Posttraumatic Stress Disorder Medication

Author T Allen Gore, MD, MBA, CMCM, DFAPA Assistant Professor, Department of Psychiatry, Howard University School of Medicine; Senior Psychiatrist and Director, Medical Education, Comprehensive Psychiatric Emergency Program, District of Columbia Department of Mental Health T Allen Gore, MD, MBA, CMCM, DFAPA is a member of the following medical societies: American College of Managed Care Medicine, American Psychiatric Association, and National Medical Association Disclosure: Nothing to disclose. Coauthor(s) Joel Z Lucas, MD Senior Medical Writer, Reckitt Benckiser Pharmaceuticals, Inc Joel Z Lucas, MD is a member of the following medical societies: American College of Physicians, American Medical Student Association/Foundation, and Student National Medical Association

Background
The formal diagnosis of posttraumatic stress disorder (PTSD) was not introduced into the Diagnostic and Statistical Manual of Mental Disorders (DSM) until its third publication, in 1980. In earlier DSM editions, this relatively new diagnosis was characterized as stress response syndrome, a type of gross stress reaction, or a situational disorder, and was often incorrectly associated with personal weakness instead of situational trauma.[1] PTSD is now defined as a pathological anxiety that usually occurs after an individual experiences or witnesses severe trauma that constitutes a threat to the physical integrity or life of the individual or of another person. The individual initially responds with intense fear, helplessness, or horror. The person later develops a response to the event that is characterized by persistently reexperiencing the event, with resultant symptoms of numbness, avoidance, and hyperarousal.[2] These symptoms result in clinically significant distress or functional impairment. To meet the full criteria for PTSD, these symptoms should be present for a minimum of 1 month following the initial traumatic event. The events experienced may be natural disasters, violent personal assaults, war, severe automobile accidents, or the diagnosis of a life-threatening condition. For children, a developmentally inappropriate sexual experience may be considered a traumatic event, even though it may not have actually involved violence or physical injury.

Brain structures associated with the bodys reaction to fear and stress can be seen in the image below.

Brain structures involved in dealing with fear and stress. PTSD can be acute (symptoms lasting < 3 mo), chronic (symptoms lasting 3 mo), or of delayed onset (6 mo elapses from event to symptom onset). Studies have pointed to a new, dissociative subtype of PTSD, with clinical and neurobiologic features that distinguish it from the nondissociative form. This dissociative subtype is described as an overmodulation of affect, or a form of emotion dysregulation, and is mediated by midline prefrontal inhibition of limbic regions. These findings are important in the treatment of PTSD, because patients can now be assessed for dissociative symptoms and treated accordingly.[3]

Complications of PTSD
Individuals with PTSD may have an increased risk of impulsive behavior, suicide, and homicide. Victims of sexual assault are at especially high risk for developing mental health problems and committing suicide. Persons with PTSD may also be at increased risk for panic disorder, agoraphobia, obsessivecompulsive disorder, social phobia, specific phobia, major depressive disorder, and somatization disorder. One study associated PTSD with a risk of developing dementia among older US male veterans. In a group of male veteran participants, those diagnosed with PTSD were twice as likely to develop dementia as were those without PTSD. Discovering the biological link between these disorders would be a monumental accomplishment in the fight to reduce the occurrence of dementia in PTSD victims.[4]

The legal system and PTSD

One major reason for litigation in the event of trauma and criminal offenses is to punish persons involved in violence and criminal activity. As a witness to an act of violence, the victim has an obligation to report the crime and to cooperate with law enforcement officials.

This may involve testifying before a grand jury, which occurs before the case formally begins. The victim acts as a witness to the case and, therefore, is not a party to the criminal proceedings and is not represented. This can be difficult after experiencing the event itself, which characterizes loss of power, control, and dignity. Victims often require the support and advocacy of legal representation, but the system does not provide it. The prosecuting attorney is the supposed advocate for the victim, but the attorney's job of defending the interests of justice may conflict with the interests of the victim. The process of a trial can be very traumatic for the victim, particularly in cases of sexual trauma. Defense tactics sometimes involve blaming the victim for the crime by tainting his or her character; this may add more pain to an already painful process. Go to Anxiety Disorders for more complete information on this topic.

Etiology
When PTSD occurs, symptoms of PTSD usually begin within 3 months of the traumatic event. However, a delay of months or years may occur before symptoms appear.

Physiologic factors
The amygdala is a key brain structure implicated in PTSD. Research has shown that exposure to traumatic stimuli can lead to fear conditioning, with resultant activation of the amygdala and associated structures, such as the hypothalamus, locus ceruleus, periaqueductal gray, and parabrachial nucleus. This activation and the accompanying autonomic neurotransmitter and endocrine activity produce many of the symptoms of PTSD. The orbitoprefrontal cortex exerts an inhibiting effect on this activation. The hippocampus also may have a modulating effect on the amygdala. However, in people who develop PTSD, the orbitoprefrontal cortex appears to be less capable of inhibiting this activation, possibly due to stress-induced atrophy of specific nuclei in this region.[5, 6]

Risk factors
As mentioned, PTSD is caused by experiencing, witnessing, or being confronted with an event involving serious injury, death, or threat to the physical integrity of an individual, along with a response involving helplessness and/or intense fear or horror. In various studies, a direct relationship has been observed between the severity of the trauma and the risk of developing PTSD.[7] When these events involve an individual with a physiologic vulnerability based on genetic (inherited) contributions and other personal characteristics, PTSD results. These personal characteristics include prior exposure to trauma, childhood adversity (eg, separation from parents), and preexisting anxiety or depression.

One of the most pivotal observations in relation to the development of PTSD in adults who were traumatized as children is the association between early trauma exposure and subsequent retraumatization.[8] Researchers have identified factors that interact to influence vulnerability to developing PTSD.[9, 10] These factors include the following:

Characteristics of the trauma exposure itself Characteristics of the individual Posttrauma factors

Regarding characteristics of the trauma exposure itself, factors that influence the development of PTSD include the traumas proximity and severity, as well as the duration of an individuals exposure to the trauma Characteristics of the individual that increase vulnerability to PTSD include prior trauma exposures, family history or prior psychiatric illness, and sex (women are at greatest risk for many of the most common assertive traumas). Posttrauma factors that influence whether PTSD develops include availability of social support, emergence of avoidance or numbing, hyperarousal, and reexperiencing symptoms. With regard to reexperiencing symptoms, a pilot monozygotic twin study showed that patients with PTSD have impaired extinction of novel conditioned fear stimuli.[11]

Combat and PTSD

Approximately 30% of men and women who have spent time in a war zone experience PTSD.[12] Studies conducted with veteran participants from Operation Iraqi Freedom and Operation Enduring Freedom (Afghanistan) determined a strong correlation between duration of combat exposure and PTSD. Service members from Operation Enduring Freedom (Afghanistan) reported less combat experience and, consequently, a lower incidence of mental health disorder compared with veterans of Operation Iraqi Freedom, who reported greater combat exposure.[13, 14] A study by Polusney et al suggests that combat-related PTSD is strongly associated with postconcussive symptoms and psychosocial outcomes one year after return from Iraq; however, little evidence of a long-term negative impact due to concussion and mild traumatic brain injury after accounting for PTSD.[15]

Epidemiology
Incidence of PTSD in the United States
PTSD has a lifetime prevalence of 8-10% and accounts for considerable disability and morbidity. One study found the prevalence of PTSD in a sample of adolescent boys to be 3.7% and the prevalence in adolescent girls to be 6.3%.[16]

Sex preference in PTSD

Females may be at higher risk for PTSD than are males. An epidemiologic survey of adult women indicated alarmingly high rates of traumatic events, particularly events associated with being crime victims. Sexual assault probably has the most impact on women, and trauma from combat probably has the most impact on men. Although earlier veteran studies were somewhat inconsistent, subsequent studies have suggested that service in Operation Iraqi Freedom presented equal PTSD risk to both sexes, with the duration and severity of combat experience having a greater influence than sex on the likelihood of a veteran having PTSD.[17, 18]

Age preference in PTSD

PTSD can occur in persons of any age, including children.

Prognosis
Prognosis in cases of PTSD is difficult to determine, because it varies significantly from patient to patient. Some individuals who do not receive care gradually recover over a period of years. Many individuals who receive appropriate medical and psychiatric care recover completely (or nearly completely). Rarely, even with intensive intervention, individuals experience worsening symptoms and commit suicide. In patients with PTSD who are receiving treatment, the average duration of symptoms is 36 months, compared with 64 months for those patients who do not receive treatment. However, more than one third of patients who have PTSD never fully recover. Factors associated with a good prognosis include rapid engagement of treatment, early and ongoing social support, avoidance of retraumatization, positive premorbid function, and an absence of other psychiatric disorders or substance abuse. Results from a pilot study in civilians suggested that patients with PTSD who experienced peritraumatic tonic immobility during the traumatic event have a poor response to pharmacologic treatment.[19]

Patient Education
When a family member is diagnosed with PTSD, the entire family may be affected. Members may experience shock, fear, anger, and pain because of their concern for the victim. Living with family members who have PTSD does not cause PTSD. Yet, it can cause some similar symptoms, such as feelings of alienation from and anger toward the victim. Other family members may find it difficult to communicate with a person with PTSD. Sleep disturbance and abuse (physical and substance) may occur among family members.

Families should engage in counseling if anger, addiction, or problems in school or work become issues. Stress and anger management and couples' therapy are possibilities. Families should try to maintain their outside relationships and should continue to be involved in pleasurable activities. For patient education information, see eMedicine's Mental Health and Behavior Center, as well as Post-traumatic Stress Disorder (PTSD) and Stress. The following Web sites also provide valuable information for patients and their families: US Department of Veteran Affairs National Center for PTSD, US Army Office of Behavioral Health, Afterdeployment.org, National Institute of Mental Health, American Academy of Child and Adolescent Psychiatry, and Mayo Clinic.

History
The information elicited from the interview with the patient must satisfy certain diagnostic criteria to make the formal diagnosis. As with many diagnoses, PTSD can be subclinical, in which the criteria are almost, but not fully, met. Diagnosis is based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM).[1] The mental status examination should routinely consist of questions about exposure to trauma or abuse.

First DSM diagnostic criterion

The first criterion has 2 components, as follows:

Experiencing, witnessing, or being confronted with an event involving serious injury, death, or a threat to a person's physical integrity A response involving helplessness, intense fear, or horror (sometimes expressed in children as agitation or disorganized behavior)

Second DSM diagnostic criterion

The second major criterion involves the persistent reexperiencing of the event in 1 of several ways. This may involve thoughts or perception, images, dreams, illusions, hallucinations, dissociative flashback episodes, or intense psychological distress or reactivity to cues that symbolize some aspect of the event. Unlike adults, however, children reexperience the event through repetitive play rather than through perception.

Third DSM diagnostic criterion

The third diagnostic criterion involves avoidance of stimuli that are associated with the trauma and numbing of general responsiveness; this is determined by the presence of 3 or more of the following:

Avoidance of thoughts, feelings, or conversations that are associated with the event

Avoidance of people, places, or activities that may trigger recollections of the event Inability to recall important aspects of the event Significantly diminished interest or participation in important activities Feeling of detachment from others Narrowed range of affect Sense of having a foreshortened future

In a study, women reported greater exposure to sexually related traumas, greater frequency and intensity of avoidance of trauma-related thoughts and feelings, and greater social impairment due to PTSD. Women also had higher rates of other anxiety disorders and of positive test results for cocaine use at treatment entry than did men.

Fourth DSM diagnostic criterion

The fourth criterion is symptoms of hyperarousal, and 2 or more of the following symptoms are required to fulfill this criterion:

Difficulty sleeping or falling asleep Decreased concentration Hypervigilance Outbursts of anger or irritable mood Exaggerated startle response

Fifth DSM diagnostic criterion

Fifth, the duration of the relevant criteria symptoms should be more than 1 month, as opposed to acute stress disorder, for which the criterion is a duration of less than 1 month.

Sixth DSM diagnostic criterion

The sixth criterion is that the disturbance is a cause of clinically significant distress or impairment in functioning.

Children and PTSD

Children may have different reactions to trauma than do adults. For children aged 5 years or younger, typical reactions can include a fear of being separated from a parent, crying, whimpering, screaming, immobility and/or aimless motion, trembling, frightened facial expressions, and excessive clinging. Parents may also notice regressive behaviors. Children of this age tend to be strongly affected by their parents' reactions to the traumatic event.[20] Children aged 6-11 years may show extreme withdrawal, disruptive behavior, and/or an inability to pay attention. Regressive behaviors, nightmares, sleep problems, irrational fears, irritability, refusal to attend school, outbursts of anger, and fighting are also common. The child may have somatic complaints with no medical basis. Schoolwork often suffers. Also, depression, anxiety,

feelings of guilt, and emotional numbing are often present. Adolescents aged 12-17 years may have responses similar to those of adults.[20]

Substance abuse in PTSD

Over time, untreated and undertreated individuals with PTSD are especially susceptible to a deterioration of personal and work relationships and to the development of substance abuse or dependence. In one study, men with PTSD reported an earlier age of onset of alcohol dependence, greater alcohol use intensity and craving, and more severe legal problems due to alcohol use. In the same study, women had higher rates of positive test results for cocaine use at treatment entry than did men. Moreover, PTSD more often preceded alcohol dependence in women than men. These findings illustrate the possibility of sex differences in the pathology of PTSD.[21] Another study found that 51.9% of men with PTSD concomitantly abused or were dependent on alcohol. In a study of 173 African American mental health outpatients, investigators noticed an increased use of analgesic medications (opiate and nonopiate) among members of this cohort who had been diagnosed with PTSD than in those patients in the study without PTSD. (However, the study had a number of limitations.)[22]

History assessment in immigrants

Individuals who have emigrated from countries experiencing political unrest may be unwilling to discuss their traumatic experiences because of legal issues.

Physical Examination
Patients with PTSD may present with physical injuries from the traumatic event (eg, bruises in victims of domestic abuse). Individuals with chronic PTSD may present with somatic complaints and, possibly, general medical conditions. Special attention should be paid to the patient's sleep hygiene. In addition, the patients general appearance may be affected by PTSD. Individuals may appear disheveled and have poor personal hygiene. In children, the combination of an elevated heart rate 24 hours posttrauma and a novel survey, the Child Trauma Screening Questionnaire, identified children likely to develop PTSD with adequate sensitivity, and with high specificity and negative predictive values at 1 and 6 months post trauma.[23]

Mental Status Examination

Patients with PTSD may display altered behavior. They may appear agitated, and their startle reaction may be extreme. Orientation is sometimes affected in patients with PTSD. The patient may report episodes of not knowing the current place or time, even though this may not have been evident during the interview. Memory is likely to be affected in PTSD. Patients may report forgetfulness, especially concerning the specific details of the traumatic event. A pilot study suggested that memory abnormalities may not be limited to the traumatic event itself.[24] Patients can also have poor concentration, poor impulse control, and an altered speech rate and flow. Mood and affect may be changed. Patients may have feelings of depression, anxiety, guilt, and/or fear. Thoughts and perception may be affected. Patients may be more concerned with the content of hallucinations, delusions, suicidal ideation, phobias, and reliving the experience; certain patients may become homicidal. Potential for suicide and homicide must be noted as part of the mental status. One study found that 48.5% of women with PTSD had major depressive disorder.

Diagnostic Considerations
Acute stress disorder Adjustment disorder Malingering (must be excluded) Mood disorder with psychotic features Psychotic disorders caused by a general medical condition Substance-induced disorders A review of PTSD trials in refugees suggested that PTSD may be a culture-specific diagnosis.[12] Care must be taken by a health care professional when applying this diagnosis to people from non-Western cultures where the diagnosis has not been validated and standard PTSD assessments have not been adapted to express non-Western concepts of disorder and idioms of distress.

Differentials

Anxiety Disorders Obsessive-Compulsive Disorder Schizophrenia

Approach Considerations
Laboratory and imaging tests have limited use in the assessment of patients with PTSD. One study found that nearly half (48%) of the patients in general medical practices with PTSD were receiving no mental health treatment at the time they entered the study. The most common reason patients gave for not receiving medication was the failure of physicians to recommend such treatment.[25]

Lab Studies
Cortisol levels may be decreased, norepinephrine and epinephrine levels may be elevated, and hypothalamic-pituitary-adrenal axis activity may be abnormal in patients with PTSD; however, these findings are still only used for research. Natural opiates, which are produced by the body to mask pain in the face of danger, may be found in higher levels in people with PTSD, even after the danger has passed. This may lead to the blunted emotions seen in persons with this condition.

Imaging Studies
Magnetic resonance imaging (MRI) studies of the brain suggest that the amount of hippocampal atrophy correlates with the intensity of PTSD symptoms, but MRI is still not a recommended diagnostic test.[24] Some studies in monozygotic twins show that a small hippocampus may be a predisposing factor to the later development of PTSD in the face of a stressor.[26]

Other Tests
Although increased arousal is not a required criterion for diagnosis, it might be measurable through studies of autonomic functioning (eg, heart rate monitoring, electromyography, sweat gland activity).

Approach Considerations
Many of the complications and disabilities associated with prolonged PTSD may be prevented by initiating assessment and treatment quickly after the traumatic event, well before a diagnosis of PTSD can be made. Treatment is often best accomplished with a combination of pharmacologic and nonpharmacologic therapies. Medications may be required to control the physiological

symptoms, which can enable the patient to tolerate and work through the highly emotional material in psychotherapy. (For adolescents and children, treatment is primarily psychotherapeutic in nature.) Treatment is often complicated by comorbid disorders. If present, alcohol or substance abuse problems should be the initial focus of treatment. In the presence of coexisting depression, treatment should focus on the PTSD, because its course, biology, and treatment response are unlike those associated with major depression. Treatment consists of group therapy, individual and family therapy, cognitive behavioral therapy, play therapy, art therapy, anxiety management, eye movement desensitization and reprocessing (EMDR), hypnosis, and relaxation techniques. EMDR has been successful in helping the survivors of various traumas, such as domestic violence, sexual abuse, crime, and combat. The method involves psychotherapy that combines various therapeutic approaches with eye movements (or other types of rhythmic stimulation) to stimulate the brain's information-processing mechanisms. A meta-analysis of studies in adults with PTSD indicated that trauma-focused cognitive-behavior treatment (CBT) and EMDR should be first-line nonpharmacologic therapies for PTSD.[27, 28, 29] In a study of service members with PTSD caused by the traumatic events of September 11, 2001, or by Operation Iraqi Freedom, self-managed, Internet-based CBT led to a greater reduction in PTSD symptoms than did Internet-based supportive counseling.[30] Studies have suggested that even a single CBT for sleep abnormalities can significantly improve daytime PTSD symptoms, as can pharmacologic treatments for sleep abnormalities.[31, 32] Some patients may benefit from psychodynamically oriented psychotherapy, especially if PTSD was caused by early sexual or physical abuse. Flooding, a technique involving prolonged exposure to the adverse stimuli, has been used with some success on veterans.

Inpatient care
Inpatient care is necessary only if the patient becomes suicidal or homicidal or if complicating comorbid conditions requiring inpatient treatment (eg, depression, substance abuse) are present. Although limited to 5 case management studies, the inpatient treatment of patients who had PTSD symptoms after returning from Global War on Terror (GWOT) missions was examined at a center. Treatment cocktails included aripiprazole and either cognitive-behavioral psychotherapy or sertraline. The therapeutic cocktail was observed to reduce the recurrence of hyperarousal episodes, which was the predominant symptom. However, in one patient, a paradoxical hyperarousal was observed.[33]

Remission criteria for PTSD

Remission criteria for patients with PTSD involve subjective goals and objective goals.[34] Objective goals include test results. Tests include the Treatment Outcome PTSD Scale, or TOPS8[35] ; the Hamilton Rating Scale for Anxiety, or HAM-A[36] ; the Hamilton Rating Scale for Depression, or HAM-D[37] ; and the Sheehan Disability Scale.[38] Criteria are as follows:

Subjective goal - No or minimal PTSD symptoms Objective goal - TOPS-8 score less than or equal to 5 or 6 Subjective goal - No or minimal anxiety Objective goal - HAM-A score less than or equal to 7-10 Subjective goal - No functional impairment Objective goal - Sheehan Disability Scale score less than or equal to 1 on each item (mildly disabled) Subjective goal - No or minimal symptoms of depression Objective goal - HAM-D score less than or equal to 7

Go to Anxiety Disorders for more complete information on this topic.

Long-Term Monitoring
Having experienced trauma, some patients with PTSD may be socially uncomfortable. Encouragement over time may be helpful to keep them therapeutically engaged, which yields optimal medical and psychiatric benefits.

Consultations
Patients with posttraumatic stress disorder (PTSD) and related conditions can be encountered in several treatment settings. Physicians practicing the following specialties are likely to encounter patients with PTSD and should request assistance from their colleagues in psychiatry.

Family practice and internal medicine

As previously mentioned, patients with PTSD are more likely to use the healthcare system, but less likely to seek mental health treatment; therefore, primary care physicians are likely to be the first encounter for a patient with untreated PTSD. Additionally, patients with chronic untreated PTSD are likely to have other chronic conditions that require treatment and/or hospitalization, further enhancing the likelihood they will encounter a primary care physician. It is important to remember that a patient with untreated PTSD is unlikely to be aware of his or her condition and PTSD can be obscured by comorbid conditions and/or somatization. When a primary care physician suspects a patient may have PTSD, referral to a psychiatrist is warranted for a definitive diagnosis.

Pediatrics
Children can develop PTSD, but their symptoms are likely to be different from those expressed by adults. Children who are known to have had traumatic experiences in the past and/or exhibit

some of the symptoms cited in Quick Guide should be referred to a psychiatrist specializing in children and adolescents for a definitive diagnosis.

Emergency department
Progression to PTSD can be prevented by treatment of acute stress disorder. If an emergency department physician encounters a patient acutely after experiencing a traumatic event, a psychiatrist should be consulted for evaluation and to establish the proper treatment to be administered as an outpatient or during inpatient hospitalization (when necessary) to prevent progression from acute stress disorder to PTSD.

Medication Summary
Many different drugs have been used to treat specific symptoms of posttraumatic stress disorder (PTSD), such as benzodiazepines for anxiety, anticonvulsants for impulsivity and emotional lability, and clonidine for nightmares. However, the principal agents of treatment have been the various antidepressants and beta-blockers. Most medication trials on PTSD have involved male combat veterans. Results of studies on civilians show fluoxetine to be effective.[39] Some studies suggest that fluoxetine demonstrates some efficacy for all 3 symptom clusters. Atypical antipsychotics have been used for patients who do not respond to antidepressants.[33] Patients with severe PTSD symptoms are likely to need longer treatment to experience beneficial results from taking these medications.[40] A study by Pollack et al suggests 3 mg of eszopiclone can improve in the short term, overall PTSD severity as well as improve sleep as compared with placebo.[41] Further studies on eszopiclone are needed. Novel pilot studies in combat veterans suggest alpha-1 antagonists have efficacy on the sleepassociated symptoms of PTSD.[32] Alpha-1 antagonists have not been FDA approved for this indication; however, low-dose glucocorticoids may have a role in decreasing recall of traumatic memories, but further research is warranted.[7] Small, double-blind, placebo controlled studies have indicated that a nighttime dose of prazosin (10-15 mg) decreases nightmares and sleep disturbances in combat veterans with PTSD and increases normal dreaming patterns. Additional pilot trials have suggested that a midmorning dose of prazosin also helps to decrease daytime PTSD symptoms in civilian and military patients.[32] However, larger, randomized, placebo-controlled trials are needed to confirm these results.

Selective serotonin reuptake inhibitors

Class Summary

The selective serotonin reuptake inhibitors (SSRIs) work by blocking the reuptake of serotonin. SSRIs such sertraline (Zoloft) and paroxetine (Paxil) have been FDA approved to treat PTSD as well as other disorders. View full drug information

Sertraline (Zoloft)

Sertraline is an SSRI that is FDA approved for the treatment of PTSD, panic disorder, social anxiety, and obsessive-compulsive disorder. It may be particularly useful in women who have experienced sexual or physical assaults. View full drug information

Paroxetine (Paxil)

Paroxetine is FDA approved to treat PTSD. It is used to reduce symptom severity of PTSD. It is a potent, selective inhibitor of neuronal serotonin reuptake. It also has a weak effect on norepinephrine and dopamine neuronal reuptake. It is also FDA approved for panic disorder, depression, social anxiety disorder, and obsessive-compulsive disorder. View full drug information

Fluoxetine (Prozac)

Fluoxetine selectively inhibits presynaptic serotonin reuptake with minimal or no effect on the reuptake of norepinephrine or dopamine. SSRIs as fluoxetine have less sedation, cardiovascular, and anticholinergic effects than the tricyclic antidepressants (TCAs). Studies have shown this drug to be superior for measures of PTSD severity, disability, and high end-state function.

Monoamine oxidase inhibitors

Class Summary
The monoamine oxidase inhibitors work by inhibiting monoamine oxidase, which causes an increase in endogenous enzymes such as norepinephrine, epinephrine, serotonin, and dopamine. View full drug information

Phenelzine (Nardil)

Phenelzine is a nonselective monoamine oxidase inhibitor. In one double-blind, placebocontrolled trial, it was suggested that phenelzine was efficient in reducing intrusion symptoms. It has demonstrated clear superiority over placebo in double-blind trials for treating specific symptoms of panic disorders. This agent is usually reserved for patients who do not tolerate or respond to traditional cyclic or second-generation antidepressants.

Tricyclic Antidepressants
Class Summary
TCAs are a class of antidepressants that work by inhibiting the reuptake of norepinephrine or serotonin at presynaptic neurons. View full drug information

Amitriptyline

Amitriptyline is a TCA that is indicated for depression. Antidepressants have been used in the treatment PTSD; however, it is not FDA approved for this indication. View full drug information

Imipramine

Imipramine is a TCA that is used to relieve the symptoms of depression. Antidepressants have been used in patients with PTSD and have shown beneficial effects. Imipramine is not FDA approved for the treatment of PTSD.

Benzodiazepines
Class Summary
Benzodiazepines are useful in treating patients with PTSD who are also experiencing anxiety. They may also play a role in symptomatic relief of irritability, sleep disturbances, and other hyperarousal symptoms. View full drug information

Lorazepam (Ativan)

Lorazepam is a benzodiazepine and sedative hypnotic with a short onset of effects and a relatively long half-life. It can be used for the short-term relief of symptoms of anxiety. By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, it may depress all levels of the CNS, including limbic and reticular formation. View full drug information

Diazepam (Valium)

Diazepam is a benzodiazepine that modulates the postsynaptic effects of GABA-A transmission, resulting in an increase in presynaptic inhibition. It appears to act on part of the limbic system, thalamus, and hypothalamus to induce a calming effect. It may be used to provide short-term relief of symptoms of anxiety

Beta-blockers
Class Summary
Beta-blockers such as propranolol are useful in controlling some symptoms of PTSD caused by hyperarousal. A pilot study revealed propranolol is effective for decreasing physiological signs of hyperarousal for up to 1 week when used shortly after patients with PTSD reexperience their traumatic event.[42] Ideally, propranolol is to be used within 6 hours of the initial traumatic event, well before a diagnosis of PTSD is made. Larger randomized, placebo-controlled studies are warranted to confirm these findings. View full drug information

Propranolol (Inderal, Betachron E-R)

Propranolol is a nonselective beta-adrenergic receptor blocking agent. It has been found to relieve exaggerated startle response, explosiveness, nightmares, and intrusive reexperiencing in some patients with PTSD. Propranolol has not been FDA approved for these indications.

Anticonvulsants
Class Summary

Anticonvulsants are commonly used in the treatment of bipolar disorder and epilepsy, as well as in patients with PTSD who are experiencing impulsivity and emotional liability. Several anticonvulsants have had positive data showing beneficial effects in PTSD; however, no anticonvulsants have been FDA approved for this disorder. View full drug information

Carbamazepine (Tegretol, Tegretol XR)

Carbamazepine is an anticonvulsant whose mechanism of action may involve depressing activity in the nucleus ventralis anterior of the thalamus, resulting in a reduction of polysynaptic responses and a blocking of posttetanic potentiation. It reduces sustained high-frequency repetitive neural firing. It has been studied in various trials for PTSD. View full drug information

Lamotrigine (Lamictal)

Triazine derivative used in neuralgia. Inhibits release of glutamate and inhibits voltage-sensitive sodium channels, leading to stabilization of neuronal membrane.

Atypical Antipsychotics
Class Summary
Several atypical antipsychotics have been studied in the treatment of PTSD. They may be helpful in alleviating the reexperiencing cluster of symptoms. These agents are not FDA approved for the treatment of PTSD. Antipsychotic agents may help patients with nightmares or flashbacks who have not responded to other treatment options. A study by Krystal et al found no significant difference between atypical antipsychotics and placebo for antidepressant-resistant symptoms of military service related PTSD. Observations were made over a 6-month period in 247 patients at 23 United States Veterans Administration outpatient medical centers.[43] View full drug information

Risperidone (Risperdal)

Risperidone is an antipsychotic that is approved to treat patients with bipolar mania, schizophrenia, and irritability associate with autistic disorder. Atypical antipsychotics have been used for patients who do not respond to antidepressants. View full drug information

Olanzapine (Zyprexa)

Olanzapine is approved for the treatment of bipolar disorder, schizophrenia, and treatmentresistant depression. It has shown benefits in the treatment of PTSD; however, it is not FDA approved for this indication.

Alpha-1 Receptor Antagonists

Class Summary
Novel pilot studies in combat veterans suggest alpha-1 antagonists have efficacy on the sleepassociated symptoms of PTSD. Alpha-1 antagonists have not been FDA approved for this indication. View full drug information

Prazosin (Minipress)

Prazosin is an alpha-1 adrenergic blocker that is indicated for hypertension. Studies indicate that a nighttime dose of prazosin (10-15 mg) decreases nightmares and sleep disturbances in combat veterans with PTSD and increases normal dreaming patterns. Additional pilot trials have suggested that a midmorning dose of prazosin also helps to decrease daytime PTSD symptoms in civilian and military patients. However, larger, randomized, placebo-controlled trials are needed to confirm these results.

Antiadrenergic Agents
Class Summary
Novel pilot studies in combat veterans suggest alpha-1 antagonists have efficacy on the sleepassociated symptoms of PTSD. Alpha-1 antagonists have not been FDA approved for this indication. View full drug information

Clonidine (Catapres, Catapres-TTS, Duraclon)

Clonidine is a central alpha-adrenergic agonist that is commonly used as an antihypertensive agent. It stimulates alpha2-adrenoreceptors in the brain stem and activates an inhibitory neuron, resulting in a decrease in vasomotor tone and heart rate. Clonidine may have potential effects on the hyperarousal symptoms of PTSD. It may also help in patients experiencing nightmares