07 Innovative Treatments for Posttraumatic Stress Disorder

Innovative Technology for PTSD therapy
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Computerized cognitive behavioural therapy is being widely used to treat PTSD[6]

Common therapeutic methods for posttraumatic stress disorder (PTSD) include psychotherapy, cognitive behavioural therapy (CBT) and drug therapy. Treatments for PTSD aim to decrease stress and hyperarousal when recalling highly traumatic events[1]. Several therapies reduce positive and negative symptoms by altering pathways involved in memory reconsolidation [2]or by interfering with the hypothalamus-pituitary-adrenal axis[3]. Detection and intervention techniques usually involve monitoring and stabilizing cortisol levels to control stress responses in patients [3]. Many treatments have shown varied results among patients with different subtypes of PTSD. As a result, current research studies are finding new therapies that cater to specific types of PTSD patients. For instance, Virtual Reality Therapy is being specifically used for treating combat-related PTSD [4]. Recent studies have shown effective new drug therapies such as propranolol [2] and more recently stellate ganglion block (SGB)[5].

Even though PTSD was only added to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) thirty years ago, the disease had been documented in literature many years before[1][7]. For instance, Henry IV in Shakespeare's historical play of the same name, displayed several symptoms of someone experiencing PTSD[7]. More recently, numerous films in popular culture feature main characters with PTSD. In particular, Rambo the famous protagonist played by Sylvester Stallone in the First Blood film series suffers from PTSD[7]. In the 2009 movie, Brothers, actor Tobey Maguire portrays a young soldier who was a prisoner of war while in Afghanistan[8]. The character displays avoidance, withdrawal and paranoia which are all indicators of the disease. Over the years, cognitive behavioural therapy (CBT) accompanied with drug therapy have been the accepted as the first line intervention for the disease[1]. This neurowiki will highlight the latest, newest and best therapies available for PTSD.

PTSD in the movie Brothers (2009)
Sam Cahill (Tobey Maguire) was a prisoner of war during deployment in Afghanistan and returns home displaying
symptoms of PTSD[8].
Warning: Video contains course language

1. Screening Tests for Early Detection & Prevention

Figure 1: Salivary Cortisol Levels in PTSD
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PTSD patients have higher cortisol levels in samples in
comparison to healthy controls[11]

Recent preventive treatments are unable to be done pre-exposure to trauma or shortly after individuals experience trauma[1]. During a traumatic event, stress hormones such as cortisol are released[9]. Increased levels of cortisol and norepinephrine interfere with the construction of memories [9]. On the other hand, some studies have implicated that stress hormones actually strengthen and promote more consolidation of memories [10].

1.1 a) Cortisol levels

A couple of days after experiencing a mildly traumatic event, plasma cortisol levels taken within this period can predict the development of PTSD[10]. Specifically, low cortisol levels predicted subsequent PTSD if cortisol was measured in saliva. These levels have to be measured during the morning, immediately or within a few days following the traumatic event [10]. However, Stoppelbein and colleagues (2011) found that female PTSD patients had higher cortisol levels than women without the disorder after viewing traumatic stimuli[9]. In addition, hair samples measuring cortisol levels have been proven to be effective biomarkers for PTSD[10]. Several months following a stressful event, cortisol levels in hair are higher among PTSD patients[10]. The larger release of stress hormones is an indicator that the individuals are in distressful states[10].

1.1 b) Biomarkers: Glucocorticoid receptors

Glucocorticoid receptors are observed in vitro in the peripheral mononuclear blood cells(PBMCs)[12]. Studies have shown that PTSD patients have monocytes with increased glucocorticoid sensitivity in comparison to controls[12]. The process involves administering dexamethasone, a synthetic glucocorticoid, and observing the resulting inhibition that occurs on PBMCs[12]. Either inhibitory processes acting on T-cells are defective or pro-inflammatory cytokines are enhanced when dexamethasone is used[12]. Currently, there are no techniques that are able to show glucocorticoid receptors and other related factors in vivo in the brain[12].

2. Intervention Treatments

Figure 2: Typical PTSD Treatment Guidelines
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Different lines of treatment for PTSD. More recently, exposure therapies have been used as first line treatment as opposed to certain drug therapies such as SSRIs[15]

2.1 Psychotherapy

There is a wide selection of different forms of psychotherapy that are useful for overcoming PTSD. Above all, the patient is the focus of any interview process[16]. Many of these strategies concentrate specifically on the cause of trauma[16]. For instance, trauma- focused exploration is a prominent component in various psychotherapeutic methods[16]. This type of therapy is intended to enhance the person’s self-esteem when encountering aversive memories[16]. Several studies have shown the influence of psychotherapy in balancing hormonal levels in patients[17]. For instance, in successful cases, an increase in the levels of cortisol was observed[17]. In addition, the individuals with ineffective treatment showed a decline in cortisol levels[17]. The manner in which therapists use these strategies and which mechanisms are affected will be discussed in the following sections. One of the most innovative therapies available for PTSD patients is Virtual Reality Therapy.

2.1a) Virtual Reality Therapy

Figure 3: Virtual Reality Therapy
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Virtual Reality Therapy is a new way to successfully treat combat-related

Virtual Reality Therapy (VRT) is currently being used as treatment for various psychological disorders. Ranging from anxiety disorders to stroke rehabilitation, VRT is being utilized to eliminate debilitating symptoms associated with each of these situations[18]. Virtual Reality therapy consists of viewing a computerized combat or war scene on a visor screen[4]. The computerized scenes closely resemble a real combat environment experienced by soldiers during deployment[4]. Common among soldiers and military personnel arriving from overseas missions, combat-related PTSD is efficiently treated with this computerized therapy[4]. After making a script of their traumatic memories, veterans undergo around six sessions of VRT[4]. In contrast to other therapeutic methods, VRT has been shown to be extremely efficient in reducing negative symptoms such as avoidance and guilt[4]. Since drug strategies and other therapies mainly treat positive symptoms and are inefficient in decreasing the negative symptoms, VRT is revolutionary for PTSD treatment[4]. As a result, the patients are able to converse with the therapist while actively re-experiencing their memories. Due to this study, computerized intervention strategies have become increasingly common for treating PTSD.

2.1b) Eye Movement Desensitization & Reprocessing (EMDR)

This form of treatment is a hybrid of many different types of interventions such as imaginal exposure as well as free association[16]. The EMDR session commences with the patient remembering their traumatic memories while simultaneously looking at external visual or auditory cues[21]. The therapist can move their finger across the individual’s visual field[21]. The patients’ eyes move in the direction of the cue[21]. However, several studies have suggested that the eye movements or sensory stimulation is not essential to the effectiveness of the therapy[21]. Further research is necessary to discover the influence and importance of the bilateral stimulation in eliminating symptoms.

2.1c) Samples of EMDR & VRT Sessions

The Virtual Iraq commonly used for US military members
Virtual Iraq, allows soldiers to re-experience and cope with their traumatic memories.The scenes, sounds, and
even odours transmitted through the different gadgets
closely resemble those experienced in Iraq. [20]

A sample session of EMDR
Light cues and sound cues are used in EMDR therapy The following is a video sample of EMDR,
including visual and auditory cues. Instructions are narrated, indicating to the viewer to attend to
the moving light.[22]

2.2 Cognitive Behavioural Therapy (CBT) & Behavioural Therapy

Perhaps the most widely practiced approach for treating PTSD is CBT[23]. Patients identify the sources of their trauma and cope with them thereby eliminating negative emotional reactions associated with the memories[23]. Therapists ask challenging questions about the source of the stress-inducing memory[23]. CBT has been shown to be successful a wide variety of PTSD subtypes of different age groups [23]. In general, around 8-12 sessions are done with the patients prolonging about 60 to 90 minutes each[23].

Figure 4: CBT Homework Assignment for PTSD
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An example of a stress log, a typical homework assignment
given in CBT therapies for stress-related illnesses such as PTSD [23].

Patients usually meet with their therapists for sessions once or twice per week[23]. The session begins with the individual closing their eyes and recalling the trauma as if the event is presently occurring[1]. The patients retell all of their emotions and physical senses while the event happened[1]. They are also given homework assignments to complete usually watching video footage of previous sessions[23]. Studies have observed symptom reduction after about two weeks of intervention therapy[24]. There are various types of CBT such as exposure therapy. There are other therapies such as eye movement desensitization and reprocessing (EMDR) that borrow similar components[24].
CBT has been linked as a source for modifying brain wave patterns in PTSD[24]. A study by Rabe and colleagues (2007) found that, after performing CBT on PTSD patients, there was less activity in the right frontal lobe than prior to therapy[24]. This indicates that the anxious feelings shown by those with PTSD is due to the right dorsolateral prefrontal cortex being overactivated[24]. Vigilance and processes associated with the retrieval of memories is associated with the right DLPFC[24]. Therefore, CBT is actively restructuring various paths within the brain that are usually dysfunctional.

2.2 a) Exposure Therapy

One of the most commonly practised interventions for the disorder is, without question, exposure therapy.Exposure therapy aims to reduce avoidance[21]. In comparison to other treatments, exposure therapy is most efficient in eliminating avoidance as well as re-experiencing[21]. According to Taylor and colleagues (2011), after receiving treatment, the highest amount of people that no longer had PTSD were those who received exposure therapy[21]. In exposure therapy, therapists identify the people, situations, locations, or objects that elicit symptoms of avoidance and anxiety[21]. The sessions involve exposing the patients to real-life scenarios and objects that elicit the anxiety characteristic of PTSD[21].
Exposing the patients to the source of their trauma in a gradual manner decreases the anxiety and avoidance of situations or objects that are usually feared when encountered
[21]. The encounters become increasingly challenging for the patient and sessions continue until the symptoms are no longer existent[21]. Conversely, past studies have reported that around one third of patients had worsened symptoms following exposure therapy[21]. In addition, the therapy is particularly ineffective for eliminating symptoms of numbing[21].

2.2b) Prolonged Exposure Therapy

Also known as flooding,prolonged exposure therapy features imaginal exposure and in-vivo exposure just as regular exposure therapy does[25]. Edna B. Foa created this strategy which is effective for a wide spectrum of PTSD patients[25]. In particular, the therapy is known to be extremely efficient for individuals who also suffer from substance abuse in combination with PTSD[25]. The treatment may be working on pathways of fear extinction where people can recall their emotion-filled memories without having to experience the associated fear[25]. However, the only shortfall of this therapy is that the counteraction that occurs when PTSD is co-morbid with other disorders like Borderline Personality Disorder[25]. A comparative study done by Taylor and colleagues (2003), showed that declines in avoidance and re-experiencing symptoms are the largest when exposure therapy is done [21]. This research compared exposure therapy to EMDR and relaxation therapy[21].

3. Drug Therapy

3.1 a) Beta Blockers: Propranolol

(i) For Prevention of PTSD Symptoms

Evidently, dysfunctional memory formation and retrieval is crucial to the manifestation of symptoms of PTSD[1]. The drug propranolol targets emotional memory pathways especially those involved in consolidation that may be causing the re-experiencing expressed by patients[2]. Propranolol is a noradrenergic (beta) blocker which can be used as a preventive and/or intervention approach for PTSD[2]. When administered before recalling an emotional memory, the subsequent memory is impaired whereas neutral memories remained intact[2]. Specifically, symptoms of hyperarousal are reduced[26]. The medication may be inhibiting the effects of norepinephrine on the amygdala which subsequently affects the formation or recall of emotionally traumatic events[26]. In a study by Nugent and colleagues (2010), propranolol was administered to children which resulted in lessened PTSD symptoms specifically in males[26]. When the children’s PTSD screening tests indicated an advanced risk for PTSD, an oral dose of propranolol was given to them[26]. Propranolol was administered for ten days[26]. Two weeks following the propranolol administration, the children were exposed to trauma by listening to a narrative and then assessed for PTSD risk once again[26]. Results revealed a decrease in PTSD risk symptoms especially in boys after taking propranolol[26]. Therefore, these findings indicate the possibility of propranolol being increasingly effective in only males as a preventative therapy[26]. Further studies may provide insight as to the inconsistency between genders to react to this specific drug.

(ii) For treatment

Studies done by Canadian research groups at McGill University and in Saskatchewan have greatly contributed to how propranolol works as an intervention plan for PTSD[27]. In an experiment by Burnet and colleagues (2008), propranolol was given to individuals who suffered from chronic PTSD[27]. Subjects were asked to write a trauma script documenting all the details from their traumatic memories [27]. After one week, there were significant changes in the patients’ physiological responses to their written trauma narrative[27]. Patients experiencing less arousal when retelling or re-listening to their stories[27]. Additional studies indicate that a 40 mg dosage shortly after memory recall with another 60 mg dose about two hours later is sufficient for lessening symptoms[27].

3.2 Selective Serotonin Reuptake Inhibitors (SSRIs)

Among the plethora of SSRIs, Sertraline (Zoloft) and paroxetine (Paxil) are the preferred medications for PTSD[28]. During recent clinical trials, paroxetine was shown to have a high dropout rate among subjects with PTSD[28]. Another SSRI, fluoxetine, had a lower dropout percentage in comparison to paroxetine[28]. This reveals that paroxetine’s side effects are causing subjects to discontinue treatment. Paroxetine is known to cause agitation in addition to sexual dysfunction[28]. Also, it is suggested that fewer people take fluoxetine for PTSD which may offset some percentages when performing comparative studies between different kinds of SSRIs[28].

3.3 Tricyclic Antidepressants

Figure 5
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Differences between Drug Therapies of PTSD in Overly Stressed Mice [29]

When choosing a tricyclic antidepressant for a PTSD patient, amitriptyline is frequently prescribed[29]. Amitriplytine has been shown to relieve intrusive re-experiencing as well as numbing symptoms in PTSD[29]. However, there are current studies revealing the ineffectiveness of amitripyline in comparison to other drug therapies in decreasing stress-related symptoms[29]. A recent study tested three pharmacological drugs tianeptine, amitriptyline, and clonidine on stressed rodents[29]. The rats were exposed to cats which elicited fear and stress responses[29].

After this initial traumatic experience, the rats were given injections of one of the drugs[29]. Then three weeks later, several behavioural tests were administrated including an elevated plus maze[29]. The rats injected with clonidine and amitriptyline showed little or no decrease in stress response[29]. In addition, the rodents in the control condition (non-stressed rats) showed undesirable side effects after being given clonidine or amitriptyline[29]. Only the selective serotonin reuptake enhancer (SSRE), tianeptine was able to thoroughly block stress responses in rats during the elevated arm maze[29].
As shown in Figure 5, tianeptine was the only drug medication that allowed for mice to be less frightened of running around in the open arms of the maze[29]. The previous fears of being preyed on, were as a result extinguished[29]. Thus, tianeptine may be a great candidate for PTSD treatment and further trials should explore the mechanisms by which this medication utilizes[29].

3.4 Side Effects

Figure 6
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Side Effects of Drug Treatment for PTSD. Among these, high dosage administration of SSRIs can result in too much nervousness, which may be counteractive to the goal of decreasing the hyperarousal symptoms. Also, as seen above, propranolol also has some effects like bradycardia [30]

4 Current Clinical Trials

4.1a) 3,4-methylenedioxy-methylamphetamine (MDMA)

Controversial use of MDMA as Treatment for PTSD
CNN broadcasts a story about a woman who is a victim of PTSD. She explains that no other accepted PTSD therapies have worked to treat her trauma. The woman now takes MDMA and describes her experience as extremely helpful for getting better[32].

Recent studies have found that MDMA when used together with psychotherapy is an extremely effective method for treating chronic PTSD[31]. MDMA had been previously used in a similar manner for other disorders[31]. Johanssen and Krebs found that oxytocin, norepinephrine, and cortisol is augmented when MDMA is given[31]. The rise in oxytocin levels allows for the patients to trust their therapist during sessions[31]. In addition, inhibition of the fear response and more control over emotions are observed[31]. This means that MDMA is interfering with the amygdala and ventromedial prefrontal cortex (VMPFC)[31]. Usually, cortisol and norepinephrine levels have effects on the emotional learning[31]. In PTSD therapy, especially in extinction learning, increasing these hormones allow for the treatment to work[31]. However, too much release can trigger more anxiety and instigate a larger stress response[31]. Therefore, administering the correct dosage is crucial to the efficacy of MDMA as well as the safety of the patients.

4.1b) Stellate Ganglion Block (SGB)

Stellate ganglion block (SGB) has been utilized as therapy for pain[5]. An injection of anesthetic is given to block sympathethic ganglions. In particular, the treatment is introduced to the cervical and thoracic regions of the spinal cord[5]. A study analyzing the effectiveness of SGB was done on military personnel with PTSD[5]. The results of this study showed over half of the subjects had declines in their PTSD symptoms in a month or so[5]. Accordingly, this treatment is very efficient by rapidly diminishing symptoms [5]. Further research can emphasize how promising this method may be.

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