PTSD: Principles of Diagnosis and Treatment

Overview

Posttraumatic stress disorder (PTSD) has been included in the Diagnostic and Statistical Manual (DSM IV-TR) of the American Psychiatric Association for over 3 decades. According to the most current version of the DSM IV-TR, PTSD can occur when a person has been exposed to a traumatic event in which the person experienced, witnessed, or was confronted with an event that was potentially life-threatening to self or others, and to which the person responded with intense fear, helplessness, or horror.^[1] Symptoms include re-experiencing the event (eg, intrusive memories or nightmares), avoiding stimuli associated with the trauma, numbing of general responsiveness, and hyperarousal. The majority of people who experience a traumatic event will have some of these symptoms within days or weeks after the event, but PTSD is not diagnosed until symptoms last at least 30 days. Although symptoms usually begin within 3 months of a traumatic event, onset can be delayed for months or longer. PTSD can become chronic in up to 40% of cases^[2] and can persist throughout a person's lifetime. A recent study found that 12% of screened veterans over the age of 65 years in a primary care practice reported PTSD symptoms.^[3]

PTSD can result from exposure to any kind of traumatic event, including (but not limited to) military combat, violent personal assault (including sexual or physical attack), childhood sexual or physical abuse, motor vehicle accidents, diagnosis of a life-threatening illness, and natural or manmade disasters.^[1] Patients have reported PTSD as a result of intimate partner violence^[4] and of traumatic medical experiences that occurred in an intensive care unit (ICU).^[5]Exposure to terrorism, such as in the September 11, 2001 attacks on the World Trade Center and Pentagon, is another potential cause of PTSD.^[6] Understandably, PTSD can also occur following war zone exposure, such as the conflicts in Iraq and Afghanistan.^[7]

As primary care clinicians provide nearly 50% of the outpatient care for patients with depression,^[8] it is likely that most primary care practices in the United States currently care for civilians and veterans who have PTSD and associated symptoms, including depression, anxiety, pain, or sleep problems.^[9] For example, in a study involving over 100,000 Iraq and Afghanistan War veterans who were treated at Department of Veterans Affairs (VA) health care facilities, 60% of the initial mental health diagnoses were made outside of mental health clinics, especially in primary care settings.^[10] There are numerous barriers that can impede the diagnosis and treatment of PTSD in primary care, ranging from patient reluctance to disclose mental health concerns for fear of the possible stigma or consequences, to insufficient knowledge or comfort among primary care clinicians in identifying this common disorder.^[9]

Epidemiology

Approximately 60% of men and 50% of women in the United States have experienced a traumatic event, and a majority of those have experienced 2 or more traumatic events.^[2] The traumas most commonly associated with PTSD include war zone exposure among men, and rape and sexual molestation among women.^[2] The lifetime prevalence of PTSD in the US population is approximately 8%.^[1] The prevalence is estimated to be up to 17% in primary care practices^[9] and may be higher than 50% among mental health treatment-seeking populations.^[11]

Civilian Versus Military PTSD

PTSD and other mental health problems are common in military and veteran populations. A study involving over 100,000 veterans of the wars in Iraq and Afghanistan who were seen at VA healthcare facilities found that 25% of these veterans received at least 1 mental health diagnosis, and 56% had more than 2 distinct diagnoses.^[10] Military personnel appear to be at greater risk, and have an elevated prevalence, of PTSD because of the increased likelihood of their exposure to traumatic events.

In the 1980s, the National Vietnam Veterans Readjustment Study estimated that 15.2% of male and 8.1% of female Vietnam veterans had PTSD.^[12] Prior to the wars in Iraq and Afghanistan, it was estimated that 11.5% of veterans in VA primary care settings met the criteria for PTSD.^[13] To date, approximately 2 million personnel have deployed in Operation Enduring Freedom and Operation Iraqi Freedom, and it is estimated that between 5% and 15% of these personnel have PTSD.^[14]

Risk Factors

Not everyone who witnesses or experiences a traumatic event will develop symptoms of PTSD. The risk varies as a function of characteristics of the event, the person's prior experiences, and the recovery environment. Research has found that current and post-trauma factors, including the severity of the trauma, concurrent life stress, and/or lack of social support, have stronger and more consistent effects on the development of PTSD than any pre-trauma factors.^[15]

Characteristics of the Event

The type and duration of a traumatic event, as well as the number of events a person has experienced, affect the risk of developing PTSD. Interpersonal trauma such as rape and physical assault are especially likely to lead to PTSD, as is combat. Longer duration of exposure to an event, and repeated exposure to the same event or multiple events also increase risk.^[1] Experiences such as killing in a war zone or being injured during an event further increase risk.^[7,16] In fact, war zone exposure substantially increases the risk for PTSD in the military, and is the sole factor that is consistently associated with PTSD.^[17]

According to VA statistics concerning military veterans of the conflicts in Iraq and Afghanistan who received VA care, 15.1% of female veterans, compared with 0.7% of male veterans, reported experiencing military sexual trauma (MST).^[18] Many veterans report at least 1 other trauma in addition to MST, including child or adult sexual abuse.^[19]MST is associated with increased likelihood of another mental disorder diagnosis, including PTSD, anxiety, or depression (especially among women), and/or substance use/abuse disorders (among men).^[18,20]

Characteristics of the Person and Prior Experiences

Event characteristics do not fully determine how a person will react to a traumatic event. Sociodemographic and psychological factors affect risk, as does a person's prior experience with trauma or other adversity. A meta-analysis that examined risk factors for PTSD in trauma-exposed adults found 3 categories of pre-trauma risk factors that varied in their association with PTSD: (1) female gender, younger age at trauma, and minority race were associated with risk of PTSD in some, but not all, populations; (2) less education, previous trauma, and general childhood adversity were more consistently associated with PTSD; and (3) personal psychiatric history, family psychiatric history, or reported childhood abuse had the most uniform predictive effects.^[15]

Even when type of exposure is taken into account, data show that women are twice as likely as men to develop PTSD.^[2,21] However, the elevated risk of PTSD in women has not been seen in response to combat, although women's role in US combat is so new, further research is needed in this area.^[22] Some minority ethnic and racial groups, especially Hispanics, appear to have increased risk of PTSD, closer examination of the studies have determined that other risk factor such as lower incomes, younger ages, greater exposure to the trauma, and less social support account for a substantial proportion of the observed higher prevalence of PTSD.^[23-25]

The Recovery Environment

Recent focus has examined the importance of the recovery environment for victims of or witnesses to traumatic events. The meta-analysis by Brewin and colleagues highlighted the heterogeneity of PTSD, emphasizing differences in risk factors between civilian and military subpopulations, and noted that pre-trauma predictive factors may not be as consistent and important as post-trauma responses or factors.^[26] Specifically, evidence indicates that a supportive recovery environment is protective against PTSD, whereas further stress and/or trauma during the post-trauma period increase the risk of developing PTSD.

Psychobiology of PTSD

Life-threatening situations impact specific hormones, neurotransmitters, and regions of the brain to allow the individual to appropriately respond to the threat. These neurobiological factors typically return to normal levels after removal of the threat. The stress response to trauma is associated with variable degrees of change in numerous neurotransmitters (including serotonin, dopamine, and norepinephrine). It is not surprising, then, that investigators have studied the neurobiological underpinnings of PTSD, with particular emphasis on physiologic reactivity and on the noradrenergic and hypothalamic-pituitary axis (HPA) systems.^[27]

The largest and most consistent body of evidence shows increased heart rate reactivity to traumatic reminders in PTSD. Other measures showing increased reactivity or decreased habituation include startle and skin conductance. Another large body of evidence shows increased activity of the noradrenergic system. Baseline measures typically show no differences between individuals with PTSD and controls, whereas measures of reactivity and 24-hour urinary and plasma measures show elevations in norepinephrine. PTSD is also associated with increased norepinephrine responses to traumatic reminders.^[27]

Functioning of the HPA axis system is dysregulated in PTSD. Some studies have found low 24-hour urinary free cortisol in PTSD versus controls, whereas other studies have found the opposite pattern.^[27] Some studies also have found increased HPA reactivity (in response to dexamethasone challenge) and negative feedback inhibition. Although these alterations are within normal ranges, they indicate that the HPA functioning is altered in individuals with PTSD.

A number of other aspects of the stress response system show alterations as well, including serotonin, glutamate, gamma-aminobutyric acid, neuropeptide-Y, as well as other systems, including dopaminergic, opiate, and thyroid.^[27]Thereis also evidence of altered brain structure and functioning. However, at the present time, most of the evidence on the pathophysiology of PTSD indicates that the numerous changes are within the normal range and do not reflect clinically significant disturbances of biological systems.

Diagnosing PTSD

By asking patients directly about possible PTSD, clinicians can obtain a more accurate diagnostic picture and therefore provide more appropriate treatment. Table 1 lists the criteria from DSM IV-TR for a diagnosis of PTSD. It is not necessary to obtain a detailed trauma history in order to screen for PTSD; however, it is useful for clinicians to ask their patients about military service.

Table 1. DSM-IV: Diagnosis of PTSD in Adults^[1]

Experience of Trauma	Manifestation	Criteria for Diagnosis
Exposure to a traumatic event	The person 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. The person's response involved intense fear, helplessness, or horror.	Patient must experience both for a diagnosis of PTSD.
Persistent re-experience of the traumatic event	Recurrent and intrusive distressing recollections of the event, including images, thoughts, or perceptions Recurrent distressing dreams of the event Acting or feeling as if the traumatic event were recurring (includes a sense of reliving the experience, illusions, hallucinations, and dissociative flashback episodes, including those that occur on awakening or when intoxicated) Intense psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event Physiological reactivity on exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event	Patient must experience at least 1 of the 5 for a diagnosis of PTSD.
Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma)	Efforts to avoid thoughts, feelings, or conversations associated with the trauma Efforts to avoid activities, places, or people that arouse recollections of the trauma Inability to recall an important aspect of the trauma Markedly diminished interest or participation in significant activities Feeling of detachment or estrangement from others Restricted range of affect Sense of a foreshortened future	Patient must experience at least 3 of 7 for a diagnosis of PTSD.
Persistent symptoms of increased arousal (not present before the trauma)	Difficulty falling or staying asleep Irritability or outbursts of anger Difficulty concentrating Hypervigilance Exaggerated startle response	Patient must experience at least 2 of 5 for a diagnosis of PTSD.

Note:The duration of the disturbances must be longer than 1 month and the disturbances must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Assessment Tools

The gold standard for assessing PTSD is a clinician-administered interview, such as the Clinician-Administered PTSD Scale or Structured Clinical Interview for DSM-IV. However, brief self-report questionnaires can be used in primary care and other settings in which mental health clinicians are not available to perform clinical interviews.

The Primary Care PTSD Screen (PC-PTSD) is a widely used 4-item questionnaire developed especially for primary care clinicians to screen veterans for PTSD (Table 2).^[28] A positive response to 3 of the 4 items indicates a likely diagnosis; one study in veterans found 85% diagnostic efficiency using this cutpoint, and excellent sensitivity and specificity.^[29]

Table 2: Primary Care PTSD Screen^[28]

Instructions  In your life, have you ever had any experience that was so frightening, horrible, or upsetting that, in the past month, you: Have had nightmares about it or thought about it when you did not want to? YES / NO Tried hard not to think about it or went out of your way to avoid situations that reminded you of it? YES / NO Were constantly on guard, watchful, or easily startled? YES / NO Felt numb or detached from others, activities, or your surroundings? YES / NO Current research suggests that the results of the PC-PTSD should be considered "positive" if a patient answers "yes" to any 3 items.

Clinicians can routinely use the PC-PTSD to screen for PTSD, and then follow up with a questionnaire like the PTSD Checklist (PCL) to obtain confirmation.^[30] The PCL consists of the 17 symptoms of PTSD rated on a 1 to 5 scale. Scores range from 17 to 85. The cutpoint for diagnostic scoring varies as a function of the population and setting. In primary care patients who are veterans, one study found 48 to be an optimally efficient cutpoint,^[29] whereas scores in the lower 30s are optimally efficient for assessing PTSD among civilian primary care patients and in active duty military personnel.^[31,32] Because it measures symptom severity, the PCL also is an excellent brief method to monitor treatment response.

Course of Disorder

There is substantial individual variation in the course of PTSD. Posttraumatic stress disorder symptoms usually present within 3 months of the traumatic event, although months or years may pass before they manifest. Posttraumatic stress disorder may abate with time or become chronic; approximately half of PTSD cases recover within 3 months, but more than one third of adults with PTSD have persistent symptoms for over a year. Symptoms also may re-emerge after long periods with few or no symptoms, typically in response to new stressors or anniversaries of a traumatic event.^[1,2] The prevalence of PTSD related to the 9/11 attack on the World Trade Center decreased from 9.6% 1 year after the attack to 4.1% at the 4-year follow-up among 455 patients in primary care practices in New York City.^[33] However, symptoms may persist for years in up to 40% of adults with PTSD.^[2]

Differential Diagnosis

Some of the symptoms that characterize PTSD occur in other psychiatric disorders. However, the specific pattern of symptoms is unique in PTSD. PTSD also is unique in that the symptoms are precipitated or are intensified by a stressor of an extreme, life-threatening nature. Patients with PTSD persistently re-experience the traumatic event, avoid stimuli associated with the trauma, experience numbing, and manifest symptoms of increased arousal.^[1] Mood disorders and other anxiety disorders should be considered in patients who have symptoms such as numbing, sleep disturbance, hyperarousal, poor concentration, and avoidance of feared stimuli, if these symptoms did not arise or intensify after traumatic exposure.

If symptoms occur within 4 weeks of a traumatic event and also resolve within that 4-week period, clinicians should consider a diagnosis of acute stress disorder. Adjustment disorders should be considered when a person has significant emotional or behavioral symptoms in response to an identifiable psychosocial stressor that is not as extreme as the stressors involved in PTSD. Diagnostic criteria for adjustment disorders specify that the symptoms must develop within 3 months after the onset of the stressor, and must resolve within 6 months of the termination of the stressor (or its consequences), and that the patient responds to the stressor with either marked distress that is in excess of what would be expected from exposure to the stressor, or with significant impairment in social or occupational (academic) functioning. The stressor can be a single event or there can be multiple stressors. It can be recurrent or continuous. Patients can manifest with anxiety, depressed mood, or mixed anxiety and depressed mood, or with disturbance of conduct or mixed disturbance of emotion and conduct.^[1]

When considering a differential diagnosis of PTSD in primary care, clinicians should inquire about the possibility of PTSD by asking if the patient has been exposed to a traumatic event or by using a brief screening questionnaire like the PC-PTSD. Asking specific questions about symptom onset can be valuable in making the correct diagnosis.

Comorbidities and Consequences

Individuals with PTSD may experience a range of additional psychiatric and medical problems. PTSD also can negatively affect quality of life, impairing psychosocial and occupational functioning and overall well-being. In the United States, 88% of men and 79% of women with lifetime PTSD have at least 1 comorbid diagnosis.^[2] A recent study found that 4 out of 5 of veterans with PTSD who used VA care had at least 1 additional psychiatric disorder (median number = 3).^[10]Depression is especially common. Among military personnel and veterans who served in Iraq or Afghanistan, two thirds of those with PTSD also had depression. Substance abuse and other anxiety disorders occur frequently as well.^[14]

Individuals with PTSD may use alcohol and other substances in an attempt to self-medicate. In addition to substance abuse, PTSD is associated with increased likelihood of other problems that primary care clinicians typically address, including smoking, obesity, negative health behaviors, and decreased likelihood of obtaining preventive care.^[34,35]For example, a study of female veterans found that PTSD due to sexual assault was related to greater fear and likelihood of maladaptive beliefs about pelvic exams.^[36]

Pain is a common complaint among some individuals with PTSD, especially among military populations.^{[37, 38]} A recent study of Army soldiers found that those with PTSD were twice as likely as those without PTSD to report back and limb pain.^[39] In fact, pain may often be a presenting complaint of individuals with PTSD who seek treatment in primary care settings, along with headache or sleep concerns.

Posttraumatic stress disorder is also associated with increased physical health problems and morbidity, and with decreased physical health functioning.^[34] Primary care clinicians may see a variety of presenting complaints because the associated problems are wide-ranging, including cardiovascular disease and pain disorders.^[34] PTSD is also associated with greater service utilization and healthcare costs. Veterans with mental health diagnoses, in general, and with PTSD specifically, utilize significantly more VA non-mental health medical services than veterans without mental health diagnoses (an adjusted rate of 55% higher utilization).^[40]

These effects on physical health and utilization may occur even in relatively young and high-functioning populations. A study of Army soldiers who served in Iraq or Afghanistan found that those who screened positive for PTSD had more somatic symptoms, more sick call visits, poorer self-rated health, and missed more workdays than soldiers who did not screen positive for PTSD.^[39] Another study found that younger veterans of the wars in Iraq and Afghanistan (mean age, 31 years) who had mental health diagnoses had significantly greater rates of cardiovascular risk factors (including hypertension, hyperlipidemia, obesity, and tobacco use) than veterans without mental health diagnoses.^[35]

The nature of the current conflicts has also resulted in mild traumatic brain injury (mTBI) among some returning veterans.^[41] Prevalence of confirmed comorbid mTBI and PTSD generally ranges from 5% to 7% of returning veterans, although figures are much higher (33% to 39%) when cases of probable PTSD and probable mTBI are included.^[42] When due to a traumatic event, the experience of mTBI is associated with an increased risk of PTSD.^[43]Veterans with mild TBI (mTBI) and PTSD are likely to have other morbidities, such as sleep problems, tension headaches, impaired concentration, and pain disorders, that also require specialized treatment.^[43,44] Primary care clinicians also may see cases of comorbid PTSD and mTBI among trauma survivors who are physically injured, such as survivors of motor vehicle accidents and domestic violence.

Treatment

There are 2 avenues of intervention for patients diagnosed with PTSD: psychotherapy and pharmacotherapy.^[45] Primary care clinicians should continue to monitor patients with PTSD throughout the course of their treatment, regardless of where and by whom it is being provided. This typically includes reassessment of symptom severity, functional status, and quality of life, and monitoring for side effects of any pharmacotherapy and compliance with the treatment. Primary care clinicians might also aim to educate the patient and his or her family about PTSD during follow-up visits if the patient is willing to have this information shared. It is also important that the clinicians treating these patients facilitate an open, trusting relationship, minimizing any bureaucratic or clinician-patient barriers whenever possible.

The aim of therapy is to treat the 3 main PTSD symptom clusters of re-experiencing, avoidance and numbing, and hyperarousal/hypervigilance. Primary care clinicians should have a basic familiarity with available treatment options and should be able to explain them, including their respective advantages and disadvantages.^[46] Referrals to specialized psychiatric care may be appropriate, depending upon the knowledge and comfort of the clinician, as well as the needs and preferences (including comorbidities) of the patient.

Psychotherapy

The United States Department of Veterans Affairs and Department of Defense (VA/DoD) Practice Guideline for PTSD recommends several types of psychotherapy for PTSD, specifically cognitive-behavior therapy (CBT) and Eye Movement Desensitization and Reprocessing (EMDR).^[47] Psychotherapy can be provided on an individual or group basis, although there is less information supporting group therapy for PTSD. Treatments known to be effective typically require 10 to 15 sessions of 60 to 90 minutes each and are best suited to be delivered in specialty care settings.^[46] Studies of brief treatments suitable for delivery by behavioral health specialists in primary care settings are being evaluated, but none have been shown to be effective. Also under investigation are collaborative care models that include nurse care managers and stepped care approaches to managing PTSD.^[46]

Pharmacotherapy

The VA/DoD Guideline also recommends the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) as first-line treatments.^[47] The most widely studied SSRIs include sertraline, paroxetine, and fluoxetine; studies demonstrate efficacy with both short-term and maintenance treatments.^[48] Currently, only sertraline and paroxetine have FDA indications for PTSD.^[49,50] The SNRI venlafaxine has both antidepressant and anxiolytic properties and is currently approved for the treatment of major depression, panic disorder, generalized anxiety disorder, and social anxiety disorder in adults.^[51]

A variety of other medications are used (off label) to manage symptoms -- including atypical antipsychotics (only as adjunctive therapy), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs) -- although there is not strong evidence supporting their use (Table 3).^[47] A recent double-blind, placebo-controlled trial found no greater benefit with adjunctive risperidone versus placebo over 6 months of treatment for veterans with treatment-refractory PTSD.^[52] Although TCAs and MAOIs have demonstrated promising results in short-duration trials, they have significant adverse event profiles that may limit their use.^[48]

Table 3. Symptom Response by Drug Class and Individual Drug^[47]

Class	Drug	Global Improvement	Re-experiencing	Avoidance/Numbing	Hyperarousal
SSRI	Fluoxetine	X	X	X	X
	Sertraline	X	X	X	X
	Paroxetine	X	X	X	X
SNRI	Venlafaxine	X	X	X	X
TCAs	Amitriptyline/Imipramine	X	X		X
MAOIs	Phenelzine	X	X		X
Sympatholytics	Prazosin	X	X		X
Other antidepressants	Mirtazapine	X	X		X
	Nefazodone	X	X		X
Atypical Antipsychotics	Risperidone		X		X
	Olanzapine				X

MAOI = monoamine oxidase inhibitor; SNRI = serotonin neuropinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant

See VA/DoD Clinical Practice Guideline for management of PTSD p160 – table 3, page I-8.

Other agents may be used to address specific symptoms. For example, sleep medications can be used to address insomnia in the short term and anxiolytics may be prescribed to address the anxiety symptoms.^[47] Benzodiazepines have not been shown to be effective and should only be used in the short term as they have potential depressogenic effects and may promote or worsen PTSD.^[48]

SSRIs and SNRIs may not be effective for the night-time manifestations (insomnia and nightmares) of PTSD.^[53] An emerging (off-label) treatment for nightmares and insomnia related to PTSD is the alpha(1)-adrenergic antagonist prazosin. Research suggests that suppression of nightmare symptoms occurs within 1 week of prazosin initiation, even with low-dose treatment.^[54] Daytime sleepiness can be minimized with slow titration and careful monitoring.^[55]

Conclusion

Primary care practices treat many civilians and veterans of all ages who exhibit symptoms of PTSD, but they do not always identify PTSD as the course of a patient's problems. Recognizing the circumstances that could lead to PTSD along with the symptoms that follow can facilitate accurate diagnosis and appropriate treatment.

References

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