Recent Advances in the Treatment of Post Traumatic Stress Disorder Jon Bisson School of Medicine Cardiff University
Agenda What are we treating Psychological approaches Pharmacological approaches Treatment resistance
What Are We Treating? How is PTSD diagnosed? How does PTSD present? Are any symptoms more important to target than others? Does time of presentation matter?
Diagnosing PTSD DSM-IV (2000) replaced by DSM-5 in 2013 ICD-10 (1992) to be replaced by ICD-11 in 2018 Definition challenged by heterogeneity of presentation and absence of diagnostic tests
DSM-5 PTSD Criterion A Exposure to actual or threatened death, serious injury, or sexual violence through: 1. Direct experience 2. Witnessing, in person 3. Learning of event happening to a close family member or friend (actual or threatened death must be violent or accidental) 4. Repeated or extreme exposure to aversive details (e.g. Human remain collection, police and details of child abuse. Not TV, etc. unless work related)
Trauma and Stressor Related Disorder Exposure to traumatic event Re-experiencing Avoidance Negative alterations in cognitions and mood Alterations in arousal and reactivity DSM-5 PTSD
ICD-11 PTSD 2 Re-experiencing Flashbacks/powerful images & nightmares 2 Avoidance Thoughts & feelings Places, people, activities 2 Hyperarousal Startle & hypervigilance
ICD-11 Complex PTSD Emotion Regulation Hyperactivation, deactivation Negative Self-Concept feeling diminished, defeated, worthless, shame, guilt, despair Disturbed Relationships difficulties in feeling close, little interest in relationships or social engagement
Borderline Personality Disorder Pervasive pattern of instability of interpersonal relationships, selfimage, and affects, beginning by early adulthood Frantic efforts to avoid real or imagined abandonment Extremes of idealization and devaluation Impulsivity Recurrent suicidal behaviour
Complex PTSD vs Borderline PD Focuses on the effects of trauma PTSD symptoms core element Trauma-focused treatment Stable negative self concept Avoidance of relationships High risk of suicide, suicide attempts and self-injurious behavior are salient features Diagnosis and effective treatment organized around these issues Lack of a stable self concept and fears of abandonment
300 and growing NCMH participants PTSD diagnosis or TSQ +ve CAPS-5, ICD-TI, ICD-TQ, PHQ, AUDIT Attachment, social support, emotional regulation, coping skills, interpersonal functioning, post traumatic cognitions, MUS PTSD Registry
PTSD Registry Participants Mean age 47.4 (12.3), range 16-76 49% female 95% white 50% married or cohabiting 34% in work Trauma characteristics Mean age 25.4 (14.6) 19.1 (14.7) years since worst trauma 14 (7.3%) MVA, 30 (15.6%) CSA, 27 (14.1%) combat 92 (49%) reported CPA or CSA
Diagnosis
ICD11 PTSD & Complex PTSD 70 60 50 40 30 Complex PTSD PTSD 20 10 0 Female Working Childhood Abuse
DSM-5 & ICD-11 13% 10% 24% 54%
Borderline PD & ICD11 Complex PTSD
Borderline PD less age & ICD11 Complex PTSD
U.S. Prevalence US National Co-morbidity Survey > 5,500 15 to 54 year olds Trauma Exposure 60.7% M, 51.25% F Lifetime Prevalence 10.4% F, 5.0% M, 6.8% 12 Month Prevalence 3.5% Kessler et al (1995 & 2005)
Adult Psychiatric Morbidity Survey 2014
Adult Psychiatric Morbidity Survey 2014
Co-morbidity Present in > 50% cases Commonest co-diagnoses Major depressive disorder Panic disorder Other anxiety disorder Substance abuse/dependence NB personality disorder
How can we prevent PTSD?
SingIe Session Early Intervention Rose et al, 2005 No certain clinical effects for any intervention tested in 12 RCTs Single session debriefing may cause harm to some individually debriefed individuals No convincing evidence emerging for group debriefing
How can we treat PTSD? Psychological treatments
Psychological Treatments for PTSD Systematic review and meta-analysis Primary outcome reduction in clinician assessed severity of PTSD symptoms Wait list/usual care control 70 studies 4,761 participants Quality low overall
PsychoRx vs Waitlist Effect Size Bisson et al, 2013
PsychoRx vs Waitlist Dropout 7 6 5 4 3 2 1 0 TFCBT EMDR Non TFCBT Group TFCBT Other Therapies Exp TFCBT Cog TFCBT Bisson et al, 2013
Guided Self Help
Pilot 2 Acceptable Empowerment Refine diary
Spring
RAPID NIHR funded phase III RCT GSH vs TFCBTCT GSH developed through phase I & II studies Multi-centre 192 participants Oct 2016 Jan 2020
How can we treat PTSD? Pharmacological treatments
Pharmacotherapy for PTSD Systematic review and meta-analysis Primary outcome reduction in clinician assessed severity of PTSD symptoms Placebo control 70 studies, 5,300 participants Quality moderate overall
PharmacoRx vs Placebo Hoskins et al, 2015
CAPS SX Reductions in Means 0-10 -20-30 -40-50 Venlafaxine Sertraline Placebo -60 12 week study 6 month study Davidson et al, 2006 x 2
How do we approach treatment resistant PTSD? Psychological Pharmacological Other
Evidence-based Practice Without clinical expertise, practice risks becoming tyrannised by evidence, for even excellent external evidence may be inapplicable to or inappropriate for an individual patient Without current best evidence, practice risks becoming rapidly out of date, to the detriment of patients Knowledge sources Invention, research, innovation, improvement, practice Sackett et al, 1996 Good healthcare professionals use both individual clinical expertise and the best available external evidence, and neither alone is enough.
Phased Approaches for Complex Presentations Phase one Physical difficulties, accommodation, food, clothes, money Emotional stabilisation Social support Psychological input stress management, skills training Pharmacological treatment Phase two Trauma focused therapy Phase three Integration to new situation
STAIR-MPE Phase I: Skills Training in Affective and Interpersonal Regulation (STAIR) Phase II: Modified Prolonged Exposure (MPE) 8 x one hour of each with handouts & homework Cloitre et al, 2002
3MDR Study Motion-assisted, multimodular memory desensitisation and reconsolidation FiMT funded Phase II RCT 42 participants Oct 2016 - Sept 2018
Background Urgent need to identify effective treatments for military veterans who do not respond to, or are unable to engage with, current first line treatments Based on therapeutic principles of virtual reality exposure therapy and EMDR Exposure by virtual reality, enhanced with walking, music and high affect pictures, eliminates cognitive avoidance during exposure and promotes presence
Background Working memory theory Working memory has limited resources A dual task uses resources Less memory available for other processes Recollection of memories less vivid and less affectladen Pilot research in the Netherlands Decrease in PTSD symptoms No dropout or adverse effects Participants positive
Other Psychosocial Approaches Mindfulness Yoga Emotional Freedom Therapy Rewind Technique Surf Therapy
Hopwood and Schutte, 2017
Other Pharmacological Approaches Trazodone Quetiapine Prazosin (alpha 1 antagonist) Phenelzine Carbamazepine Cortisol Oxytocin D-cycloserine 3,4-methylenedioxy methamphetamine Raskind et al (2013) American Journal of Psychiatry
What would be an appropriate treatment pathway for PTSD? First line Second line Third line? Fourth line When do you stop treatment?
Possible Treatment Pathway Full assessment First line Individual TFCBT or EMDR Second line Alternative TFPT, Non TFCBT, Group TFCBT, pharmacotherapy (paroxetine, fluoxetine, sertraline or venlafaxine) Third line Further pharmacotherapy (quetiapine, prazosin, trazodone, carabmazepine) Other issues To phase or not to phase Stabilisation Stepped/stratified/precision approach Individual choice
Cardiff University Traumatic Stress Kali Barawi Jon Bisson Sarah Cosgrove Tony Downes Mat Hoskins Neil Kitchiner Catrin Lewis Neil Roberts Ben Sessa Natalie Simon Rob Sinnerton Stan Zammitt Research Group