A.

PTSD - EPIDEMIOLOGY
A. Prevalence a. PTSD 3.6% b. Estimated that ~50% of men and 60% of women are exposed to a lifethreatening traumatic event i. 8.2% of men exposed will develop PTSD ii. 20% of women exposed will develop PTSD c. Previous exposure to trauma and intensity of the response increase the risk of PTSD d. Individuals with a history of childhood sexual abuse are at a higher risk e. Genetic factors can increase vulnerability

Lifetime Prevalence Rates of Trauma and Their Association with PTSD Men Natural Disaster Criminal Assault Combat Rape Any trauma 18.9% 11.1% 6.4% 0.7% 60.7% PTSD 3.7% 1.8% 38.8% 65.0% 8.2% Women 15.2% 6.9% 0.0% 9.2% 51.2% PTSD 5.4% 21.3% -49.5% 20.4%

B. Age at onset is variable; can occur at any age C. Presentation is not predictable related to duration / intensity of trauma, other psychiatric disorders, how patient deals with the trauma D. Men with PTSD are more likely from exposure to military combat and witnessing someone being badly injured or killed E. Women with PTSD are more likely associated with rape and sexual molestation Severity, duration, and proximity of exposure to trauma are most important factors in likelihood of development of disorder Studies indicate lifetime prevalence is 1 to 14% Studies of at-risk persons (veterans of combat, victims of natural disasters or crimes) indicate lifetime prevalence of 3 to 58%

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3 fold increase has been observed in combat-exposed military personnel since 2001

I.

PATHOPHYSIOLOGY OF PTSD

A. NEUROENDOCRINE THEORIES
a. Abnormalities occurring pretrauma, during trauma, and posttrauma contribute to PTSD b. Normally, the immediate reaction to stress occurs as an autonomic response from the amygdala to the sympathetic and parasympathetic systems and the HPA axis c. Release of corticotropin-releasing factor stimulates cortisol secretion from the adrenal gland d. Cortisol reduces the stress response by tempering the sympathetic reaction through negative feedback on the pituitary and hypothalamus e. Patients with PTSD have hypersecretion of corticotropic-releasing factor but demonstrate subnormal levels of cortisol at the time of trauma and chronically

B. NEUROCHEMICAL THEORIES
f. 5HT and NE are associated with processing of emotional and somatic contents of memories in the amygdala g. Noradrenergic theory posits that the autonomic nervous system of anxious patients is hypersensitive and overreacts to stimuli h. The alarm center, the locus ceruleus, releases NE to stimulate the sympathetic and parasympathetic nervous systems i. Patients with PTSD tend to experience sustained elevated heart rates during trauma and enhanced startle effects starting a month after trauma exposure j. Patients with chronic central NE overactivity have downregulated alpha-2 adrenoreceptors k. Dysregulation of the processing of sensory input and memories may contribute to the dissociative and hypervigilant symptoms in PTSD l. Abnormalities of GABA inhibition may lead to increased awareness or response to stress, as seen in PTSD

C. NEUROIMAGING STUDIES
m. Increased activation of the amygdala n. Decreased hippocampal volume o. Hypofunctioning of the ventromedial prefrontal cortex

II.

CLINICAL PRESENTATION OF PTSD

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A. DIAGNOSTIC CRITERIA FOR POST TRAUMATIC STRESS DISORDER

a. Exposure to traumatic event is required for a diagnosis of PTSD i. Physical attacks by an intimate partner ii. Motor vehicle accidents iii. Natural disasters iv. Rape v. Being held hostage vi. Child sexual abuse vii. Witnessing a murder or injury of another Person has been exposed to a traumatic event in which both of following were present: (1) Person experienced, witnessed, or was confronted with events that involved actual or threatened death or serious injury, or a bodily threat to self or others (2) Persons response involved intense fear, helplessness, or horror Traumatic event persistently reexperienced in one (or more) ways: o o o o Recurrent and intrusive distressing recollections of event Recurrent distressing dreams of the event Acting or feeling as if the traumatic event is reoccurring Intense psychological distress at exposure to internal or external cues which symbolize or resemble an aspect of the event Physiologic reactivity on exposure to internal or external cues symbolizing the event

Persistent avoidance of stimuli associated with trauma and numbing of general responsiveness as evidenced by three or more of the following: o Efforts to avoid thoughts, feelings, or conversations associated with trauma Efforts to avoid activities, places, or people that arouse recollections of the trauma Inability to recall important aspect of trauma Markedly diminished interest or participation in significant activities Feelings of detachment or estrangement from others Restricted range of affect

o o o o

Anxiety Disorders o Sense of foreshortened future

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Persistent symptoms of increased arousal (not present prior to trauma) as evidenced by two or more of the following: o o o o o Difficulty falling or staying asleep Irritability or outbursts of anger Difficulty concentrating Hypervigilance Exaggerated startle response

Duration of symptoms for greater than one month Causes clinically significant distress or impairment in functioning

Detachment Reexperiencing the event Event had emotional effects Avoidance Month in duration Sympathetic hyperactivity or hypervigilance

B.

SYMPTOMS
May initially be diagnosed with acute stress disorder o Characterized by anxiety and dissociative symptoms emerging within 1 month after exposure to a traumatic stressor (can last for at least 2 days and resolve within 4 weeks)

May describe intense guilt feelings about surviving when others did not May include depression, anxiety, poor concentration May also exhibit aggression, violence, poor impulse control, depression, and substance use or abuse 1/3 to of substance abusers also have PTSD

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In children: Dreams may be generalized of monsters, other threats, etc. Reliving of trauma may occur by repetitive play Physical symptoms stomachaches and headaches

C.

ONSET
Can occur at any age Symptoms usually begin within first 3 months after trauma Symptoms can be delayed months or years in some cases

D.

DIFFERENTIAL DIAGNOSIS
Adjustment disorder Acute stress disorder (duration of < 4 weeks) Obsessive-compulsive disorder Substance-induced disorders Mood disorder with psychotic features Schizophrenia Delirium Malingering

E.

COURSE AND PROGNOSIS

Duration of symptoms varies

III.

TREATMENT: POSTTRAUM ATIC STRESS DISORDER

A. DESIRED OUTCOME
Short-term: reduction in core symptoms intrusive reexperiencing, avoidance and hyperarousal

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B. GENERAL APPROACH TO TREATMENT

Treat those in acute distress based on presenting symptoms (e.g., a nonbenzodiazepine for difficulty sleeping) Short courses of trauma-focused cognitive behavioral therapy can be helpful to prevent chronic symptoms in patients presenting within the first 3 months of the event If symptoms persist for 3-4 weeks and the patient experiences marked social, occupational, and/or interpersonal impairment, they can be treated with pharmacotherapy, psychotherapy, or both

C. NONPHARMACOLOGIC THERAPY
Psychotherapy used for mild symptoms, in patients who prefer not to use medications, or in conjunction with drugs for severe symptoms to improve response o Stress management o Group therapy o Hypnosis o Psychodynamic therapy Cognitive / behavioral therapies are more effective than stress management or group therapy to reduce PTSD symptoms Psychoeducation information about disease state, treatment options, and avoidance of excessive use of alcohol, nicotine, and other substances of abuse

D. PHARMACOLOGIC THERAPY 1) ANTIDEPRESSANT THERAPY

Major therapeutic treatment for PTSD; SSRIs are first-line agents Also effective for concurrent depression and anxiety disorders Sertraline and paroxetine are approved for acute treatment of PTSD; sertraline for the long-term management of PTSD

2) OTHER ANTIDEPRESSANTS
Venlafaxine, TCAs and MAOIs can also be effective Side effect profiles may limit their use compared to SSRIs

3) ALTERNATIVE DRUG TREATMENTS: ATYPICAL ANTIPSYCHOTICS

Used as augmenting agent for partial SSRI response

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4) ALTERNATIVE DRUG TREATMENTS: ANTIADRENERGIC AGENTS

Clonidine Prazosin reduces nightmares and sleep disturbances

5) ALTERNATIVE DRUG TREATMENTS: BENZODIAZEPINES

NOT EFFECTIVE FOR TREATMENT OF PTSD

E. DOSING AND ADMINISTRATION 1) ACUTE PHASE

PTSD symptoms respond slowly; some never experience full resolution of symptoms SSRI should be started 3-4 weeks after exposure to a trauma in patients with no improvement in their acute stress response Initiation should be at a low dose with gradual titration upward to antidepressant doses 8-12 weeks is an appropriate duration to determine response

2) CONTINUATION PHASE
Dosages may vary with ongoing psychotherapy dealing with past experiences Symptoms continue to improve and maximal drug benefit accrues Low-relapse rates seen with fluoxetine and sertraline compared to placebo

3) MAINTENANCE AND DISCONTINUATION

Patients who respond to pharmacotherapy should continue treatment for at least 12 months If residual symptoms are present, drug therapy should be continued Decision to discontinue therapy is based on overall response to therapy, ongoing stressors, and adverse effects Drug therapy should be slowly withdrawn over a period of at least 1 month to prevent relapse

F. PHARMACOECONOMIC CONSIDERATIONS
PTSD compares with depression in the level of disability it imposes on patients with the disorder fail to realize potentials for career development, marriage and education Decreased productivity leads to financial loss of more than $3 billion per year

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G. EVALUATION OF THERAPEUTIC OUTCOMES

Evaluate previously identified target symptoms of PTSD as well as other symptoms including sleep, anger outbursts, irritability, and disability Remission or good response defined as greater than 75% reduction in symptoms and response maintained for at least 3 months 25-75% reduction in symptoms are considered partial responders