Despite the lack of guidance available for practitioners, extensive polypharmacy has become the primary method of treating patients with severe and chronic mood, anxiety, psychotic or behavioral disorders. This ground-breaking new book provides an overview of psychopharmacology knowledge and decision-making strategies, integrating findings from evidence-based trials with real-world clinical presentations. It adopts the approach and mind-set of a clinical investigator and reveals how prescribers can practice 'bespoke psychopharmacology', tailoring care to the individualized needs of patients.
Trauma and Post-traumatic Stress Disorder
That which does not kill us makes us stronger.
▢ Recognize the impact of trauma, particularly during early development, as a moderator of poor outcome across many psychiatric disorders
▢ Describe the importance of resilience and its enhancement as a treatment goal across psychiatric disorders
▢ Recognize the varied symptom targets of treatment in PTSD
▢ Describe the strengths and limitations of existing evidence-based pharmacotherapies for acute stress disorders
▢ Identify controversies regarding the use of benzodiazepines in patients with PTSD
▢ Discuss the evidence base for antidepressants, anticonvulsants, antipsychotics, α agonists, ketamine, and novel/emerging pharmacotherapies for PTSD
Trauma and dissociation are together often thought of as falling more within the treatment realm of cognitive-behavioral psychotherapy than psychopharmacology. Indeed, in the case of PTSD, trauma-focused psychotherapies collectively exert larger effect sizes than seen with pharmacotherapies (Watts et al., 2013; Lee et al., 2016), which in the aggregate yield response rates only of about 20–30%. Yet, in order to understand the potential relevance of pharmacotherapy to psychological trauma, one must first appreciate the interplay between trauma’s psychological and neurobiological corollaries. Traumatic events form durable, emotionally based memories consolidated through limbic circuitry – in turn affecting emotional regulation and broad cognitive domains (attentional processing and vigilance, executive function, and impulse control). Environmental cues that become associated with threats to one’s physical and/or emotional well-being become aversive and can elicit fear responses, involving autonomic hyperarousal and vigilance, and can prompt intrusive, repetitive thought patterns laced with negative affect states. PTSD itself is viewed by some as fundamentally a behavioral disorder involving abnormal fear extinction. Furthermore, trauma and abuse occurring in childhood may influence neuronal development, perhaps thereby imposing one of the more devastating moderators of treatment outcome across a range of psychiatric disorders.
Whether or not formal diagnoses of PTSD ensue after traumatic exposures, survivors of significant trauma in both childhood and adulthood can incur brain volumetric (e.g., hippocampal) changes (Woon et al., 2010); some studies suggest that small hippocampal volume may result from, rather than predispose to, the development of PTSD in adult trauma victims (Winter and Irle, 2004). Trauma challenges resilience (see Box 19.1) yet at the same time can shape and strengthen it. Developmentally, it disrupts the formation of normal attachment styles and patterns, and at any stage in life can impart punitive expectations in response to life stresses through operant conditioning, and the fostering of learned helplessness.
The term “resilience” is often used to describe an intact capacity for effective coping in response to stress. Resilience also implies an ability to withstand adversity without developing consequent psychopathology. It likely contributes to overall risk for developing depression, anxiety, and PTSD (among other conditions), as well as being a moderator of treatment outcomes. Charney (2004) links resilience with intact reward and motivation, fear responsiveness, and adaptive social behaviors (such as altruism and social bonding); it is also thought to involve a cognitive style characterized by accurate (rather than excessively positive or negative) threat appraisal (Southwick et al., 2015).
From the above, one could envision an array of potential pharmacotherapy targets.
It is not difficult to envision trauma and abnormal or exaggerated stress responses as widely impacting the trajectory of psychopathology across virtually all domains of emotional, perceptual, cognitive, and behavioral functioning. Our approach in this chapter will therefore be no less dimensional than in previous chapters. Beyond the DSM-5/ICD-10 categories of PTSD (for which only two medications carry FDA indications (sertraline and paroxetine and acute stress disorders (where no drugs carry regulatory agency approval), we will consider the rationales and evidence base for varied drug classes and putative mechanisms, focusing as always on having clearly defined goals of treatment.
Stress involves any environmental stimulus that demands a response from the individual. In some conceptualizations, stresses may be beneficial or fortuitous (so-called “eustress,” e.g., job promotions, marriages, having a child) or detrimental (“distress,” encompassing reversals of fortune, illness, unreasonable work or social demands, loss of social supports). Stresses can become traumatic when they overwhelm someone’s ability to cope and threaten one’s basic sense of physical and emotional safety and well-being. Abuse is a type of trauma that involves deliberate and purposefully inflicted harm that violates someone’s personal boundaries, jeopardizing one’s physical or emotional safety and well-being. It may be overtly physical, emotional, verbal, or sexual, and may involve acts of commission or omission (e.g., assault versus physical or emotional neglect).
It can be useful to ask patients to compare themselves to themselves at their prior personal best. Do they think the magnitude of their anxiety or distress in response to a given stress is commensurate with the situation, and on par with their usual reaction in relative rather than absolute terms?
It becomes difficult and subjective to quantify the magnitude of psychological distress resulting from any stressor – particularly since people can easily differ in how they experience or interpret the same objective stressor. Nevertheless, Holmes and Rahe (1967) devised a 43-item measure of stressful life events (referred to in the literature as the Holmes–Rahe Scale, or the Social Readjustment Rating Scale; see Box 19.2) that has become widely adopted in studies attempting to quantify stress and trauma. Particular life stresses are accorded a numerical score (identified as “life-changing units”); in their original studies, total scores above 300 were associated with the highest probability of developing a significant medical illness, while scores <150 carried the least risk, and those 150–299 held moderate risk. Critics have noted that the scale does not differentiate events that involve eustress versus distress, are sudden versus planned, or acute from chronic.
|Life event||Mean value|
|Death of spouse b||100|
|Death of close family member||63|
|Personal injury or loss||53|
|Fired from work||47|
a Adapted from Holmes and Rahe, 1967
b Some authors have modified the original Holmes–Rahe scale also to include death of a child, alongside death of spouse, as the most devastating of stressful life events
An example of emotional trauma related to persistent depression is presented in Clinical Vignette 19.1.
Manny was a 19-year-old undergraduate with significant social anxiety, risk aversion, and avoidant behavior. He took an academic medical leave of absence after failing two classes during a major depressive episode. Within three months of starting duloxetine his mood and vegetative symptoms improved, but he had persistent low motivation and minimal structured daily activity. Low motivation was construed as a residual depressive symptom but did not improve with optimized dosing, adjunctive bupropion, stimulants, or aripiprazole. In psychotherapy he described his “low motivation” as a paralysis driven by fears of being “criticized and ridiculed” and feeling mortified about past failures. Rather than pursue “amotivation and apathy” as signs of anhedonia, his therapist suggested that he felt paralyzed by fear and a sense of trauma over the consequences of his depression and pre-existing social anxiety. She advised augmenting his pharmacotherapy with a structured psychotherapy approach that challenged his phobic avoidance and distorted beliefs about himself, and his expectations of repeated failure, as emotional consequences from the trauma associated with his depression.