steffens and McQuoid, Am J Geriatr Psychiatry. 2005; 13:40-47.

  39. Effect of Baseline Anxietyon Time to Recurrence in MDD Chi-square=7.05, df=1, p = 0.00895% CI hazard ratio = 1.22-3.72 1 . 0 0 . 8 Time to Recurrence (%) 0 . 6 0 . 4 D r u g + L o w B S I ( n = 3 5 ) 0 . 2 D r u g + H i g h B S I ( n = 2 3 ) P l a c e b o + L o w B S I ( n = 3 1 ) P l a c e b o + H i g h B S I ( n = 2 0 ) 0 . 0 0 2 0 4 0 6 0 8 0 1 0 0 1 2 0 W e e k s Andreescu et al, 2007

  40. MDD with comorbid GAD/panic: memory decline over 4 years f/u * *p=0.05 for group x time comparison DeLuca et al, 2005

  41. Medications efficacious for GAD From clinical trials in young adults: • FDA-approved: escitalopram, paroxetine, venlafaxine XR, duloxetine, buspirone. • Also efficacious: other SSRIs, benzodiazepines, pregabalin, antihistamines

  42. Prospective controlled studies in late-life GAD Koepke HH, et al. Psychosomatics. 1982;23:641-645. Bresolin N, et al. Clin Ther. 1988;10:536-546. Frattola L, et al. Clin Neuropharmacol. 1992;15:477-487. Small GW, Bystritsky A. J Clin Psychiatry. 1997;58(suppl):24-29.

  43. Benzodiazepines efficacious BUT Already heavily prescribed in elderly Problems With Benzodiazepines

  44. Benzodiazepines efficacious BUT Already heavily prescribed in elderly Associated with falls Problems With Benzodiazepines *P<.05. Landi F, et al. J Gerontol A Biol Sci Med Sci. 2005;60:622-626.

  45. Problems With Benzodiazepines • Benzodiazepines efficacious BUT • Already heavily prescribed in elderly • Associated with falls • Associated with cognitive impairment *P<.05. Landi F, et al. J Gerontol A Biol Sci Med Sci. 2005;60:622-626.

  46. Venlafaxine ER in older GAD pts Week 8 LOCF Week 8 observed * *p < 0.01 for change compared to placebo Katz et al, 2002

  47. Citalopram in geriatric anxiety disorders Lenze et al, Am J Psychiatry, 2005

  48. Citalopram for Geriatric Anxiety Disorders • 30 subjects received citalopram for up to 32 weeks • Significant decreases in 4 of the 6 most common individual symptoms: • Fatigue/asthenia • Headache • Gastrointestinal distress • Palpitations Blank S, et al. J Clin Psychiatry. 2006;67:468-472.Lenze EJ, et al. Am J Psychiatry. 2005;162:146-150.

  49. Cognitive-Behavioral Therapy (CBT) for anxiety • Relaxation training • Slow, deep breathing • Progressive muscle relaxation • Imagery • Changing negative automatic thoughts • Overestimation of risk • Catastrophization • Exposure to anxiety-provoking situations • e.g., systematic desensitization

  50. Comparison of CBT and attention placebo for late-life GAD Wetherell et al., 2003

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