The Use of Psychotherapeutic Medications in War Veterans

Release Date: November 1, 2010

Expiration Date: November 30, 2012


Angie Eaton-Maxwell, PharmD
Assistant Professor of Pharmacy Practice

Uche Anadu Ndefo, PharmD, BCPS
Assistant Professor of Pharmacy Practice

Adlia Ebeid, PharmD
Director of IPPE

Regina Ramirez, PharmD

Ketal Patel, PharmD
Drug Information Resident

Daniel Begnaud, PharmD
Texas Southern University
College of Pharmacy and Health Sciences
Houston, Texas

(Drs. Eaton-Maxwell and Ndefo are also Drug Information Specialists with the Harris County, Texas, Hospital District. Drs. Patel, Ramirez, and Begnaud were PharmD Interns at the time this manuscript was prepared.)


Drs. Eaton-Maxwell, Ndefo, Ebeid, Ramirez, Patel, and Begnaud have no actual or potential conflict of interest in relation to this activity.

Postgraduate Healthcare Education, LLC, does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.


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Credits: 2.0 hours (0.20 ceu)
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This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.

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Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.


To discuss the prevalence of posttraumatic stress disorder in war veterans along with the various pharmacologic and nonpharmacologic treatment modalities available to the practicing clinician.


After completing this activity, participants should be able to:

  1. Differentiate between posttraumatic stress disorder and other mental illnesses affecting war veterans.
  2. Recognize various social issues associated with the homecoming of veteran soldiers.
  3. Distinguish different pharmacologic and nonpharmacologic treatments for war veterans suffering from posttraumatic stress disorder.
  4. Acknowledge the pharmacist’s role in medication management and the implications of its benefit for war veterans.
  5. Discuss postcombat stress and traumatic brain injuries and the effects on posttraumatic stress disorder.

The United States Department of Veterans Affairs reports that over 100,000 war veterans are currently seeking care for mental illness. Soldiers show signs of mental illness, such as depression and posttraumatic stress disorder (PTSD), shortly upon their return from war. Soldiers are more likely to develop severe symptoms of depression and PTSD at 6 months after their return versus immediately upon their homecoming.1 The U.S. Department of Defense evaluates soldiers using their Post-Deployment Health Assessment (PDHA) survey immediately upon return from war and re-evaluates them again using a PDHA survey several months later. Pharmacists play a vital role in facilitating treatment recommendations and counseling in hopes of preventing future possible underlying causes of suicide, including PTSD; early prevention or management of PTSD may lead to decreased suicides. Along with psychotherapy, pharmacists must be vigilant when pharmacotherapy is used (along with psychotherapy) to help manage PTSD, postcombat stress, depression, etc. The American Journal of Psychiatry reported that adults who commit suicide were likely to have seen a health care provider within the previous year; this makes the diagnosis of such diseases and the recognition of risk factors associated with PTSD to be equally important in the early detection and ultimate prevention of posttraumatic stress and combat related suicide.2

Posttramatic Stress Disorder

PTSD is an anxiety disorder affecting those who have experienced a life threatening event or intense trauma and have displayed persistent symptoms that may interfere with their everyday life. Diagnostic criteria for PTSD can be found in TABLE 1.3 Symptoms associated with PTSD can include flashbacks or hallucinations, withdrawal, hyperanxiety, aggression, and blunted affect. These symptoms can develop into other disorders and may affect physical, emotional, social, and vocational aspects of life. Men and women who have served in the military may have been wounded in action, exposed to war-zone trauma or stress, been held as prisoners of war, been sexually assaulted, or harassed repeatedly.4


Stress disorders are usually triggered by a significant traumatic event, where the patient experiences bouts of anxiety. The two types of stress disorders are differentiated by the onset of anxiety. Acute stress disorder occurs directly following the traumatic event, while PTSD may not occur until a later time with possible recurrences. The manifestation of PTSD is triggered by different indicators recalled by the patient from the traumatic event. The symptoms may range from the patient being numb or withdrawn from any association with the indicator to being outwardly disturbed (i.e., overly vigilant or angry).5

PTSD is considered a debilitating condition that may lead to alcoholism and other psychological disorders. Because it is a complex disorder that occurs over a long period of time, combination therapy consisting of pharmacologic and nonpharmacologic treatments is necessary.

Postcombat Stress

Stress associated with being in combat is a major contributor to possible outstanding effects of combat regardless of whether the patient suffered physical injury. Another disorder is postcombat stress disorder, commonly referred to as shell shock. Although there are no set diagnostic criteria, this short-term condition is similar to PTSD—soldiers and veterans present with tremor or nervous exhaustion and find themselves unable to function normally.6 Postcombat stress can also trigger other long-term disorders associated with neurologic effects of combat. This form of PTSD can be treated and slightly improved with appropriate stress therapy such as counseling and debriefing time after combat.

Traumatic Brain Injury

Traumatic brain injury (TBI) is the medical term for a concussion or contusion and can range from a mild injury to a severe, life-threatening dilemma. Each year, Americans suffer from injuries resulting in TBI, and a majority of patients experience long-term disability and impaired cognition. In relation to veterans returning from war, firearm use is one of the leading causes of TBI and can result in cognitive, physical, and behavioral changes. Cognitive symptoms include attention difficulties, memory problems, and difficulty concentrating. These symptoms, along with physical and behavioral changes, are nondifferential, often making the diagnosis of TBI difficult. In addition, the symptoms may take anywhere from a few days to a few months following injury to manifest. Use of the Glasgow Coma Scale may be beneficial in determining the severity of TBI, but the diagnosis should be confirmed with neurologic imaging and other psychological tests. Head injuries often coincide with other more serious injuries and are forgotten. Symptoms may also be intentionally left out by the patient from fear of showing weakness or inadequacy.7

Sufferers of TBIs present with symptoms shortly after sustaining the injury, but the onset of symptoms may be as long as a week in many cases. Due to the broad range of symptoms characterizing TBIs and their varying severities, therapeutic modalities applied in treatment vary on a case-by-case basis and generally encompass tailored treatment programs directed towards addressing each individual patient’s symptoms.8

Family Involvement

The effects of war do not just impact veterans. Many families may also be affected by traumatic events that happened to war veterans, and a couple’s risk for psychological and marital distress is increased due to traumatic events. In a study consisting of 49 male soldiers deployed to Iraq for 12 months, soldiers and spouses were asked to complete questionnaires 3 months after the soldiers’ return.9 The forms assessed symptoms of PTSD, depression, and relationship satisfaction. Other measures included the extent and severity of traumatic combat events. In soldiers who experienced combat exposure, 46% showed signs of PTSD symptoms, and 49% had symptoms of depression (P ≤.001). Spouse surveys revealed that 42% believed their husbands had symptoms of depression, and 38% believed they had symptoms of PTSD (P ≤.01 and P <.05, respectively). Thirty-eight percent of wives also showed symptoms of depression (P <.01). Spouses’ marital satisfaction was 6%, 28%, and 36% for soldiers who experienced combat exposure, PTSD symptoms, and depressive symptoms, respectively (P <.05).9

Other mental disorders suffered as a result of combat exposure may result from experiential avoidance, which occurs when a person who has suffered a traumatic event engages in efforts to cope with distressing internal events, possibly via social withdrawal, substance use, or dissociation. Couples therapy is a way to maintain marital satisfaction by reducing conflict and increasing intimacy as well as fostering acceptance, tolerance, and expression of emotions such as fear or sadness.10


Mental illness in a soldier who has suffered traumatic combat experience may project outwardly as anger, hostility, and aggression. A study conducted on 117 Iraq and Afghanistan War veterans demonstrated 47 positive screenings for PTSD. Twenty-one additional individuals had a positive screening for subthreshold PTSD. Specific aggressive acts were classified as destruction of property, threatening physical violence with no weapon, threatening someone with a weapon, and having a physical fight with another individual. As seen in TABLE 2, the occurrence of these specific aggressive acts in the PTSD group was 19.1%, 25.5%, 2.1%, and 17.0%, respectively. The occurrence seen in the subthreshold PTSD group was 23.8%, 38.1%, 14.3%, and 9.5%, respectively. Of the individuals classified as having no symptoms of PTSD and engaged in aggressive acts, the results were 6.1%, 10.2%, 4.1%, and 4.1%, respectively.11


Increased aggression seen in individuals with a mental illness due to traumatic combat experiences may also lead to a higher risk of crime and incarceration. A cohort followed from 1993 to 1997 who were treated in an inpatient unit (n = 36,385) of the Connecticut Department of Veterans’ Affairs health care system was used to assess risk factors for incarceration. The frequency of individuals who were incarcerated and had mental illness was measured. The percentage of incarcerations in veterans (n = 228) having bipolar disorder, anxiety disorder, major depression, personality disorder, PTSD, schizophrenia, alcohol abuse, and drug abuse was 2.7%, 16.3%, 25.4%, 6.6%, 18.9%, 12.3%, 43.9%, and 48.7%, respectively (P <.001). Prediction factors for incarceration were also measured and were the highest among veterans with drug abuse, alcohol abuse, major depression, and PTSD, with odds ratios of 3.02, 2.88, 1.85, and 1.12, respectively (P <.001).12


The number of veterans with diagnosed PTSD is on the rise, and therefore the costs incurred as a result have risen as well. The number of disability payments for patients with PTSD rose 148.8% from 1999 to 2004, averaging approximately $4.3 billon annually during those years.13,14 The cost associated with mental illness also varies depending on the severity of a patient’s condition. The total cost to treat all patients with TBIs in the U.S. is conservatively estimated to be $56 billion for a lifetime of treatment, whereas mild brain injuries make up approximately 75% of all diagnosed head injuries and cost $17 billion each year.

Nonpharmacologic Treatments

Management of PTSD includes a variety of therapies, some pharmacologic and some involving psychotherapeutic interventions. Psychotherapeutic interventions available include different techniques of cognitive-behavioral therapy such as exposure therapy, cognitive therapy, and cognitive processing therapy.15

Exposure therapy attempts to desensitize the patient to the cues that trigger the PTSD episode by progressively exposing participants to the cue according to tolerability. The different types of exposure include mental imagery, pictures, role playing, virtual reality, and causing the patient to have the physiologic symptoms experienced during the trauma.

Cognitive therapy attempts to adjust how the patient views and feels the traumatic event. Therapy includes identifying the cues that trigger thoughts of fear and anxiety and challenging the basis of those emotions. The different techniques utilized are alternative hypothesis generation, reality testing, cognitive reframing, cognitive restructuring, decatastrophizing, and relaxation techniques.

Cognitive processing therapy is similar to cognitive therapy; however, processing therapy explores other emotions seen in PTSD, i.e., guilt and shame. This has been shown to be useful in victims of rape and other crimes. The patient dissects his or her emotions through the use of narrative writing.15

Nonpharmacologic modalities can be utilized for treating TBIs, and the use of novel therapies for such injuries may help in the restoration of cognitive, physical, and behavioral characteristics for this particular population.

TBI is, unfortunately, a common occurrence experienced by millions each year in the U.S. It is a condition characterized by a wide array of symptoms varying from patient to patient and, therefore, lacks concrete treatment protocols. Most often, therapy is individualized to each case. It is with continued research that more beneficial treatment options will be discovered.

Pharmacologic Management of PTSD

The Veterans Health Administration, Department of Defense clinical practice guidelines for the treatment of PTSD were revised in 2004 after veterans began to return from the war in Iraq.16 The guidelines recommend the use of selective serotonin reuptake inhibitors (SSRIs) as first-line treatment, with tricyclic anti-depressants (TCAs) and monoamine oxidase inhibitors (MAOIs) recommended as second-line treatments. The guidelines also recommend an antidepressant be tried for at least 12 weeks. Options presented in the guidelines for the augmentation of anti-depressants include prazosin or other sympatholytics and novel anti-depressants. Insufficient evidence to recommend anticonvulsants, atypical antipsychotics, buspirone, or nonbenzodiazepine hypnotics is also noted in the guidelines for the treatment of PTSD. Typical antipsychotics are not considered useful in PTSD, and the use of long-term benzodiazepines is not recommended for the management of core symptoms. Pharmacotherapy for PTSD can be seen in TABLE 3.


A study of war veterans with PTSD conducted in 2004 at the U.S. Department of Veterans Affairs found that 80% were prescribed psychotropic medications.17 Of the patients receiving this therapy, 89% were prescribed anti-depressants, 61% were prescribed sedatives/hypnotics or anxiolytics, and 34% were prescribed antipsychotics. The study also found that comorbid conditions were the greatest predictor of the selection of therapy.

Dysregulation of neurotransmitters leads to the symptoms of PTSD, which are modulated by SSRIs. SSRIs are thought to reduce feelings of fear and hopelessness, but can have the paradoxical effect of stimulation, making sleeping disturbances worse. Sertraline is approved by the FDA for the treatment of PTSD; it has been proven to be effective in the treatment of PTSD and when maintained during extended treatment.18,19 Paroxetine is also FDA approved for the treatment of PTSD and has shown effectiveness in three components of PTSD, including re-experiencing, avoidan/USPExams/numbing, and hyperarousal.20 Other SSRIs, such as fluoxetine, have been evaluated in combat veterans and have shown efficacy in the treatment of PTSD but do not currently hold FDA approval for the treatment of PTSD.21

Evidence for the use of serotonin norepinephrine reuptake inhibitors (SNRIs) for the treatment of PTSD favors efficacy. In a study comparing venlafaxine to sertraline and placebo, venlafaxine was deemed superior to placebo; however, its superior efficacy compared to that of sertraline was considered clinically insignificant.22

Other anti-depressants, including TCAs such as amitriptyline and MAOIs such as phenelzine, have also been evaluated for efficacy in the treatment of this condition. Limited and inconclusive evidence and the adverse effect profiles have limited the use of these medications for the management of PTSD.

Psychotic symptoms are common in patients with more severe symptoms of PTSD. Generally, psychotic symptoms predict less treatment success with conventional therapy. Atypical antipscychotics have been studied as adjunct therapy in the treatment of PTSD, particularly in patients with psychotic symptoms. Olanzapine has been studied alone and as an adjunct with SSRIs for the treatment of PTSD in combat veterans. Adjunctive therapy with sertraline was more effective than placebo in reducing PTSD symptoms, but did not significantly change clinical global improvement response rates.23 In an open-label trial of olanzapine alone, olanzapine was found to improve all outcome measures of PTSD; however, there was a high dropout rate and a high incidence of adverse effects.24 Risperidone was studied in an openlabel trial as monotherapy in combat veterans with psychotic PTSD resistant to anti-depressants.25 The study found that risperidone decreased most psychotic and PTSD symptoms. Risperidone has also been tested for the augmentation of antidepressant therapy in a placebo controlled, double-blind study of combat veterans. The risperidone-treated group was found to have a modest decrease in psychotic symptoms and a suggested decrease in re-experiencing symptoms.26

Excessive stimulation of adrenergic receptors is believed to occur with PTSD, and adrenergic inhibitors such as clonidine, prazosin, and propranolol have exhibited some levels of efficacy in its treatment. These agents are especially effective in patients whose primary symptoms include insomnia and nightmares. In two studies involving combat veterans with recurrent distressing dreams or nightmares, treatment with prazosin led to a reduction in these dreams and increased the veterans’ sleep quality.27,28

The evidence on the utilization of benzodiazepines is inconclusive and controversial due to the potential for drug abuse in patients with PTSD; however, benzodiazepine use can alleviate some of the symptoms of PTSD such as anxiety, irritability, and sleep disturbances.

Anticonvulsants and mood stabilizers have also been considered for the treatment of PTSD. Topiramate has been evaluated for efficacy in PTSD and is believed to work by stabilizing the α-amino-3-hydroxy-5 methyl-4 isoxazole propionic acid (AMPA) receptor; antagonists of AMPA are believed to decrease the acoustic startle response. Although topiramate has shown effectiveness in civilian PTSD, one study conducted in veterans where topiramate was used for augmentation found no difference when compared to placebo.29-32 Other anticonvulsants studied for the treatment of PTSD include divalproex, lamotrigine, and levetiracetam.33-35

Psychotropic Medication Effect

At treatment initiation, all patients should be advised about the effect the medications will have and that the effects will not be immediate. Patients should also be informed of potential side effects.36 SSRIs are associated with several side effects such as akathisia, anxiety, suicide ideation, agitation, and possible sexual dysfunction. Monoamine oxidase inhibitors are associated with significant side effects as well, and counseling must include information regarding interactions with numerous medications and foods.37 Patients are advised to contact a clinician if any side effects occur. In regard to discontinuation, patients should be informed that tapering generally occurs over 4 weeks to minimize any potential side effects.

Pharmacist Role and Appropriate Diagnosis

The Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) is the current guide used to diagnose PTSD and should only be consulted after medical disorders have been ruled out.38 It is the health care provider’s primary role to understand that many patients may not present with symptoms easily recognizable as PTSD. Symptoms may range through a variety of differential diagnoses: physical traumatic injury, physical abuse, and psychological effects of witnessing traumatic events including depression, hyperarousal, avoidance, re-experiencing, drug and alcohol misuse, or anger.36,39 Therefore, it is the clinician’s responsibility to ask specific and appropriate questions in an effort to make a clear and accurate diagnosis; this, in turn, allows the pharmacist to treat the patient accordingly and with the proper medications. Questions can include topics such as re-experiencing and how it causes the patient to relive the event via nightmares or flashbacks. However, and more important, the pharmacist’s focus should be geared towards how the patient is responding to medications. This information can come from questions regarding the number of flashbacks the patient is experiencing or whether the patient is experiencing any possible adverse events or reactions. Pharmacists may inquire whether a patient has been experiencing increased thoughts of suicide and thus needs a change in medications. Managing conditions such as PTSD requires a team of experts, and anytime pharmacologic therapy is involved, the role of the pharmacist is the frontline of defense.


Patients taking medications for PTSD should be informed of the effects of their medications and appropriate use. In addition, patients must be informed that with many of the medications, discontinuation or withdrawal symptoms can occur up to 5 days after cessation of use and are not necessarily associated with medication dependence. These symptoms might even be hard to differentiate from the original symptoms of PTSD, so patients and pharmacists and clinicians should be aware of this potential in order to prevent additional medication use due to misdiagnosis. Pharmacists occupy an imperative role, so the understanding of and ability to recognize correct criteria for diagnosing patients with PTSD are crucial. In addition, pharmacists should be aware of the possible comorbid conditions that can occur with patients as well as those conditionns that may complicate treatment. Appropriate medication management is a key feature in the process of ensuring that pertinent care is delivered to all patients. Psychotropic medications offer a way of providing effective relief of symptoms in patients with PTSD, especially when used in combination with other, nonpharmacologic treatments. It is incumbent upon pharmacists and clinicians to provide the appropriate background knowledge and ongoing support to those suffering from these disorders.


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