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Anxiety disorder and medical comorbidity

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Presented in National Conference of Indonesian Psychiatric Association 27 August 2016 in Semarang, Central Java.

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Anxiety disorder and medical comorbidity

  1. 1. Anxiety Disorder and Medical Comorbidity Andri Division of Psychiatry Faculty of Medicine Krida Wacana Christian University Psychosomatic Clinic Omni Hospital Alam Sutera
  2. 2. Outline today’s talk • Epidemiology anxiety • Medical Comorbidity • Treatment approach • Conclusion
  3. 3. Epidemiology of anxiety disorders Damsa C. et al. Current status of brain imaging in anxiety disorders. Curr Opin Psychiatry 2009;22:96-110
  4. 4. The differential diagnosis of anxiety. Psychiatric and Medical disorders. Psychiatr Clin North Am 1985 Mar;8(1):3-23 Primary versus Secondary Anxiety Anxiety may be due to one of the primary anxiety disorders OR : – secondary to substance abuse (Substance-Induced Anxiety Disorder) – a medical condition (Anxiety Disorder Due to a General Medical Condition) – another psychiatric condition, or psychosocial stressors (Adjustment Disorder with Anxiety)
  5. 5. What characteristics of primary anxiety disorders predict subsequent major depressive disorder. J Clin Psychiatry 2004 May;65(5):618-25 Comorbid diagnoses • Once an anxiety disorder is diagnoses it is critical to screen for other psychiatric diagnoses
  6. 6. Anxiety and Physiology of the Body • Research on the physiology of anxiety- related illness is still young • Growing evidence of mutual influence between emotions and physical functioning. • Anxiety in somatoform disorders : pain, nausea, weakness, or dizziness that have no apparent physical cause. Anxiety and physical illness. http://www.health.harvard.edu/staying-healthy/anxiety_and_physical_illness
  7. 7. Anxiety and Physiology of the Body (2) • Anxiety has now been implicated in several chronic physical illnesses, including heart disease, chronic respiratory disorders, and gastrointestinal conditions. • People with anxiety related illness who have untreated anxiety : –the disease itself is more difficult to treat –their physical symptoms often become worse –and in some cases they die sooner Anxiety and physical illness. http://www.health.harvard.edu/staying-healthy/anxiety_and_physical_illness
  8. 8. Anxiety due to medical condition • Prominent symptoms of anxiety that are judged to be a direct physiological consequence of a general medical condition.
  9. 9. Somatic Comorbidities of Anxiety Disorders Inflammatory Bowel Disease DiabetesHypertension Cardiovascular Disease Anxiety Disorders
  10. 10. Medical problems that can be linked to anxiety • Heart disease • Diabetes • Thyroid problems, such as hyperthyroidism • Respiratory disorders, such as chronic obstructive pulmonary disease (COPD) and asthma • Drug abuse or withdrawal • Withdrawal from alcohol, anti-anxiety medications (benzodiazepines) or other medications • Chronic pain or irritable bowel syndrome http://www.mayoclinic.org/diseases-conditions/anxiety/symptoms-causes/dxc-20168124
  11. 11. The effect of anxiety on the heart • Rapid heart rate (tachycardia) – In serious cases, can interfere with normal heart function and increase the risk of sudden cardiac arrest • Increased blood pressure – If chronic, can lead to coronary disease, weakening of the heart muscle, and heart failure • Decreased heart rate variability – May result in higher incidence of death after an acute heart attack http://www.hopkinsmedicine.org/heart_vascular_institute/clinical_services/c enters_excellence/womens_cardiovascular_health_center/patient_informatio n/health_topics/anxiety_heart_disease.html
  12. 12. Distinguishing a panic attack from a heart attack • Panic attacks and heart attacks can share similar if not identical symptoms. • Anyone suffering from sudden and severe chest pain—whether being treated for anxiety disorder or not— should go to the emergency room. • A cardiologist sensitive to the issues of anxiety and depression will know how to sort out panic attack symptoms from heart attack symptoms  Refer the patient http://www.hopkinsmedicine.org/heart_vascular_institute/clinical_services/c enters_excellence/womens_cardiovascular_health_center/patient_informatio n/health_topics/anxiety_heart_disease.html
  13. 13. Anxiety and Heart Disease • Anxiety was associated with a 26% increased risk of coronary heart disease and a 48% increased risk of heart-related death over the follow-up period, even after adjusting for known heart disease risk factors. (Annelieke M. Roest, et al 2010)
  14. 14. Anxiety and Heart Disease • Anxiety disorders are predictive of future heart disease even after controlling for other risk factors such as blood pressure and smoking (Imre Janszky, et al. 2010)
  15. 15. Anxiety and Heart Disease • Anxiety is associated with increased risk of mortality in CHD patients, particularly when comorbid with depression. (Watkins LL, et al, 2013)
  16. 16. Pharmacotherapy and Cognitive-Behavioral Therapy Effective Treatment of Anxiety Disorders Both Removes Symptoms and Prevents Relapse Anxiety Disorder Treatment Bandelow B, et al. Int J Psychiatry Clin Pract. 2012;16(2):77-84. Goals of treatment:  Removal of symptoms  Prevention of relapse
  17. 17. • Pharmacotherapy – Selective serotonin reuptake inhibitors (SSRIs) • Sertraline, Escitalopram, Fluoxetine – Serotonin-norepinephrine reuptake inhibitors (SNRIs) • Venlafaxine, Duloxetine – Pregabalin – Benzodiazepine • Alprazolam, Clonazepam, Diazepam, Lorazepam • Psychotherapy – Cognitive Behaviour Therapy (CBT) – Interpersonal psychotherapy Treatment of Anxiety Disorder International Journal of Psychiatry in Clinical Practice, 2012; 16: 77–84
  18. 18. Treatment Recommendations for Anxiety Disorder International Journal of Psychiatry in Clinical Practice, 2012; 16: 77–84
  19. 19. Alprazolam Speed of Action to Remove Symptoms of Anxiety Magnitude Average Benefit Observed 1 Hour After Morning Dose Hours Average Time to Peak Benefit Percent(%) Patients Achieving Peak Benefit Within 1 Hour Results from a 9-week, open-label, switch-over study in 30 patients with DSM-IV panic disorder. Patients stable on alprazolam compressed tablet for 3 weeks were switched to alprazolam extended release. Analysis of profile data derived from the clinician and patient from daily diary records was used to determine magnitude of benefit.  According to several measures, alprazolam demonstrated a rapid onset of action in the majority of patients  In patients treated with alprazolam, 90% of the peak benefit occurred within the first hour post-dose 64% DSM=Diagnostic and Statistical Manual of Mental Disorders.
  20. 20. Alprazolam for Myocardial Infarction In acute myocardial infarction, alprazolam (Xanax) may offer advantages over more traditional antidepressant (Postgrad Med 1991, Feb 15: 89(3) : 83-9)
  21. 21. The alprazolam use before electrophysiology studies &radiofrequency catheter ablation can improve the patients' psychological status and reduce the hospitalization costs (Zhu et al, 2007).
  22. 22. • Sertraline was first developed and approved for the treatment of depression. 1 • Sertraline has been tested extensively in the treatment of panic and obsessive-compulsive disorders.1 • Sertraline appears to be efficacious and well tolerated in the treatment of generalized anxiety disorder.2 • The reviewed studies show that sertraline is an effective and well-tolerated treatment of all of these disorders. 1 Sertraline for Anxiety Disorder 1.Depress Anxiety. 2000;11(4):139-57 2. Am J Psychiatry. 2004 Sep;161(9):1642-9
  23. 23. Cipriani A, et al. Lancet. 2009;373(9665):746-758. Meta-Analysis of 12 New-Generation Antidepressants Reports Benefits of First-Line Sertraline Multiple treatments meta-analysis of 117 randomized controlled trials (n=25,928) from 1991 to 2007. Line width is representative of the number of comparator trials, while node size is representative of the number of patients. “Sertraline might be the best choice when starting treatment for moderate to severe major depression in adults because it has the most favorable balance between benefits, acceptability, and acquisition cost” Best Choice Efficacy  Mirtazapine  Escitalopram  Venlafaxine  Sertraline Acceptability  Escitalopram  Sertraline Cost  Sertraline
  24. 24. Löwe B, et al. J Affect Disord. 2005;87(2-3):271-279. Sertraline’s Long History: Success in Clinical Practice  Results from a large-scale study of patients in the clinical practice setting suggest excellent treatment response and tolerability profiles 87.7 87.2 0 20 40 60 80 100 PHQ-9 CGI-I Sertraline (n=1878) Response Rates Patients(%)  Complete remission was achieved in 56.9% of patients  95% of physicians judged the tolerability of sertraline as good or very good  Among other factors, predictors of medication response included:  Non-chronic course of depression  No previous antidepressant medication  Non-psychiatric treatment setting CGI-I = Clinical Global Impression – Improvement scale; PHQ = Patient Health Questionnaire.
  25. 25. Effects of Comorbidity and Polypharmacy on Sertraline Use in Elderly Patients  Results from an observational study of elderly depressed outpatients indicate an absence of clinically important drug interactions and confirm the effectiveness and safety of sertraline in routine clinical practice1  In elderly patients, neither comorbidity nor polypharmacy significantly affected sertraline efficacy, dosing, or safety and tolerability1,2 1. Arranz FJ, Ros S. J Affect Disord. 1997;46(3):285-291. 2. Sheikh JI, et al. J Am Geriatr Soc. 2004;52(1):86-92. 19.4 21 23.6 23 0 10 20 30 40 50 Comorbidity Polypharmacy without with Side Effects Patients(%) 87.3 88.2 84.6 83.8 70 80 90 100 Comorbidity Polypharmacy without with Dosing Sertraline(mg/d) Results from an 8-week open-label, non-blind, noncomparative, observational, multicenter study assessing the efficacy and tolerability of flexible-dose sertraline (50-200 mg/d) in depressed outpatients ages 60 and older (n=1437) with 78.1% of patients having associated pathological conditions (comorbidity) and 68.0% of patients taking concurrent medications1
  26. 26. Latest BPOM approved Zoloft Local Product Document. 2015 Sertraline Tolerability Profile: Common Adverse Reactions in Clinical Trials of MDD Adverse Event Sertraline (n=861) Agitation 1% Diarrhea/Loose Stools 2% Dry Mouth 1% Ejaculation Failure (males) 1% Headache 2% Insomnia 1% Nausea 4% Somnolence 1% Tremor 2% Discontinuation Due to Common Adverse Eventsb a TEAEs reported if incidence ≥ 5% b Data reported for MDD and other premarketing controlled trials. Adverse Event Sertraline (n=861) Placebo (n=853) Ejaculation Failure (males) 7% <1% Dry Mouth 16% 9% Sweating Increased 8% 3% Somnolence 13% 6% Tremor 11% 3% Dizziness 12% 7% Fatigue 11% 8% Constipation 8% 6% Diarrhea/Loose Stools 18% 9% Dyspepsia 6% 3% Nausea 26% 12% Agitation 6% 4% Insomnia 16% 9% Common TEAEs in Placebo- Controlled Clinical Trialsa,b MDD = major depressive disorder; TEAE = treatment-emergent adverse event
  27. 27. Pharmacokinetic in Heart Disease Saphiro PA. Cardiovascular Disorder. Clinical Manual of Psychopharmacology in the Medically Ill. 2010
  28. 28. Take Home Messages • Anxiety disorder in medical illnesses are common • Anxiety has been implicated in several chronic physical illnesses, including heart disease, chronic respiratory disorders, and gastrointestinal conditions. • Anxiety disorders are predictive of future heart disease even after controlling for other risk factors • Effective treatments are necessary to relieve the symptoms and make patient comfortable

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