Topic: Posttraumatic Stress Disorder (PTSD)

Author: Ala’ Moh’d Al Barbarawi

Scientific Editor: Ahda Jbarah

Linguistic Editor: Aroob Awwad Awwad.

(31)

 

Understanding PTSD

Posttraumatic stress disorder (PTSD) has adopted multiple names throughout history, including ‘shell shock’ during the first world war, and ‘combat fatigue’ the WWII. However, PTSD isn’t only present in soldiers who fought during war. It is a psychiatric disorder that can occur in people who have been through or witnessed a traumatic event which can be a natural disaster, a life-threatening accident, a terrorist act, war, combat, or rape. It can also happen to individuals who have been threatened with death, sexual violence, or serious injury. (1)

 

Epidemiology

PTSD is not specific to a certain age group, nationality, culture, or ethnicity. It affects approximately 3.5% of U.S. adults every year, and it is estimated that around 1 in 11 persons will be diagnosed with PTSD in their lifetime. That being said, PTSD was found to occur twice more likely in women as well as three ethnic groups, (U.S. Latinos, African Americans, and American Indians), who were shown to have higher rates of PTSD than non-Latino whites. (1)

Assaultive violence holds the highest potential for developing PTSD. In males, the preeminent factor for acquiring PTSD is combat-related violence. However, in females, sexual violence is the strongest predictor. Women and younger people are more vulnerable to this disorder. Nevertheless, it is increasingly being recognized among the elderly. (2)

 

Etiology

PTSD is a syndrome that results from exposure to threatened or serious injury or sexual assault. Its signs and symptoms appear to arise from complex interactions of psychological and neurobiological factors (e.g. certain genes can increase the risk).

In PTSD patients, alterations have been found to occur in the amygdala, prefrontal cortex, hippocampus, anterior cingulate, corpus callosum, as well as altered functioning of the hypothalamic-pituitary axis (HPA).

 

Risk and Prognostic Factors

Most people can quickly recover from certain trauma, meaning that they do not experience the dangerous psychological and physiological consequences of severe stress. However, those who do suffer from PTSD show some levels of vulnerability to these consequences. There are specific factors that promote resilience or vulnerability. (2)

According to DSM-5, risk and protective factors are generally divided into pre-traumatic, peritraumatic, and posttraumatic factors.

Pre-traumatic factors:

1. Temperamental factors: consist of childhood emotional problems up to the age of 6 years (e.g., prior traumatic exposure, externalizing, or anxiety problems) and prior mental disorders (e.g., panic disorder, depressive disorder, PTSD, or obsessive-compulsive disorder [OCD]).
2. Environmental factors: include exposure to prior trauma (especially during childhood), lower socioeconomic status, childhood adversity (e.g. economic deprivation, family dysfunction, parental separation or death), cultural characteristics (e.g., fatalistic [one who believes that bad events cannot be avoided] or self-blaming coping strategies), minority ethnic status, lower intelligence, and a family history of psychiatric disorders. Social support before traumatic event exposure is protective.
3. Genetic and physiological factors: include female gender and younger age at the time of trauma exposure (for adults). Specific genotypes can either protect against or increase the risk of PTSD after exposure to traumatic events.
   1. Genetic Risk Factors
      1. Polymorphisms in the Serotonin transporter gene affect the outcome; the long allele (l) in the SLC6A4 gene may have a protective effect while the short allele (s) may contribute to developing stress-related psychopathology(2,3).
      2. Higher risk is seen in different single nucleotide polymorphisms of the gene encoding a chaperone protein that influences the transcriptional effects of the glucocorticoid receptor (FKBP5). This higher risk is observed in children exposed to physical and sexual abuse. (4)
      3. Single nucleotide polymorphism in the BDNF gene influences the process of fear extinction; a physiologic mechanism relevant to PTSD pathophysiology (5).
      4. Different single nucleotide polymorphisms in the gene encoding the corticotropin-releasing hormone receptor-1 (CRHR1) appear to lower the risk of developing stress-related disorders among women with a history of childhood abuse(6). Similarly, the long-form variant of the neuropeptide Y (NPY) gene has been linked with a decreased risk of developing PTSD(7).
   2. Gender: Women may be at higher risk due to variations in hormonal levels. The levels of testosterone and dehydroepiandrosterone (DHEA) are positively correlated with resilient behavior (8,9,10) while the fluctuating levels of ovarian hormones (estrogen and progesterone) are correlated positively with anxious responses to stress (vulnerability)(11). However, high levels of oxytocin may decrease the risk of stress-related psychopathology(12).
   3. Lower performance on neuropsychological tasks assessing fluid intelligence (which is the ability to solve novel problems independently of previously acquired knowledge) was more vulnerable(13,14).

Peritraumatic factors

1. Environmental factors: these include trauma severity (the greater the magnitude of the trauma, the greater the possibility of acquiring PTSD), perceived life threat, personal injury, and interpersonal violence (particularly if the trauma is caused by a caregiver or witnessing a threat to a caregiver in children). Also, adults with a history of childhood abuse are more likely to develop PTSD after adulthood trauma(2).
2. Being in the military(2): being a perpetrator, witnessing atrocities, or killing the enemy.
3. Dissociation taking place during the trauma and persisting

Posttraumatic factors

1. Temperamental factors: compromised of negative appraisal, inappropriate coping mechanisms, and development of acute stress disorder.
2. Environmental factors: include subsequent exposure to repeated upsetting reminders, subsequent adverse life events, and financial or other trauma-related losses. Family stability and support for children is a protective factor.

 

Differential Diagnosis(15)

PTSD must be differentiated from other post-traumatic disorders and conditions, adjustment disorders, acute stress disorder, anxiety disorders, OCD, major depressive disorder, personality disorders, dissociative disorders, conversion disorder (functional neurological symptom disorder), psychotic disorders, and traumatic brain injury.

 

DSM-5 Diagnostic Criteria(15)

For adults, adolescents, and children older than 6 years:

1. being exposed to death (whether real or threatened), severe injury, or sexual abuse through one or more of the following methods:
   1. Directly experiencing the traumatic event(s) (e.g., car accident, natural disaster, war).
   2. Being present, in person, as the event(s) occurred to others.
   3. Knowing that the traumatic event(s) occurred to a close family member or close friend. If there was actual or threatened death of a family member or friend, the event(s) must be violent or accidental.
   4. Repeated or extreme exposure to aversive details of the traumatic event(s) (e.g., first responders collecting human remains, police officers repeatedly exposed to details of child abuse, and medical personnel dealing with terminally ill patients). This criterion does not apply to exposure through electronic media, TV, movies, shows, or pictures unless this exposure is related to work.
2. One or more of the following intrusion symptoms associated with the trauma, starting after the event(s) occurred:
   1. Recurrent, involuntary, intrusive distressing memories of the event(s). In children older than 6 years, themes or aspects of the traumatic event (s) may be expressed through repetitive play.
   2. Repeated nightmares whose content and/or effect are related to the traumatic event(s). In children, there may be frightening dreams without recognizing the content.
   3. Flashbacks where the person feels or acts as if the traumatic event(s) were recurring (these may occur continuously, their most extreme expression is the complete loss of awareness of present surroundings). In children, trauma-specific reenactment may occur when the child is playing.
   4. Intense or prolonged psychological distress when exposed to internal or external cues that symbolize or resemble an aspect of the traumatic event(s), (e.g., the individual may hear a certain sound related to the event, which can trigger psychological distress).
3. Consistent avoidance of stimuli associated with the traumatic event(s), beginning after the traumatic event(s) occurred, as evidenced by one or both of the following:
   1. Avoiding or trying to avoid disturbing thoughts, memories, or feelings regarding the traumatic event(s).
   2. Avoiding or trying to avoid external reminders (people, places, conversations, activities, situations, objects) that trigger the disturbing memories, thoughts, or feelings related to the traumatic event(s).
4. Negative alterations in cognitions and mood associated with the traumatic event(s), which begin or worsen after the traumatic event(s) occur, as evidenced by two or more of the following:
   1. Inability to remember an important aspect of the traumatic event(s), due to dissociative amnesia and not other factors such as head injury, alcohol, or drugs.
   2. Persistent and exaggerated negative beliefs or expectations about oneself (e.g. “I am a bad person”), others (e.g., “I can’t trust anyone”), or the world (e.g., “The world is dangerous”).
   3. Constant cognitive distortion regarding causes or consequences of the traumatic event(s) leads to the individual blaming themselves or others.
   4. Persistently negative emotions (e.g., fear, horror, anger, guilt, or shame).
   5. Markedly decreased interest or desire to participate in significant activities.
   6. Feeling detached or isolated from other people.
   7. Continuous inability to experience positive emotions (e.g., happiness, satisfaction, love, etc.,).
5. Marked alteration in arousal and reactivity linked to the traumatic event(s), beginning or worsening after the event(s) occurred, as evidenced by two or more of the following:
   1. Irritability and angry outbursts (without or with some provocation) manifested as verbal or physical aggression towards people or objects.
   2. Reckless or self-destructive behavior (e.g., drinking and driving, carrying concealed weapons).
   3. Hypervigilance (a state of increased alertness).
   4. Exaggerated startle response.
   5. Concentration problems.
   6. Disturbances in sleep (e.g., difficulty falling or staying asleep or restless sleep).
6. The disturbance, evidenced by criteria B to E above, lasts more than one month.
7. The disturbance leads to clinically significant distress or impairment in social, occupational, or other important areas of functioning.
8. The disturbance is not caused by the physiological effects of a substance (e.g., medication, alcohol) or another medical condition.

After confirming the diagnosis of PTSD, specify whether:

1. The patient has dissociative symptoms: the individual will meet the diagnostic criteria for PTSD in addition to experiencing persistent or recurrent symptoms of either of the following in response to the stressor:
   1. Depersonalization: the persistent or recurrent feeling of being detached from an individual’s mental processes or body as if they were an outside observer (e.g., feeling a sense of unreality as if one were in a dream or out of their body).
   2. Derealization: persistent or recurrent experiences of unreal surroundings (e.g., the world around the individual is experienced as unreal, dreamlike, distant, or distorted; people or objects may seem unreal). Note: To specify this subtype, these symptoms must not be caused by or associated with physiological effects of substance abuse (e.g., behavior during alcohol intoxication) or another medical condition (e.g., complex partial seizures).
2. With delayed expression: specified if the full diagnostic criteria are not met until at least 6 months after the traumatic event (although the onset and expression of some symptoms may be immediate).

 

PTSD in Children Six Years and Younger

To diagnose a child 6 years or younger the following criteria must apply:

1. Being exposed to death (whether real or threatened), severe injury, or sexual abuse through one or more of the following methods:
   1. Experiencing the traumatic event(s) directly.
   2. Witnessing, in person, the traumatic event(s) as it occurred to others, especially primary caregivers (does not include events that are witnessed only in electronic media, television, movies, or pictures).
   3. Learning that the traumatic event(s) occurred to a parent or caregiver.
2. Having one or more of the following intrusion symptoms related to, and beginning after, the traumatic event(s):
   1. Repeated, involuntary, and intrusive distressing memories of the traumatic event(s).
   2. Recurrent distressing dreams related to the traumatic event(s). However, it may not be possible to declare or decide that the frightening content is related to the traumatic event.
   3. Dissociative reactions (e.g., flashbacks) in which the child feels or acts as if the traumatic event(s) were taking place again.
   4. Exposure to internal and external cues that symbolize or resemble an aspect of the traumatic event(s) causes intense or prolonged psychological distress.
   5. Reminders of the traumatic event(s) result in marked physiological reactions.
3. One or more of the following symptoms must be present, beginning or worsening after the event: either persistent avoidance of the stimuli or negative cognitive and mood changes associated with the traumatic event(s), the earlier manifests as:
   1. Avoiding or efforts to avoid activities, places, or physical reminders of the traumatic event(s).
   2. Avoiding or efforts to avoid people, conversations, or interpersonal situations
   that arouse recollections of the trauma.
   While the latter can manifest as:
   1. Significantly increased frequency of negative emotions (e.g., fear, guilt, shame,
   sadness, confusion).
   2. Diminished interest or participation in activities, including constriction of play.
   3. Socially withdrawn behavior.
   4. Persistently reduced expression of positive emotions
4. Changes in arousal and reactivity associated with the traumatic event(s) as evidenced by two or more of the following, beginning or worsening after the traumatic event(s) occurred:
   1. Angry outbursts and irritability (with little or no provocation), usually expressed as verbal or physical aggression toward people or objects and extreme temper tantrums.
   2. Hypervigilance (a state of increased alertness).
   3. Exaggerated startle response.
   4. Concentration problems.
   5. Disturbance in sleep (e.g., difficulty falling or staying asleep or restless sleep).
5. The disturbance lasts more than 1 month.
6. The disturbance causes clinically significant impairment in school behavior or social relationships.
7. The disturbance is not due to nor associated with the physiological effects of certain substances (e.g., medication or alcohol) or another medical condition.

Once diagnosed, specify whether PTSD is with:

1. Dissociative symptoms: The child’s symptoms meet the diagnostic criteria for PTSD. In addition, the child experiences persistent or recurrent symptoms of depersonalization or d Also, to use this subtype, the dissociative symptoms must not be caused by or associated with the physiological effects of a substance or another medical condition.
2. Delayed expression: when the diagnostic criteria are not fully met until 6 months or more after the traumatic event.

 

Treatment

Treatment for PTSD is divided into two categories: psychotherapy and pharmacotherapy.

1. Psychotherapy

The two most successful psychotherapy approaches are controlled exposure to aversive memories and cognitive processing(2). Other alternatives include are mentioned in Table 1 (16-22):

Table 1: Psychotherapy for the Treatment of Posttraumatic Stress Disorder
Exposure-Based
Systematic Desensitization	Education* about disorder and treatment, involves imaginal exposure to aversive memories paired with relaxation to inhibit the feared stimuli.
Eye Movement Desensitization and Reprocessing (EMDR)	Combines traumatic image exposure with the simultaneous performance of eye saccadic movements (usually lateral eye movements)
Stress Inoculation	Education*and training involving teaching coping skills to manage stress and anxiety associated with the traumatic event, training in deep muscle relaxation, exposure to aversive memories, role-playing, breathing exercises, assertiveness skills, and thought-stopping.
Prolonged Exposure	Education*, exposure to traumatic memories, confrontation of feelings/thoughts, cognitive restructuring
Virtual Reality Exposure	Exposure to computerized, vividly recreated environments of the trauma (e.g., war, accidents, etc.,)
Cognitive-Based
Trauma-Focused Psychodynamic Therapy	Includes education*, free association, dream interpretation, and cognitive restructuring.
Cognitive Processing Therapy	Education* (with limited exposure to traumatic memories) along with Socratic questioning, and identification of maladaptive cognition and automatic thoughts (the patient becomes aware of the relationship between thoughts and emotions).
Acceptance and Commitment Therapy (ACT)	Individuals open up to unpleasant feelings and learn not to overreact and to face situations where they are invoked.
Other
Biofeedback	Voluntary regulation of physiologic responses (e.g., muscle activity, heart rate). A mind-body technique involving visual or auditory feedback to gain control over involuntary bodily functions such as blood flow, blood pressure, and heart rate (23).
Mindfulness-Based Cognitive Therapy	Involves meditation, awareness, breath-focused imagery, silent repetition of words, and letting go of intrusive thoughts.

*Note: Education involves psychoeducation regarding PTSD, thoughts, and emotions

2. Pharmacotherapy

Pharmacologic treatment of PTSD is usually indicated either to prevent its onset after trauma exposure or to reduce the severity of PTSD symptoms once the condition is established. A recent meta-analysis of preventive interventions indicated that hydrocortisone may be used to prevent PTSD onset when given acutely after trauma(24). On the other hand, no preventive effect was seen when propranolol, benzodiazepines, or selective serotonin reuptake inhibitors (SSRIs) were given(24). However, the clinical trials conducted in the analysis were small and had multiple methodologic flaws(24).

Another recent meta-analysis of pharmacologic interventions to reduce the severity of PTSD symptoms suggests that placebo is less effective than active pharmacologic agents. However, the side effects observed in the concisely controlled trials were smaller than those observed in controlled trials of psychotherapeutic options. Furthermore, little evidence exists proving that the combination of medications and psychotherapy has a synergistic effect, and no effectiveness studies comparing pharmacotherapy with psychotherapy exist. (25)

It is unlikely that one particular medication is equally efficacious in treating all PTSD symptom clusters (e.g., intrusive symptoms, avoidance, dysphoric experiences) since symptoms are heterogeneous and have different pathophysiologic mechanisms.  Moreover, the longitudinal course of PTSD may influence efficacy. In other words, a pharmacologic agent might be more effective in the early stages of PTSD while another is better given in the more refractory, chronic period. (2)

A summary of the medications that have shown some efficacy in treating PTSD is shown in Table 2 below (2):

Table 2: Medications That Have Shown Efficacy in Treating PTSD
Class	Drug	Total Daily Dosage
Antidepressants
Selective Serotonin Reuptake Inhibitors (SSRIs)	Fluoxetine Sertraline Paroxetine Citalopram	20-60 mg/d 50-200 mg/d 20-30 mg/d 20-40 mg/d
Serotonin Norepinephrine   Reuptake Inhibitors (SNRIs)	Venlafaxine Venlafaxine- extended-release Duloxetine	75-300 mg/d 75-225 mg/d   40-60 mg/d
Tricyclic Antidepressants (TCAs)	Amitriptyline Imipramine	50-300 mg/d 50-300 mg/d
Monoamine Oxidase Inhibitors	Phenelzine	15-90 mg/d
Other	Mirtazapine	7.5-45 mg/d
Sympatholytic
Beta-blockers	Propranolol	40-160 mg/d
Alpha-2 Receptor agonists	Clonidine Guanfacine	0.2-0.6 mg/d 0.5-3 mg/d
Alpha-1 Receptor antagonists	Prazosin	2-10 mg/d
Mood Stabilizers
	Divalproex sodium or valproic acid Lithium Carbamazepine Topiramate	500-2000 mg/d   600-1500 mg/d 400-1000 mg/d 50-200 mg/d
Antipsychotics
	Risperidone Olanzapine Quetiapine Aripiprazole	0.5-6 mg/d 5-20 mg/d 25-300 mg/d 5-15 mg/d
Anxiolytics
Benzodiazepines	Alprazolam Clonazepam	0.25-4 mg/d 0.5-4 mg/d
5-HT1A receptor agonists	Buspirone	15-60 mg/d
Others
N-methyl-D-aspartate	D-Cycloserine	8-12 mg/d
(NMDA) antagonists	Ketamine	0.5 mg/kg/d IV

 

When initiating pharmacotherapy for PTSD treatment, SSRIs are the drugs of choice as they have the best safety profile compared to other medications (2). When compared to placebo, previous studies have shown that sertraline(26), paroxetine(27), and fluoxetine(28) are significantly more efficacious in reducing the severity of PTSD symptoms. However, it should be noted that this efficacy is due to differences in gender, type of traumatic event, refractoriness of PTSD, and symptom clusters(2). For instance, military populations tend to be less responsive to treatment with SSRIs(2). A randomized double-blind trial performed in 10 US Department of Veteran Affairs medical centers shows that sertraline is not more effective than a placebo to treat combat-related PTSD(29). SNRIs like venlafaxine might be more effective in PTSD treatment(2).

Antiadrenergic agents may influence specific PTSD-symptom dimensions. For example, the alpha₁ receptor antagonist prazosin shows efficacy in reducing the frequency and severity of intrusive symptoms (e.g., nightmares)(30). Mood stabilizers such as lithium, valproate, and carbamazepine are ineffective in treating PTSD, but they can be helpful for those patients with coexistent bipolar disorder(2). Similarly, comorbidities including impulsivity and substance misuse in PTSD patients may be decreased with the use of topiramate. The addictive potential of benzodiazepines limits their use for the treatment of PTSD. Moreover, it may lead to aggravating avoidance and depressive symptoms(2). Lastly, although the use of antipsychotics is discouraged, atypical neuroleptics might constitute a last-resort solution to control disturbing psychotic symptoms(2).

 

Prognosis

Certain genetic factors may be protective, leading to a better prognosis when compared to susceptibility genes. The severity of the trauma also plays an important role in prognosis. Does PTSD regress with time or does it worsen with time? This mainly depends on how soon symptoms develop, their severity, early diagnosis, and treatment. (1)

 

 

 

References...

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