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Psychopharmacology of Anxiety: Part II OCD & PTSD

Nov 03, 2014

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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 & OCDBrian J. Piper, Ph.D., [email protected] Hours: T/Th 3-4 or byappointment February 1, 2013

2. Objectives Pharmacy students should be able to: List the key characteristics of Post-TraumaticStress Disorder & Obsessive Compulsive Disorder Rank the therapeutic options by efficacy anddifferentiate the pharmacotherapies by MOA andadverse events. 3. Psychotherapy & Anxiety Disorders Specific therapies, typically brief ( < 12 weeks) have solid empirical support Effects are delayed but sustained Important option for vulnerable populationsAnxiety DisorderImportance of PsychotherapyPhobias Systematic desensitization is gold standard.Social Anxiety Disorder >50% of patients show response to CBTDGAD CBT and pharmacotherapy have similar efficacyDPanic DisorderCBT produces improvements in 75% of patientsDObsessive Compulsive Dis CBT (with or without SSRI) is recommended as first-line txDPost-Traumatic Stress Dis EMDR > fluoxetine in maintaining improvementsDDDiPiro et al. (2012). Pharmacotherapy: A Pathophysiologic Approach, Chapters 79 & 80. 4. Obsessive Compulsive Disorder------- -------- ------- --------Example Patient #1 (0 to 2:50): http://www.youtube.com/watch?v=tPFQMRx2l3Y 5. Common Obsessions1) Dirty 2) Aggression 3) Religion 4) Sex 6. Famous OCD Cases 7. Yale Brown Obsessive CompulsiveScale 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 withwork? Not at all ----- Extreme (Incapacitating) Compulsions (5 items) How much time do you spend performing compulsivebehaviors? None ---- 8+ hours/day How much control do you have over the rituals?Complete Control ---- No control, unable to even delay7To take test: http://www.psymed.info/psymed/default.aspx?m=Test&id=52&l=3 8. OCD Options2nd Line1st LineModified 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--------------------------- ------------------------------ 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 -> Aggressionhttp://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 await-list. Clinicians completed the Yale-Brown Obsessive CompulsiveScale (0 40) normal = 0-7 mild = 8-15; moderate = 16 -23 24-31 = severe 32-40 = extremeBaseline 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 BaselineVon 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 >778.1%73.7% Additional CBT53%72% Using Anti-depressants19%51%* No Longer OCD 62.5%51.3%*p < .005van Oppen et al. (2005). J of Clinical Psychiatry, 66, 1415-1422. 13. Early OCD Age of OnsetEarly OnsetLate-onset(N = 141)(N = 20)MDD 36.2%66.6%*ADHD31.2%25.0%Tourettes26.9%0.0%*GAD 11.3%41.2%** p < .01Delorme 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, transientgastrointestinalCheer & 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 33-62temporarily, 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 FJong 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, orgasmSertralineVenlafaxineCitalopramParoxetineFluoxetineImipraminePhenelzineDuloxetineEscitalopramFluvoamineSerretti et al. (2009). Journal of Clinical Psychopharmacology, 29, 259 266. 18. Males > FemalesSerretti 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 impairmentExample (1st 3 min): http://www.youtube.com/watch?v=7aFs6695VyQSummarized 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 neurogenesisStahl et al. (2008). Essential Psychopharmacology, p. 748. 21. PTSD & Reduced Hippocampal VolumeKarl et al. (2006). Neuroscience & Biobehavioral Reviews, 30, 104-131. 22. PTSD Options (DiPiro/Stahl)**FDAApprovedsertralineparoxetineModified from Stahl, S. (2008). Essential Psychopharmacology, p. 770. 23. PTSD Treatment Hierarchy Department of Defense/Veterans Affairs 2010 Psychotherapy is the preferred treatmentoption. 1st Line Pharmacotherapies: SSRI, SNRI Not Recommended: Benzos & anti-psychoticsas mono-therapy or used adjunctivelyJeffreys et al. (2012). Journal of Rehabilitation Research & Development, 49(5), 703-715. 24. Rationale For Avoiding Benzos with PTSDThe veteran was diagnosed with PTSD and panic disorder by a psychiatristin the PTSD Clinic. He was started on sertraline and after several monthsat a dose of 200 mg daily, he reported only modest reductions in PTSDsymptoms. The panic disorder improved but he continued to takeclonazepam 1 mg 13 times per week to prevent panic attacks whenleaving his home. He was referred for PE (Prolonged Exposure) therapy.Although the PE went well in the initial weeks, both the patient and histherapist noted that he was relatively unaffected by anxiety in sometherapy sessions. A careful review of his medication use found he wastaking clonazepam prior to driving from his home to the VA medicalcenter because driving alone was a common trigger for panic attacks. Hewas encouraged to not use clonazepam within 24 hours of a PE session,and after several more weeks, he completed PE without difficulty. Thepost-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 psychiatricconditions that require multi-disciplinarytreatment. SSRIs are first-line pharmacotherapies for OCD &PTSD although there are substantial differencesamong members of this class. 26. Cingulate Cortex 27. Anterior Cingulate & OCD OCD and controls completeda difficult continuousperformance test duringfMRI. OCD > controls in AnteriorCingulate CortexUrsu et al. (2003). Psychological Science, 14, 347-353. 28. More OCD Patients 1st Two Minutes:http://www.youtube.com/watch?v=44DCWslbsNM Or: http://www.youtube.com/watch?v=Rn1OYlYzgm8 28

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