This document discusses the relationship between anxiety disorders and medical comorbidities. It begins by outlining the talk and reviewing the epidemiology of anxiety disorders. It then examines how anxiety can be both primary or secondary to medical conditions and substance abuse. Several studies are cited showing links between anxiety and increased risks of heart disease, respiratory illness, and gastrointestinal problems. The document also reviews treatment approaches for anxiety disorders like SSRIs, SNRIs, benzodiazepines, and cognitive behavioral therapy. It provides efficacy evidence and tolerability profiles for sertraline and alprazolam in particular. Finally, it emphasizes that treating anxiety in medically ill patients can improve disease management and reduce risks.

1. Anxiety Disorder and Medical
Comorbidity
Andri
Division of Psychiatry
Faculty of Medicine Krida Wacana Christian University
Psychosomatic Clinic Omni Hospital Alam Sutera

2. Outline today’s talk
• Epidemiology anxiety
• Medical Comorbidity
• Treatment approach
• Conclusion

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. 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. 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. 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. 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. Anxiety due to medical condition
• Prominent symptoms of anxiety that are
judged to be a direct physiological
consequence of a general medical
condition.

9. Somatic Comorbidities of Anxiety Disorders
Inflammatory
Bowel Disease
DiabetesHypertension
Cardiovascular
Disease
Anxiety
Disorders

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. 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. 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. 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. 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. 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. 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. • 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. Treatment Recommendations for Anxiety Disorder
International Journal of Psychiatry in Clinical Practice, 2012; 16: 77–84

20. 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.

21. 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)

22. The alprazolam use before electrophysiology studies
&radiofrequency catheter ablation
can improve the patients' psychological status and reduce
the hospitalization costs (Zhu et al, 2007).

23. • 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

24. 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

25. 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.

26. 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

28. 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

29. Pharmacokinetic in Heart Disease
Saphiro PA. Cardiovascular Disorder. Clinical Manual of
Psychopharmacology in the Medically Ill. 2010

30. 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