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POST-TRAUMATIC STRESS DISORDER Comorbidity and Treatment

POST-TRAUMATIC STRESS DISORDER Comorbidity and Treatment. Thomas A. Mellman, M.D. Howard University, Washington DC. Major Teaching Points. PTSD develops in a substantial minority of individuals exposed to severe trauma PTSD is highly comorbid with other psychiatric disorders

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POST-TRAUMATIC STRESS DISORDER Comorbidity and Treatment

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  1. POST-TRAUMATIC STRESS DISORDERComorbidity and Treatment Thomas A. Mellman, M.D. Howard University, Washington DC

  2. Major Teaching Points • PTSD develops in a substantial minority of individuals exposed to severe trauma • PTSD is highly comorbid with other psychiatric disorders • SSRI medications have FDA approval for PTSD and efficacy for some PTSD subpopulations • Other antidepressants, new generation antipsychotic medications, noradrenergic antagonists, and mood stabilizers have a role in treating some PTSD cases • Cognitive behavioral therapy is an important evidence-based intervention for PTSD

  3. Pre-Lecture ExamQuestion 1 • True or False: • The prevalence of PTSD is higher in women than men.

  4. Pre-Lecture ExamQuestion 2 • True or False: • All individuals exposed to severely threatening trauma will develop PTSD.

  5. Pre-Lecture ExamQuestion 3 • True or False: • Cortisol activity in chronic PTSD is similar to major depression.

  6. Question 4 • The psychosocial PTSD treatment with the strongest evidence for efficacy is: • EDMR • Breathing relaxation • Exposure • Thought-stopping

  7. Question5 • The weakest evidence for efficacy for PTSD is for which class of pharmacological agents: • SSRI’s • TCA’s • MAOI’s • Benzodiazepines • Risperidone

  8. Overview • Epidemiology • Diagnosis • Psychiatric Comorbidity • Treatment

  9. Post-Traumatic Stress Disorder (PTSD) • Lifetime prevalence in community of 1% to 14%, recent estimates from NCS of 7-8% • PTSD is associated with sexual abuse, physical assault, military combat, torture, accidental trauma, natural or man-made disasters, diagnosis of threatening illness American Psychiatric Association, 1994 Kessler et al., ’95, 05

  10. POST-TRAUMATIC STRESS DISORDER • A characteristic set of symptoms following exposure to extreme traumatic stress • experience, witness, or confronted with actual or threatened death or injury • Response involves intense fear, helplessness, or horror • Duration more than one month • Significant functional impairment

  11. POST-TRAUMATIC STRESS DISORDER • Re-experiencing symptoms (need 1) • intrusive recollections • trauma-related nightmares • flashbacks • psychological distress with reminders • physiologic reactivity with reminders

  12. POST-TRAUMATIC STRESS DISORDER • Avoidance symptoms (need 3) • avoid thoughts/feelings/conversations • avoid activities, places, people • inability to remember • diminished interest • feelings of detachment • restricted affect • foreshortened future

  13. POST-TRAUMATIC STRESS DISORDER • Arousal symptoms (need 2) • impaired sleep initiation/maintenance • irritability • concentration • hypervigilance • exaggerated startle

  14. PTSDAssociated Features • Alcohol/drug problems • Aggression/violence • Suicidal ideation, intent, attempts • Dissociation • Distancing • Problems at work • Marital problems • Homelessness

  15. Lifetime Prevalence of DSM-III-RMajor Psychiatric DisordersNCS Data % Mood Disorders Major depressive episode 17.1 Dysthymia 6.4 Manic episode 1.6 Anxiety Disorders Social phobia 13.3 Simple phobia 11.3 PTSD 7.8 Agoraphobia without panic 5.3 GAD 5.1 Panic disorder 3.5 Substance Use Disorders Alcohol abuse/dependence 23.5 Drug abuse/dependence 11.9 Adapted from: Kessler et al. Arch Gen Psychiatry. 1994;51:8–19. Kessler et al. Arch Gen Psychiatry. 1995;52:1048–1060.

  16. Men Women PTSDRisks of Specific Traumasin the US Population Percentage N/A Natural Disaster Criminal Assault Combat Rape Kessler RC et al. Arch Gen Psychiatry. 1995;52:1048–1060.

  17. PTSDRisk Factors for PTSD Severity of trauma (i.e., threat, duration, injury, loss) Prior trauma Gender Prior mood and/or anxiety disorders Family history of mood or anxiety disorders Low Education

  18. Men Women PTSDRates Related to Specific Traumas Percentage Natural Disaster Criminal Assault Combat Rape Kessler RC et al. Arch Gen Psychiatry. 1995;52:1048–1060.

  19. PTSDPersistence Over Time (Untreated Group) 100 75 % Without Recovery 50 25 0 1 2 3 4 5 6 7 10 Years Kessler RC et al. Arch Gen Psychiatry. 1995;52:1048–1060.

  20. PTSDFunction and Quality of LifeIn VietnamVeterans With and Without PTSD PTSD Non-PTSD Percent Not Working Fair orPoorHealth ReducedWell-Being PhysicalLimitation Violent BehaviorPast Year Zatzick DF et al. Am J Psychiatry. 1997;154:1690–1695.

  21. PTSDPsychiatric Comorbidity Lifetime Rates (%) Men Women PTSD Non-PTSD PTSD Non-PTSD Depression 48 12 48 19 Mania 12 1 6 1 Panic Disorder 7 2 13 4 Social Phobia 28 11 28 14 GAD 17 3 15 6 Alcohol Abuse/Dependency 52 34 28 13 Substance Abuse/Dependency 34 15 27 8 Any Diagnosis 88 55 79 46 Kessler RC et al. Arch Gen Psychiatry. 1995;52:1048–1060.

  22. Comorbidity in PTSDNational Comorbidity Study MEN 1 Other Diagnoses 2 Other Diagnoses 3 Other Diagnoses No Other Diagnosis WOMEN 1 Other Diagnoses 2 Other Diagnoses 3 Other Diagnoses No Other Diagnosis

  23. PTSDImpact of Comorbid PTSD in Subjects With Other Anxiety Disorders 80 Anxiety DisorderWith PTSD Anxiety DisorderWithout PTSD 60 48 38 (%) Rates 40 30 30 21 20 6 0 AttemptedSuicide Hospitalized AlcoholProblems Warshaw MG et al. Am J Psychiatry. 1993;150:1512–1516.

  24. DIAGNOSTIC SPECTRA Depression Psychosis Personality Disorder Substance Use Disorders Panic Disorder PTSD Somatization Obsessive Compulsive Disorder Dissociation

  25. PTSDModel Sequence of Comorbidity MDDPANIC Disability---> Substance Abuse PTSD GAD Age 23 24 25 30 Davidson JR et al. Compr Psychiatry. 1990;31:162–170. Mellman TA et al. Am J Psychiatry. 1992;149:1568–1574.

  26. Lifetime History of Suicidal Attempts by Anxiety Disorder % General US population lifetime rates of suicide attempts range from 2.9% to 4.6%. Kessler RC, Archives of General Psychiatry. 1999; Moscicki EK, Yale Journal of Biology and Medicine. 1988

  27. 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 PTSD blindness psychosis paraplegia agoraphobia borderline PD panic disorder bipolar disorder anorexia nervosa severe depression opioid dependence moderate depression Disability Weights (Rating Scale) Score Sanderson K and Andrews G, Australian and New Zealand Jnl of Psych 2001

  28. PTSDImpact of Treatment on Recovery (N = 459) Treated Untreated Median Months to Recovery Kessler RC et al. Arch Gen Psychiatry. 1995;52:1048–1060.

  29. PTSDTreatment Options Psychotherapy Pharmacotherapy Combined treatments

  30. PTSDConsiderations for Psychotherapy • Capacity to tolerate distress with exposure • Motivation/preference • Ability to participate and follow structure • Problems with interpersonal adjustment

  31. Cognitive Restructuring and Combination Treatments

  32. EXPOSURE STUDIES

  33. PTSDTreatment of PTSD by Exposureand/or Cognitive Restructuring r = relaxationc = cognitive restructuringe = prolonged exposureec = e + c r c IES Scores ec e Treatment Follow Up 1 mo 3 mos 6 mos Marks I et al. Arch Gen Psychiatry. 1998;55:317–325.

  34. Conclusions of the IOM report on the Treatment of PTSD (2007) • “The evidence is sufficient to conclude the efficacy of (psychotherapy that utilize) exposure therapies in the treatment of PTSD” (PE, CPT)

  35. PHARMACOTHERAPY • Neurobiological factors • Evidence of efficacy • What responds PTSD related pathology • Who responds Type of trauma comorbidity gender

  36. PTSD: Neurobiological Alterations of Memory Processing • Greater physiologic reactivity to trauma-related stimuli • Selective attention to trauma stimuli • Fragmentary trauma narratives • Deficits in standard tests of verbal memory • Suggested abnormalities from structural and functional brain imaging

  37. PTSD: Hormones and Neurotransmitters • Cortisol: reduced secretion and increased sensitivity to feedback inhibition with PTSD (Yehuda et al., 1993) • Role of noradrenergic activity in fear-enhanced learning (Cahill, 1997) • Noradrenergic and serotonergic probes stimulate panic and flashback symptoms in combat-related PTSD (Southwick et al., 1997)

  38. PTSD: Dysregulated sleep • Subjective Trauma-related nightmares Insomnia/nonrestorative sleep • Objective (EEG findings) Mixed findings regarding sleep maintenance and duration Increased REM density/ Disrupted REM sleep continuity Increased motor activity Ross et al., 1994; Mellman et al., 1997, 2002, Breslau et al., 2004

  39. AIMS OF PHARMACOTHERAPY • Reduce core symptoms • Reduce associated symptoms • Facilitate other therapy

  40. Medication Treatment for PTSD: Nature of the Evidence • At least 7 published RCTs supporting efficacy of SSRIs for acute Rx of PTSD Mean N participants = 236.3 (range: 47-551) • FDA approval for sertraline (’99), paroxetine (’01) • Maintenance efficacy established for sertraline for up to 52 weeks (Davidson et al. ‘01) • Improvement in all 3 sx clusters and QOL measures, treatments safe

  41. Medication Treatment for PTSD: Nature of the Evidence • Additional RCTs not demonstrating benefit for SSRIs. Some are underpowered. The one large and well designed negative study featured male combat veterans with chronic PTSD treated in VA settings (Friedman et al., 2007)

  42. Medication Treatment for PTSD: Nature of the Evidence • Efficacy supported by smaller RCTs TCAs, MAOIs, lamotrigine; adjunctive olanzapine and risperidone, prazosin for sleep disturbances • Efficacy not supported by trials benzodiazepines • Benefits suggested in open trials Other SSRIs, Novel APs, AEDs, trazodone, nefazodone, noradrenergic suppressor/antagonists

  43. Medication Treatment for PTSD:Recommendations • 1st Line SSRIs (sertraline, paroxetine, fluoxetine) 2nd Line other novel and traditional ADs; noradrenergic agents; anticonvulsant/mood stabilizers; novel AP medications Not recommended traditional APs, benzodiazepines* Friedman et al., 2000

  44. DOES COMORBID PERSONALITY DISORDER AFFECT THE RESPONSE TO AN SSRI? PD No PD FLU PBO FLU PBO p=0.002 ns

  45. DOES COMORBID DEPRESSION AFFECT THE RESPONSE TO AN SSRI? p=0.003 ns

  46. PTSD Treatment With SSRIsOpen-Label Sertraline in Comorbid PTSDand Alcoholism 60 140 (n = 9) IESScore StandardDrinks/Week 0 0 Pre Post Pre Post IES Alcohol Use Brady KT et al. J Clin Psychiatry. 1995;56:502–505.

  47. PTSD Treatment With SSRIsEffect of Fluoxetine in Symptom Clusters 30 Fluoxetine Total (N = 53) Placebo 20 17.3 15.1 13.5 Final DTS 9.0 10 6.7 6.3 6.2 3.0 0 Intrusive Avoidant Numbing Hyperarousal P = 0.02 P = 0.08 P = 0.01 P = 0.01 Davidson JR et al. Int Clin Psychopharmacol. 1997;12:291–296.

  48. EFFECT OF FLUOXETINE ON QUALITY OF LIFE (SF36) IN PTSD:Pre- to Post-Treatment General Health Mental Health Pre Post Pre Post Pre Post Pre Post p=0.006 ns Davidson et al., 1997

  49. IMPROVEMENT IN DISABILITY:Fluoxetine vs Placebo p=0.02 p=0.02 p=0.02 p=0.01 Davidson et al., 1997

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