INT’L. J. PSYCHIATRY IN MEDICINE, Vol. 47(4) 337-346, 2014

POST-TRAUMATIC STRESS DISORDER: THEORY AND TREATMENT UPDATE*

HEATHER A. KIRKPATRICK, PHD, MSCP GRANT M. HELLER, PHD Michigan State University and Genesys Regional Medical Center

ABSTRACT

Post-traumatic stress disorder (PTSD) is one of the few mental disorders in which the cause is readily identifiable. In this article, we review the new Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria, prevalence, and presentation of patients with PTSD in primary care. The purpose of this article is to review current literature regarding theory, etiology, and treatment effectiveness. Key findings in terms of neurobiological underpinnings with implications for future treatment are discussed. Recommendations regarding effective psychotherapy and pharmacotherapy, emerging treatment, and management issues in primary care settings are offered. (Int’l. J. Psychiatry in Medicine 2014;47:337-346)

Key Words: PTSD, trauma, post-traumatic stress disorder, primary care, trauma and stress-related disorders

*Based on a presentation given at The 34th Forum for Behavioral Science in Family Medicine, Chicago, IL, September 19-22, 2013. 337 Ó 2014, Baywood Publishing Co., Inc. doi: http://dx.doi.org/10.2190/PM.47.4.h http://baywood.com

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TOPIC: POST-TRAUMATIC STRESS DISORDER Post-Traumatic Stress Disorder (PTSD) is a disorder in which a person who has directly experienced a traumatic event develops a characteristic set of symptoms. Recent revisions in the DSM-5 [1] categorize symptoms into four clusters: intrusion/re-experiencing symptoms, avoidance symptoms, negative cognitions and mood, and symptoms of hyper-arousal. Examples of how these symptoms can present are listed in Table 1. Epidemiology The U.S. estimate of lifetime prevalence of PTSD in adults is 7.8%, with women more at risk than men (20.4% vs. 8.2%) despite experiencing fewer traumas [2, 3]. Higher rates are also seen in African-Americans [4], Native Americans (14-16%) [5], and in refugees from conflict-ridden areas of the world (9-60%) [6]. The types Table 1. Key Symptoms of PTSD Key symptoms of intrusion/re-experiencing the trauma (at least one required) •recurrent and intrusive memories, images, thoughts •distressing dreams •dissociative reactions such as flashbacks •strong emotional and physical reactions to cues that resemble or symbolize an aspect of the trauma Key symptoms of avoidance (at least one required) •efforts to avoid thoughts, feelings, conversation or activities, places or people connected to trauma Key symptoms of negative cognitions and mood (at least one required) •amnesia for important aspects of the trauma •a persistent and distorted sense of blame of self or others •persistent negative emotional state (e.g., fear, horror, guilt, shame) •inability to experience positive emotions •feelings of detachment or estrangement from others •markedly diminished interest in activities Key symptoms of hyper-arousal (at least one required) •increased anxiety •sleep difficulties •poor concentration •increased irritability •outbursts of anger •reckless or self-destructive behavior •hypervigilence •exaggerated startle response

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of events experienced as the initial trauma vary widely and include combat, personal assault, natural disasters, motor-vehicle accidents, rape, childhood physical and sexual abuse, loss of loved ones [7], and medical crises such as burns, cancer, and myocardial infarction [8, 9]. Risk factors can be considered in three areas: Pre-trauma, Peri-trauma, and Post-trauma [10]. See Table 2. Symptoms can occur at any age, and generally present within 3 months of the trauma, but may occur years later. In Acute Stress Disorder (ASD), symptoms are present for more than 3 days, but less than 1 month, after the trauma. In contrast, diagnosis of PTSD requires symptoms persisting more than 1 month. Symptom duration varies widely, with over 50% resolving within 3 months, while many have persisting symptoms for longer than 1 year [1]. Symptoms are often intermittent and relapse can occur. PTSD can be strongly associated with physical illness complaints, particularly musculoskeletal, nervous, sensory, cardio-respiratory, gastro-intestinal, and vague symptom presentations [11]. Etiology PTSD is conceptualized as a failure of recovery caused in part by altered fear learning; i.e., the failure to extinguish behavioral responses to stimuli associated with the trauma. Following a trauma, the symptoms of PTSD are almost universal; however, many people are able to eventually confront fearful stimuli such as memories, reminders, or visual cues with a gradual decrease of fear. When this decrease does not occur, people tend to develop cognitive and avoidance strategies in an attempt to avoid distressing emotions. Subsequently, these strategies interfere with the extinction of fear by limiting exposure to safe reminders. Alterations in fear learning involve the hippocampus, amygdala, and prefrontal cortex. The hippocampus appears to be involved in the ability to recall safe episodes when

Table 2. Risk Factors for PTSD Pre-trauma factors

Lower socioeconomic status Parental neglect Personal or family psychiatric disease Female Poor social support

Peri-trauma factors

Severity, intensity, frequency, and duration of trauma Initial severity of person’s reaction to trauma Unpredictability and uncontrollability of the trauma

Post-trauma factors

Lack of social support Life stress Failure for early identification and treatment

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faced with fearful stimuli. Research has shown that hippocampal volumes are decreased in patients with PTSD, but this may be a risk factor rather than a sequella [12]. There is also increasing attention to the role of the ventral medial prefrontal cortex (VMPFC). Via its inhibitory control of the amygdala, the VMPFC may allow the mind to “overwrite” the original fear, allowing safe episode memories to become dominant [13]. There has also been extensive research regarding aberrations in the hypothalamic-pituitary-adrenal axis function in patients with PTSD; the dominant finding is that patients have increased levels of corticotrophin releasing factor [14]. There is still little consensus in the literature regarding the role of cortisol, with studies finding both higher and lower levels of cortisol secretion in patients with PTSD [14]. Despite much investigation, there are no reliable biological markers for at-risk patients [15]. Research continues in the area of chemical prophylaxis (the prevention of PTSD pre- or immediately post-trauma via interruption of fear learning), but controversy remains as study findings are not consistent [16]. LITERATURE REVIEW Assessment in Primary Care The National Institute for Health and Clinical Excellence (NICE) 2005 guidelines caution against routine, crisis debriefings after a traumatic incident [17]; “watchful waiting” is recommended instead. There are a variety of screening instruments available to providers, including the Primary Care PTSD Screen (PC-PTSD) [18] and the PTSD Checklist (PCL) [19]. While the PCL can be used to track symptoms throughout treatment; the PC-PTSD may be more useful for initial screening in primary care. The PC-PTSD has four items, with a recommended cutoff of three (although a cutoff of two can be used to increase sensitivity.) A positive screen should prompt more in-depth discussion and assessment. Providers may wish to refer such patients for further evaluation from behavioral health providers, such as a psychologist, counselor, or clinical social worker. See Figure 1 for the PC-PTSD. PTSD may be recognized in primary care after a traumatic event, such as a motor vehicle accident, work related injury, or assault. The patient may also report history of prolonged or chronic exposure to trauma, such as repeated childhood abuse or domestic violence. Frequent medical visits with unexplainable symptoms would warrant probing for possible trauma history. Providers may also wish to inquire about specific symptoms of intrusion/re-experiencing, avoidance, and hyperarousal. Children and adolescents may present differently than adults and may not express direct complaints of symptoms after a trauma. Traumatic experiences may be repetitively reenacted through play. Constriction of play activities, social withdrawal, sleep changes, as well as decreased display of affect or explosive

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In your life, have you ever had any experience that was so frightening, horrible, or upsetting that, in the past month you: 1. Have had nightmares about it or thought about it when you did not want to? YES NO 2. Tried hard not to think about it or went out of your way to avoid situations that reminded you of it? YES NO 3. Were constantly on guard, watchful, or easily startled?

YES NO

4. Felt numb or detached from others, activities, or your surroundings? YES NO

Figure 1. The Primary Care PTSD (PC-PTSD) [18].

tantrums are potential indicators that would justify further exploration. Children and adolescents may also present with a sense of a foreshortened future. Symptoms may often present somatically through complaints of headaches, stomach aches, or other maladies [17, 20]. Collateral information attained from parents and/or caregivers about behavioral changes can be especially useful. Assessment is also improved by asking children directly about their experiences. Psychotherapeutic Treatment There are many effective psychotherapeutic treatments for individuals experiencing PTSD. Although the trauma-related therapies are generally effective at symptom remission, they require adequate levels of psychological stability to be successful. Patients with poor psychological stability can benefit from supportive, ego-strengthening, or motivational treatment before beginning trauma-related therapies [21]. The best evidence for remission of symptoms is for the trauma related therapies: exposure therapy and cognitive behavioral therapy (CBT). Exposure therapy involves graded exposure to situations causing the fear response, allowing the individual to become desensitized to fear cues (habituation). The Institute of Medicine’s (IOM) most recent review found exposure therapy to be effective in significantly improving PTSD symptoms [22]. The IOM examined 23 randomized trials, seven of which were found to be very methodologically sound. All seven found clinically significant improvement in PTSD symptoms. CBT engages the patient in challenging dysfunctional beliefs about the world or themselves while simultaneously engaging the patient in more healthy behaviors such as

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exercise, sleep management, social activation, and management of substance abuse. Overall, the IOM found reasonably good evidence in favor of cognitive therapy, although the authors acknowledged the superiority of evidence for exposure therapy [22]. Other therapies that show good evidence for symptom treatment include cognitive processing therapy (an information processing therapy that includes education, exposure, and cognitive components that challenge dysfunctional thoughts and modify beliefs related to the trauma experience) and motivational interviewing (a set of techniques designed to reduce resistance to change) [22]. For comorbid PTSD and substance abuse, Seeking Safety (a treatment that teaches skills around emotional regulation and substance abstinence simultaneously) has been shown to improve outcomes [23]. Pharmacological Treatment There are a wide variety of pharmacological treatments to consider. Medications are generally most effective in decreasing hyperarousal and improving mood; they are less effective for symptoms of re-experiencing, numbing, and avoidance. Sleep disturbance is especially difficult to manage and can easily lead to polypharmacy. First-line treatment is the utilization of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs) [24, 25]. SSRIs available in the United States include fluoxetine, sertraline, paroxetine, luvoxamine, citalopram, escitalopram, and vortioxetine. Stein and colleagues conducted a meta-analysis of seven randomized treatment trials utilizing SSRI medication and found a relative risk ratio of 1.59 (with a 95% confidence interval of 1.39-1.82) for the effectiveness of SSRIs in improving symptoms of PTSD, indicating strong effectiveness compared to placebo (which would have a relative risk ratio of 1) [25]. Serotoninnorepinephrine reuptake inhibitors (SNRIs) also can be effective for improvement in PTSD symptoms. These medications include venlafaxine and duloxetine. Patients receiving venlafaxine ER have had better symptom control (50.9%) than those receiving placebo (37.5%) [26]. Adjunctive treatments include alpha-adrenergic receptor blockers, with prazosin being the most studied. Prazosin has been shown to decrease nightmares and improve sleep [27]. In addition, mirtazapine (a NaSSA antidepressant) has been shown to be effective in managing insomnia symptoms associated with PTSD, as well as in treating depressive symptoms [28]. Medications shown to be ineffective include older antidepressants such as amitriptyline and nortriptyline, monoamine oxidase inhibitors, mood stabilizers, gabapentin, pregabalin, and atypical antipsychotics [24]. Older antidepressants are not considered first-line due to their safety and adverse effect profiles. Mood stabilizers and atypical antipsychotics have had negative evidence in randomized controlled trials and are not recommended [29, 30]. Particular caution is urged

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in using benzodiazepine medications as they have been shown to be ineffective, and the risk of abuse and dependence are high [31, 32]. Practitioners are strongly encouraged to weigh the risks and benefits of using benzodiazepines beyond a short-term course early in the trauma recovery process. KNOWLEDGE GAPS AND NEW FRONTIERS Despite being the most common approach, there is a paucity of studies examining combined pharmacologic and psychological treatment [33]. With a lack of these studies, it is best to rely upon expert opinion recommending SSRIs and CBT that includes exposure [33-35]. In addition, common real-world presentations of PTSD often include other conditions, including pain, somatization, substance abuse, mild traumatic brain injury (TBI), and suicide, while relatively little evidence indicates appropriate treatment for comorbid illnesses. Dialectical Behavior Therapy strategies to improve distress tolerance skills would appear to be theoretically helpful but have not been fully examined for effectiveness in the PTSD realm [35, 36]. Similarly, Acceptance and Commitment Therapy shows promise in helping therapists and patients accept and improve the willingness to explore painful private experiences and to realign one’s life in accordance with one’s values, but it has not yet amassed good evidence to be recommended beyond adjunctive therapy [37]. Without clear etiology for why some individuals develop or maintain PTSD symptoms after trauma while others do not, more work is needed to determine recommended treatments for prevention or symptom reduction. There are many promising neurobiological treatments under examination to alter memory consolidation (glucocorticoids, corticoptropin-releasing factor, norepinephrine signaling modulators) or alter fear extinction (glucocorticoid receptor modulators, glutamate receptor modulators, and D-cycloserine, a glycine receptor agonist) [16]. There is limited research examining the role of the use of empathomimetics such as 3,4-methylenedioxymethamphetamine (MDMA, also known as “ecstasy”) to facilitate rapid rapport and improve the efficacy of trauma-based psychotherapies [38]. SUMMARY In summary, PTSD is best characterized as a disorder of failed recovery. It represents one of the few mental disorders in which the inciting event or cause is generally known. Practitioners should recognize that avoidance is often the “glue” that causes the disorder to endure, and treatments should be targeted toward reduction of avoidance and titration of exposure to facilitate habituation. Practitioners of primary care can educate patients that there are many effective treatments for PTSD, and remission is very possible for many patients. We are fortunate to be practicing during a time of explosive research on effective

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treatments of PTSD, many of which show good results. Psychotherapy is considered the first-line treatment, with many medications offering assistance in the management of some symptoms. Practitioners should be mindful and cautious in prescribing sedatives, hypnotics, and anxiolytics, as these medications carry a high risk of dependence and can also maintain avoidance, which compromises psychotherapeutic effectiveness. Key therapeutic messages for patients include hope for recovery through many effective treatments: asking for support from those who listen; communicating their experiences; identification of self as a survivor; engaging in healthy behaviors such as adequate sleep, good nutrition, and the avoidance of substance use; and establishing or re-establishing the routine activities of daily living. REFERENCES 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing, 2013:991 pp. 2. Kessler RC, Berglund PA, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Archives of General Psychiatry 2005;62(6):593-602. 3. Ditlevsen DN, Elklit A. Gender, trauma type, and PTSD prevalence: A re-analysis of 18 nordic convenience samples. Annals of General Psychiatry 2012;11:26. 4. Asnaani A, Richey JA, Dimaite R, Hinton DE, Hofmann SG. A cross-ethnic comparison of lifetime prevalence rates of anxiety disorders. Journal of Nervous and Mental Diseases 2010;198(8):551-555. 5. Robin RW, Chester B, Rasmussen JK, Jaranson JM, Goldman D. Prevalence and characteristics of trauma and posttraumatic stress disorder in a southwestern American Indian community. American Journal of Psychiatry 1997;154(11):1582-1588. 6. Fazel M, Wheeler J, Danesh J. Prevalence of serious mental disorder in 7000 refugees resettled in Western countries: A systematic review. Lancet 2005;365(9467):1309-1314. 7. Breslau N, Kessler RC, Chilcoat HD, Schultz LR, Davis GC, Andreski P. Trauma and posttraumatic stress disorder in the community: The 1996 Detroit Area Survey of Trauma. Archives of General Psychiatry 1998;55:626-631. 8. Tedstone JE, Tarrier N. Posttraumatic stress disorder following medical illness and treatment. Clinical Psychology Review 2003;23(3):409-448. 9. Kangas M, Henry JL, Bryant RA. Posttraumatic stress disorder following cancer: A conceptual and empirical review. Clinical Psychology Review 2002;22(4):499-524. 10. Maes M, Delmeire L, Mylle J, Altamura CA. Risk and preventive factors of posttraumatic stress disorder (PTSD): Alcohol consumption and intoxication prior to a traumatic event diminishes the relative risk to develop PTSD in response to that trauma. Journal of Affective Disorders 2001;63(1-3):113-121. 11. Pacella ML, Hruska B, Delahanty DL. The physical health consequences of PTSD and PTSD symptoms: A meta-analytic review. Journal of Anxiety Disorders 2013; 27(1):33-46. 12. Bonne OB, Brandes D, Gilboa A, Gomori JM, Shenton ME, Pitman RK, et al. Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD. American Journal of Psychiatry 2001;158(8):1248-1251.

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Direct reprint requests to: Heather A Kirkpatrick, Ph.D. Genesys Downtown Health Center 420 S. Saginaw St. Flint, MI 48502 e-mail: [email protected]