This PPT is part 2 of 2 lectures given to second year pharmacy students in a pharmacology & toxicology class.

1. Anxiety II: Agents for PTSD &
OCD
Brian J. Piper, Ph.D., M.S.
piperbj@husson.edu
Office Hours: T/Th 3-4 or by
appointment
February 1, 2013

2. Objectives
• Pharmacy students should be able to:
– List the key characteristics of Post-Traumatic
Stress Disorder & Obsessive Compulsive Disorder
– Rank the therapeutic options by efficacy and
differentiate the pharmacotherapies by MOA and
adverse events.

3. Psychotherapy & Anxiety Disorders
• Specific therapies, typically brief ( < 12 weeks) have
solid empirical support
• Effects are delayed but sustained
• Important option for vulnerable populations
Anxiety Disorder Importance of Psychotherapy
Phobias Systematic desensitization is gold standard.
Social Anxiety Disorder >50% of patients show response to CBTD
GAD CBT and pharmacotherapy have similar efficacyD
Panic Disorder CBT produces improvements in 75% of patientsD
Obsessive Compulsive Dis CBT (with or without SSRI) is recommended as first-line txD
Post-Traumatic Stress Dis EMDR > fluoxetine in maintaining improvementsD
DDiPiro et al. (2012). Pharmacotherapy: A Pathophysiologic Approach, Chapters 79 & 80.

4. Obsessive Compulsive Disorder
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Example Patient #1 (0 to 2:50): http://www.youtube.com/watch?v=tPFQMRx2l3Y

5. Common Obsessions
1) Dirty 2) Aggression 3) Religion 4) Sex

6. Famous OCD Cases

7. Yale Brown Obsessive Compulsive
Scale
• Obsessions (5 items)
– How much of your time do you occupy with obsessions?
None ------ Extreme (8+ hours/day)
– How much do your obsession interfere socially or with
work? Not at all ----- Extreme (Incapacitating)
• Compulsions (5 items)
– How much time do you spend performing compulsive
behaviors? None ---- 8+ hours/day
– How much control do you have over the rituals?
Complete Control ---- No control, unable to even delay
7
To take test: http://www.psymed.info/psymed/default.aspx?m=Test&id=52&l=3

8. OCD Options
2nd Line
1st Line
Modified from Stahl, S. (2008). Essential Psychopharmacology, p. 770.

9. Fluvoxamine
• MOA: SRI
• Indications: FDA approved for OCD (adult & pediatric)
• Half-Life: 16 hours
• Adverse Effects: nausea, vomiting, weight gain, sexual
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10. Paradoxical Aggression?
• Animal studies demonstrate inverse
relationship between 5-HT & aggression
• E.H. receives sertraline, later fluvoxamine
• Parents of E.H. sue Solvay
• Solvay withdraws fluvoxamine (2002 – 2008)
• Aggressive patients -> drug
Drug -> Aggression
http://www.denverpost.com/golf/ci_5094436 1981 - 1999

11. OCD: SSRI, CBT, or Both?
• OCD patients randomized to Cognitive Behavior Therapy
(CBT), CBT & Fluvoxamine (50-300, Mean = 235 mg/day), or a
wait-list.
• Clinicians completed the Yale-Brown Obsessive Compulsive
Scale (0 – 40)
– normal = 0-7
– mild = 8-15; moderate = 16 -23
– 24-31 = severe
– 32-40 = extreme
Baseline Week 8 (Change) Week 16 (Change)
Control (Wait List) 26.8 26.4 (-0.4) NA
CBT (1-16) 25.3 21.5 (-3.8)* 13.5 (11.8)*
FLVX (1-16) + CBT (9-16) 27.2 20.8 (-6.4)* 15.6 (11.6)*
*p < .01 versus Baseline
Von Balkom et al. (1998). Journal of Nervous & Mental Disease, 186(8), 492-499.

12. 5 Year Follow-Up
CBT (N = 32) CBT + Fluvoxamine (N = 39)
Current YBOCS (SD) 12.3 (8.9) 14.9 (9.1)
YBOCS Improved by >7 78.1% 73.7%
Additional CBT 53% 72%
Using Anti-depressants 19% 51%*
No Longer OCD 62.5% 51.3%
*p < .005
van Oppen et al. (2005). J of Clinical Psychiatry, 66, 1415-1422.

13. Early OCD Age of Onset
Early Onset Late-onset
(N = 141) (N = 20)
MDD 36.2% 66.6%*
ADHD 31.2% 25.0%
Tourette’s 26.9% 0.0%*
GAD 11.3% 41.2%*
* p < .01
Delorme et al. (2005). Psychological Medicine, 35(2), 237-243.
General description (Skip Ad, 0 to 2:25): http://www.youtube.com/watch?v=izT40QNFXuM

14. Fluvoxamine & Age
• Max dose
– Adults: 300 mg/day
– Adolescents: 300 mg/day
– Children: 200 mg/day
• Efficacy: similar across age
• Contraindications: MAO-Is
• Other: CYP1A2
• Adverse Effects: similar across age, transient
gastrointestinal
Cheer & Figgitt (2002). CNS Drugs, 16(2), 139-144.
http://www.pdr.net/drugpages/concisemonograph.aspx?concise=1452

15. SRIs & Adolescence
• The 5-HT system undergoes dynamic changes during adolescence
• Does chronic anti-depressant treatment alter neurobehavioral development?
• Oral paroxetine (15 mg/kg), but not fluvoxamine (30 mg/kg), from PD 33-62
temporarily, reduced weight.
Jong et al (2006). European Neuropsychopharmacology, 16, 39-48.

16. SRIs & Adolescence
• The 5-HT system undergoes dynamic changes during adolescence
• Does chronic anti-depressant treatment alter neurobehavioral development?
• After a 23 day drug free period, the rats were tested on the elevated plus maze
V P F
Jong et al (2006). European Neuropsychopharmacology, 16, 39-48.

17. Common Sexual Effects
• Sexual dysfunction (SD) is common among
patients with anxiety & depression
• Drug-induced SD is under-reported unless
patients queried directly
• SD = ↓ desire, ↓ arousal, ↓ orgasm
Sertraline
Venlafaxine
Citalopram
Paroxetine
Fluoxetine
Imipramine
Phenelzine
Duloxetine
Escitalopram
Fluvoamine
Serretti et al. (2009). Journal of Clinical Psychopharmacology, 29, 259 – 266.

18. Males > Females
Serretti et al. (2009). Journal of Clinical Psychopharmacology, 29, 259 – 266.

19. Post Traumatic Stress Disorder
• A) Exposure to actual or threatened
death, serious injury, or sexual violation
• B) Intrusion symptom(s):
– spontaneous or cued memories
– dreams
– flashbacks
• C) Avoidance of stimuli associated with
traumatic event
• D) Social or occupational impairment
Example (1st 3 min): http://www.youtube.com/watch?v=7aFs6695VyQ
Summarized from: http://www.dsm5.org/ProposedRevision/Pages/proposedrevision.aspx?rid=165

20. Neural Substrate of PTSD?
SSRIs increase 5-HT but therapeutic
lag
SSRIs increases Brain Derived
Neurotrophic Factor (BDNF)
BDNF increases neurogenesis
Stahl et al. (2008). Essential Psychopharmacology, p. 748.

21. PTSD & Reduced Hippocampal Volume
Karl et al. (2006). Neuroscience & Biobehavioral Reviews, 30, 104-131.

22. PTSD Options (DiPiro/Stahl)
*
*FDA Approved
sertraline
paroxetine
Modified from Stahl, S. (2008). Essential Psychopharmacology, p. 770.

23. PTSD Treatment Hierarchy
Department of Defense/Veterans Affairs 2010
• “Psychotherapy is the preferred treatment
option.”
• 1st Line Pharmacotherapies: SSRI, SNRI
• Not Recommended: Benzos & anti-psychotics
as mono-therapy or used adjunctively
Jeffreys et al. (2012). Journal of Rehabilitation Research & Development, 49(5), 703-715.

24. Rationale For Avoiding Benzos with PTSD
The veteran was diagnosed with PTSD and panic disorder by a psychiatrist
in the PTSD Clinic. He was started on sertraline and after several months
at a dose of 200 mg daily, he reported only modest reductions in PTSD
symptoms. The panic disorder improved but he continued to take
clonazepam 1 mg 1–3 times per week to prevent panic attacks when
leaving his home. He was referred for PE (Prolonged Exposure) therapy.
Although the PE went well in the initial weeks, both the patient and his
therapist noted that he was relatively unaffected by anxiety in some
therapy sessions. A careful review of his medication use found he was
taking clonazepam prior to driving from his home to the VA medical
center because driving alone was a common trigger for panic attacks. He
was encouraged to not use clonazepam within 24 hours of a PE session,
and after several more weeks, he completed PE without difficulty. The
post-PE score on the PCL was below the cutoff for PTSD diagnosis.
Jeffreys et al. (2012). Journal of Rehabilitation Research & Development, 49(5), 703-715.

25. Summary
• Anxiety Disorders are complex psychiatric
conditions that require multi-disciplinary
treatment.
• SSRIs are first-line pharmacotherapies for OCD &
PTSD although there are substantial differences
among members of this class.

26. Cingulate Cortex

27. Anterior Cingulate & OCD
• OCD and controls completed
a difficult continuous
performance test during
fMRI.
• OCD > controls in Anterior
Cingulate Cortex
Ursu et al. (2003). Psychological Science, 14, 347-353.

28. More OCD Patients
• 1st Two Minutes:
http://www.youtube.com/watch?v=44DCWslb
sNM
• Or: http://www.youtube.com/watch?v=Rn1OYlYzgm8
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