Chapter 11 Kathleen F. Pagulayan1,2 and Jesse R. Fann2,3,4 1 VA Puget Sound Health Care System, University of Washington, Seattle, WA, USA 2 Departments of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA 3 Departments of Rehabilitation Medicine, University of Washington, Seattle, WA, USA 4 Departments of Epidemiology, University of Washington, Seattle, WA, USA Neuropsychiatric symptoms and behavioral changes are significant contributors to disability following traumatic brain injury (TBI) [1]. The risk for developing a neuropsychiatric disorder increases after TBI, especially in the first year postinjury [2–4]. Due to the negative impact that these symptoms can have on rehabilitation and functional outcome [5], early diagnosis and treatment of these conditions is critical. Many factors contribute to the development and maintenance of postinjury psychiatric symptoms, including both preinjury characteristics (e.g., education, vocational history, psychiatric disorders) and postinjury functioning (e.g., injury-related disabilities, awareness of deficits) [6]. Comorbid conditions, preexisting psychiatric symptoms, and TBI-related cognitive impairment can complicate the clinical picture. Additional subthreshold psychiatric symptoms that detrimentally affect functioning may be present and should be monitored and potentially treated. The complexity and multifaceted nature of potential contributors to the clinical picture support the use of a biopsychosocial framework for assessment. This approach integrates injury-related factors with relevant psychiatric history, postinjury psychological adjustment, and the social impact of the injury (e.g., change in family, occupational/educational, or social functioning). Some critical elements of a post-TBI psychiatric evaluation are listed below. Neurobehavioral and psychiatric symptoms after TBI likely represent the interaction between premorbid conditions, personality characteristics, TBI-related changes in brain function, and reactions to postinjury functional changes. Race and ethnicity, age at time of injury, and preinjury alcohol use are important predictors of postinjury psychiatric symptoms [7]. In addition, preinjury educational and vocational attainment, social support, and involvement with the legal system provide a context for understanding current symptoms and their functional impact. Common behavioral sequelae include personality change, impulsivity, disinhibition, reduced frustration tolerance, decreased motivation, and sleep disturbance. Current symptom levels and change from baseline should be evaluated. Common emotional changes include mood dysregulation, depression, irritability, anxiety, and apathy [8]. Restricted affect or expressive dysprosody can also occur and may result in an incongruence between verbally expressed emotion and affect [9]. In these cases, it is recommended that the provider focus on the content of the information being expressed. Many psychiatric symptoms overlap with TBI sequelae (e.g., sleep disturbances, concentration difficulties, psychomotor agitation/retardation), and this should be considered in the diagnostic process. In addition, rates of suicidal ideation, suicide attempts, and completed suicide are increased relative to the general population following TBI [10–13]. Finally, evaluation of familial relationships and support systems, current psychosocial stressors, and coping mechanisms can be important for treatment planning. Injury severity, brain regions affected, pain, and comorbid medical conditions (e.g., motor dysfunction, headaches, chronic pain from physical injuries, visual/sensory disturbances, hypothyroidism, seizures) can all contribute to the clinical picture. Reduced awareness of deficits is common after TBI, especially as injury severity increases [14]. This, as well as injury-related cognitive impairment, may limit the accuracy of self-reported psychiatric symptoms. In cases where this is a concern, collateral information can be used to evaluate current symptoms. Premorbid psychiatric and substance abuse histories are strong risk factors for postinjury psychiatric symptoms, although individuals with no psychiatric history are still at increased risk for developing symptoms [15]. Younger age, female gender, lower education, unstable preinjury employment, poorer functioning, and shorter time since injury have also been reported as risk factors, particularly for depression [6, 16–19], although these associations have not been present across all studies. Injury severity has not consistently been correlated with development of a psychiatric disorder [7, 16, 20]. The most frequently occurring neuropsychiatric and behavioral conditions are presented in the following and summarized in Table 11.1. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, (DSM-IV) criteria were used in the majority of the research summarized [22]. Of note, individuals with TBI often experience symptoms in more than one of these categories during the first year after their injury [7]. Table 11.1 Core features, correlates and treatment of post-TBI psychiatric problems. Source: Adapted with permission from Vaishnavi et al. [21]. © Elsevier. Major depression is the most common psychiatric disorder after TBI [23], with approximately 50% of hospitalized patients developing major depression within the first year postinjury [16]. Preinjury psychiatric illness significantly increases risk for postinjury depression [15]. Depression is associated with numerous negative outcomes, including reduced participation in rehabilitation, reduced overall functioning, and increased aggression and anxiety [5, 16, 24]. TBI is also associated with an increased risk for suicide attempt [10], especially when a psychiatric disorder and substance abuse are both present [25]. The presence of repeated TBIs may increase the risk for suicidal thoughts and behaviors as well [26]. Researchers have observed that major depressive disorder (MDD) may be more biologically determined soon after TBI [4]. Conversely, psychosocial factors, such as poor social support, family discord, and an unstable job situation, can be stronger determinants of MDD as time since injury increases [27]. In theory, pharmacotherapy, psychotherapy, and alternative approaches might be combined and balanced for individual circumstances, risk factors, and time postinjury. Clinically, it is important to differentiate between the rapid mood fluctuations and emotional lability that can occur following TBI and a more prolonged, sustained depressed mood that would be suggestive of major depression [9]. DSM-IV diagnostic criteria for depression are applicable [28], but in patients with TBI, symptoms such as feeling hopeless and worthless, frustration, aggression, and difficulty enjoying activities may be the most useful in differentiating depressed and nondepressed individuals [29]. Assessment of suicide risk and protective factors can help identify individuals who may have increased risk for self-harm and allow for the development of appropriate treatment to mitigate this risk [30]. Finally, apathy and fatigue are often associated with CNS impairment. These symptoms can occur concomitantly with or independently of depression [8, 31] and are often mistaken for primary depression [32]. Risk for depression remains elevated through the first year of recovery and possibly longer [16]. The average duration of depression in two studies was 4–5 months, although there was significant individual variability [4, 16]. Self-report measures such as the Patient Health Questionnaire-9 (PHQ-9) [33] and the Neurobehavioral Functioning Inventory—Depression Scale (NFI-D) [34] have been shown to be valid in TBI populations and may complement the clinical interview or serve as screening instruments. Empirical evidence for treatment of post-TBI depression is limited [35, 36]. The pharmacotherapy data do not provide definitive evidence of efficacy for any specific class of medications. The literature does suggest that we cannot assume that standard antidepressant medications will have the same efficacy and tolerability in persons with TBI as in persons without neurologic insult. However, few adverse effects were reported in studies of antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), with the most severe adverse effects (e.g., seizures) and the most dropouts occurring with tricyclic antidepressants (TCAs). Some data suggest that antidepressants, especially TCAs and bupropion, are associated with an increased risk of seizures [37], a particular concern following severe TBI [38]; however, if the drugs are titrated cautiously, most patients will not experience increased seizures, particularly if they are taking an anticonvulsant [39]. Because of the potentially problematic adverse effects of TCAs and monoamine oxidase inhibitors (MAOIs) (e.g., sedation, hypotension, and anticholinergic effects) in patients with CNS impairment and their narrow therapeutic index (which can lead to inadvertent overdose in patients with cognitive impairment), these medications should be used with extreme caution in TBI patients. Among the 27 studies meeting criteria for inclusion in a recent systematic review [35] there were only two evidence class I studies. The class I pharmacotherapy study [40] showed trends toward superiority of sertraline (25–200 mg/d) over placebo in a demographically heterogeneous sample that was temporally far removed from their TBI. Other SSRIs, such as citalopram, and serotonin–norepinephrine receptor inhibitors (SNRIs), such as venlafaxine, may also be effective, but more data are needed. For apathy and fatigue, medications that augment dopaminergic activity appear to be the most useful [41]. Methylphenidate and dextroamphetamine are generally safe at standard dosages [42] (e.g., methylphenidate 10–30 mg/d in divided doses) and have been used successfully to enhance participation in rehabilitation. Therapeutic use of these oral psychostimulants in the medically ill rarely leads to abuse in patients without a personal or family history of substance abuse. Modafinil has been efficacious in treating excessive daytime sleepiness in patients with TBI [43, 44]. Bupropion [41] and dopamine agonists, such as amantadine [45], bromocriptine [46], and levodopa/carbidopa [47], have been used for apathy states, fatigue, and cognitive impairment. Stimulants and dopamine agonists can increase the risk for delirium and psychosis and thus should be used with caution in more vulnerable patients. Amantadine has been associated with an increased risk of seizures [48], but methylphenidate, dextroamphetamine, and bromocriptine do not appear to lower seizure threshold at typical doses. Preliminary evidence supports the use of cognitive behavioral therapy (CBT) for depression following TBI [49, 50]. Problem-solving and behavioral activation approaches delivered via regular phone interventions in the first year postinjury may also be effective in reducing depressive symptoms [51]. Patients may prefer physical exercise as a therapeutic intervention [52] and there is some evidence that higher levels of exercise may be associated with improvements in mood, sleep, and overall quality of life [53, 54]. There are also limited data supporting the efficacy and tolerability of electroconvulsive therapy (ECT), low-intensity magnetic field exposure, biofeedback, and acupuncture for treating depression after TBI [35]. However, the narrowly selected and small samples and divergent TBI severity and proximity characteristics make these results highly preliminary. Overall, TBI does not appear to significantly increase the risk of mania [55], except for possibly in the first year postinjury. One study closely tracked individuals after their injury and found that 9% of their sample met diagnostic criteria for mania within 12 months of the injury but that symptoms lasted 2 months on average and resolved over time [56]. Lower estimates, ranging from 0% to 2%, have been found in studies evaluating the presence of psychiatric disorders multiple years postinjury (e.g., 2–30 years) [10, 23, 24, 57]. The best evidence for treatment of manic symptoms in TBI consists of case series, with positive results for lithium (at 900 mg/d) [58], valproate (up to 750–1000 mg/d) [59], clonidine (150–600 μg/d) [60], ECT [61], and thioridazine (50 mg/d) with amitriptyline (100 mg/d) [61]. A reasonable approach is to use valproate as a first-line agent due to the evidence for efficacy and relatively low side effect risks. Lithium should be a second-line agent because it can lower the seizure threshold and TBI patients are more prone to seizures already [21]. Additionally, lithium has a narrow therapeutic index, and TBI patients may be particularly prone to neurotoxic effects due to lack of self-care (such as not hydrating properly) and difficulty with dose adherence. Anxiety frequently presents along with depression [16] and can range from mild mood changes to disabling symptoms such as severe panic and agoraphobia [62]. Symptoms can occur at any point postinjury but may increase at critical time points such as hospital discharge, return to school or work, anniversary of injury, or changes in rehabilitation (e.g., introduction of new skill or alteration of routine). Clinical differentiation between brief symptoms that present in response to specific triggers and the more persistent debilitating symptoms is important. Acute stress disorder (ASD) and posttraumatic stress disorder (PTSD) are disorders that develop in response to a traumatic event. In the DSM-IV, these were considered anxiety disorders. However, in the recently released DSM-5, ASD and PTSD are classified as trauma- and stressor-related disorders, and the diagnostic criteria have been modified. At present, there is minimal research in TBI on the updated DSM-5 criteria, so the information presented in the following summarizes the literature regarding ASD and PTSD according to DSM-IV criteria. Both disorders involve exposure to a traumatic event followed by the presence of reexperiencing, avoidance, and hyperarousal symptoms. ASD also involves dissociative symptoms. In ASD, the symptoms are present for 2 days to 4 weeks, while in PTSD the symptoms are present for at least 1 month. ASD occurs in approximately 4.5–13% of individuals with mild TBI (mTBI) [63, 64]; in this population, high endorsement of postconcussive symptoms that overlap with ASD is common (e.g., sleep disturbance, irritability, and poor concentration) [64]. Prevalence of ASD in more severely injured individuals is not well documented. ASD after mTBI is a significant predictor of later PTSD [65], and early treatment can reduce or prevent the development of PTSD [66]. PTSD can occur after TBI of all severities, with prevalence estimates ranging from 12 to 27% in the first year postinjury [67, 68]. Posttraumatic amnesia (PTA) and loss of consciousness (LOC) may have a protective role against the development of PTSD [69]. Risk factors for PTSD include postinjury ASD, recall of the traumatic event, assault-related injury, intoxication at time of injury, and history of psychiatric illness [69, 70]. Similar to ASD, the symptom overlap between some TBI and PTSD symptoms can cause diagnostic challenges. Avoidance and hyperarousal symptoms may be prominent, while reexperiencing symptoms are less common among those with PTA [69]. If present, the reexperiencing symptoms may relate to events surrounding the injury, such as being rescued or the postinjury hospitalization, as opposed to the injury itself [71]. Self-report measures such as the PTSD checklist can be useful but may overestimate the prevalence of PTSD due to the overlap between some PTSD and TBI symptoms [72]. Generalized anxiety disorder (GAD) involves at least 6 months of excessive anxiety and worry that interferes with daily functioning and is associated with symptoms such as fatigue, difficulty concentrating, irritability, muscle tension, restlessness or psychomotor agitation, and impaired sleep. Many of these symptoms overlap with TBI-related sequelae, so examination of their association with anxiety symptoms is needed for accurate diagnosis. The prevalence of GAD in TBI samples is around 10–15% [2, 73, 74]. High rates of GAD have been documented up to 15 years postinjury [23, 75]. The GAD-7 [76] and Brief Symptom Inventory [77] may be useful for assessing anxiety symptoms. Panic disorder has been documented following TBI of all severities, with estimates ranging from approximately 7 to 15% [23, 78]. Clinically, it may present as a sudden onset of increased anxiety accompanied by autonomic response (e.g., agitation, sweating, shaking, shortness of breath, chest pain). Many individuals with postinjury panic disorder did not have a prior history of that condition [79]. Although panic disorder has been documented soon after the injury, one study found a latency period of over 10 years in most cases where panic disorder developed after TBI [57]. Obsessive–compulsive disorder (OCD) involves the presence of recurrent disabling obsessions and/or compulsions. OCD has been documented following TBI of all severities [80, 81], but prevalence rates at 1 year postinjury are low, ranging from less than 1 to 4% [74, 78]. Comorbid mood and anxiety disorders are common [81]. Diagnosis can be challenging in individuals with TBI because differentiating between obsessive–compulsive behaviors and neurologically driven perseveration or repetition due to poor memory may be difficult [82]. Checking and repetitive behaviors that require a significant amount of time and interfere with daily functioning should raise concern about the possibility of OCD [82].
Neuropsychiatric and behavioral sequelae
Assessment of psychiatric disorders following TBI: A biopsychosocial approach
Relevant premorbid factors
Emotional and behavioral functioning
Injury-related factors
Awareness of deficits/cognitive impairment
Risk factors
Epidemiology, clinical presentation, and treatment
Psychiatric problems
Core features
Correlates
First-(and second)-line medication management
Major depression
Episodes of sadness, loss of pleasure, feelings of hopelessness or worthlessness, and suicidal thoughts, with or without psychosis
Lesions to left dorsolateral frontal and/or basal ganglia regions
Selective serotonin reuptake inhibitors (SSRIs)
Poor pre-TBI psychosocial functioning
Tricyclic antidepressants (TCAs)
Mania
Episodes of irritability and/or elated mood, increased energy, impulsivity with or without psychosis
Lesions to temporal lobe and right orbitofrontal cortex
Valproate (lithium)
Psychosis
Loss of touch with reality, disorganized thought process, and presence of hallucinations and/or delusions
TBI prior to adolescence
Atypical antipsychotics (typical antipsychotics)
Congenital neurological disorder
Frontal and temporal lesions
Anxiety
Feeling of apprehension, panic or dread, with or without autonomic signs/symptoms
Lesions to the right hemisphere in anxious depression
SSRIs (short-term benzodiazepines)
PTSD symptoms include reexperiencing the trauma, avoidant behavior, emotional numbing, and hypervigilance
PTSD more common with mild TBI
Apathy
Lack of motivation and initiative in the absence of dysphoria
Damage to the mesial frontal lobe and its subcortical structures
Psychostimulants, dopamine agonists
Insomnia
Problems falling or staying asleep or early morning awakenings
Mild TBI, depression, anxiety, and pain
Sleep hygiene prior to initiation of medications
Trazodone, mirtazapine (short-term sedative/hypnotic)
Anger/aggression
Verbal outbursts, physical assaults, property destruction
Preinjury substance abuse and aggressive behavior, frontal lobe injuries
Beta-blockers
Valproate, SSRIs (antipsychotics in acute setting)
Depression
Treatments
Mania
Treatment
Anxiety disorders, obsessive–compulsive disorder, and trauma- and stressor-related disorders
Acute stress disorder/posttraumatic stress disorder
Generalized anxiety disorder
Panic disorder
Obsessive–compulsive disorder
Treatment of anxiety disorders, OCD, and trauma-and stressor-related disorders
Related posts:
ICU care: surgical and medical management—systemic treatment
Out-of-hospital management in traumatic brain injury
Emergency department evaluation of mild traumatic brain injury
Neuroimaging in traumatic brain injury
Follow-up and community integration of mild traumatic brain injury
ICU care: surgical and medical management—neurological monitoring and treatment
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
