1. Management of Anxiety Throughout Life’s Stages
Gabriela Dimitrievski, PharmD, BCPS, BCPP
Clinical Pharmacy Specialist – Psychiatry
Eskenazi Health
April 20, 2016
This speaker has no actual or potential conflicts of interest to
disclose in relation to this presentation

2. Objectives
Review the types of anxiety, with a consideration to prevalence at different stages of life
Outline pharmacologic treatment options for the management of different types of anxiety
Discuss the appropriate use of pharmacologic and non-pharmacologic treatment options at different ages

3. Overview of Anxiety Disorders
Disorders characterized by excessive and persistent fear and anxiety
Differentiation based on the items and/or situations linked to the fear, anxiety, or avoidance
Significant stress in social, occupational, or other important aspects of life
Linked to adverse effects on health and cognitive functioning
American Psychiatric Association. (2013)

4. DSM-5 Anxiety Disorders
Separation Anxiety Disorder
Substance/Medication- Induced Anxiety Disorder
Selective Mutism
Anxiety Disorder Due to Another Medical Condition
Specific Phobia
Social Anxiety Disorder
Other Specified Anxiety Disorder
Panic Disorder
Panic Attack Specifier
Unspecified Anxiety Disorder
Agoraphobia
Generalized Anxiety Disorder
American Psychiatric Association. (2013)

5. DSM-5 Anxiety Disorders
Separation Anxiety Disorder
Excessive and inappropriate fear and/or anxiety in regards to separation from key individuals
Symptoms last > 4 weeks in children/adolescents and > 6 months in adults
Cause of significant impairment
Selective Mutism
Continuing failure to speak in certain social situations,
Symptoms persist for > 1 month
Not related to lack of knowledge or another communication or mental disorder disorder
American Psychiatric Association. (2013)

6. DSM-5 Anxiety Disorders
Specific Phobia
Fear and anxiety centered around a specific entity or circumstance
Avoidance of specific “trigger”
Persistence > 6 months
Social Anxiety Disorder
Fear and anxiety related to being under the potential scrutiny of others
Fear of embarrassment, humiliation, rejection
American Psychiatric Association. (2013)

7. DSM-5 Anxiety Disorders
Panic Disorder
Recurrent panic attacks, defined as “abrupt surges of intense fear or intense discomfort”
Attack is followed by > 1 month of persistent fear/anxiety about subsequent panic attacks or behavioral changes made to avoid further attacks
Agoraphobia
Fear and anxiety related to: public transportation, open vs. enclosed spaces, lines/crowds, leaving the home alone
Avoidance of individual triggers
Persistence > 6 months
American Psychiatric Association. (2013)

8. DSM-5 Anxiety Disorders
Generalized Anxiety Disorder
Anxiety and worry associated with a multitude of situations
Defined by: restlessness, fatigue, concentration difficulties, irritability, muscle tension, sleep abnormalities
Occurs more days than not within a 6 month period
Substance/Medication-Induced Anxiety Disorder
Panic attacks and anxiety
Symptoms experienced during or closely after substance/medication use or withdrawal
American Psychiatric Association. (2013)

9. DSM-5 Anxiety Disorders
Anxiety Disorder Due to Another Medical Condition
Panic attacks or anxiety
Directly related to another medical condition
Other Specified Anxiety Disorder
Characteristic anxiety symptoms that do not meet criteria for other defined anxiety disorders
Documented reason on why criteria not met
Unspecified Anxiety Disorder
No documented reason on why criteria not met
American Psychiatric Association. (2013)

10. Prevalence of Anxiety Disorders
National Institute of Mental Health.

11. Prevalence of Anxiety Disorders
Lenze et al. Dialogues Clin Neurosci 2011;13(4):381-99

12. Prevalence of Anxiety Disorders in Adults
Diagnosis
Prevalence
Separation anxiety disorder
0.9%-1.9%
Specific phobia
8.7%
Social anxiety disorder
6.8%
Panic disorder
2.7%
Agoraphobia
0.8%
Generalized anxiety disorder
3.1%
National Institute of Mental Health.
American Psychiatric Association. (2013)

13. Prevalence of Anxiety Disorders in Children/Adolescents
Separation anxiety disorder
Children: 4%
Adolescents: 1.4%
Selective mutism: 0.03%-1%
Specific Phobia:
Children: 5%
Adolescents: 16%
Social anxiety disorder: 7%
National Institute of Mental Health.
American Psychiatric Association. (2013)

14. Prevalence of Anxiety Disorders in Children/Adolescents
Panic disorder:
Children: <0.4%
Adolescents: 2.3%
Agoraphobia:
Adolescents: 2.4%
Generalized anxiety disorder: 0.9%
National Institute of Mental Health.
American Psychiatric Association. (2013)

15. Prevalence of Anxiety Disorders in the Elderly
Diagnosis
Prevalence
Specific phobia
3-5%
Social anxiety disorder
2-5%
Panic disorder
0.7%
Agoraphobia
0.4%
Generalized anxiety disorder
1.2%-7.3%
American Psychiatric Association. (2013)
Lenze et al. Dialogues Clin Neurosci 2011;13(4):381-99

16. Pharmacologic Treatment of Anxiety Disorders

17. Key Considerations Treatment of each patient must be individualized
Treatment may utilize pharmacotherapy, psychotherapy, and/or other therapy modalities
Potential risks and benefits should be considered when assessing pharmacologic treatment options

18. Treatment of Separation Anxiety Disorder
Lack of extensive studies related to treatment
Multifactoral treatment including pharmacologic and non-pharmacologic therapies recommended
SSRIs considered first-line pharmacotherapy option
Wehry et al. Curr Psychiatr Rep 2015;17(7):52
Strawn et al. Child Adolesc Psychiatric Clin N Am 2012;21:527-39
Baldwin et al. J Psychopharmacol 2014;28(5):403-39

19. Treatment of Selective Mutism and Phobias
Some data to suggest use of SSRI treatment
Fluoxetine most cited in current literature
Most evidence to support non-pharmacologic treatment modalities
Specific Phobias
Treatment based in behavioral interventions
Lack of data examining overall role of medications in treatment
Role of d-cycloserine in enhancing exposure therapy benefits
Hua et al. Curr Opin Pediatr 2016;28(1):114-20
Choy et al. Clin Psychol Rev 2007;27(3):266-86
Smits et al. Biol Psychiatry 2013;73(11):

20. Treatment of Social Anxiety Disorder
Treatment guidelines:
Guideline
First Line Pharmacotherapy Recommendation
British Association for Psychopharmacology (2014)
SSRIs: escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline
SNRI: venlafaxine
MAOIs: phenelzine, moclobemide
Benzodiazepines: bromazepam, clonazepam
Anticonvulsants: Gabapentin, pregabalin
Olanzapine
Canadian Psychiatric Association (2006)
SSRIs: escitalopram, fluvoxamine, paroxetine, sertraline
World Federation of Biological Psychiatry (2012)
SSRIs
*SSRI = selective serotonin reuptake inhibitor; SNRI = serotonin norephinephrine reuptake inhibitor; MAOI = monoamine oxidase inhibitor
Baldwin et al. J Psychopharmacol 2014;28(5):403-39
Canadian Psychiatric Association. (2006)
Bandelow et al. Int J Psychiatry Clin Pract 2012;16:77-84

21. Antidepressant Use in Social Anxiety Disorder
Serotonin Reuptake Inhibitors (SSRIs)
FDA-approved: sertraline, paroxetine
Systemic review and meta-analysis found overall good evidence to support use of escitalopram, fluvoxamine, paroxetine, and sertraline
Three-time higher odds of response with SSRIs
Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)
FDA-approved: venlafaxine XR
Hansen et al. Int Clin Psychopharmcol 2008;23(3):170-79
College of Psychiatric and Neurologic Pharmacists. (2014)

22. Miscellaneous Treatment Options in Social Anxiety Disorder
Benzodiazepines
Clonazepam linked with significant improvements in clinical presentation
38% response rate with alprazolam
Risk vs. benefit profile
Monoamine oxidase inhibitors
Phenelzine with most consistent data
One of the first defined treatment options
Consider drug and food interactions and risk for hypertensive crisis
Muller et al. CNS Drugs 2005;19(5):377-91

23. Miscellaneous Treatment Options in Social Anxiety Disorder
Anticonvulsants
Gabapentin linked to improved scores on Liebowitz Social Anxiety scale as compared to placebo
43% response rate with pregabalin vs. 22% response rate with placebo
Beta-blockers
Mixed results to support use
Lack of efficacy for generalized SAD
Potential clinical efficacy in performance- based anxiety
Muller et al. CNS Drugs 2005;19(5):377-91
Bruce et al. Am Fam Physician 1999;60(8):

24. Self-Assessment Question
Which of the following selective serotonin reuptake inhibitors is FDA- approved for use in social anxiety disorder?
Fluoxetine
Escitalopram
Citalopram
Sertraline

25. Treatment of Panic Disorder
Treatment guidelines:
Guideline
First Line Pharmacotherapy Recommendation
American Psychiatric Association (2009)
SSRIs
SNRI: venlafaxine XR
British Association for Psychopharmacology (2014)
SNRI: venlafaxine
TCAs: clomipramine, desipramine, imipramine, lofepramine
NRI: reboxetine
Benzodiazepines: alprazolam, clonazepam, diazepam, lorazepam
Anticonvulsants: gabapentin, sodium valproate
*SSRI = selective serotonin reuptake inhibitor; SNRI = serotonin norepinephrine reuptake inhibitor; TCA = tricyclic antidepressant; NRI = norepinephrine reuptake inhibitor
American Psychiatric Association. (2009)
Baldwin et al. J Psychopharmacol 2014;28(5):403-39

26. Treatment of Panic Disorder
Guideline
First Line Pharmacotherapy Recommendation
Canadian Psychiatric Association (2006)
SSRIs
SNRI: venlafaxine XR
National Institute for Health and Clinical Excellence (2011)
World Federation of Biological Psychiatry (2012)
SNRIs: venlafaxine
Short acting benzodiazepines (severe attacks)
*SSRI = selective serotonin reuptake inhibitor; SNRI = serotonin norephinephrine reuptake inhibitor
Canadian Psychiatric Association. (2006)
National Institute for Health and Care Excellence (2011)
Bandelow et al. Int J Psychiatry Clin Pract 2012;16:77-84

27. Antidepressant Use in Panic Disorder
SSRIs
FDA approved: fluoxetine, sertraline, paroxetine
Clinical data has supported effectiveness of all SSRI medications
SNRIs
FDA-approved: venlafaxine XR
Other antidepressants
Tricyclic antidepressants
Monoamine oxidase inhibitors
Mirtazapine
American Psychiatric Association. (2009)

28. Benzodiazepine Use in Panic Disorder
FDA-approved: alprazolam, clonazepam
Quick onset may lend itself to use in severe, acute presentations
Risk vs. benefit profile:
Tolerance
Abuse potential
Cognitive and motor disturbances
Not considered first-line therapy option
American Psychiatric Association. (2009)

29. Treatment of Generalized Anxiety Disorder
Treatment guidelines:
Guideline
First Line Pharmacotherapy Recommendation
British Association for Psychopharmagology (2014)
SSRIs: citalopram, escitalopram, paroxetine, sertraline
SNRIs: duloxetine, venlafaxine
Pregabalin
Agomelatine
Quetiapine
Benzodiazepines: alprazolam, diazepam, lorazepam
Imipramine
Buspirone
Hydroxyzine
Trazodone
*SSRI = selective serotonin reuptake inhibitor; SNRI = serotonin norephinephrine reuptake inhibitor
Baldwin et al. J Psychopharmacol 2014;28(5):403-39

30. Treatment of Generalized Anxiety Disorder
Guideline
First Line Pharmacotherapy Recommendation
Canadian Psychiatric Association (2006)
SSRIs: paroxetine, escitalopram, sertraline
SNRIs: venlafaxine XR
International Psychopharmacology Algorithm Project (2006)
SSRIs: escitalopram, paroxetine, sertraline
SNRIs: venlafaxine XR, duloxetine
National Institute for Health and Clinical Excellence (2011)
SSRI: sertraline
World Federation of Biological Psychiatry (2012)
SSRIs
SNRIs
Pregabalin
*SSRI = selective serotonin reuptake inhibitor; SNRI = serotonin norephinephrine reuptake inhibitor
Canadian Psychiatric Association. (2006)
International Psychopharmacology Algorithm Project (2006)
National Institute for Health and Care Excellence (2011)
Bandelow et al. Int J Psychiatry Clin Pract 2012;16:77-84

31. Antidepressant Use in Generalized Anxiety Disorder
SSRIs
FDA approved: paroxetine, escitalopram
Sertraline, citalopram not FDA approved, but found to be effective in short-term clinical trials
SNRIs
FDA-approved: venlafaxine XR, duloxetine
Other antidepressants
Imipramine, trazodone, mirtazapine, bupropion, vortioxetine, and vilazodone have all be studied
College of Psychiatric and Neurologic Pharmacists. (2014)

32. Benzodiazepine Use in Generalized Anxiety Disorder
Frequently prescribed medications for the acute treatment of anxiety disorders
Quick and effective
Consideration of risk vs. benefits:
Tolerance
Abuse potential
Cognitive and motor disturbances
Should be considered as short-term management
Cloos et al. Curr Opin Psychiatry 2009;22(1):90-5
Martin et al. J Psychopharmacol 2007;21(7):774-82

33. Miscellaneous Treatment Options in Generalized Anxiety Disorder
Buspirone
FDA approved for the treatment of GAD
5-HT1A partial agonist
Appropriate second-line or adjunctive treatment
Overall well-tolerated medication
Delayed time to onset
Hydroxyzine
Approved for use in adults and children
Histamine receptor antagonist
Potential for numerous side effects
Lack of long-term use data
Stein et al. N Engl J Med 2015;373:

34. Miscellaneous Treatment Options in Generalized Anxiety Disorder
Pregabalin
Non-FDA approved treatment for GAD
Modulates and reduces calcium-dependent excitatory neurotransmitter release
Efficacy demonstrated in short-term and long-term clinical trials
C-V controlled substance
Second Generation Antipsychotics
Systematic review has identified potential use as augmentation in treatment-resistant GAD
Use limited by more robust supporting data and extensive adverse effect profile
Baldwin et al. Neuropsychiatr Dis Treat 2007;3(2):
Lorenz et al. Pharmacotherapy 2010;30(9):942-51

35. Self-Assessment Question
Which of the following medications is a 5-HT1A partial agonist approved for use in generalized anxiety disorder?
Buspirone
Pregabalin
Quetiapine
Alprazolam

36. Antidepressant Clinical Pearls
Delayed time to full benefit
Individual side effect profiles of each medication
“Jitteriness syndrome”
Slow taper upon discontinuation
Start at a lower dose and titrate as tolerated
Black box warning of increased suicidality risk in children and adolescents
Consider individual responses to therapy

37. Benzodiazepine Clinical Pearls
Second-line and/or short-term treatment options
Abuse and dependence potential
Potentially fatal withdrawal syndrome
Consider comorbid mental health concerns
Potential long-term adverse effects
Extensive side effect potential
Billioti de Gage et al. BMJ 2014;9:349:g5205
Gray et al. BMJ 2016;2:352:i90

38. Considerations Throughout the Lifespan

39. Anxiety Treatment in Children and Adolescents
Associated with significant morbidity and mortality concerns
Physical symptoms may be prominent in children with anxiety disorders
Recommended that psychotherapy be considered part of the treatment plan
Exposure-based cognitive behavioral therapy (CBT)
Family-child therapy
College of Psychiatric and Neurologic Pharmacists. (2014)
Connolly et al. J Am Acad Child Adolesc Psychiatry 2007;46(2):267-83
Wehry et al. Curr Psychiatry Rep 2015:17:52

40. Anxiety Treatment in Children and Adolescents
SSRIs considered pharmacologic treatment of choice
Short-term efficacy found in the treatment of selective mutism, generalized anxiety, separation anxiety, and social anxiety
Combination of non-pharmacologic + pharmacologic treatments should be considered
Superior reduction of anxiety symptoms seen with combination of sertraline and CBT
Connolly et al. J Am Acad Child Adolesc Psychiatry 2007;46(2):267-83
Wehry et al. Curr Psychiatry Rep 2015:17:52
Walkup et al. N Engl J Med 2008;359(26):

41. Medication Use in Children and Adolescents
Black box warning on all antidepressants for increased suicidality risk in children and adolescents
Consider altered pharmacokinetics when dosing medications
Half-life differences
Non-linear kinetics
Monitor patients closely, particularly when starting pharmacotherapy or with changes in dosing
Findling et al. Current Psychaitry 2007;6(6)

42. Anxiety Treatment in the Elderly
Consequences of anxiety in the elderly:
Increased disability
Increased mortality risk
Enhanced cognitive decline
Consideration of disease-related or medication-related contribution to anxiety
Presentation may include: declining concentration/memory, sleep disturbances, somatic complaints
Lenze et al. Dialogues Clin Neurosci 2011;13(4):381-99

43. Anxiety Treatment in the Elderly
Pharmacotherapy and behavioral based treatment considered effective
More robust treatment effects noted with pharmacotherapy
Consider cognitive functioning if pursuing CBT based therapies
Novel treatment approaches:
Mindful meditation
Guided self-help
Lenze et al. Dialogues Clin Neurosci 2011;13(4):381-99
Pinquart et al. Am J Geriatr Psychiatry 2007;15(8):639-51

44. Medication Use in the Elderly
Antidepressants as mainstay of pharmacologic treatment
SSRIs and SNRIs
Avoid TCAs and MAOIs as able given tolerability and side effect profiles
Avoid benzodiazepines
“Reverse index” in elderly
Associated with falls, disability, cognitive adverse effects
Potential paradoxical effects
Lenze et al. Dialogues Clin Neurosci 2011;13(4):381-99

45. Medication Use in the Elderly
Risk/benefit of first-line antidepressant therapy
Gait impairment
Increased fall risk
Platelet dysfunction and increased bleeding risk
SIADH and hyponatremia
Increased fracture risk
Serotonin syndrome
Start low and go slow
Lenze et al. Dialogues Clin Neurosci 2011;13(4):381-99

46. Self-Assessment Question
Antidepressant medications carry a black box warning for an increased risk of which adverse event in children and adolescents?
Hyperkalemia
Intracranial hemorrhage
Suicidality
Falls

47. Review & Considerations

48. Review & Considerations
Anxiety disorders span through life’s stages and can cause significant distress
Treatment of each patient must be individualized and may require psychotherapy and/or pharmacologic treatment modalities
Antidepressants considered first-line pharmacologic management, but age- specific factors should be considered in use

49. Management of Anxiety Throughout Life’s Stages
Gabriela Dimitrievski, PharmD, BCPS, BCPP
Clinical Pharmacy Specialist – Psychiatry
Eskenazi Health
April 20, 2016
This speaker has no actual or potential conflicts of interest to
disclose in relation to this presentation