Posttraumatic Stress Disorder

Ms. U

Ms. U is a 22-year-old, single woman who presented with symptoms of depression following a sexual assault during her senior year in college. She began to experience periods of sadness and crying, loss of sleep, loss of energy, and feelings that she did not want to live. Ms. U also reported flashbacks, a sense of hypervigilance and feeling “on edge.” Ms. U had no prior psychiatric history. She was experiencing difficulty finding a job and pursuing her career following graduation.

Posttraumatic stress disorder (PTSD) involves reexperiencing a severe trauma with intense fear, helplessness, or horror accompanied by increased arousal and avoidance of any associated stimuli. These symptoms should persist for at least 1 month and cause significant disability. Events that may precipitate this condition include:

Combat
Violent personal assault (e.g., rape)
Kidnapping
Torture
Hostage taking
Natural or man-made disasters (e.g., Hurricane Katrina, September 11, 2001)
Severe accidents (e.g., brain trauma secondary to an explosion)
Life-threatening illness

Symptoms of PTSD may include:

Reexperiencing (memories or “flashbacks” of the event)
Avoidance/numbing
- Avoiding stimuli that bring back memories
- Feeling numb or emotionless
- Withdrawal from social contact
- Abuse of alcohol or other drugs
Hyperarousal
- Easily startled
- Angry outbursts
- Feeling “on guard” or irritable

Although 50% or more of the population may experience a traumatic event, most do not develop acute stress disorder (ASD) or PTSD. The National Comorbidity Survey (NCS) estimates the lifetime prevalence of PTSD at 7.8%. The female to male lifetime prevalence ratio is 2:1. This syndrome is also associated with significant disability (e.g., occupational, psychosocial) and occurs more frequently in those with prior adverse childhood experiences or acomorbid diagnosis. There is also a high comorbidity with other psychiatric disorders (e.g.,major depression, substance abuse). In addition, there is an increased suicide risk.

Recently, the criteria for PTSD have been questioned with data finding equal percentages of patients with or without a history of trauma meeting the other inclusion criteria based on
the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV).¹ Malingering has also been raised as a possible basis for this diagnosis in up to 50% of cases.² These observations have led to discussions about making the criteria for PTSD more restrictive to improve their reliability.

DIFFERENTIAL DIAGNOSIS

With PTSD, the event must be extreme. By contrast, adjustment disorder can involve a stressor at any level of severity. ASD must occur within 4 weeks of the event, last at least 2 days, involve dissociative symptoms during or immediately after the event, and resolve during that 4-week time frame. Obsessive compulsive disorder (OCD) and malingering are also differential diagnostic considerations. Symptoms of PTSD can also overlap with concurrent psychiatric problems such as major depressive disorder, other anxiety disorders, and substance use disorders.

Ms. U began to experience significant fear soon after the assault, and stated that she constantly felt like she was in danger or at risk. Because the attack happened near the end of the year, she was able to complete her remaining coursework; however, her concentration was greatly diminished with flashbacks and she began to withdraw to feel safe. After graduating and returning home, she began to experience periods of sadness and crying, diminished energy, weight loss, and feeling hopelessness and helplessness. She began to contemplate suicide, feeling that she would never be the same again. She was terrorized at night with vivid dreams and flashbacks. Ms. U met criteria for both PTSD and a major depressive episode.

NEUROBIOLOGY OF POSTTRAUMATIC STRESS DISORDER

There are potential factors that may predict who will develop ASD or PTSD. They include biological (e.g., genetic, gender), prior traumatic experiences, and specific acute reactions to an event (e.g., dissociation; panic attacks).

Biological predisposition has been explored in the context of genes that regulate:

The serotonin transporter
Corticotropin-releasing factor (CRF)
Brain-derived neurotrophic factor (BDNF)

Imaging studies have identified possible abnormalities in hippocampal volumes associated with increases in regional cerebral blood flow (rCBF) to this area.³ Further, functional magnetic resonance imaging (fMRI) studies find evidence for an exaggerated amygdalar activity in conjunction with a decreased medial cortical response.⁴

TREATMENT OF POSTTRAUMATIC STRESS DISORDER

Strategies to manage PTSD include both psychotherapy and pharmacotherapy, frequently in combination.

Pharmacotherapy for Posttraumatic Stress Disorder

Antidepressants (ADs) represent the pharmacotherapy of choice for PTSD. Because of a substantial controlled trial database and safety-tolerability profile, selective serotonin reuptake inhibitors (SSRIs) are the preferred class of ADs. Studies indicate that these agents can benefit all three major symptoms (i.e., reexperiencing, avoidance, hyperarousal). Further, they often improve symptoms of comorbid disorders (e.g., depression). More recent short-term and continuation trials with venlafaxine XR have also shown promise. Table 2-4 lists the common adverse effects associated with various ADs.

Benzodiazepines (BZDs) are usually add-on agents to help reduce anxiety and improve sleep. Caution in their use, however, is required given the high rates of substance abuse in this population. Chapter 10 discusses other adverse effects of BZDs in more detail.

Second-generation antipsychotics (SGAs), certain antiepileptic drugs (AEDs) (e.g., lamotrigine, topiramate, divalproex sodium), α₂–adrenergic agonists (e.g., clonidine), and β-adrenergic antagonists
(e.g., propranolol) have also been studied for the treatment of PTSD. For each of these classes of drugs, the data is more limited and at times contradictory.

Factors that increase riskmay help predictwho will ultimately develop ASD or PTSD in reaction to severe trauma and allow “preemptive” interruption of the processes of fear conditioning and reconsolidation. Drug candidates for such an approach, include: