Traumatic Brain Injury and Psychosis: Clinical Considerations

January 16, 2018

Psychosis can preexist TBI, and psychosis may increase the risk of TBI. This review, however, focuses on cases of psychosis following TBI.

Premiere Date: January 20, 2018
Expiration Date: July 20, 2019

This activity offers CE credits for:

1. Physicians (CME)
2. Other

All other clinicians either will receive a CME Attendance Certificate or may choose any of the types of CE credit being offered.

ACTIVITY GOAL

To understand the manifestation of psychosis as a sequela of traumatic brain injury.

LEARNING OBJECTIVES

At the end of this CE activity, participants should be able to:

• Describe the clinical features of psychosis following traumatic brain injury (PFTBI)

• Explain the risk factors associated with PFTBI

• Assess and manage PFTBI

TARGET AUDIENCE

This continuing medical education activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.

CREDIT INFORMATION

CME Credit (Physicians):This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of CME Outfitters, LLC, and Psychiatric Times. CME Outfitters, LLC, is accredited by the ACCME to provide continuing medical education for physicians.

CME Outfitters designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Note to Nurse Practitioners and Physician Assistants: AANPCP and AAPA accept certificates of participation for educational activities certified for AMA PRA Category 1 Credit ™.

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Robert van Reekum, MD, FRCPC, has no disclosures to report.

Emma Alaine van Reekum has no disclosures to report.

Daryl Fujii, MD, (peer/content reviewer) has no disclosures to report.

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Dr. van Reekum is Assistant Clinical Professor, Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada and Assistant Professor, Department of Psychiatry, University of Toronto, Toronto; Ms. van Reekum is a medical student, McMaster University School of Medicine, Hamilton, ON.

Patients with traumatic brain injury (TBI) and their caregivers are often faced with significant distress (for the patient and his or her family), functional impairment, disability, challenges for rehabilitation and treatment teams, and costs to themselves and society. Although not adequately studied to date, it is likely that all of these consequences are exacerbated when TBI and psychosis co-occur. Psychosis can preexist TBI, and psychosis may increase the risk of TBI. This review, however, focuses on cases of psychosis following TBI (PFTBI).

Psychotic symptoms may also manifest in the period immediately following coma post-TBI, when patients may experience fluctuating levels of arousal, cognitive confusion, and episodic agitation-a clinical presentation that strongly resembles delirium. Psychotic symptoms that arise during this period, generally termed “post-traumatic amnesia,” usually resolve and are not addressed in this paper, beyond noting that if antipsychotic medications (eg, ziprasidone) are used to treat psychosis and/or agitation, they should be used only if necessary (ie, for safety and comfort), at very low doses, and with frequent attempts at dose reduction and discontinuation.

It is hoped that this review will be of assistance to clinicians who work with individuals suffering from PFTBI-while also highlighting the limitations of the research available to inform treatment decisions. Caution about the conclusions and recommendations offered in this article is warranted given the relative dearth of methodologically sound research to date.

A diagnosis of TBI requires exposure of the head to acceleration and/or deceleration forces, along with the clinical evidence available at the time of, or immediately after, this exposure. The clinical presentation of TBI includes an alteration in consciousness, and/or in cognition, and sometimes neurological signs (eg, pupillary abnormalities, changes in reflexes). Typical TBI-related sequelae (eg, cognitive impairment, post-concussive symptoms) are not diagnostic of TBI nor required for the diagnosis of TBI.

Psychotic symptoms may include any of a number of symptoms/impairments, including hallucinations, delusions, and thought disorders (eg, tangentiality, loosening of associations). Negative symptoms such as apathy and cognitive impairment are sometimes included in the definition of psychosis; this is problematic in the case of TBI because apathy and cognitive impairment are common post-TBI and are likely related to TBI pathology that involves anterior temporal and frontal systems.1 Thus, we recommend that a diagnosis of PFTBI be restricted to cases of TBI in which hallucinations, delusions, or thought disorders arise after the TBI. Indeed, this approach seems to be the one generally taken in the available research literature. The exception (for which there is little/no research available) may be in cases of TBI in which the recovery of motivational or cognitive functioning plateaus earlier than expected, or in which a decline in motivational or cognitive functioning is seen. In these cases, it is important to consider and assess for other potential causes (eg, complications of TBI such as hydrocephalus; onset of delirium due to medical/metabolic factors; mood disorder; medication adverse effects).

Clinical features of PFTBI

The research into psychosis post-TBI has thus far lacked standardized operational definitions and criteria, and has employed various terms such as PFTBI, schizophrenia-like psychosis, and psychotic disorder due to TBI or general medical condition. Research also varies with respect to the type of psychotic symptoms being assessed for; consequently, findings have also varied, perhaps at least in part for these reasons. Nonetheless, some common themes appear to have emerged. Delusions and hallucinations are likely to be the most common features seen in PFTBI.2 Delusions tend to be persecutory in nature; however, a full range of delusional themes can be seen (eg, grandiosity, religiosity, misidentification). Hallucinations are most often auditory but can also be visual. Olfactory and gustatory hallucinations can also occur post-TBI, most often in relation to seizures.3

Behavioral disturbances, including agitation and aggression, are often present.3 Negative symptoms, such as apathy, are also frequent, although they may be less common than in schizophrenia. Comorbid cognitive impairments, particularly involving attention, memory, and executive/frontal functions, are common. Cognitive impairments generally resemble those seen in schizophrenia and in TBI (in the absence of psychosis).

Time to onset of PFTBI has been found to vary considerably. Typical onset is within the first year or two after the TBI; however, some data indicate the mean time to onset may be greater than this, at roughly 55 months.4 The latter finding should be interpreted with caution because of the wide range of time to onset, from weeks to nearly 2 decades was observed.5 Other findings indicate that the rate at which PFTBI arises does not vary significantly over time (up to a maximum of 17 years’ follow-up) post-TBI.5 It appears that psychotic symptoms can arise at any time post-TBI.

Because of their similarity to psychosis seen in other disorders (eg, schizophrenia, mood disorders), the clinical features of PFTBI cannot be relied on to distinguish between various diagnostic possibilities. Rather, differential diagnosis must rely on prior history, presence of associated symptoms and, when present, neuroimaging abnormalities consistent with TBI (eg, hemorrhagic contusions, diffuse axonal injury). Guerreiro and colleagues6 suggest that neuropsychological and laboratory testing, along with EEG, may be useful in distinguishing PFTBI from other psychotic disorders.

It should be noted that TBI appears to considerably increase the risk of mood disorders and of schizophrenia or bipolar disorder.2,7 As such, PFTBI may arise as part of another disorder such as schizophrenia. Indeed, it remains uncertain that PFTBI exists as a separate entity; it may be that PFTBI should be managed as would psychosis caused by any other mental illness. Because diagnostic certainty cannot be ensured, clinicians must maintain a flexible approach, with ongoing assessment over time.

Epidemiology

Findings in adult populations have varied widely, from 0% to 20%.5,8 Most studies place the incidence of psychotic symptoms in the 3% to 8% range.9 Duration of psychotic episodes and prevalence (aside from point prevalence) have not been well studied. A meta-analysis yielded an odds ratio of 1.65 for schizophrenia following moderate to severe TBI.10 Another review concluded that the initial severity of TBI may influence the frequency of subsequent psychosis, with rates of 2% to 5% in mild to moderate cases, and 10% or more in severe cases.11 However, this conclusion has not been adequately validated, and other studies have found that the initial severity of the TBI does not influence the frequency of subsequent psychosis.12 Overall, the frequency of PFTBI appears to be much lower than that of mood and anxiety disorders post-TBI.7

Risk factors for PFTBI

Research into risk factors for PFTBI has been relatively sparse and has yielded significantly different (and sometimes diametrically opposed) results. The Table presents potential risk factors for PFTBI. In addition, mood and seizure disorders post-TBI may lead to psychosis.3,13 The presence of psychotic symptoms has also been noted in individuals who have developed chronic traumatic encephalopathy following exposure to repeated acceleration-deceleration forces directed toward the head.14

Monitoring for the future onset of psychosis in the TBI population is clearly warranted. Our current understanding suggests some possible risk factors for future onset of PFTBI; however, the limitations of the research data highlight the importance of monitoring for PFTBI in all cases of TBI. Remediation of modifiable risk factors (eg, cessation of psychoactive drug use, improvement in sleep) is likely to be important in the management of PFTBI when it does arise, and consideration of the possible risk factors (eg, caution with medications such as dopaminergic agents, efforts to reduce substance use) might contribute to reduction in the future onset of PFTBI.

Approach to differential diagnosis

The first step in working through the differential diagnoses for PFTBI is to determine whether symptoms are truly psychotic in nature, versus the affective, behavioral, cognitive, and motivational impairments often seen after TBI. This differentiation can be particularly problematic for cognitive symptoms, such as the identification of delusions versus confabulation, or thought disorder versus cognitive impairment. Evoking the possibility of psychosis as a cause for these impairments often involves assessment for premature plateauing (eg, less than 2 years or so after the TBI) or worsening of impairments. If this is the case, additional assessments should be conducted to rule out other possible causes (eg, hydrocephalus, onset of seizure disorder, medical illnesses, substance use).

Assessment for hallucinations is also not without challenge, in large part because of possible cognitive impairments such as lack of insight and communication impairments after TBI.15

Reliance on all sources of data, including the observations of family members and the rehabilitation team, is important. Any change in affect, behavior, cognition, motivation, or functioning should elicit at least consideration for the possibility of PFTBI. The second step in working through the differential diagnosis of PFTBI follows determining that psychotic symptoms are present, and involves identification of potential risk factors and of potential causative comorbidities.

Mechanisms

TBI can produce disturbances in neurotransmitter systems (eg, dopamine, acetylcholine) and, more generally, in neuronal systems (particularly involving frontal, temporal, and subcortical structures).3,7 It is at least possible that these neurobiological disturbances underlie the production of psychotic symptoms in many cases of PFTBI. Although the cerebral lateralization of TBI pathology and consequent production of psychotic symptoms have been examined, the research is limited and has produced contradictory results.16,17 This is not surprising given that TBI tends to produce widespread cerebral pathology (eg, coup-contrecoup contusional lesions, diffuse axonal injury).

Factors such as seizure disorder, mood disorders, and substance use may contribute to the onset of PFTBI. It may be that TBI-and its associated stresses and losses-also leads to a stress-diathesis interaction with preexisting neurobiological vulnerability.18 It may also be that the cognitive impairments of TBI lead to psychotic symptoms, with semantic processing, language, and executive impairments and impaired verbal memory/learning implicated as potential contributors.5

Clinical management

Assessment for PFTBI involves a full history and complete medical, neurological, and mental status examinations. Use of neuropsychiatric symptom inventories can be helpful for initial quantification of psychotic symptom severity and for monitoring treatment response over time. Evaluation for potential contributors to the psychotic symptoms should be considered, including metabolic/drug testing and EEG (should seizures be suspected). It is unlikely that currently available neuroimaging modalities (eg, CT, MRI) are helpful in the assessment of PFTBI.

There is little evidence for pharmacological management of PFTBI, and to the best of our knowledge, there are no randomized clinical trials. As such, pharmacological interventions should be considered with caution, especially given the likelihood of increased risk of adverse effects in the TBI population with most available agents. Indeed, it is prudent to question whether psychotic symptoms warrant pharmacological intervention with each patient; factors such as the level of distress and/or the behavioral/functional impairment resulting from the psychotic symptoms should be considered.

Not all psychotic symptoms require pharmacological intervention. As a general recommendation, it is probably most appropriate to first treat delirium, seizure disorder, mood disorder, and substance disorders if present, and to eliminate any potential contributing medications. Exceptions include cases in which the psychotic symptoms are producing significant distress, safety risk, and/or significant behavioral/functional impairments. In particular, first-generation antipsychotics should be avoided given the increased risk of falls, parkinsonian adverse effects, tardive dyskinesia, and possible delay of neuronal recovery post-TBI.

Antipsychotics with significant anticholinergic activity should also be avoided, particularly given the risk of worsening TBI sequelae such as anergia and attentional/memory impairment. Low doses of second-generation antipsychotics may be first-line agents for PFTBI that is causing significant distress and/or behavioral/functional impairment. Arciniegas and colleagues19 recommend starting doses of one-third to one-half of the usual starting dose for PFTBI. Periodic trials of decreasing doses and discontinuing medications altogether are advised given the risks of antipsychotic medications in the TBI population.

Non-pharmacological interventions for PFTBI have received little in the way of research attention but are widely used in clinical practice. It is likely that rehabilitation with a focus on cognitive, behavioral, affective, and functional impairments of TBI will also be of benefit for PFTBI. However, PFTBI may limit the ability of the affected individual to participate in, and benefit from, rehabilitation efforts; when this is the case, considerable multidisciplinary planning and problem-solving may be required. Pharmacological interventions may first be necessary in some cases.

Conclusions

Clearly, much more research into our understanding and management of PFTBI is warranted and required. In the meantime, clinical judgment, with a focus on minimizing risk, is necessary. TBI commonly produces impairments in mood, behavior, motivational functioning, and cognition, and less commonly is associated with psychosis. When present, psychotic symptoms can exacerbate TBI impairments and result in distress, safety risk, and reduced response to rehabilitation efforts.

Monitoring for future onset of psychosis in the TBI population is clearly warranted. Our current understanding suggests some possible risk factors for future onset of PFTBI; however, the limitations of the research data highlight the importance of monitoring for PFTBI in all cases of TBI. A history should be taken with respect to the possibility of previous TBI for all patients with psychosis who present to a mental health clinic or primary care center.

Clinicians may find working with PFTBI cases to be difficult and disconcerting. Teamwork, ideally involving multiple disciplines and areas of expertise, should be stressed for both the patient’s and the provider’s benefit.

 

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References:

1. van Reekum R, van Reekum EA. Apathy. In: Arciniegas D, Jaffee M, Vanderploeg R, Zasler N, eds. Clinical Manual for the Management of Adults With Traumatic Brain Injury. Arlington, VA: American Psychiatric Publishing; 2013:283-302.

2. Stefan A, Mathe JF, for the SOFMER group. What are the disruptive symptoms of behavioral disorders after traumatic brain injury? A systematic review leading to recommendations for good practices. Ann Phys Rehab Med. 2016;59:5-17.

3. Fujii D, Ahmed I. Psychotic disorder following traumatic brain injury: a conceptual framework. Cog Neuropsychiatry. 2002;7:41-62.

4. Sachdev P, Smith JS, Cathcart S. Schizophrenia-like psychosis following traumatic brain injury: a chart-based descriptive and case-control study. Psychol Med. 2001;31:231-239.

5. Batty R, Rossell SL, Francis AJP, Ponsford J. Psychosis following traumatic brain injury. Brain Impair. 2013;14:21-41.

6. Guerreiro DF, Navarro R, Silva M, et al. Psychosis secondary to traumatic brain injury. Brain Inj. 2009;23:358-361.

7. van Reekum R, Cohen T, Wong J. Can traumatic brain injury cause psychiatric disorders? J Neuropsychiatry Clin Neurosci. 2000;12:316-327.

8. Sudarsanan BS, Chaudhary S, Pawar AA, Srivastava K. Psychiatric effects of traumatic brain injury. Med J Armed Forces India. 2007;63:259-263.

9. Bhalerao SU, Geurtjens C, Thomas GR, et al. Understanding the neuropsychiatric consequences associated with significant traumatic brain injury. Brain Inj. 2013;27:767-774.

10. Molloy C, Conroy RM, Cotter DR, Cannon M. Is traumatic brain injury a risk factor for schizophrenia? A meta-analysis of case-controlled population-based studies. Schizophr Bull. 2011;37:1104-1110.

11. Gualtieri T, Cox DR. The delayed neurobehavioural sequelae of traumatic brain injury. Brain Inj. 1991;5:219-232.

12. Sherer M, Yablon SA, Nick TG. Psychotic symptoms as manifestations of posttraumatic confusional state: prevalence, risk factors, and association with outcome. J Head Trauma Rehab. 2014;29:11-18.

13. McHenry M, Wilson R. The challenge of unintelligible speech following traumatic brain injury. Brain Inj. 1994;8:363-375.

14. DeKosky ST, Blennow K, Ikonomovic MD, Gandy S. Acute and chronic traumatic encephalopathies: pathogenesis and biomarkers. Nat Rev Neurol. 2013;9:192-200.

15. Draper J, Ponsford J. Cognitive functioning ten years following traumatic brain injury and rehabilitation. Neuropsychol. 2008;22:618-625.

16. Borek LL, Butler R, Fleminger S. Are neuropsychiatric symptoms associated with evidence of right brain injury in referrals to a neuropsychiatric brain injury unit? Brain Inj. 2001;15:65-69.

17. Cummings JL. Neuropsychiatric manifestations of right hemisphere lesions. Brain Lang. 1997;57:22-37.

18. Kim E. Does traumatic brain injury predispose individuals to develop schizophrenia? Curr Opin Psychiatry. 2008;21:286-289.

19. Arciniegas DB, Harris SN, Brousseau KM. Psychosis following traumatic brain injury. Int Rev Psychiatry. 2003;15:328-340.

20. Kim E, Lauterbach EC, Reeve A, et al. Neuropsychiatric complications of traumatic brain injury: a critical review of the literature (a report by the ANPA committee on research). J Neuropsychiatric Clin Neurosci. 2007;19:106-127.

Additional reading

• Fujii DE, Ahmed I. Psychotic disorder caused by traumatic brain injury. Psychiatr Clin North Am. 2014;37:113-124.

• Halbauer JD, Ashford JW, Zeitzer JM, et al. Neuropsychiatric diagnosis and management of chronic sequelae of war-related mild to moderate traumatic brain injury. J Rehab Res Devel. 2009;46:757-796.

• Hesdorffer DC, Rauch SL, Tamminga CA. Long-term psychiatric outcomes following traumatic brain injury: a review of the literature. J Head Trauma Rehab. 2009;24:452-459.

• Lee HB, Lyketsos CG, Rao V. Pharmacological management of the psychiatric aspects of traumatic brain injury. Int Rev Psychiatry. 2003;15:359-370.

• Luz WE. A neuropsychiatric perspective on traumatic brain injury. J Rehab Res Devel. 2007;44:951-962.