Management of Posttraumatic Stress Disorder and Related Disorders

Educational Objectives

The goal of this program is to improve the management of posttraumatic stress disorder (PTSD). After hearing and assimilating this program, the clinician will be better able to:

1. Describe the physiologic impacts of symptoms of PTSD.
2. Select an appropriate therapeutic approach based on the origin of the traumatic incident.
3. Categorize symptoms of PTSD into the dominant symptom clusters.
4. Identify comorbid medical and psychiatric conditions associated with PTSD.
5. Initiate medication therapy to treat symptoms associated with PTSD.

Summary

Etiology and presentation of posttraumatic stress disorder (PTSD)

Adults: PTSD may arise from single fear-based incidents (eg, accidents, robberies, witnessing or discovering the death of a loved one, natural disasters) or multiple incidents; individuals subjected to interpersonal trauma also experience guilt and shame; complicated bereavement (experienced by patients who survive, eg, rape, combat) invokes additional emotions which help direct treatment; a review found that urban women who experience an average of 8 traumatic events (including, eg, human trafficking, multiple tours of combat duty, involvement in street violence or gang warfare, displacement from home) develop symptoms of PTSD; experience of multiple incidents or a single significant incident results in dysregulation of neural response and disproportionate activation of the startle and fight-flight-freeze (FFF) responses

Children: present with fear, confusion, and trust issues; employ self-blame (a defense mechanism) to provide hope during situations of helplessness and despair; chronic abuse and neglect may lead to significant guilt and shame; the adverse childhood experience (ACE) study (Felitti et al 1998) examined the impacts of chronic stress hormone exposure on development, which include, eg, inadequate blood-brain and gut barriers, impaired immune system, decreased neurogenesis of brain cells in the hippocampus (diminishes learning ability); children who have adapted to stressors do not adapt to a normal environment

Therapy: ensure basic needs (eg, housing, food, clean water, transportation) are met prior to initiation; studies indicate that consistent support at home is essential for improvement

Re-exposure therapy: effective for fear-based trauma and helps regain the ability to regulate neural networks, but may actually worsen symptoms following shame- or guilt-based trauma

Eye movement desensitization and reprocessing (EMDR): evidence-based; preferred by the American Psychiatric Association; works well for shame- and guilt-based trauma despite partial event recall

Trauma rescripting: uses experiential visualization of full sensory recall to alter the imagining of the occurrence of a trauma; can change the emotional valence encoding the trauma; helps treat patients with guilt- and shame-based traumas; typically involves imagining an interruption prior to the occurrence of a traumatic event (eg, a neighbor, relative, or the therapist arrives in time to protect a child from abuse)

Erase negative beliefs: through, eg, psychodynamic psychotherapy, cognitive behavioral therapy (CBT); exploring existential and philosophical questions may help

Goal: re-regulate brain network responses to increase the threshold for the triggering of the FFF response and promote earlier identification of, eg, thoughts, intrusive memories that create interruption

Treatment of PTSD in children: children may not have learned key skills and may have unmet dependency needs (eg, alexithymia); emotional regulation — tasks of psychotherapy include emotional attunement, affect regulation, and co-creation of a historical narrative; teach children to manage feelings of impulsivity and to abide by realistic limits (a basic need); goal — treatment (eg, CBT, psychodynamic psychotherapy, EMDR augmentation [EMDR alone may work for adults], dialectical behavior therapy, schema therapy) aims to strengthen the connections between the prefrontal cortex and the limbic system

Prominent symptom domains: intrusion symptoms — include intrusive memories and flashbacks (interrupt interaction with the world) which may trigger intense distress; avoidance symptoms — involve major efforts to avoid feelings, thoughts, people, places, objects, and situations related to the trauma; negative alterations in cognition and mood — associated with complex traumas; include inability to recall key aspects, persistent negative thoughts and expectations, changes in core beliefs, blame of self or others, decreased interest in activities, feelings of detachment or estrangement, and inability to experience positive emotions; many patients meet diagnostic criteria for major depressive disorder; alterations in arousal and reactivity — symptoms include irritability, impulsivity, reckless self-destructive behavior, exaggerated startle response, difficulty focusing, and sleep disturbances; misdiagnosis as bipolar disorder (BD) is possible; presence ofdissociative symptoms — Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) favors specifying depersonalization and derealization; definite diagnostic codes exist for symptoms of amnesia, identity confusion, and identity alteration

Comorbid conditions: psychiatric — include substance use disorders, eating disorders, BD, personality disorders, dissociative disorders, impulse control disorders (eg, kleptomania), and obsessive compulsive disorder (OCD; may appear early in patients who recently experienced trauma); medical — secondary to chronic elevation of levels of stress hormones; include, eg, hypertension, asthma, chronic obstructive pulmonary disease, irritable bowel syndrome, inflammatory bowel disease, migraines, fibromyalgia, chronic pain, systemic lupus erythematosus; nutrition — decreased appetite and caloric intake are common; patients with nausea and vomiting may tolerate protein shakes; avoid caffeine overuse

Medication therapy

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs): the Food and Drug Administration approved sertraline (Lustral, Zoloft) and paroxetine (Brisdelle, Paxil, Pexeva); other drugs are used off-label; may improve serotonin transportation in the amygdala; venlafaxine — strongly recommended by the Department of Veterans Affairs (VA); effective starting dose is 150 mg daily (compared with 75 mg for depression)

Typical antidepressants: studies show benefit from mirtazapine and nefazodone, which impart lower levels of sexual dysfunction, compared with SSRIs and SNRIs (≈30% risk for sexual dysfunction in men and women); the sedative effect of mirtazapine is useful to treat insomnia

Anticonvulsants: topiramate (Qudexy XR, Topamax, Trokendi XR) — may reduce reexperiencing symptoms; treatment-limiting side effects include cognition impairment and word-finding difficulty; altered sense of taste, another side effect, may help patients reduce sugar intake; divalproex sodium (Depakote) — studies reveal mixed evidence; one study showed possible improvement in global symptom score with levels of valproic acid ≈86 mg/L; increases risk for falls but not orthostatic hypertension; 500 mg may help to treat nightmares; higher doses may help with mood instability and triggering of FFF response; oxcarbazepine (Oxtellar XR, Trileptal) — may reduce irritability; monitor patients for sodium depletion

Atypical antipsychotics: recommended as adjunct therapy with SSRIs and SNRIs; olanzapine — preferred by the VA for combat-related PTSD, though concerns exist regarding side effects; asenapine — blocks adrenaline; may reduce reexperiencing symptoms (ie, nightmares, flashbacks); risperidone (Okedi, Risperdal) — results from studies conducted by the VA contraindicate against use for PTSD and reveal a delay in recovery

α₁-adrenoceptor antagonists: prazosin — effective in some patients for nightmares; dosed 2 to 20 mg daily, with an average dose of 6 to 8 mg daily; wean patients following abatement of nightmares

α₂-adrenoceptor agonists: clonidine — increases noradrenergic tone in the prefrontal cortex and norepinephrine input from the locus ceruleus; tablet is dosed 0.1 mg twice daily to 0.2 mg three times daily; avoid use in conjunction with β-blockers; once-weekly clonidine patch provides even serum levels, does not cause sedation, and helps prevent nightmares in patients with treatment-resistant PTSD

β-blockers: propranolol — alleviates symptoms associated with hyperarousal; monitor blood pressure; trials failed to show statistical significance of sufficiently early dosing to prevent PTSD symptoms

Typical antipsychotics: loxapine — inhalation powder received FDA approval for treatment of agitation in acute-care psychiatric units; starting dose for the capsule formulation is 5 mg twice daily, with increase to 10 mg twice daily; oversedation is rare

μ opioid receptor antagonists: naltrexone — reduces dissociative activity (ie, depersonalization, derealization); refrain from use in patients with suspected (untreated) dissociative identity disorder who lack developed coping mechanisms, as well as in patients who do not remember their life prior to age 14 yr; only available in 50-mg tablets, but a starting dose of ≈12.5 mg (1/4 tablet) daily is recommended for 1 to 2 weeks prior to upward titration; naltrexone may provide additional benefits for addictive disorders and comorbid self-injury

Nutritional supplementation: supplement omega-3 fatty acids (eg, fish oil, flaxseed oil) in patients who do not consume, eg, fish, avocado; check vitamin D levels to ensure optimal neurologic function; provide education about anti-inflammatory diet and supplements (eg, turmeric, ginger, blueberry, green tea); aromatherapy and mint can activate cranial nerves and enhance grounding for dissociative and reexperiencing symptoms

Considerations: L-methylfolate supplementation — interacts with lamotrigine (Lamictal) and stimulants (induce dopaminergic side effects, eg, diaphoresis, anxiety, gastric upset) in patients with the homozygous TT genotype; β-catenin — expressed in the nucleus accumbens; upregulation facilitates extinction of stress responses to triggers; associated with addictive behaviors and memory formation in cocaine use disorder; mifepristone — used in some trials to manipulate the hypothalamic–pituitary–adrenal axis to treat psychotic depression

Questions and answers: naltrexone — blocks endogenous μ opioid receptors and interrupts behavior reinforcement in patients who experience release of endorphins during states of pain (eg, cutting); dissociation and psychosis in PTSD — data are lacking about the prevalence of dissociative symptoms in PTSD; ≈33% of patients with PTSD have symptoms of psychosis

Readings

Alexander W. Pharmacotherapy for post-traumatic stress disorder in combat veterans: focus on antidepressants and atypical antipsychotic agents. P T. 2012;37(1):32-8; Berlant J, van Kammen DP. Open-label topiramate as primary or adjunctive therapy in chronic civilian posttraumatic stress disorder: a preliminary report. J Clin Psychiatry. 2002;63(1):15-20. doi:10.4088/jcp.v63n0104; Cameron HA, Schoenfeld TJ. Behavioral and structural adaptations to stress. Front Neuroendocrinol. 2018;49:106-113. doi:10.1016/j.yfrne.2018.02.002; Davidson J, Rothbaum BO, Tucker P, et al. Venlafaxine extended release in posttraumatic stress disorder: a sertraline- and placebo-controlled study. J Clin Psychopharmacol. 2006;26(3):259-67. doi: 10.1097/01.jcp.0000222514.71390.c1. Erratum in: J Clin Psychopharmacol. 2006;26(5):473. Dosage error in article text; Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245-58. doi: 10.1016/s0749-3797(98)00017-8; Garakani A, Murrough JW, Freire RC, et al. Pharmacotherapy of anxiety disorders: current and emerging treatment options. Front Psychiatry. 2020;11:595584. doi:10.3389/fpsyt.2020.595584; Kleim B, Graham B, Bryant RA, et al. Capturing intrusive re-experiencing in trauma survivors' daily lives using ecological momentary assessment. J Abnorm Psychol. 2013;122(4):998-1009. doi: 10.1037/a0034957; Lewey JH, Smith CL, Burcham B, et al. Comparing the effectiveness of EMDR and TF-CBT for children and adolescents: a meta-analysis. J Child Adolesc Trauma. 2018;11(4):457-472. doi:10.1007/s40653-018-0212-1; Petrakis IL, Ralevski E, Desai N, et al. Noradrenergic vs serotonergic antidepressant with or without naltrexone for veterans with PTSD and comorbid alcohol dependence. Neuropsychopharmacology. 2012;37(4):996-1004. doi: 10.1038/npp.2011.283; Schrader C, Ross A. A review of PTSD and current treatment strategies. Mo Med. 2021;118(6):546-551; Stoner SC, Dahmen MM. Extended-release divalproex in bipolar and other psychiatric disorders: a comprehensive review. Neuropsychiatr Dis Treat. 2007;3(6):839-46. doi: 10.2147/ndt.s1264; Varma A, Moore MB, Miller CWT, et al. Topiramate as monotherapy or adjunctive treatment for posttraumatic stress disorder: a meta-analysis. J Trauma Stress. 2018;31(1):125-133. doi:10.1002/jts.22251; VA/DOD clinical practice guideline for the management of posttraumatic stress disorder and acute stress disorder: clinician summary. Focus (Am Psychiatr Publ). 2018;16(4):430-448. doi:10.1176/appi.focus.16408; Zoellner LA, Feeny NC, Bittinger JN, et al. Teaching trauma-focused exposure therapy for PTSD: critical clinical lessons for novice exposure therapists. Psychol Trauma. 2011;3(3):300-308. doi: 10.1037/a0024642.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose. Dr. Fretwell's lecture includes information related to the off-label or investigational use of a product, therapy, or device.

Acknowledgements

Dr. Fretwell was recorded at the 2022 Regional Integrated Mental Health Conference, held September 16-18, 2022, in West Baden Springs, IN, and presented by the American Psychiatric Association in joint providership with the Indiana Psychiatric Society. For more information about upcoming CME activities from this presenter, please visit www.pdallc.com. Audio Digest thanks Dr. Fretwell, the American Psychiatric Association, and the Indiana Psychiatric Society for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 2.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 2.00 CE contact hours.

Lecture ID:

PS512401

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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