**2.2 Treatment**

54 Post Traumatic Stress Disorders in a Global Context

Council, 2007). The psychiatric assessment should detail the presenting symptoms and elicit a trauma history, including childhood and adolescent trauma, and exposure to military trauma (combat or peacekeeping operations) (Friedman, 2006). The details of the traumatic event should be limited to information that clarifies the diagnosis as the recounting of an extremely traumatic event is often highly triggering and can lead to significant symptom

Clinically, PTSD presents as four symptom clusters: reexperiencing the traumatic events, avoidance of reminders and emotional numbing (which are grouped together as one symptoms cluster in DSM-IV but are seen as distinct and will likely be denoted as such in DSM-5), and hyperarousal symptoms (American Psychiatric Association, 2004, American Psychiatric Association, 2001). Military members with PTSD relive their trauma in intrusive recollections during the day, including flashbacks, or at night as bad dreams or nightmares. Many complain of both physical and emotional symptoms of anxiety when exposed to reminders of their traumatic event. They may avoid reminders of the trauma and describe emotional numbness or an inability to experience a normal range of emotions with family or friends. They may complain of hyperarousal symptoms such as insomnia, irritability, frequent anger outburst, poor concentration and hypervigilance. According to DSM-IV-TR, acute PTSD has a duration of between 1 and 3 months, whilst chronic PTSD has a duration

The clinician can screen for PTSD using available short screening instruments such as the four-item yes/no screening instrument—the Primary Care PTSD Screen—designed for use by primary care practitioners. It has a sensitivity of 78% and specificity of 87% for PTSD in patients who endorse three or more items, (Friedman, 2006) figure 1. Patients who screen positive should be assessed for PTSD using the DSM IV diagnostic criteria, figure 2, or using more elaborative screening instruments such as the Clinician Administered PTSD Scale (CAPS)(Blake et al., 1995) or a self-rating scale such as the PTSD Checklist (Military Version) (Weathers et al., 1993). Veterans may also present with some symptoms of PTSD without meeting the full diagnostic criteria (Zlotnick et al., 2002, Schützwohl and Maercker, 1999, Stein et al., 1997, Charney et al., 1986, Weiss et al., 1992). Even if the full criteria are not met, studies indicate that these individuals may experience significant functional impairment (Olfson et al., 2001). In a study of Canadian veterans, Asmundson and colleagues (Asmundson et al., 2002) demonstrated increased psychopathology in veterans with sub-

threshold PTSD when compared to the non-deployed, non-traumatized veterans.

Assessing suicide risk is also critical. The presence of PTSD symptoms increases the possibility of suicidal ideation (Marshall et al., 2001). PTSD often presents with comorbidities such as depression and addictions (Kessler et al., 1995, Forbes et al., 2003). Studies have estimated that more than 50% of PTSD patients have symptoms of a major depressive disorder (Kessler et al., 1995), but in the veteran population, possibly due to delayed treatment, the percentage may be much higher (Keane and Wolfe, 1990, Southwick et al., 1991, Forbes et al., 2003). Co-morbid depression also significantly increases suicide risk (Kaufman and Charney, 2000). Issues of aggression and anger are also well documented in war veterans, (Lewis, 1990, Forbes et al., 2003, Forbes et al., 2004, Biddle et al., 2002) and during the initial PTSD assessment, male military members may report violent thoughts and aggressive behavior, including homicidal thoughts. Assessing comorbidity, suicidal or homicidal ideations and social support is important in order to determine the need for inpatient treatment or referral for specialist care (American

of more than three months (American Psychiatric Association, 2001).

exacerbation.

Psychiatric Association, 2004).

Once a firm diagnosis has been established, psychoeducation in group format or individually regarding diagnosis and treatment is critical for both patient and family (American Psychiatric Association, 2004, Turnbull and McFarland, 1996, Van Der Kolk et al., 1996a, Foa et al., 2000). Patient education is a fundamental component of the treatment of as PTSD. Providing psychoeducation can enhance patient satisfaction and improve treatment compliance (Gray et al., 2004). Effective treatment requires that patients understand the treatment plans and return for follow-up assessment and treatment (American Psychiatric Association, 2004). Veterans need information soon after the initial assessment of the different stages of treatment for PTSD (Herman, 1992). The initial phase of treatment focuses on symptom stabilization and the treatment of co-morbid conditions such as depression, addictions and anxiety disorders. Educating patients regarding the phases of treatment reassures those frightened by the notion of psychiatric medication and psychotherapy as well as to set appropriate expectations for treatment. Some patients expect they will be forced to talk about feared traumatic events from the outset and are relieved to know that trauma work comes after their anxiety and distress are more manageable. While symptoms might initially be overwhelming and require pharmacological intervention, early work on mastering anxiety and anger using psychological tools, provides a sense of self- control. Safety in therapy is paramount and only after acute symptoms, particularly suicidality and homicidality, are addressed should the exploration of traumatic events be approached. Once symptoms stabilize, patients are more able to engage in psychotherapy (Van Der Kolk et al., 1996b).

Psychiatric Management of Military-Related PTSD: Focus on Psychopharmacology 57

The therapeutic relationship focuses on the "therapeutic use of self", the interpersonal process and the authentic relationship between clinician and client (Carper, 1978). Developing a trusting therapeutic relationship is a challenge and one of paramount importance. Establishing trust in therapy takes time, and so it is often helpful to set the timeframe for therapy soon after the initial assessment. Patients need to be reassured that their clinician does not expect that trust will develop immediately, but requires time to develop. Genuineness and empathy are essential in order to develop an authentic, trusting therapeutic relationship with a veteran. Because of their initial paucity of basic trust, especially of individuals in authority (Glover, 1988.), younger veterans seeking help will

It is crucial to find a therapist with experience in treating PTSD and knowledgeable on military culture. Both prolonged exposure and cognitive behavioral psychotherapy (CBT) are considered first-line treatment for PTSD. In prolonged exposure, the patient reiterates the trauma during planned treatment sessions, including every sensory experience associated with it, until the memory no longer provokes significant anxiety. With CBT, both the conditioned fear and cognitive distortions associated with PTSD are addressed. Common cognitive distortions include perceiving the world as dangerous, seeing oneself as powerless or inadequate, or feeling guilty for outcomes that could not have been prevented (Friedman, 2006). Most clinical guidelines have also accepted that Eye Movement Desensitization and Reprocessing (EMDR) is an evidence-based treatment for PTSD (American Psychiatric Association, 2004, Friedman, 2006). In EMDR, patients are instructed to imagine painful traumatic memories and associated negative cognitions such as guilt and shame while visually focusing on the rapid movement of the clinician's finger (Friedman, 2006). However dismantling studies have demonstrated that the "eye movement" component is not necessary for the treatment response and that the theoretical bases for its method of action has yet to be determined (Davidson and Parker, 2001). Regardless of the treatment modality, stabilization is critical as the potential danger of initiating "traumafocused psychotherapy" prior to stabilization may exacerbate pre-existing co-morbid

Group based psychotherapy is also commonly used, focusing on psychoeducation, anger, depression, substance use, social and vocational skills, relaxation training as well as other

As demonstrated in Table 1, a number of medications have been used to treat PTSD. Selective Serotonin Reuptake Inhibitors (SSRIs) have the most empirical evidence for efficacy in the treatment of all three PTSD symptom clusters and are usually considered as a first-line treatment for PTSD (American Psychiatric Association, 2004, National Institute for Clinical Excellence, 2005, Schoenfeld et al., 2004b). SSRIs are also effective agents for the treatment of co-morbid mood and anxiety disorders commonly associated with PTSD. Both paroxetine and sertraline have received FDA approval for the treatment of PTSD in the United States (American Psychiatric Association, 2004). In Canada, only paroxetine has

Second-generation, dual acting antidepressants such as venlafaxine and mirtazepine, are widely used in treating major depression and other anxiety disorders but have less

facets of PTSD (American Psychiatric Association, 2004, Foy et al., 2000).

often challenge their clinician to determine if the clinician is indeed "genuine."

symptoms of depression and substance abuse.

Health Canada approval for the treatment of PTSD**.** 

**2.2.2 Pharmacological management** 

**2.2.1 Psychotherapy** 

The person has been exposed to a traumatic event in which both of the following were present:

	- 1. recurrent and intrusive distressing recollections of the event, including images, thoughts, or perceptions. Note: In young children, repetitive play may occur in which themes or aspects of the trauma are expressed.
	- 2. recurrent distressing dreams of the event. Note: In children, there may be frightening dreams without recognizable content.
	- 3. acting or feeling as if the traumatic event were recurring (includes a sense of reliving the experience, illusions, hallucinations, and dissociative flashback episodes, including those that occur on awakening or when intoxicated). Note: In young children, traumaspecific reenactment may occur.
	- 4. intense psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event
	- 5. physiological reactivity on exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event
	- 1. efforts to avoid thoughts, feelings, or conversations associated with the trauma
	- 2. efforts to avoid activities, places, or people that arouse recollections of the trauma
	- 3. inability to recall an important aspect of the trauma
	- 4. markedly diminished interest or participation in significant activities
	- 5. feeling of detachment or estrangement from others
	- 6. restricted range of affect (e.g., unable to have loving feelings)
	- 7. sense of a foreshortened future (e.g., does not expect to have a career, marriage, children, or a normal life span)
	- 1. difficulty falling or staying asleep
	- 2. irritability or outbursts of anger
	- 3. difficulty concentrating
	- 4. hypervigilance
	- 5. exaggerated startle response

Chronic: if duration of symptoms is 3 months or more Specify if:

With Delayed Onset: if onset of symptoms is at least 6 months after the stressor.

a Reprinted from *Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision.* Washington, DC, American Psychiatric Association, 2000. Copyright © 2000. American Psychiatric Association.

Fig. 2. DSM-IV-TR Diagnostic Criteria for Posttraumatic Stress Disorder (DSM-IV-TR code 309.81)a

#### **2.2.1 Psychotherapy**

56 Post Traumatic Stress Disorders in a Global Context

The person has been exposed to a traumatic event in which both of the following were

this may be expressed instead by disorganized or agitated behavior

themes or aspects of the trauma are expressed.

dreams without recognizable content.

resemble an aspect of the traumatic event

5. physiological reactivity on exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event

1. efforts to avoid thoughts, feelings, or conversations associated

6. restricted range of affect (e.g., unable to have loving feelings) 7. sense of a foreshortened future (e.g., does not expect to have a

occupational, or other important areas of functioning. Specify if:

Acute: if duration of symptoms is less than 3 months Chronic: if duration of symptoms is 3 months or more

3. inability to recall an important aspect of the trauma

5. feeling of detachment or estrangement from others

career, marriage, children, or a normal life span)

specific reenactment may occur.

1. the person experienced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical

B. The traumatic event is persistently reexperienced in one (or more) of the following ways: 1. recurrent and intrusive distressing recollections of the event, including images,

2. recurrent distressing dreams of the event. Note: In children, there may be frightening

3. acting or feeling as if the traumatic event were recurring (includes a sense of reliving the experience, illusions, hallucinations, and dissociative flashback episodes, including those that occur on awakening or when intoxicated). Note: In young children, trauma-

4. intense psychological distress at exposure to internal or external cues that symbolize or

D. Persistent symptoms of increased arousal (not present before the trauma), as indicated by

E. Duration of the disturbance (symptoms in Criteria B, C, and D) is more than 1 month. F. The disturbance causes clinically significant distress or impairment in social,

With Delayed Onset: if onset of symptoms is at least 6 months after the stressor. a Reprinted from *Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision.* Washington, DC, American Psychiatric Association, 2000. Copyright © 2000.

C. Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by three (or more) of the

2. efforts to avoid activities, places, or people that arouse recollections of the

4. markedly diminished interest or participation in significant activities

thoughts, or perceptions. Note: In young children, repetitive play may occur in which

s response involved intense fear, helplessness, or horror. Note: In children,

Fig. 2. DSM-IV-TR Diagnostic Criteria for Posttraumatic Stress Disorder (DSM-IV-TR code

309.81)a

Specify if:

present:

2. the person'

following:

trauma

with the trauma

two (or more) of the following: 1. difficulty falling or staying asleep 2. irritability or outbursts of anger 3. difficulty concentrating 4. hypervigilance

5. exaggerated startle response

American Psychiatric Association.

integrity of self or others

The therapeutic relationship focuses on the "therapeutic use of self", the interpersonal process and the authentic relationship between clinician and client (Carper, 1978). Developing a trusting therapeutic relationship is a challenge and one of paramount importance. Establishing trust in therapy takes time, and so it is often helpful to set the timeframe for therapy soon after the initial assessment. Patients need to be reassured that their clinician does not expect that trust will develop immediately, but requires time to develop. Genuineness and empathy are essential in order to develop an authentic, trusting therapeutic relationship with a veteran. Because of their initial paucity of basic trust, especially of individuals in authority (Glover, 1988.), younger veterans seeking help will often challenge their clinician to determine if the clinician is indeed "genuine."

It is crucial to find a therapist with experience in treating PTSD and knowledgeable on military culture. Both prolonged exposure and cognitive behavioral psychotherapy (CBT) are considered first-line treatment for PTSD. In prolonged exposure, the patient reiterates the trauma during planned treatment sessions, including every sensory experience associated with it, until the memory no longer provokes significant anxiety. With CBT, both the conditioned fear and cognitive distortions associated with PTSD are addressed. Common cognitive distortions include perceiving the world as dangerous, seeing oneself as powerless or inadequate, or feeling guilty for outcomes that could not have been prevented (Friedman, 2006). Most clinical guidelines have also accepted that Eye Movement Desensitization and Reprocessing (EMDR) is an evidence-based treatment for PTSD (American Psychiatric Association, 2004, Friedman, 2006). In EMDR, patients are instructed to imagine painful traumatic memories and associated negative cognitions such as guilt and shame while visually focusing on the rapid movement of the clinician's finger (Friedman, 2006). However dismantling studies have demonstrated that the "eye movement" component is not necessary for the treatment response and that the theoretical bases for its method of action has yet to be determined (Davidson and Parker, 2001). Regardless of the treatment modality, stabilization is critical as the potential danger of initiating "traumafocused psychotherapy" prior to stabilization may exacerbate pre-existing co-morbid symptoms of depression and substance abuse.

Group based psychotherapy is also commonly used, focusing on psychoeducation, anger, depression, substance use, social and vocational skills, relaxation training as well as other facets of PTSD (American Psychiatric Association, 2004, Foy et al., 2000).

#### **2.2.2 Pharmacological management**

As demonstrated in Table 1, a number of medications have been used to treat PTSD. Selective Serotonin Reuptake Inhibitors (SSRIs) have the most empirical evidence for efficacy in the treatment of all three PTSD symptom clusters and are usually considered as a first-line treatment for PTSD (American Psychiatric Association, 2004, National Institute for Clinical Excellence, 2005, Schoenfeld et al., 2004b). SSRIs are also effective agents for the treatment of co-morbid mood and anxiety disorders commonly associated with PTSD. Both paroxetine and sertraline have received FDA approval for the treatment of PTSD in the United States (American Psychiatric Association, 2004). In Canada, only paroxetine has Health Canada approval for the treatment of PTSD**.** 

Second-generation, dual acting antidepressants such as venlafaxine and mirtazepine, are widely used in treating major depression and other anxiety disorders but have less

Psychiatric Management of Military-Related PTSD: Focus on Psychopharmacology 59

empirical data demonstrating their efficacy for the specific treatment of PTSD (Hopwood et al., 2000, Smajkic et al., 2001, Davidson et al., 2003, Chung et al., 2004, Connor et al., 1999). They are often considered as a second-line treatment in patients who have failed to respond to a trial of an SSRI. However, since SSRIs have not demonstrated their efficacy in the treatment of Vietnam or combat-related PTSD thus far, (Schoenfeld et al., 2004b, Friedman et al., 2007) second generation antidepressants may be considered as first-line treatment. The tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) have some limited data to support their use in the treatment of combat-related PTSD; (Kosten et al., 1991, Davidson et al., 1990) however, they are not commonly used because of their side

Benzodiazepines are not recommended as monotherapy for the treatment of PTSD, (Friedman, 2006, Braun et al., 1990, Gelpin et al., 1996) but are sometimes used as adjuncts in treating anxiety or insomnia (American Psychiatric Association, 2004). There is a risk of rebound insomnia when a benzodiazepine, used as a hypnotic, is discontinued especially after long-term use (Cooper et al., 2005). The use of benzodiazepines among patients with

In the veteran population, response to treatment might be significantly affected by the severity and chronicity of PTSD (Friedman et al., 2000). Although there is no treatment algorithm for reference, patients who demonstrate a partial response (25-50% improvement) after 8 to 12 weeks of treatment with the first antidepressant trial, augmentation or combination strategies could be considered. Of note though, optimization of monotherapy is critical and close monitoring of potential side effects, especially in the early stages of combination pharmacotherapy, is essential when considering augmentation or combination strategies (Cooper et al., 2005). Common combination treatments include adding mirtazapine or bupropion to an SSRI or venlafaxine. Other augmenting agents for PTSD include atypical antipsychotics and anticonvulsants, although the patient should be fully

The utility of atypical antipsychotics such as risperidone, olanzapine and aripiprazole for the treatment of PTSD in combination with an antidepressant has been demonstrated in numerous studies, including randomized controlled trials (Richardson et al., 2011, Stein et al., 2002, Bartzokis et al., 2001, Hamner et al., 2003, Monnelly et al., 2003). However, a recent study with military-related PTSD did not find that risperidone significantly decreased PTSD symptoms when compared to placebo (Krystal et al., 2011). These agents have been particularly beneficial in managing hyperarousal symptoms such as hypervigilance and irritability as well as for severe dissociation symptoms (Schoenfeld et al., 2004b). There is no

established role for the use of conventional antipsychotics in the treatment of PTSD.

Anticonvulsants such as carbamazapine, valproate, topiramate, lamotrigine are increasingly used in combination with antidepressants to treat symptoms of depression, mood instability and impulsivity observed in PTSD (Lipper et al., 1986, Keck et al., 1992, Fesler, 1991, Berlant and Van Kammen, 2002, Hertzberg et al., 1999, Hamner et al., 2001). These agents are generally reserved as third line agents and used in combination with first or second line

Antiadrenergic agents such as propranolol and prazosin may have a role as a preventive strategy in the acute traumatic stress reaction (Friedman et al., 1993, Cooper et al., 2005,

military-related PTSD who have comorbid substance abuse should be avoided.

effect profile and toxicity.

**2.3 Combining treatment resistant PTSD** 

informed about potential benefits and side effects

agents, due to the paucity of evidence for their efficacy.


a Dosage recommandations repesent clinical consensus.

b Selective serotonin reuptake inhibitors

Table 1. Dosage and common side effects of drugs used to treat PTSD (adapted from Current Concepts in Pharmacotherapy for PTSD, Schoenfeld et al., 2004)

empirical data demonstrating their efficacy for the specific treatment of PTSD (Hopwood et al., 2000, Smajkic et al., 2001, Davidson et al., 2003, Chung et al., 2004, Connor et al., 1999). They are often considered as a second-line treatment in patients who have failed to respond to a trial of an SSRI. However, since SSRIs have not demonstrated their efficacy in the treatment of Vietnam or combat-related PTSD thus far, (Schoenfeld et al., 2004b, Friedman et al., 2007) second generation antidepressants may be considered as first-line treatment. The tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) have some limited data to support their use in the treatment of combat-related PTSD; (Kosten et al., 1991, Davidson et al., 1990) however, they are not commonly used because of their side effect profile and toxicity.

Benzodiazepines are not recommended as monotherapy for the treatment of PTSD, (Friedman, 2006, Braun et al., 1990, Gelpin et al., 1996) but are sometimes used as adjuncts in treating anxiety or insomnia (American Psychiatric Association, 2004). There is a risk of rebound insomnia when a benzodiazepine, used as a hypnotic, is discontinued especially after long-term use (Cooper et al., 2005). The use of benzodiazepines among patients with military-related PTSD who have comorbid substance abuse should be avoided.

#### **2.3 Combining treatment resistant PTSD**

58 Post Traumatic Stress Disorders in a Global Context

**(mg/Day)a Common side effects** 

dysfunction Escitalopram 10-30 Nausea, fatigue, dry mouth, sexual dysfunction Fluvoxamine 100–250 Anxiety, Nausea, headache, sedation , insomnia,

sexual dysfunction

sweating, hypertension

anemia, agranulocytosis

dizziness, anorexia, sexual dysfunction, hypertension

rash, Stevens-Johnson syndrome syndrome (rare)

sedation, tremor, hepatic failure, teratogenic

Drowsiness, dizziness, weight gain, dry mouth, akathesia, parkinsonism events; risk of new-onset

fatigue, blurred vision, constipation.

Citalopram 20–60 Anxiety, fatigue, nausea, dry mouth, sexual

Fluoxetine 20–80 Nausea, insomnia, tremor, sexual dysfunction Paroxetine 20–60 Anxiety, Nausea, drowsiness, insomnia, sexual dysfunction Sertraline 50–200 Nausea, insomnia, loose stools, sexual dysfunction

Bupropion (SR or XL) 150–300 Agitation, tremor, dizziness, insomnia, excessive

Venlafaxine 75–375 Nausea, Nervousness, insomnia, somnolence,

Prazosin 2–10 Dizziness, headache, drowsiness, fatigue, risk of syncope

Carbamazepine 400–1,000 Dizziness, drowsiness, nausea; risk of aplastic

Lamotrigine 25–400 Dizziness, ataxia, drowsiness, headache; risk of skin

Valproate 250–2,000 Nausea, gastrointestinal problems, weight change,

Aripiprazole 5-10 Restlessness or need to move (akathisia), insomnia,

Quetiapine 50–300 Somnolence, dizziness, postural hypotension Risperidone 0.5–4 Extrapyramidal symptoms, agitation, anxiety,

Table 1. Dosage and common side effects of drugs used to treat PTSD (adapted from

Current Concepts in Pharmacotherapy for PTSD, Schoenfeld et al., 2004)

diabetes mellitus

insomnia, rhinitis

Gabapentin 300–3000 Drowsiness, dizziness, ataxia, fatigue

Topiramate 50–400 Drowsiness, dizziness, ataxia, confusion

Mirtazapine 15–45 Sedation, increased appetite, weight gain, dry mouth

**Class and drug Adult** 

**Antidepressant- SSRIsb**

**Dual acting antidepressant** 

**Adrenergic inhibitors** 

**Mood Stabilizers** 

**Antipsychotics** 

Olanzapine 5–10

b Selective serotonin reuptake inhibitors

a Dosage recommandations repesent clinical consensus.

In the veteran population, response to treatment might be significantly affected by the severity and chronicity of PTSD (Friedman et al., 2000). Although there is no treatment algorithm for reference, patients who demonstrate a partial response (25-50% improvement) after 8 to 12 weeks of treatment with the first antidepressant trial, augmentation or combination strategies could be considered. Of note though, optimization of monotherapy is critical and close monitoring of potential side effects, especially in the early stages of combination pharmacotherapy, is essential when considering augmentation or combination strategies (Cooper et al., 2005). Common combination treatments include adding mirtazapine or bupropion to an SSRI or venlafaxine. Other augmenting agents for PTSD include atypical antipsychotics and anticonvulsants, although the patient should be fully informed about potential benefits and side effects

The utility of atypical antipsychotics such as risperidone, olanzapine and aripiprazole for the treatment of PTSD in combination with an antidepressant has been demonstrated in numerous studies, including randomized controlled trials (Richardson et al., 2011, Stein et al., 2002, Bartzokis et al., 2001, Hamner et al., 2003, Monnelly et al., 2003). However, a recent study with military-related PTSD did not find that risperidone significantly decreased PTSD symptoms when compared to placebo (Krystal et al., 2011). These agents have been particularly beneficial in managing hyperarousal symptoms such as hypervigilance and irritability as well as for severe dissociation symptoms (Schoenfeld et al., 2004b). There is no established role for the use of conventional antipsychotics in the treatment of PTSD.

Anticonvulsants such as carbamazapine, valproate, topiramate, lamotrigine are increasingly used in combination with antidepressants to treat symptoms of depression, mood instability and impulsivity observed in PTSD (Lipper et al., 1986, Keck et al., 1992, Fesler, 1991, Berlant and Van Kammen, 2002, Hertzberg et al., 1999, Hamner et al., 2001). These agents are generally reserved as third line agents and used in combination with first or second line agents, due to the paucity of evidence for their efficacy.

Antiadrenergic agents such as propranolol and prazosin may have a role as a preventive strategy in the acute traumatic stress reaction (Friedman et al., 1993, Cooper et al., 2005,

Psychiatric Management of Military-Related PTSD: Focus on Psychopharmacology 61

associated with antidepressant medication, particularly at the time of initiation of treatment, should be discussed and reviewed with the patient (National Institute for Clinical

Patients may wish to discontinue their medication once they start to feel better or can no longer tolerate side effects such as weight gain or sexual dysfunction. However, studies have demonstrated the benefits of continuing medication at least up to one year (Richardson et al., 2011). There are no published guidelines on the length of time that patients suffering from anxiety disorders should continue taking their medication; however, existing guidelines for major depression suggest that the medication should be continued for at least six months after

Since veterans with PTSD often present with marked anxiety, they may be very sensitive to the potential heightened anxiety sometimes seen early in treatment with antidepressants. Patients benefit from a "start low, go slow" approach to medication titration, such as starting at ¼ to ½ the usual starting dose and then gradually increasing to a therapeutic level (Cooper et al., 2005, American Psychiatric Association, 1998). While the initiation of medication might be slow and cautious, ultimately the dose should be titrated to full

The presentation of military-related PTSD is often complex. The primary care clinician should consider early referral for specialist military psychological and psychiatric care. Understanding military culture and the nature of military deployments helps the clinician appreciate the challenges veterans' face, which is essential to establishing a trusting therapeutic alliance. Treatment often involves a combination of medications making compliance more challenging. Although remission is not always possible, pharmacological interventions assist with symptom reduction and improve functioning and quality of life. Pharmacological interventions also assist with stabilization and facilitate psychotherapeutic

The treatment of veterans with PTSD often involves a multidisciplinary team of health professionals and it is important that the physician maintain a close interagency liaison with

Preparation of this article was supported by a Canadian Institutes of Health Research New Investigator award (#152348), and the Manitoba Health Research Council Chair award to (Dr. Sareen). The views expressed in this manuscript are those of the authors and do not

Alderman, C. P., McCarthy, L. C. & Marwood, A. C. 2009. Pharmacotherapy for Posttraumatic Stress Disorder. *Expert Review of Clinical Pharmacology,* 2**,** 77-86.

symptom remission has been reached (Canadian Psychiatric Association, 2001).

Excellence, 2005).

**4. Conclusion** 

a view to 'shared care'.

**5. Acknowledgment** 

**6. References** 

**3.2 Dosing considerations** 

symptom remission at maximum tolerated doses.

interventions such as trauma-focused psychotherapy.

necessarily represent the views of the Veterans Affairs Canada.

Vaiva et al., 2003) or in combination with antidepressants to treat excessive hyperarousal or hyperactive symptoms (Friedman, 2006).

For significant symptoms of insomnia that persist with the use of therapeutic doses of antidepressants, a trial of low-dose mirtazepine (15 mg) or trazodone (50- 100 mg) may be helpful. Alternative non-benzodiazepine hypnotics include zopiclone and zaleplon. Zaleplon may be helpful for patients presenting with middle insomnia resulting from nightmares. Its rapid onset of action and very short half-life (approximately one hour) permits patients to take it in the middle of the night (Samuels, 2005). There is evidence demonstrating the benefits of using prazosin, an adrenergic inhibitors to reduce nightmares in combat veterans (Raskind et al., 2002, Raskind et al., 2003; Miller, 2008; Peterson et al., 2011).

## **2.3.1 Combining psychotherapy and pharmacotherapy**

In clinical practice, despite limited empirical evidence, most veterans with PTSD receive psychotherapy in combination with pharmacotherapy either concurrently (at the same time) or sequentially (one modality after another) (Alderman et al., 2009). There is limited research using combination treatment for PTSD (Canadian Psychiatric Association, 2006, Marshall and Cloitre, 2000). A recent Cochrane systematic review of four clinical trials using SSRI with PE/CBT concluded that not enough evidence is available to support or refute the effectiveness of combined psychological & pharmacotherapy" (Hetrick et al., 2010). Many patients receive psychotherapy and pharmacotherapy either at the same time or one after another. Even though this is generally considered standard clinical practice in our specialty clinics, there is very limited research demonstrating the benefit of combination treatment. A recent Cochrane review published this year, found only four published trials of combination treatment and concluded that there was not sufficient evidence at this time to either support or refute the effectiveness of combined psychological and pharmacotherapy (Hetrick et al., 2010). One study demonstrated the benefits of psychotherapy augmentation in patients who have had a partial response to pharmacotherapy (Rothbaum et al., 2006).

#### **3. Special treatment consideration**

#### **3.1 Treatment adherence**

Medication compliance is crucial for treatment to be effective. Medication non-compliance may be related to the psychological meaning of taking medication (Fenton and McGlashan, 2000). Veterans may believe that taking medication means they are weak or defective, or they fear that they will become addicted to the medication, (National Institute for Clinical Excellence, 2005) that it will change their personality or lead to job loss. These false beliefs or fears about medications should be explored and confronted prior to starting medication. Providing a safe environment and a positive doctor-patient interaction will help develop trust and may make the veteran more accepting of treatment, improving medication compliance (Weiden and Rao, 2005, Kluft, 2002). Engaging and educating all care providers is essential so the veteran feels safe and comfortable with treatment. Peer social support programs, such as Operational Stress Injury Social Support Program (OSISS) in Canada, may play a valuable role in encouraging medication and treatment compliance. Family involvement may also assist treatment adherence, although this requires further study (Phillips et al., 2001). Education about the potential risk of increased suicidal thoughts associated with antidepressant medication, particularly at the time of initiation of treatment, should be discussed and reviewed with the patient (National Institute for Clinical Excellence, 2005).

Patients may wish to discontinue their medication once they start to feel better or can no longer tolerate side effects such as weight gain or sexual dysfunction. However, studies have demonstrated the benefits of continuing medication at least up to one year (Richardson et al., 2011). There are no published guidelines on the length of time that patients suffering from anxiety disorders should continue taking their medication; however, existing guidelines for major depression suggest that the medication should be continued for at least six months after symptom remission has been reached (Canadian Psychiatric Association, 2001).
