Anxiety Disorders II: Posttraumatic Stress Disorder and Obsessive-Compulsive Disorder
The short-term goal in posttraumatic stress disorder (PTSD) is reduction in core symptoms, while the long-term goal is remission.
Cognitive behavioral therapy and eye movement desensitization and reprocessing are the most effective nonpharmacologic methods to reduce symptoms of PTSD.
The selective serotonin reuptake inhibitors (SSRIs) and venlafaxine are considered first-line treatments for PTSD.
An adequate trial of SSRIs in PTSD requires appropriate dosing and duration of treatment.
Patients with PTSD who respond to pharmacotherapy should continue treatment for at least 12 months.
SSRIs are the drugs of choice for the treatment of obsessive-compulsive disorder (OCD).
Augmentation of SSRI treatment with low doses of antipsychotics may be helpful.
If an inadequate response to an SSRI for OCD occurs after 4 to 6 weeks at the maximum dose, switch to another SSRI.
Medication taper can be considered after 1 to 2 years of treatment in patients with OCD.
Traumatic world or local events (e.g., wars, terrorist attacks, natural disasters, kidnappings, interpersonal violence) can lead to development of posttraumatic stress disorder (PTSD). Initially diagnosed in veterans of war, PTSD is now acknowledged as a significant psychiatric illness in the civilian population and more recently among deployed service personnel of the Afghanistan and Iraq campaigns in whom the suicide rate has escalated.1–3 PTSD continues to be poorly recognized and diagnosed in clinical practice.4 Because of its co-occurrence with other anxiety disorders, depression, substance abuse, and traumatic brain injury, the overlapping symptoms can lead to diagnostic uncertainty. Advances in the science and treatment of PTSD can assist clinicians in all fields of healthcare to screen patients for a history of trauma and effectively manage PTSD if it is present.
Intrusive obsessive thoughts and compulsive ritualistic behaviors characterize obsessive-compulsive disorder (OCD). OCD can be severely debilitating and impair functioning in social, family, and work settings, with an overall decrease in quality of life (QOL). OCD is associated with an increased risk of suicide, with 15% of patients reporting a previous history of suicide attempt.5 Increased understanding of symptom dimensions and treatment response can improve QOL in patients suffering from OCD.
PTSD is associated with the incidence of trauma. It is estimated that approximately 60% of men and 50% of women are exposed to a life-threatening traumatic event.6 Of these individuals 8.2% of men and 20% of women will develop PTSD. Previous exposure to a trauma and the intensity of response to the event increase the risk of PTSD. Men tend to be assaulted more frequently, but women have a higher rate of PTSD after assaults being more likely to experience rape and sexual abuse.6 Genetic factors can increase vulnerability to PTSD if an individual is exposed to a traumatic event. Offspring of Holocaust survivors had a higher lifetime prevalence rate of PTSD compared with a control group.6
The epidemiology of OCD is influenced by age and gender. OCD typically begins early in life, with 20% of cases occurring in childhood, 29% in adolescence, and 49% of cases occurring by age 20.1 Age of onset has a bimodal distribution with peaks around 10 and 21 years.7 The onset of illness is earlier in men than in women.8 Higher rates of other anxiety disorders are reported in first-degree relatives of patients with OCD.9 Early age of onset has been associated with higher probabilities of comorbid impulse control, somatoform, eating, and tic disorders.10 Heredity is stronger when there is an early age of onset or comorbidity with tic disorder.11
The exact etiologies of PTSD and OCD are not known. It is likely that abnormalities in several areas of brain functioning interact to cause these chronic anxiety disorders. Genetics may play a role in expression of PTSD and OCD, but environmental factors likely are also involved. A genome-wide association study did not detect any single nucleotide polymorphisms (SNPs) associated with OCD but there was a significant enrichment of methylation quantitative trait loci (mQTLs) and frontal lobe expression of quantitative trait loci (eQTLs) in the highest ranked autosomal SNPs, suggesting that these signals may influence gene expression and perhaps the etiology of OCD.11 Genetic etiologies of both PTSD and OCD are current research areas.
Controversy exists over the existence of a subtype of OCD characterized as a pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). A relationship between the sudden onset of OCD and chronic tic disorder with an age of onset between 3 years and puberty with possible exacerbations and remissions, and a temporal association with streptococcal infection associated with symptoms of OCD or neurologic abnormalities has been proposed.12 Although most patients with OCD do not have a streptococcal etiology, an accurate medical history regarding onset of illness is imperative because specific treatment strategies are indicated.
Research findings in the areas of neuroendocrinology, neurobiology, and neuroimaging have advanced a number of theories on the pathophysiology of anxiety disorders. Neuroendocrine changes in the hypothalamic–pituitary–adrenal (HPA) axis are implicated in the pathophysiology of PTSD.13 As reviewed in Chapter 53, data from neurochemical and neuroimaging studies indicate that the modulation of normal and pathologic anxiety states is associated with multiple regions of the brain (e.g., amygdala, hippocampus, thalamus, and prefrontal cortex).13,14 Abnormal function in several neurotransmitter systems, including norepinephrine (NE), γ-aminobutyric acid (GABA), glutamate, dopamine (DA), and serotonin (5-HT), may affect the manifestations of anxiety disorders.13,15
Neuroendocrine studies provide data that abnormalities occurring pretrauma, during trauma, and posttrauma contribute to PTSD. Normally the immediate reaction to stress occurs as an automatic response from the amygdala to the sympathetic and parasympathetic systems and the HPA axis.13 The release of corticotropin-releasing factor (CRF) stimulates cortisol secretion from the adrenal gland. Both catecholamines and cortisol levels rise in tandem. Cortisol reduces the stress response by tempering the sympathetic reaction through negative feedback on the pituitary and hypothalamus.13 These systems return to normal after a few hours.
Recent data implicate a role for the neuropeptides CRF and neuropeptide Y (NPY) in PTSD. Patients with PTSD have a hypersecretion of CRF but demonstrate subnormal levels of cortisol at the time of trauma and chronically.13 Lower plasma cortisol concentrations were associated with greater severity of PTSD symptoms in nonmilitary patients.15 Dysregulation of the HPA axis is postulated to be a risk factor for eventual development of PTSD.13 Higher plasma concentrations of NPY were found in combat-exposed men who did not develop PTSD and could play a role in resiliency.15
Several neurotransmitters may be involved in the pathophysiology of PTSD. 5-HT, NE, and glutamate are associated with the processing of emotional and somatic contents of memories in the amygdala. The cortex and hippocampus are involved in storing the facts and related cues of memory.15 The noradrenergic theory posits that the autonomic nervous system of anxious patients is hypersensitive and overreacts to stimuli. The alarm center, the locus ceruleus, releases NE to stimulate the sympathetic and parasympathetic nervous systems. Hyperactive noradrenergic signaling in patients with PTSD is a consistent research finding and includes increased 24-hour catecholamine excretion.15 Glutamate signaling abnormalities may result in distortion of amygdala-dependent emotional processing under stress.13,15 Dysregulation of the processing of sensory input and memories may contribute to the dissociative and hypervigilant symptoms in PTSD. Abnormalities of GABA inhibition may lead to increased awareness or response to stress, as seen in PTSD.15
Both 5-HT and DA are implicated in the pathogenesis of OCD. Selective and potent serotonergic reuptake inhibitors have consistently been shown effective for symptoms of the illness.16–19 A recent meta-analysis concluded that higher doses of selective serotonin reuptake inhibitors (SSRIs) were associated with improved efficacy in the treatment of OCD.19 A Cochrane systematic review of 17 studies found that SSRIs were more effective than placebo in treating symptoms of OCD, and that SSRIs were similar to each other in efficacy.18 DA dysregulation may contribute to some forms of OCD. Neurologic symptoms (e.g., tics) are part of the clinical presentation in some patients with OCD. Tourette’s disorder, a disorder of DA function, is often a concurrent disease.1 Augmentation with antipsychotic drugs may improve symptoms in patients with OCD who are partially responsive to SSRIs.20
Neuroimaging studies suggest that certain areas of the brain are altered by psychological trauma. In PTSD most functional neuroimaging studies have involved the amygdala, ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), and hippocampus. Findings of increased activation of the amygdala after trauma-related imagery, sounds, or smells indicate that this structure plays a role in the persistence of traumatic memory.14 Decreased amygdala activation is correlated with resilience to PTSD and response to cognitive behavioral therapy (CBT).14 Hypofunctioning of the vmPFC is theorized to prevent extinction in patients with PTSD and is inversely correlated with severity of symptoms.14 Hyperresponsivity of the dACC and the insular cortex may correlate with impaired response to emotional stimuli or those that predict threat. The most consistent findings are decreased hippocampus volumes and N-acetylaspartate levels in patients with PTSD.13,14 In twin studies, the unaffected twin of patients with PTSD also demonstrated smaller hippocampi compared with twins without PTSD. These findings suggest that lower hippocampal volumes in patients with PTSD are likely a precursor associated with vulnerability for subsequent development of PTSD.13
Neuroimaging studies suggest that dysfunction in the cortical–striatal–thalamic circuits is responsible for impulsive behavior and inability to regulate socially acceptable behaviors.21 Drugs that decrease hyperactivity in the cortical–striatal–thalamic circuits decrease symptoms of OCD.11,22 Glutamate may play a role in OCD symptomatology.23
The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision classifies anxiety disorders into several categories: generalized anxiety disorder, panic disorder (with or without agoraphobia), social anxiety disorder, specific phobia, OCD, PTSD, and acute stress disorder (ASD).1 The characteristic features of these illnesses are anxiety and avoidance behavior. Generalized anxiety disorder, panic disorder, and social anxiety disorder are discussed in Chapter 53.
Posttraumatic Stress Disorder
Exposure to a traumatic event is required for a diagnosis of PTSD.1 The person must have witnessed, experienced, or been confronted with a situation that involved definite or threatened death or serious injury, or possible harm to himself or herself or others. The patient’s response to the trauma must include intense fear, helplessness, or horror.1 Some examples of traumatic events include physical attacks by an intimate partner, traffic accidents, military combat, earthquakes, being held hostage, child sexual abuse, and witnessing a murder or injury of another.
The resulting PTSD symptoms include persistent reexperiencing of the traumatic event, avoidance of stimuli associated with the trauma, numbing of general responsiveness, and persistent symptoms of hyperarousal. Patients must have at least one reexperiencing symptom, at least three signs or symptoms of persistent avoidance of stimuli associated with the trauma, and at least two symptoms of increased arousal.1 Symptoms from each category need to be present for longer than 1 month and cause significant distress or impairment in functioning. Most persons diagnosed with PTSD also meet criteria for another mental disorder.1
CLINICAL PRESENTATION Posttraumatic Stress Disorder
Anxiety and dissociative symptoms (e.g., absence of emotional responsiveness, derealization, inability to recall important features of the trauma) emerging within 1 month after exposure to a traumatic stressor are classified as ASD. Symptoms of ASD are experienced during or immediately after the trauma, last for at least 2 days, and resolve within 4 weeks.1
The age of onset and course of PTSD are variable. PTSD can occur at any age. The presentation is not predictable because symptoms are related to the duration and intensity of the trauma, the presence of other psychiatric disorders, and how the patient deals with the trauma. Symptoms emerge soon after a traumatic event and either dissipate or chronically persist in survivors.24 About 95% of patients who recover do so within a year, and 40% have persistent symptoms 6 years later. PTSD co-occurs with mood, anxiety, and substance use disorders. The course of illness is fluctuating, worsening with life stressors.24
CLINICAL PRESENTATION Obsessive-Compulsive Disorder
Patients with OCD exhibit a great variety of symptoms on presentation to clinicians. The diversity and oddity of symptoms that manifest can obscure accurate diagnosis and delay appropriate treatment of the disorder. Patients can be secretive about symptoms and purposefully refuse to report symptoms.5 Patients can present in a seemingly incongruous manner to nonpsychiatrists for other complaints—dermatologists for eczema or chapped skin, pediatricians for parental concerns over a child’s compulsive hand washing, neurologists for tics, or dentists for gum lesions from compulsive teeth brushing.
The diagnostic criteria for OCD require the presence of obsessions and/or compulsions (although most patients have both) that are severe enough to cause marked distress, to be time-consuming (occupy more than 1 hour/day), and to cause significant impairment in social or occupational functioning.1 An obsession is a recurrent, persistent idea, thought, impulse, or image that is experienced as intrusive and inappropriate and produces marked anxiety. Common obsessions involve thoughts about contamination (e.g., concern with germs or dirt) and repeated doubts.1
Individuals must recognize that their obsessions or compulsions are excessive or unreasonable. Obsessions must be acknowledged as products of the individual’s own mind, and attempts must be made to ignore or suppress them. The obsessions produce marked feelings of anxiety and are not simply excessive worry about a real-life situation.1
A compulsion is defined as a repetitive behavior or mental act generally performed in response to an obsession. Diagnostically, compulsive behavior is not pleasurable and is designed to prevent discomfort or the occurrence of a dreaded event that is often unknown. For example, many patients are obsessed with feelings of doubt (e.g., whether a door was left unlocked), causing them marked distress and leading to repetitive checking (or compulsive behaviors). These behaviors are usually performed according to certain rules or in a stereotyped fashion. Because patients recognize their compulsive behavior as silly or senseless, they become extremely adept at denying symptoms, disguising their rituals, and concealing their illness from friends and family.1
Patients with OCD often have concurrent depression, other anxiety disorders, and substance abuse. It is a chronic illness in most patients, with severity of symptoms varying in intensity over time. Many patients with OCD have significantly impaired QOL and ability to function.5
Posttraumatic Stress Disorder
The short-term goal of therapy in the management of PTSD is reduction in core symptoms (i.e., intrusive reexperiencing, avoidance, and hyperarousal). Patients should also have improvements in disability, concurrent psychiatric conditions, and QOL. The long-term goal in PTSD is remission.
General Approach to Treatment
In general, patients who seek treatment acutely after a trauma and are in intense distress should receive therapy based on their presenting symptoms (e.g., a nonbenzodiazepine hypnotic for difficulty sleeping). Short courses of exposure-based, trauma-focused cognitive behavioral therapy (TFCBT) can be helpful to prevent chronic PTSD in patients who present during the first 3 months of the event.26 If symptoms (e.g., hyperarousal, avoidance, dissociation, sleep difficulties, or depressed mood) persist for 3 to 4 weeks and the patient experiences marked social, occupational, and/or interpersonal impairment, they can be treated with pharmacotherapy, psychotherapy, or both. Many patients with PTSD will improve substantially with pharmacotherapy but retain some symptoms. Treatment regimens usually combine psychoeducation, psychosocial support and/or treatment, and pharmacotherapy.24,25
Psychotherapy can be used when a patient suffers from mild symptoms, in patients who prefer not to use medications, or in conjunction with drugs in patients with severe symptoms to improve response. Patients who have experienced trauma should be educated that they can experience anxiety, depression, nightmares, and even flashbacks as a reaction to the event. Brief courses of prolonged exposure, a form of CBT, in close proximity to the traumatic event resulted in lower rates of PTSD 3 and 6 months later.4,26 Single-session critical incident stress debriefing was not shown to be effective in preventing development of PTSD and actually can cause harm.26,27
Psychotherapies for treating PTSD include stress management, TFCBT, eye movement desensitization and reprocessing (EMDR), and psychoeducation.28 Short-term reductions in symptoms can be achieved with stress management, group therapy, hypnosis, or psychodynamic therapy.27,28 The cognitive and behavioral approaches of TFCBT and EMDR are more effective than stress management or group therapy to reduce symptoms of PTSD.28 Psychoeducation includes information about the disease state, treatment options, and avoidance of excessive use of alcohol and other substances of abuse. Novel nonpharmacologic approaches (e.g., interpersonal psychotherapy, narrative exposure therapy, imagery modification) and delivery methods (e.g., telemedicine, computer-delivered CBT) are under study.29
Antidepressants are the major pharmacotherapeutic treatment for PTSD. In addition to their efficacy in PTSD, these agents are also effective for concurrent depression and anxiety disorders. SSRIs and venlafaxine are the first-line pharmacotherapy of PTSD.27,30–32 The tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) can also be effective, but they have less favorable side effect profiles (Table 54-1). Both sertraline and paroxetine are approved for the acute treatment of PTSD,33,34 and sertraline is approved for the long-term (i.e., 52 weeks) management of PTSD.34 A number of drugs can be used as augmentation agents (e.g., antiadrenergic drugs and atypical antipsychotics).31,32 Benzodiazepines are not effective for PTSD.31,32 A number of treatment guidelines are published.35 Table 54-2 provides a summary of key points from the treatment guidelines for PTSD. An algorithm for the treatment of PTSD appears in Figure 54-1.
TABLE 54-1 Dosing of Antidepressants in the Treatment of Posttraumatic Stress Disorder