PTSD DR JON LANE FRANZCP PTSD PRIMER What

PTSD… DR JON LANE, FRANZCP

PTSD PRIMER • What is PTSD? • What causes PTSD? • What are the comorbid problems people with PTSD have? • How to diagnose PTSD • Treatment…

What is psychological trauma? Trauma - wound or injury To the psyche Potentially Traumatic Event (PTE) DSM-5 diagnostic criteria Objective Subjective – no longer included Traumatic Event Actual harm

Potential Response to a PTE • The impact of experiencing a PTE on psychological well being may be: Valence: Good, bad, mixed Severity: Negligible, mild, moderate, severe Duration: Brief, long-lasting, permanent • The vast majority of people do not develop long term mental health problems

COMMON PATTERNS OF RESPONSE FOLLOWING TRAUMA OR DISASTER Resilient Recovery Delayed Persistent

EPIDEMIOLOGY Note that PTE does NOT have to mean PTSD…

PTSD in Women • Lifetime risk is twice as high as men • Probably due to greater likelihood of exposure to PTE’s (rape, abuse) • More likely to be re-victimised than men during later lifetime • There seems to be a genetic vulnerability as well – higher heritability risk, demonstrated by pituitary allelic variation (adenylate cyclase activating polypeptide) • Roughly 39% of sex-risk for women explained by increased exposure and vulnerability

FUNCTION OF THE HPA AXIS IN PTSD • Increased corticotrophin-releasing hormone from the hypothalamus in ptsd is represented by the thick black line. • Decreased adrenal release of cortisol in ptsd is represented by the thin black line. • Increased negative feedback inhibition of the HPA by cortisol is represented by the thick red lines. • Cortisol binds to the glucocorticoid receptor and modulates gene expression. • Several systems are affected by differential glucocorticoid signalling.

Systemic effects of PTSD • Nervous System – Memory, cognition, stress symptoms • Immune System – suppression of pro-inflammatory cytokines, regulation of immune cell maturation, migration and apoptosis • Cardiovascular system – cardiovascular and metabolic disease • Glucose and liver metabolism – glucose dysregulation, lipid homeostasis, obesity • Reproductive system – epigenetic transmission

Evidence for emerging neurobiological dysregulation in PTSD • Inflammatory mediators (Michopoulos et al, 2016, Gola et al, 2013) • Glucocorticoid receptor sensitivity (de Kloet et al 2007) • Epigenetic changes (Yehuda et al, 2015) • Increased GSR and HR in response to challenge (Costanzo et al, 2016) • Modified lipid metabolism (Michopoulos et al, 2016)

Emotional modulation problems

Emotional Modulation • Emotional Undermodulation – diminished control or heightened emotional and autonomic responses – RE-EXPERIENCING • Include the fear, anger, shame, guilt responses • Emotional overmodulation – increased control of emotional responses, hence related emotional detachment • Includes depersonalisation and derealisation, emotional numbing and analgesia • People can fluctuate between the two states

• With diminished prefrontal inhibition of limbic regions during emotional undermodulation, studies have indicated decreased ventromedial prefrontal cortex and rostral anterior cingulate activation and increased amygdala activation in response to trauma and non-trauma-related emotional stimuli in those with PTSD (triggers for re-experiencing and increased emotions) • By contrast, patients who have emotional overmodulation have shown increased activation of medial prefrontal cortex and rostral anterior cingulate regions, which have been suggested to lead to decreased amygdala activation (therefore hypoarousal, detachment, etc)

CONSEQUENCES OF REDUCED CORTISOL SIGNALLING AFTER TRAUMA

SALIENCE NETWORKS • Central executive network - Cognitive dysfunction • Salience network Altered arousal and interoception • Default mode network altered self-referential processing

Primary Construct-Phenomenology of PTSD • Intrusive memories • Avoidance - behavioural response • Numbing and loss of pleasure • Difficulty with memory, concentration, irritability • Somatic distress FEAR CIRCUITS DEFAULT NETWORKS WORKING MEMORY AUTONOMIC DYSFUNCTION

PTSD DIAGNOSIS – DSM 5 Criterion DSM IV DSM 5 Chapter Anxiety Disorders Trauma & Stressor-Related Disorders A - stressor exposure to a traumatic event in which both of the following were present: 1. experienced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others 2. response involved intense fear, helplessness, or horror exposure to: death, threatened death, actual or threatened serious injury, or actual or threatened sexual violence, as follows: (1 required) Via: 1. direct 2. witnessed 3. indirectly 4. exposure to aversive details 19

Criterion DSM IV DSM 5 B - intrusions traumatic event is persistently re-experienced in one (or more) of the following: 1. recurrent and intrusive distressing recollections of the event 2. recurrent distressing dreams of the event 3. acting or feeling as if the traumatic event were recurring 4. intense psychological distress at exposure to internal or external cues 5. physiologic reactivity on exposure to internal or external cues traumatic event is persistently reexperienced in the following way(s): (1 required) 1. recurrent, involuntary, and intrusive memories 2. traumatic nightmares 3. dissociative reactions (e. g. , flashbacks) which may occur on a continuum from brief episodes to complete loss of consciousness 4. intense or prolonged distress after exposure to traumatic reminders 5. marked physiologic reactivity after exposure to trauma-related stimuli.

Criterion DSM IV DSM 5 C - avoidance persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by three (or more) of the following: persistent effortful avoidance of distressing trauma-related stimuli after the event: (1 required) 1. trauma-related thoughts or feelings 2. trauma-related external reminders (e. g. , people, places, conversations, 1. efforts to avoid thoughts, activities, objects, or situations) feelings, or conversations associated with the trauma 2. efforts to avoid activities, places, or people that arouse recollections of the trauma

Criterion THE PTSD – DSM 5 DSMNEW IV DSM 5 CONT. D (5) negative alterations in cognitions and mood C – continued: (emotional numbing) 3. inability to recall an important aspect of the trauma 4. markedly diminished interest or participation in significant activities 5. feeling of detachment or estrangement from others 6. restricted range of affect (e. g. , unable to have loving feelings) 7. sense of foreshortened future (e. g. , does not expect to have a normal life) negative alterations in cognitions and mood that began or worsened after the traumatic event: (2 required) 1. inability to recall key features 2. persistent (and often distorted) negative beliefs and expectations about oneself or the world 3. persistent distorted blame of self or others … 4. persistent negative trauma-related emotions 5. markedly diminished interest in (pre-traumatic) significant activities 6. feeling alienated from others 7. constricted affect: persistent inability to experience positive emotions

Criterion DSM IV (crit D) DSM 5 Ealterations in arousal and reactivity persistent increased trauma-related alterations in arousal indicated by at and reactivity that began or least two of the following: worsened after the traumatic event: (2 required) 1. difficulty falling or 1. irritable or aggressive behavior staying asleep 2. self-destructive or reckless 2. irritability or outbursts behavior of anger 3. difficulty concentrating 3. hypervigilance 4. exaggerated startle response 4. hyper-vigilance 5. problems in concentration 5. exaggerated startle 6. sleep disturbance response F - duration > 1 month G - functional significance significant symptom-related distress or functional impairment H - attribution not due to medication, substance use, or other illness

QUALITY OF LIFE ISSUES WITH PTSD The problem often becomes selfperpetuating, and hence the common development of comorbid conditions

COMMON COMORBIDITIES MOST RELEVANT TO CHRONIC PTSD • DEPRESSION (SUICIDAL IDEATION/BEHAVIOUR) • OTHER ANXIETY DISORDERS • SUBSTANCE USE DISORDERS • PAIN • OTHER MEDICAL CONDITIONS • OCCUPATIONAL IMPAIRMENT • INTERPERSONAL PROBLEMS & RELATIONSHIP BREAKDOWN • SOCIAL WITHDRAWAL - DISENGAGEMENT

THE NEED FOR CLINICAL STAGING IN PTSD • Different phenotypes that need to be addressed in treatment • Staging is a method for clarifying the issue of longitudinal course and the changing neurobiology Mc. Farlane et al Clinical Psychiatric Reports 2017

STAGING MODEL OF PTSD 0. TRAUMA EXPOSED NO SYMPTOMS BUT AT GREATER RISK WITH FURTHER EXPOSURE 1 A. MINOR SYMPTOMS 1 B. SUBSYNDROMAL PTSD – SIMILAR TO PTSD 2. FIRST EPISODE OF BRIEF DURATION 3. MORE ENDURING OR RELAPSING DISORDER FOLLOWING TREATMENT 4. CHRONIC, SEVERE AND TREATMENT UNRESPONSIVE

PREVENTIVE STANCE OF STAGING • Emphasis on progression or transition • Not inevitable • Earlier stages of treatment have fewer complications and greater tolerability • Cross sectional and longitudinal biomarkers for the different phenotypes of the disorder • Different treatment strategies at different stages

AUSTRALIAN PTSD GUIDELINES Developed in consultation with experts and people affected by PTSD Supported by the Australian Government and approved by peak health research body - NHMRC Endorsed by professional associations – RACGP, RANZCP, APS Available from www. acpmh. unimelb. edu. au 29

Practice Guidelines – Caveats • Absence of evidence is not evidence of absence • Guidelines support clinical decision-making they do not replace it; they recommend, they do not mandate • Clinical priorities, the impact of comorbid conditions, patient preferences - may influence timing, order and combination of treatments

GUIDELINE RECOMMENDATIONS: ADULTS • Trauma focussed CBT or EMDR is the treatment of choice for • PTSD: Trauma focused CBT included In vivo and imaginal exposure Cognitive therapy or cognitive processing therapy Medication should not be used as routine 1 st line in preference to TF psychological treatment • Where prescribed: SSRIs Other newer antidepressants, adjunctive agents 31

TREATMENT CONTEXT: THREE-LEVEL RESPONSE TO PROMOTING RECOVERY FOLLOWING TRAUMA Level 1: Interventions for all: Psychological first aid (PFA), community development activities (little evidence) Level 2: Interventions for persisting mild/ subclinical problems: Simple intervention strategies for use by primary care, general counsellors, etc (moderate evidence) Level 3: Interventions for disorder: Interventions for use by mental health providers (strong evidence)

Effective psychological treatments: • TFCBT = trauma focused cognitive behavioural therapy • CPT = cognitive processing therapy • EMDR = eye movement desensitisation and reprocessing • To be effective: • Enable patient to confront distressing memories • Manage avoidance responses • Reduce and manage associated arousal & distress

PTSD: STAGES OF CBT TREATMENT 1: Stabilisation and engagement 2: Education and information 3: Anxiety management 4: Trauma exposure 5: Cognitive restructuring 6: Relapse prevention and maintenance

How effective are psychological therapies? � Reasonably effective: in most studies, around 70% show substantial symptom reduction � Many people have some residual symptoms and/or vulnerability � Women do better than men, civilians better than veterans, single better than multiple trauma � We need more research on tailoring treatment to clinical presentation � The biggest challenge is dissemination of best treatments and changing clinical practice

Pharmacotherapy for PTSD: Overview There is no “silver bullet” • Medication should not be used as routine 1 st line in preference to TF psychological treatment • When medication is used antidepressants are the first line treatment • the evidence is strongest for the SSRI class • The evidence for efficacy of other medications used alone or added to antidepressants is not strong • there is some evidence to support the strategy of adding prazosin or atypical antipsychotic medication to an antidepressant when there is a poor or partial response to antidepressant alone

Role of Antidepressants in PTSD • Need to consider role of peripheral inflammation • Different phenotypes of PTSD (MST, Moral Injury, combat PTSD, etc) • Need a staging model • Different antidepressants may have different impact on these inflammatory systems in PTSD treatment • Mc. Farlane et al Clinical Psychiatric Reports 2017

Antidepressants Act on Peripheral Inflammation Hashimoto Int J Mol Sci 2015

CRP PREDICTS DIFFERENTIAL RESPONSE TO SSRI VS. SSRI+BUPROPION Jah MK et al. Psychoneuroendocrinol 2017; 78: 105 -13

Meta Analysis of Treatment in Military Populations • Mean post treatment scores for CPT and PE remained at or above clinical criteria for PTSD • Approximately 66% of patients retained their PTSD diagnosis after treatment (range 60 -72%) • Prolonged exposure marginally superior compared to nontrauma focused psychotherapies • Need to improve existing treatments and test novel evidence based treatments Steenkamp et al JAMA 2015, 314; 489 -500

Evidence Based Care • Important that evidence based treatments are provided • Limitations of the literature • Little comorbidity eg substance abuse • Low levels of suicidality • Need a systematic strategy for how to deal with non response • Issue of multiple versus single trauma • No consideration of phenotypes/personalised approach • Can be used as a method of restricting treatment rather than optimising outcomes

Melatonin • Maintenance of circadian cycle • Improves sleep • Cortical binding • Maintenance of somatic self regulation and decreasing arousal • Agomelatine can be prescribed through RPBS

Cases?

Questions?