OMED- Seattle Washington October 28, 2014 ACONP Dual Diagnosis -Post Traumatic Stress Disorder and Substance Use Disorder, Michael McNamara, DO, FACN Manchester NH
Outline Co-morbidity of PTSD & SUD Trauma Populations & Subtypes DSM 5 & PTSD Therapies for SUD/PTSD patient DSM 5 & SUD Assessment & Monitoring for PTSD Treatment of Nightmares Medications for PTSD and SUD Conclusion/Discussion
Comorbidity of PTSD and SUDs Prevalent across a diverse range of populations More complex and costly clinical course when compared with either disorder alone Increased chronic physical health problems Poorer social functioning Higher rates of suicide attempts Legal problems Increased risk of violence Worse treatment adherence Less improvement during treatment 2012, McCauley et al.
National Comorbidity Survey (NCS; N = 5,877) NCS data indicated a 7.8% lifetime prevalence of PTSD 26.6% lifetime prevalence of SUDs Individuals with PTSD were 2 to 4 times more likely than individuals without PTSD to meet criteria for an SUD Comorbidity Survey Replication N = 9,282-10 years later-ptsd (6.4%) and lifetime SUDs (35.3%)
Etiology and Order of Onset PTSD & AUD High-risk hypothesis Susceptibility hypothesis Common factors- play a role in the development of comorbid PTSD and SUD
Etiology and Order of Onset PTSD & SUD Historically, the standard of care has been to treat the SUD first and defer treatment of trauma/ptsd- sequential model/pandora s Box hypothesis Parallel model Integrated model- linked with the self-medication hypothesis
SUBSTANCE USE, CHILDHOOD TRAUMATIC EXPERIENCE, AND POSTTRAUMATIC STRESS DISORDER 2010, Khory
Difference Score (uv) Substance Use Attenuates Physiological Responses Associated With PTSD among Individuals with Co-Morbid PTSD and SUDs 60 Difference in Startle Magnitude 50 40 30 20 10 0 Control PTSD Only SUD Only PTSD +SUD 2013, Davis et al CS+ CS-
DiGrande L et al. Am. J. Epidemiol. 2011;173:271-281 Location on September 11, 2001, reported by adult civilian survivors of the attacks on the World Trade Center.
Some Trauma Populations Combat- Military/with TBI Displaced refugees exposed to combat/war Civilian Rape CSA IPV MVA Disasters- man made vs natural Medical- eg Breast CA/MI
Nunber of Veterans 140,000 NUMBER OF VETERANS VA WITH PTSD DIAGNOSIS AND SUD 120,000 22.4 23.7 24 100,000 19 20.8 80,000 14.5 15.2 15.7 17 17.4 60,000 40,000 20,000 0 FY02 FY03 FY04 FY05 FY06 FY07 FY08 FY09 FY10 FY11
Type I & Type II Trauma
Trauma Subtypes Complex PTSD Subsyndromal PTSD Distant Trauma Complicated Grief PTSD-SP, PTSD with secondary psychosis
ICD- 11 Proposed Traumatic Stress Disorders PTSD Re-experiencing Avoidance Sense of threat COMPLEX PTSD Re-experiencing Avoidance Sense of threat Affect dysregulation Negative self-concept Interpersonal disturbances
Complex PTSD 2013, Cloitre et a,l European Journal of Psychotraumatology
PTSD with Secondary Psychotic Features(PTSD-SP)- Proposed Criteria Pts meet DSM criteria for PTSD Positive psychotic symptoms including Hallucinations or delusions Psychotic features do not occur exclusively with flashbacks No formal thought disorder is present No brief psychotic disorder is present PTSD precedes the onset of psychotic features There is no history of Psychotic symptoms before trauma Another psychiatric disorder does not better explain the symptoms 2011, Hammar
DSM 5: Trauma- and Stressor-Related Disorders Several new sections were created in DSM-5 New section separates PTSD, ASD, and AD from the anxiety disorders (e.g., panic disorder and social phobia). DID-Dissociative Identity Disorder- Placed in separate section with Dissociative Disorders- DID, Dissociative Amnesia, Depersonalization/Derealization Disorder
DSM 5 PTSD In DSM-5, avoidance and numbing are placed into separate categories B-Re-experiencing C-Avoidance D-Numbing E-Hyperarousal Duration of the disturbance (criteria B, C, D, and E) is more than 1 month- Acute and chronic eliminated
DSM 5- New PTSD Subtype DSM-5 adds a new subtype, with dissociative symptoms The individual recurrently experiences depersonalization and/or derealization Dissociative symptoms confer a worse prognosis? More Resistant to treatment Biological markers for study- glutmate- e.g. NMDA receptor/genetic ratio variation in some indiviuals.(krystal et al)
60 SUD Treatments Used Most Often by SUD-PTSD Specialists 50 40 30 20 10 0 Cognitive Behavioral Relapse Prev Motivational Enhancement Therapy Motivational Interviewing 12 Step Seeking Safety Other SUD Treatments Used Most Often by SUD-PTSD Specialists
JAMA. 2013;310(5):488-495, Foa et al
Substance Use Disorder DSM 5 May 2013 Mild 2-3 Symptoms Moderate 4-5 Symptoms Severe 6 or more Symptoms Abuse Full addiction
% endorsing craving Craving identifies addiction? 100% 90% 80% 70% 60% 50% 40% 79.8 30% 20% 10% 0% 55 33 19.7 8.9 0.25 1.3 2.9 0 1 2 3 4 5 6 7 # DSM IV dependence criteria percent shaded in blue endorse alcohol craving 2012 Addictive Behaviors
Assessment Detection of trauma exposure(s) Screening for problematic substance use behaviors Assess for symptoms PTSD clusters Assess SUD- pattern of use/amount & craving? Integrated model- meds?/ Therapy. Treat both conditions
Monitoring for PTSD Trauma At one month At three months PTSD symptoms getting better? Quality of Sleep Nightmares? Depression? Avoidance/numbing symptoms Social supports? Refer to therapy? PTSD symptoms getting worse?
PTSD Trajectories- Systematic Review of Studies from 1998-2010 Spiegel,Friedman et al 2013
FIGURE 1. Prevalence of probable post-traumatic stress disorder (PTSD) and subsyndromal PTSD in Manhattan south of 110th Street during the first 6 months after the September 11, 2001, terrorist attacks. Galea S et al. Am. J. Epidemiol. 2003;158:514-524
Sleep Disturbances as the Hallmark of PTSD Chronic sleep disruption associated with nightmares may affect the efficacy of first-line PTSD treatments Targeted sleep treatments may accelerate recovery from PTSD No consensus or guideline regarding the inclusion of evidence-based sleep treatment strategies in the context of trauma and PTSD management 2013, Germain & 1989, Ross
Are hippocampal size differences in posttraumatic stress disorder mediated by sleep pathology? 2014, Mohlenhoff,Alzheimer s & Dementia
PTSD & Nightmares Defining nightmares as intensely disturbing dreams that awaken the dreamer to a fully conscious state and generally occur in the latter half of the sleep period Nightmares primarily originate in rapid-eye movement (REM) sleep Nightmares lead to sleep disturbance rather than vice versa Episodes are vividly recalled the following morning Continuum? Nightmares are a core feature of PTSD With up to 90% of individuals with PTSD reporting disturbing dreams with some degree of resemblance to the actual traumatic event May continue to occur up to 40 50 years after the original trauma persistent nightmares in the wake of a traumatic incident predict later posttraumatic symptoms 2009, Hasler & Germain
Meds for nightmares Cyproheptadine Trazodone and Nefazodone Clonidine Guanfacine Benzodiazepines Zolpidem, gabapentin, mirtazapine SGA s- Risperidone/Seroquel others
Clinical use of Prazosin for PTSD related Nightmares Enhanced CNS adrenergic activity contributes to pathophysiology of PTSD PTSD symptoms in hyperarousal cluster- excessive CNS adrenergic activity Prazosin an inexpensive generic alpha-1 noradrenergic antagonist Minimal sedation, sexual dysfunction, dyslipidemia, hyperglycemia,or weight gain Four randomized controlled trials Four open- label studies Level A rating for nightmares by AASM- American Academy of Sleep Medicine Raskind & Peskind
Mean Sleep Time (Minutes, +/- SD) Prazosin Effect on Sleep Measures- Civilian PTSD 400 Effects of Prazosin vs Placebo on Sleep Measures in PSTD Subjects N=10 350 300 250 200 150 100 50 0 Total Sleep Time REM Sleep Time Sleep Latency REM Latency Mean REM Period Duration Placebo Prazosin Mellman,Raskind,Peskind et al, 2008, Biol Psychiarty
Prazosin for Combat PTSD 15-week randomized controlled trial For combat trauma nightmares Sixty-seven soldiers were randomly assigned to treatment with prazosin or placebo 15.6 mg of prazosin (SD=6.0) and 18.8 mg of placebo (SD=3.3) for men 7.0 mg of prazosin (SD=3.5) and 10.0 mg of placebo (SD=0.0) for women. Raskind et al, Am J Psychiatry 2013; 170:1003 1010
Raskind et al, Am J Psychiatry 2013; 170:1003 1010
Prazosin for Combat PTSD Raskind et al, Am J Psychiatry 2013
Prazosin for Combat PTSD CAPS NIGHTMARE ITEM Week 15 Week 11 Week 7 Week 0 0 1 2 3 4 5 6 7 8 Raskind et al, Am J Psychiatry 2013 Placebo Prazosin
Common side effects- Prazosin Dizziness (10%), headache (8%), drowsiness (8%), lack of energy (7%), weakness (7%), palpitations (5%) and nausea (5%). In 1 4% of patients taking prazosin the following side effects have been reported: vomiting, diarrhea, constipation, edema, orthostatic hypotension, dyspnea, syncope, vertigo, and nasal congestion. Raskind et al, Am J Psychiatry 2013
Prazosin effects on stress- and cue-induced craving and stress response in alcohol-dependent individuals 2012, Fox et al:alcohol Clin Exp Res. 2012 February ; 36(2): 351 360
Topiramate for Alcohol Dependency Johnson 2008
Topiramate for Treating Alcohol Dependence: RCT 2007, Johnson et al JAMA
Topiramate for Treating Alcohol Dependence: RCT 2007, Johnson et al JAMA
Topiramate for Treating Alcohol Dependence: RCT 2007, Johnson et al JAMA
Comparing Topiramate with Naltrexone in Treatment of Alcohol Dependence 80 % Remaining Continuously Abstinent 70 60 67.3 53.1 61.5 50 40 30 42.6 40.8 31.5 46.2 28.6 27.8 20 10 0 Week 4 Week 8 Week 12 Topiramate Naltrexone Placebo 2008, Baltieri et al, Addiction
A meta-analysis of Topiramate's effects for individuals with alcohol use disorders 2014,Blogett et al, Alcohol Clin Exp Res
Topiramate for Nightmares & PTSD symptoms Based on Kindling Hypothesis of PTSD(Berlant 2002) Topiramate decreased nightmares in 79% (19/24) With full suppression of nightmares in 50% Nightmares or intrusions partially improved in mean 11 days Were fully absent in mean 35 days Response was seen in 95% of partial responders at a dosage of 75 mg/day or less 91% of full responders at a dosage of 100 mg/day or less Improved other PTSD symptoms Dosage titration started at 12.5 to 25 mg/day and increased in 25- to 50- mg increments every 3 to 4 days until a therapeutic response
Add on Study Topiramate for Civilian PTSD Responder status, n(%) Full 26/33 (79%) Partial 3/33 (9%) None 4/33 (12) Mean time to response, days SD, (range) Full response (n= 25) 15-18(1-83) Mean dose at time of response, mg/day Full response 60 Partial response 32 Improvement of nightmares 17/18 (94%) Improvement of intrusions Full cessation of intrusions 26/33 (79%) Partial improvement 3/33 (9%) No improvement 4/33(12%) 2004, Berlant
RTC- Efficacy of Topiramate in Civilian PTSD 12 week study/rtc study N= 28 Male-30 %, Female=70% 82% for PTSD symptoms in Topamax group Significant reduction in all three PTSD symptom cluster groups Mean dose=103 mg(range 50-200) 2011, Yeh et al, CNS Neuroscience & Therapeutics 90 80 70 60 50 40 30 20 10 0 Reduction of CAPS PTSD Total score * Baseline Week 12 Topamax Placebo *P=0.007 for Topamax vs Placebo endpoint
Topiramate Treatment of Alcohol Use Disorder in Veterans with Posttraumatic Stress Disorder: A Randomized Controlled Pilot Trial 2014, Petrakis Alcoholism: Clinical and Experimental Research
Topiramate Treatment of Alcohol Use Disorder in Veterans with Posttraumatic Stress Disorder: A Randomized Controlled Pilot Trial 2014, Petrakis Alcoholism: Clinical and Experimental Research
Zohar,2011 Neurobiology of PTSD
Rates of ASD/PTSD Rates of acute stress disorder/post-traumatic stress disorder after early administration of IV hydrocortisone (100 to 140 mg) or placebo. 80 70 60 50 40 30 Cortisol Placebo 20 10 0 2 Weeks 1 Month 3 Months Zohar,2011
Medications for PTSD SSRI- Both Paxil & Zoloft are FDA approved SNRI- Venlaxine ER- high rating- 2 + RCT Remeron/Serzone- some benefit Wellbutrin No Benefit AEDS- Topamax & Tegretol BZD-???- avoid use in some pts with PTSD SGA?- Risperdal/Seroquel/Zyprexa Inderal? /Hydrocortisone Prazosin- possible benefit for all three clusters
Percentage of Patients With Treatment Response Response to Paroxetine for Patients With Chronic PTSD 70 60 * * 50 40 30 20 Placebo N=183 Paroxetine 20 mg/day N= 183 Paroxetine 40 mg/day N=182 10 0 2001, Marshall et al, AJP * p<000.1
Efficacy and Safety of Paroxetine Treatment for Chronic PTSD: A Fixed-Dose, Placebo-Controlled Study p<0.001 for a,b,c,d for both 20 mg & 40 mg dose vs placebo 2001 Marshall et al, AJP
Noradrenergic vs Serotonergic Antidepressant with or without Naltrexone for Veterans with PTSD and Comorbid Alcohol Dependence 2012 Perakis et al,neuropsychopharmacology (2012) 37, 996-1004
Patients Who Achieved Remission % 60 Treatment of PTSD with Venlafaxine ER : 6 Month RCT Placebo (n=168) Venlafaxine ER (n=161) 50 40 30 20 10 0 2 4 6 8 12 18 24 Time Receiving Therapy, wk 2006, Davidson et al, Arch Gen Psychiatry
Conclusion/Discussion Civilian and military personnel with PTSD- up to 52% suffer from comorbid PTSD Co-occurrence of PTSD & SUD- poor psychosocial and medical outcomes. Screen & Assess for comorbid PTSD & SUD in trauma cases. Treating PTSD does not usually have a negative impact on SUD