Advertisement

Posttraumatic Stress Disorder: Clinical Features, Pathophysiology, and Treatment

      Abstract

      Posttraumatic stress disorder (PSTD), classified as an anxiety disorder, has become increasingly important because of wars overseas, natural disasters, and domestic violence. After trauma exposes the victim to actual or threatened death or serious injury, 3 dimensions of PTSD unfold: (1) reexperiencing the event with distressing recollections, dreams, flashbacks, and/or psychologic and physical distress; (2) persistent avoidance of stimuli that might invite memories or experiences of the trauma; and (3) increased arousal. Traumatic events sufficient to produce PTSD in susceptible subjects may reach a lifetime prevalence of 50% to 90%. The actual lifetime prevalence of PTSD among US citizens is approximately 8%, with the clinical course driven by pathophysiologic changes in the amygdala and hippocampus. Comorbid depression and other anxiety disorders are common. General principles of treatment include the immediate management of PTSD symptoms and signs; management of any trauma-related comorbid conditions; nonpharmacologic interventions including cognitive behavioral treatment; and psychopharmacologic agents including antidepressants (selective serotonin reuptake inhibitors most commonly), antianxiety medications, mood stabilizing drugs, and antipsychotics. This review of PTSD will provide the reader with a clearer understanding of this condition, an increased capacity to recognize and treat this syndrome, and a greater appreciation for the role of the internist in PTSD.

      Keywords

      The internist has long been interested in war-induced extreme and enduring reactions to psychologic trauma. Jacob Mendez DaCosta introduced the term soldier’s heart (DaCosta’s syndrome) in an extensive Civil War study published in 1871.
      • Wooley C.F.
      Jacob Mendez DaCosta medical teacher, clinician, and clinical investigator.
      Subsequent labels for traumatic events leading to psychologic disturbances include fright neurosis; traumatic, combat, or war neurosis; railway spine; concentration camp syndrome; rape-trauma syndrome; combat fatigue; post-Vietnam syndrome; and shell shock. The current Diagnostic and Statistical Manual of Mental Disorders (1994) uses “posttraumatic stress disorder” to label this stress-induced condition.
      American Psychiatric Association
      (“Stress” may be defined as the totality of the experience in response to unpleasant external stimuli that signal danger—often by causing physical or emotional pain.) The most recent Cecil Textbook of Medicine (2004),
      • Goldman L.
      • Ausiello D.
      however, lists neither posttraumatic stress disorder (PTSD) nor PTSD in the index. Thus, a review of PTSD is in order for the internist.
      PTSD is classified as an anxiety disorder.
      American Psychiatric Association
      Disorders of anxiety are the most common forms of psychiatric illnesses, with 19.3% of Americans experiencing some form of an anxiety disorder in a 12-month period. Anxiety has many of the symptoms and signs of fear. Anxiety, however, lingers long after the stress stimulus has lifted and the threat has passed. Just as chronic pain is a type of pain that no longer serves a useful purpose, chronic anxiety/fear also serves no useful purpose.
      Anxiety disorders not only contribute to biopsychosocial morbidity but also may constitute a risk factor for sudden cardiac death. Cardiac arrhythmias, rather than induction or exacerbation of coronary atherosclerosis, seem to be the culprit in this setting.
      • Albert C.M.
      • Chae C.U.
      • Rexrode K.M.
      • Manson J.E.
      • Kawachi I.
      Phobic anxiety and risk of coronary heart disease and sudden cardiac death among women.
      The terrorist attacks on the World Trade Center and the Pentagon on September 11, 2001, coupled with the current wars in Iraq and Afghanistan, have thrust PTSD further into the limelight. According to data from the bombing of the Oklahoma City Murrah Federal Building in 1995, approximately one-third of the more than 100000 people witnessing the terrorists attack on September 11, 2001, have developed or will develop PTSD.
      • Yehuda R.
      Post-traumatic stress disorder.
      The intense combat operations in the current wars in Iraq and Afghanistan have created a series of mental health problems for US troops.
      • Hoge C.W.
      • Castro C.A.
      • Messer S.C.
      • McGurk D.
      • Cotting D.I.
      • Koffman R.L.
      Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care.
      These problems include major depressive disorder, generalized anxiety disorder, and PTSD. Compared with pre-deployment mental health problems, the greatest increase was in PTSD. The US Department of Defense has shown an increased awareness of combat-related mental health problems compared with previous wars and military engagements.
      • Friedman M.J.
      Acknowledging the psychiatric cost of war.
      Even though most mental health issues enter the medical area through primary care, little has been written about PTSD in primary care.
      • Lecrubier Y.
      Posttraumatic stress disorder in primary care a hidden diagnosis.
      The underreporting of domestic violence and other traumas may lead to low recognition of PTSD in primary care. Simply integrating questions about trauma exposure together with screening for depressive and anxiety symptoms into routine medical examinations may enhance the recognition of PTSD in primary care.
      • Lecrubier Y.
      Posttraumatic stress disorder in primary care a hidden diagnosis.
      Alternatively, features of alcohol or other substance abuse, excessive use of health services, other signs of psychologic distress, and suicidality coupled with a history of trauma exposure may also lead the primary care provider to a diagnosis of PTSD.

      Clinical features

      The term posttraumatic stress disorder was first used in the third edition (1980) of the Diagnostic and Statistical Manual of Mental Disorders, in which it was classified as an anxiety disorder.
      American Psychiatric Association
      In this third edition, a diagnosis of PTSD required exposure to trauma that would provoke symptoms and signs of PTSD in almost everyone. In the 1987 revision of the Diagnostic and Statistical Manual of Mental Disorders,
      American Psychiatric Association
      diagnostic criteria were modified to emphasize the avoidance phenomena in which there are deliberate efforts to avoid thoughts, feelings, activities, and situations that simulated trauma recollection. In the fourth edition (1994) of the Diagnostic and Statistical Manual of Mental Disorders PTSD remains an anxiety disorder.
      American Psychiatric Association
      There was a redefinition of the trauma. The traumatic event had to involve actual or threatened death or serious injury or a threat to the physical integrity of self or others. Also, the subject with PTSD had to respond with intense fear, helplessness, or horror. Furthermore, there had to be clinically significant distress and impairment in social, occupational, or other important areas of functioning for at least 1 month. Table 1 lists the diagnostic criteria for PTSD (Diagnostic and Statistical Manual of Mental Disorders and International Classification of Diseases-9 CM code = 309.81).
      American Psychiatric Association
      • Post-traumatic stress disorder consists of re-experiencing trauma with distressing recollections, dreams, flashbacks, and/or psychological/physical distress; persistent avoidance of stimuli that might invite traumatic memories or experiences; and increased arousal.
      • The clinical course is driven by pathophysiological changes in the amygdala and hippocampus.
      • Treatment includes immediate management of symptoms and signs and any trauma-related comorbid conditions; non-pharmacological interventions including cognitive behavioral treatment; and psychopharmacologic agents including antidepressants, antianxiety medications, mood stabilizing drugs, and antipsychotics.
      Table 1Diagnostic Criteria for 309.81 Posttraumatic Stress Disorder
      American Psychiatric Association
      A. The person has been exposed to a traumatic event in which both of the following were present:
       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 integrity of self or others.
       2. The person’s response involved intense fear, helplessness, or horror. Note: In children, this may be expressed instead by disorganized or agitated behavior.
      B. The traumatic event is persistently reexperienced in 1 (or more) of the following ways:
       1. Recurrent and intrusive distressing recollection 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, trauma-specific reenactment may occur.
       4. Intense psychologic distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event.
       5. Physiologic reactivity on exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event.
      C. Persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by 3 (or more) of the following:
       1. efforts to avoid thoughts, feelings, or conversations associated with the trauma
       2. efforts to avoid activities, places, or people who 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 (eg, unable to have loving feelings)
       7. sense of a foreshortened future (eg, does not expect to have a career, marriage, children, or a normal life span)
      D. Persistent symptoms of increased arousal (not present before the trauma), as indicated by 2 (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
      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, 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
      Specify if:
       With delayed onset: if onset of symptoms is at least 6 months after the stressor
      PTSD symptoms and signs are readily identifiable by the general internist. There is, however, considerable overlap between features of PTSD and other anxiety disorders, mood disorders, and substance abuse. Not uncommonly, patients with PTSD will be found to have several other psychiatric disorders. Specific questions must be asked about the occurrence of a traumatic event and subsequent onset of the clinical features of PTSD. Practitioners may be reluctant to ask about and patients may be reluctant to reveal distressing events that might involve shame or secrecy.
      Essential features of PTSD include: (1) exposure to a traumatic event that involved actual or threatened death or serious injury, (2) reexperiencing that event with distressing recollections, dreams, flashbacks, and/or psychologic and physical distress, (3) persistent avoidance of stimuli that might invite memories or experiences of the trauma, and (4) increased arousal. PSTD comprises an original traumatic event with the later emergence of a triad of symptom-behaviors that include reexperiencing, avoidance/numbing, and hyperarousal/hypervigilance of sufficient severity to interfere with important aspects of the person’s life. Internists in their role as primary care providers are likely to be the first health care professionals to see patients with PTSD.
      • Lange J.T.
      • Lange C.L.
      • Cabaltica R.B.
      Primary care treatment of post-traumatic stress disorder.

       Reexperiencing

      The most dramatic form of reexperiencing is the flashback. Here the patient feels and acts as if the trauma is recurring. Reexperiencing also includes distressing memories or dreams (nightmares) when faced with stimuli linked to the traumatic event. There may be physiologic or psychologic stress reactions, including full-blown panic attacks, associated with this reexperiencing. To establish a diagnosis of PTSD, at least 1 aspect of reexperiencing must be present (Table 1).

       Avoidance/Numbing

      Patients with PTSD may attempt to avoid thoughts or activities related to the trauma. There may be a markedly diminished capacity to experience pleasure (anhedonia), difficulty in remembering aspects of the trauma, blunted affect, a feeling of detachment or estrangement from others, and a perception of a foreshortened future. Three or more parameters of avoidance/numbing must be found to establish a diagnosis of PTSD (Table 1). In PTSD there are both similarities and differences with major depressive disorder.
      American Psychiatric Association
      There is considerable overlap between PTSD and various mood disorders.

       Hyperarousal/Hypervigilance

      Increased arousal may disrupt sleep, contribute to irritability and anger, and impair concentration. Hypervigilance may coexist with an exaggerated startle response. Two or more parameters of hyperarousal/hypervigilance must be present to establish a diagnosis of PTSD (Table 1). There is considerable overlap between PTSD and other anxiety disorders such as generalized anxiety disorder and panic disorder.

       Prevalence

      When the diagnosis of PTSD was introduced in 1980, traumatic events sufficient to induce this condition were considered rare.
      • Schnurr P.P.
      • Friedman M.J.
      • Bernardy N.C.
      Research on posttraumatic stress disorder epidemiology, pathophysiology, and assessment.
      Since then, epidemiologic surveys have documented such events to be highly prevalent, with 50% to 90% of the population receiving exposure over the course of a lifetime.
      • Kessler R.C.
      • Sonnega A.
      • Bromet E.
      • Hughes M.
      • Nelson C.B.
      Posttraumatic stress disorder in the National Comorbidity Survey.
      • Breslau N.
      • Kessler R.C.
      • Chilcoat H.D.
      • Schultz L.R.
      • Davis G.C.
      • Andreski P.
      Trauma and posttraumatic stress disorder in the community the 1996 Detroit Area Survey of Trauma.
      Lifetime prevalence of PTSD is approximately 8%.
      • Kessler R.C.
      • Sonnega A.
      • Bromet E.
      • Hughes M.
      • Nelson C.B.
      Posttraumatic stress disorder in the National Comorbidity Survey.
      Medical reports of recent military experiences in Afghanistan and Iraq described a striking increase in the prevalence of PTSD largely related to the number of firefights engaged in by the veteran.
      • Hoge C.W.
      • Castro C.A.
      • Messer S.C.
      • McGurk D.
      • Cotting D.I.
      • Koffman R.L.
      Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care.
      Overall the most common traumatic events are witnessing a severe injury or death, involvement in a fire or other natural disaster, and involvement in a life-threatening accident (all 3 are more common in men than women).
      • Schnurr P.P.
      • Friedman M.J.
      • Bernardy N.C.
      Research on posttraumatic stress disorder epidemiology, pathophysiology, and assessment.
      Physical attack, combat-related trauma, being threatened with a weapon, captured, or kidnapped are also more common among men than women. Rape, sexual molestation, and parental neglect and physical abuse during childhood are more common among women than men. Note that trauma exposure meeting criteria for increased PTSD risk may be acute, such as assault or accidental injury, or chronic and recurrent, such as childhood abuse or domestic violence.
      Sexual differences in the type of trauma experienced also may drive aspects of PTSD. Women are more than 4 times more likely to develop PTSD than men after normalizing for the traumatic event. Rape is the trauma most likely to lead to PTSD and occurs more commonly among women (9%) than men (<1%).
      • Schnurr P.P.
      • Friedman M.J.
      • Bernardy N.C.
      Research on posttraumatic stress disorder epidemiology, pathophysiology, and assessment.
      Other risk factors for PTSD include youth, lower socioeconomic status, preexisting psychiatric condition, childhood conduct problems, parental neglect, family history of a psychiatric condition, severity of reaction to initial trauma including dissociation, and poor social support system.
      • Schnurr P.P.
      • Friedman M.J.
      • Bernardy N.C.
      Research on posttraumatic stress disorder epidemiology, pathophysiology, and assessment.

       Comorbidity

      Other anxiety disorders and depression in varying degrees of severity commonly accompany PTSD and may make the diagnosis of each condition more difficult.
      • Schnurr P.P.
      • Friedman M.J.
      • Bernardy N.C.
      Research on posttraumatic stress disorder epidemiology, pathophysiology, and assessment.
      Substance abuse is a common condition developing after the onset of PTSD. Temporal discordance is the clearest evidence of comorbidity. That is, depression and/or an anxiety disorder preceding the traumatic event leading to PTSD and substance abuse after the traumatic event offer the most compelling evidence for multiple psychiatric conditions.
      Not uncommonly, especially among older patients, medical conditions may be comorbid with PTSD. Exposure to trauma increases the risk of poor physical health.
      • Schnurr P.P.
      • Jankowski M.K.
      Physical health and post-traumatic stress disorder review and synthesis.
      • Schnurr P.P.
      • Spiro A.
      • Paris A.H.
      Physician-diagnosed medical disorders in relation to PTSD symptoms in older male military veterans.
      Boscarino
      • Boscarino J.A.
      Diseases among men 20 years after exposure to severe stress implications for clinical research and medical care.
      reported a direct link between trauma and a broad spectrum of medical conditions in a 20-year follow-up of men initially exposed to severe stress. David et al
      • David D.
      • Woodward C.
      • Esquenazi C.
      • Mellman T.A.
      Comparison of comorbid physical illnesses among veterans with PTSD and veterans with alcohol dependence.
      compared male veterans admitted to a rehabilitation unit for PTSD or alcohol dependence and reported that PTSD subjects were more likely to have diabetes mellitus, heart disease, obesity, and osteoarthritis than their substance abuse counterparts.

       Clinical Course

      The initial clinical response to a traumatic event is driven by the amygdala and is often in the form of the “fight or flight response.” Subsequently, the clinical course is modified by memories managed in the hippocampus and a cognitive understanding of stimulus, experience, and expectations governed by the prefrontal cortex. That is, both the external event phenomena and the (internal) biopsychosocial dimensions of the person involved determine the short-term, mid-range, and long-term biologic and psychologic responses to the traumatic event.
      In a well-studied group of rape victims, Foa et al
      • Foa E.B.
      • Rothbaum B.O.
      • Riggs D.S.
      • Murdock T.B.
      Treatment of posttraumatic stress disorder in rape victims a comparison between cognitive-behavioral procedures and counseling.
      reported that 94% of study subjects had all the clinical symptoms and signs of PTSD 1 week after the rape. This would suggest that PTSD features constitute an expected reaction to such trauma. Three and 9 months after the rape, only 15% to 25% of subjects, respectively, met criteria for PTSD. Thereafter, this percentage remained stable consistent with unremitting and chronic PTSD that may last for any length of time.

       Disability Associated with Posttraumatic Stress Disorder

      Chronic PTSD is often debilitating with work impairment or even unemployment, altered life trajectories, compromised social relations, marital discord and divorce, and onset of impulse dyscontrol and even violence. Among US military veterans, chronic PTSD commonly leads to disability compensation.
      • Davidson J.R.T.
      • Stein D.J.
      • Shalev A.Y.
      • Yehuda R.
      Posttraumatic stress disorder acquisition, recognition, course, and treatment.

      Pathophysiology

      The centerpiece of the central nervous system involved in the fear response is the amygdala. This brain structure governs our ability to experience fear and learn to avoid pain by interceding between emotion and attention in 2 related ways.
      • Helmuth L.
      Fear and trembling in the amygdala.
      Amygdala signals enhance processing of fear-inducing information by higher cortical structures. That is, they increase the emotional valence assigned to information and memory in the cortex thereby making this information easier to access in future settings. Also, the amygdala is able to recognize danger signals quickly by primitive visual pathways that bypass the cortex and neocortex. In so doing, the amygdala evaluates objects and organisms in the environment before interacting with them. This brain structure can quickly activate just about every system in the body to fight ferociously or retreat rapidly. In addition to placing the body on alert, the amygdala stimulates the nearby hippocampus to help the brain to learn and form new memories specific to danger. The magnitude and experience of the threat followed later by reexperiencing, avoidance/numbing, and hyperarousal/hypervigilance constitute important determinants of the clinical course leading to PTSD. Figure 1 outlines the body’s initial response to a threat.
      Figure thumbnail gr1
      Figure 1Body’s response to a threat or perceived threat. See text below for detailed analysis of central nervous system structures and their role in the fear response. After the diagram in the June 10, 2002, issue of Time Magazine.
      • Lertola J.
      • Park A.
      • Charney D.S.
      The anatomy of anxiety.
      Event A: Immediate (subcortical) response to threat
      •  Visual and auditory stimuli reach the thalamus on sighting or hearing the menacing animal.
      •  This information immediately leaves the thalamus and goes to the fear center in the amygdala.
      •  The amygdala alerts other brain structures including the hypothalamus and locus ceruleus producing sweaty palms, tachycardia, increased blood pressure, and a surge in norepinephrine.
      •  The subject is then prepared for a “fight or flight response.”
      Event B: Cognitive processing of immediate response to threat
      •  After fear activation, information is sent from the thalamus to the cortex for cognitive processing.
      •  The neocortex (executive portion of the cortex) analyzes the raw data from the sensory organs and decides whether to continue or discontinue the fear response.
      •  If the neocortex decides to maintain the fear response, the amygdala remains on the alert.
      General comments
      •  Olfactory and tactile stimuli are sent directly to the amygdala bypassing the thalamus, evoking stronger memories and feelings than do sights and sounds.
      •  The thalamus is the hub for sights and sounds with visual cues separated according to size, shape, and color, and auditory cues separated by volume and dissonance.
      •  The cortex gives meaning to the sights and sounds and determines whether to turn off or continue anxiety and fear responses.
      •  The amygdala is the emotion center of the brain and gives emotional valence to memories processed in the hippocampus.
      •  Stimulating the bed nucleus of stria terminalis causes longer-term unease characteristic of anxiety.
      •  The hippocampus is the memory center of the brain, an important regulator of the stress response, and a major feedback site for glucocorticoids.

      Treatment

      The American Psychiatric Association has recently published guidelines for the treatment of patients with PTSD.
      American Psychiatric Association
      Practice guidelines for the treatment of patients with acute stress disorder and posttraumatic stress disorder.
      Included in these guidelines is treatment of patients with acute stress disorder. Acute stress disorder is a common precursor to PTSD. For an in-depth review of treatments for PTSD, the reader is referred to the practice guidelines developed by the International Society for Traumatic Stress Studies edited by Foa et al.

       General Principles

      The first task is to reduce or eliminate the symptoms and signs of PTSD and any trauma-related comorbid conditions. Next, the clinician seeks to improve adaptive functioning and return the patient to a psychologic state of safety and trust. Finally, general treatment focuses on limiting any generalization of the initial trauma and protecting the patient with PTSD against subsequent relapse.

       Nonpharmacologic Treatment

      In randomized clinical trials, most patients with PTSD treated with psychotherapy improve or recover. Bradley et al
      • Bradley R.
      • Greene J.
      • Russ E.
      • Dutra L.
      • Westen D.
      A multidimensional meta-analysis of psychotherapy for PTSD.
      conducted a multidimensional meta-analysis of psychotherapy for PTSD including studies published between 1980 and 2003. More than one-half of patients with PTSD completing treatment with “various forms of cognitive behavior therapy or eye movement desensitization and reprocessing improve.”
      • Bradley R.
      • Greene J.
      • Russ E.
      • Dutra L.
      • Westen D.
      A multidimensional meta-analysis of psychotherapy for PTSD.
      The authors cautioned, however, that most patients continued to have significant symptoms and signs of PTSD posttreatment. Follow-up data beyond brief intervals were also largely absent.
      The principal role for the primary care physician in PTSD is psychoeducation and referral as necessary. These clinicians should have a practice that allows weekly follow-up for several weeks after initiation of treatment. Follow-up can move to biweekly and then monthly visits. Referral to support groups may be appropriate.
      Nonpharmacologic models of treatment for PTSD are built on a biopsychologic understanding of this condition.
      • Brewin C.R.
      • Holmes E.A.
      Psychological theories of posttraumatic stress.
      Disturbances in PTSD are associated with a broad range of psychologic processes including attention, beliefs, cognitive-affective responses, coping styles, memory, and social-support systems.
      • Brewin C.R.
      • Holmes E.A.
      Psychological theories of posttraumatic stress.
      For a review of the 3 major theories of PTSD—emotional processing theory, dual representation theory, and cognitive theory—the reader is referred to a recent review by Brewin and Holmes.
      • Brewin C.R.
      • Holmes E.A.
      Psychological theories of posttraumatic stress.

       Psychopharmacology

      After a traumatic event, no specific drug or combination of drugs prevents the emergence of acute stress disorder or later of PTSD. However, selective serotonin reuptake inhibitors are considered the first-line drug treatment for PTSD and the only ones to have received Food and Drug Administration indication.
      American Psychiatric Association
      Practice guidelines for the treatment of patients with acute stress disorder and posttraumatic stress disorder.
      Selective serotonin reuptake inhibitors include fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, and escitalopram. Selective serotonin reuptake inhibitors may reduce or eliminate the clinical features of the 3 symptoms clusters of PTSD (reexperiencing, avoidance/numbness, and hyperarousal). Other antidepressants including tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors (venlafaxine and duloxetine), and monoamine oxidase inhibitors may be of benefit in treating the patient with PTSD.
      Benzodiazepines may reduce anxiety and improve sleep in PTSD. They may not control or eliminate the core triad of PTSD, however. A significant limitation of this class of drugs is that subjects with PTSD who are prone to addiction may abuse or become dependent on benzodiazepines. Also, these drugs may interfere with the cognitive processing of the trauma necessary for psychotherapeutic interventions to be successful.
      Psychotropic drugs other than antidepressants and antianxiety agents may be necessary to target residual PTSD symptoms and signs. Second-generation (newer, atypical) antipsychotic drugs may be needed to treat comorbid psychotic-like features or anxiety refractory to other agents. These second-generation agents include clozapine, risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole. Because of the side effects of leukopenia, seizures, and myocarditis/cardiomyopathy, clozapine would be the least attractive choice among the second-generation antipsychotic drugs. First-generation (older, typical) antipsychotic drugs are more likely than second-generation drugs to produce significant motor side effects (tardive dyskinesia and the extrapyramidal syndromes of dystonic reactions, drug-induced Parkinsonism, and akathisia) at clinically effective doses and are a second-line choice to treat psychotic-like features in PTSD.
      American Psychiatric Association
      Practice guidelines for the treatment of patients with acute stress disorder and posttraumatic stress disorder.
      Second-generation antipsychotic drugs are more likely to be associated with drug-induced weight gain than first-generation agents. Clozapine and olanzapine are most likely implicated in drug-induced weight gain and features associated with the metabolic syndrome. Ziprasidone and aripiprazole are least likely to induce weight gain. Risperidone and quetiapine have a moderate capacity to induce weight gain. Table 2 outlines recommended cardiovascular and endocrine follow-up of patients taking second-generation antipsychotic drugs.
      American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity
      Consensus development conference on antipsychotic drugs and obesity and diabetes.
      Table 2Recommended Monitoring of Patients Receiving Second-Generation Antipsychotic Drugs
      • Brewin C.R.
      • Holmes E.A.
      Psychological theories of posttraumatic stress.
      IntervalPersonal/Family HistoryWeight (BMI)Waist CircumferenceBlood PressureFasting Plasma GlucoseFasting Lipids
      Baseline444444
      4 wk4
      8 wk4
      12 wk4444
      Quarterly4
      Annually4444
      Every 5 y4
      BMI = body mass index.
      Various symptom clusters and mood instability may be treated with so-called mood stabilizer anticonvulsants (divalproex, carbamazepine, topiramate, and lamotrigine). Central nervous system adrenergic hyperarousal may drive PTSD symptoms, including nightmares and flashbacks, prompting trials of α2-adrenergic agonists and β-adrenergic blockers. There is an emerging interest in treating PTSD-associated nightmares with the postsynaptic alpha-adrenoceptor blocker prazosin.
      • Raskind M.A.
      • Dobie D.J.
      • Kanter E.D.
      • Petrie E.C.
      • Thompson C.E.
      • Peskind E.R.
      The alpha1-adrenergic antagonist prazosin ameliorates combat trauma nightmares in veterans with posttraumatic stress disorder a report of 4 cases.
      • Raskind M.A.
      • Thompson C.
      • Petrie E.C.
      • et al.
      Prazosin reduces nightmares in combat veterans with posttraumatic stress disorder.
      • Raskind M.A.
      • Peskind E.R.
      • Kanter E.D.
      • et al.
      Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin a placebo-controlled study.
      Almost certainly, the patient with PTSD who is referred to the psychopharmacologist will require multiple psychotropic drugs from different classes of drugs.

      Conclusions

      Interest in PTSD extends beyond the field of mental health to engage the speciality of internal medicine and its various subspecialities. Combat-related trauma is a common cause of PTSD among men, and rape is a common cause of PTSD among women. The initial response to the traumatic stress is largely biologic and driven by the amygdala. Memories managed by the hippocampus and executive decisions managed in the neocortex drive the short-term, mid-range, and long-term outcomes of subjects exposed to severe stress. That is, the later response to the traumatic event will determine whether acute and chronic PTSD will persist. (PTSD is probably a recovery failure from a universal set of emotions and reactions to severe stress.) One-quarter or fewer of the subjects exposed to the traumatic event will have chronic PTSD.
      The primary care physician will usually be the first health-care professional to engage the potential subject with PTSD. Including PTSD in the differential diagnosis of persons presenting with multiple psychologic and somatic complaints and asking about possible exposure to severe stress are essential steps in better managing PTSD.
      Education and supportive psychotherapy can be within the purview of the primary care provider of the potential subject with PTSD. Selective serotonin reuptake inhibitors can also be started by the primary care physician. Referral to specialists should be a ready choice. Continued engagement with the patient and specialist by the primary care physician offers the best course for potential subjects with PTSD.
      Systematic studies of PTSD engaging primary care, psychiatrists, psychologists, neurophysiologists, and neuroradiologists will lead to earlier recognition of PTSD, better management, and improved outcome of this condition. Internal medicine has a vital role to play in such efforts.

      References

        • Wooley C.F.
        Jacob Mendez DaCosta.
        Am J Cardiol. 1982; 50: 1145-1148
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders. 4th edition ed. American Psychiatric Association, Washington, DC1994
        • Goldman L.
        • Ausiello D.
        Cecil Textbook of Medicine e-dition, 22nd edition—text with continually updated online reference, single volume. 2004
        • Albert C.M.
        • Chae C.U.
        • Rexrode K.M.
        • Manson J.E.
        • Kawachi I.
        Phobic anxiety and risk of coronary heart disease and sudden cardiac death among women.
        Circulation. 2005; 111: 480-487
        • Yehuda R.
        Post-traumatic stress disorder.
        N Engl J Med. 2002; 346: 108-114
        • Hoge C.W.
        • Castro C.A.
        • Messer S.C.
        • McGurk D.
        • Cotting D.I.
        • Koffman R.L.
        Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care.
        N Engl J Med. 2004; 351: 13-22
        • Friedman M.J.
        Acknowledging the psychiatric cost of war.
        N Engl J Med. 2004; 351: 75-77
        • Lecrubier Y.
        Posttraumatic stress disorder in primary care.
        J Clin Psychiatry. 2004; 65: 49-54
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders. 3rd ed (DSM-III) ed. American Psychiatric Association, Washington, DC1980
        • American Psychiatric Association
        Diagnostic and Stastical Manual of Mental Disorders. 3rd ed, revised (DSM-III-R) ed. American Psychiatric Association, Washington, DC1987
        • Lange J.T.
        • Lange C.L.
        • Cabaltica R.B.
        Primary care treatment of post-traumatic stress disorder.
        Am Fam Physician. 2000; 62: 1035-1040
        • Schnurr P.P.
        • Friedman M.J.
        • Bernardy N.C.
        Research on posttraumatic stress disorder.
        J Clin Psychol. 2002; 58: 877-889
        • Kessler R.C.
        • Sonnega A.
        • Bromet E.
        • Hughes M.
        • Nelson C.B.
        Posttraumatic stress disorder in the National Comorbidity Survey.
        Arch Gen Psychiatry. 1995; 52: 1048-1060
        • Breslau N.
        • Kessler R.C.
        • Chilcoat H.D.
        • Schultz L.R.
        • Davis G.C.
        • Andreski P.
        Trauma and posttraumatic stress disorder in the community.
        Arch Gen Psychiatry. 1998; 55: 626-632
        • Schnurr P.P.
        • Jankowski M.K.
        Physical health and post-traumatic stress disorder.
        Sem Clin Neuropsychiatry. 1999; 4: 295-304
        • Schnurr P.P.
        • Spiro A.
        • Paris A.H.
        Physician-diagnosed medical disorders in relation to PTSD symptoms in older male military veterans.
        Health Psychol. 2000; 19: 91-97
        • Boscarino J.A.
        Diseases among men 20 years after exposure to severe stress.
        Psychosom Med. 1997; 59: 605-614
        • David D.
        • Woodward C.
        • Esquenazi C.
        • Mellman T.A.
        Comparison of comorbid physical illnesses among veterans with PTSD and veterans with alcohol dependence.
        Psychiatr Serv. 2004; 55: 82-85
      1. Yehuda R. Risk Factors for Posttraumatic Stress Disorder. American Psychiatric Press, Washington, DC1999
        • Foa E.B.
        • Rothbaum B.O.
        • Riggs D.S.
        • Murdock T.B.
        Treatment of posttraumatic stress disorder in rape victims.
        J Consult Clin Psychol. 1991; 59: 715-723
        • Davidson J.R.T.
        • Stein D.J.
        • Shalev A.Y.
        • Yehuda R.
        Posttraumatic stress disorder.
        J Neuropsychiatry Clin Neurosci. 2004; 16: 135-147
        • Helmuth L.
        Fear and trembling in the amygdala.
        Science. 2003; 300: 568-569
        • American Psychiatric Association
        Practice guidelines for the treatment of patients with acute stress disorder and posttraumatic stress disorder.
        Am J Psychiatry. 2004; 161: 1-31
      2. Foa E.B. Keane T.M. Friedman M.J. Effective Treatments for PTSD. Guilford Press, New York2000
        • Bradley R.
        • Greene J.
        • Russ E.
        • Dutra L.
        • Westen D.
        A multidimensional meta-analysis of psychotherapy for PTSD.
        Am J Psychiatry. 2005; 162: 214-227
        • Brewin C.R.
        • Holmes E.A.
        Psychological theories of posttraumatic stress.
        Clin Psychology Rev. 2003; 23: 339-376
        • American Diabetes Association, American Psychiatric Association, American Association of Clinical Endocrinologists, North American Association for the Study of Obesity
        Consensus development conference on antipsychotic drugs and obesity and diabetes.
        Diabetes Care. 2004; 27: 596-601
        • Raskind M.A.
        • Dobie D.J.
        • Kanter E.D.
        • Petrie E.C.
        • Thompson C.E.
        • Peskind E.R.
        The alpha1-adrenergic antagonist prazosin ameliorates combat trauma nightmares in veterans with posttraumatic stress disorder.
        J Clin Psychiatry. 2000; 61: 129-133
        • Raskind M.A.
        • Thompson C.
        • Petrie E.C.
        • et al.
        Prazosin reduces nightmares in combat veterans with posttraumatic stress disorder.
        J Clin Psychiatry. 2002; 63: 565-568
        • Raskind M.A.
        • Peskind E.R.
        • Kanter E.D.
        • et al.
        Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin.
        Am J Psychiatry. 2003; 160: 371-373
        • Lertola J.
        • Park A.
        • Charney D.S.
        The anatomy of anxiety.
        Time Magazine. 2002; (June 10)