International Review of Psychiatry

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Psychosis following traumatic brain injury

David B. Arciniegas, Susie N. Harris & Kristin M. Brousseau

To cite this article: David B. Arciniegas, Susie N. Harris & Kristin M. Brousseau (2003) Psychosis
following traumatic brain injury, International Review of Psychiatry, 15:4, 328-340, DOI:
10.1080/09540260310001606719

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Published online: 11 Jul 2009.

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International Review of Psychiatry (November 2003), 15, 328–340

Psychosis following traumatic brain injury

DAVID B. ARCINIEGAS,1,2,3 SUSIE N. HARRIS1,3 & KRISTIN M. BROUSSEAU1,3

1
Neuropsychiatry Service, Department of Psychiatry; 2Behavioral Neurology Section, Department of Neurology,
University of Colorado Health Sciences Center, Denver, CO; 3Brain Injury Rehabilitation Unit,
Spalding Rehabilitation Hospital, Aurora, CO, USA

Summary
Psychosis is a relatively infrequent but potentially serious and debilitating consequence of traumatic brain injury (TBI), and one about
which there is considerable scientific uncertainty and disagreement. There are several substantial clinical, epidemiological, and
neurobiological differences between the post-traumatic psychoses and the primary psychotic disorders. The recognition of these differences
may facilitate identification and treatment of patients whose psychosis is most appropriately regarded as post-traumatic. In the service of
assisting psychiatrists and other mental health clinicians in the diagnosis and treatment of persons with post-traumatic psychoses, this
article will review post-traumatic psychosis, including definitions relevant to describing the clinical syndrome, as well as epidemiologic,
neurobiological, and neurogenetic factors attendant to it. An approach to evaluation and treatment will then be offered, emphasizing
identification of the syndrome of post-traumatic psychosis, consideration of the differential diagnosis of this condition, and careful
selection and administration of treatment interventions.

Introduction (Hillbom, 1960; Fujii & Ahmed, 1996) and/or

Psychosis is a relatively infrequent but potentially
serious and debilitating consequence of traumatic
brain injury (TBI). However, the role of TBI in the
genesis of psychosis is a complex matter about which
there is considerable scientific uncertainty and
disagreement. Although the frequency of psychosis
following TBI exceeds that of the general population
(Davison & Bagley, 1969; Achte et al., 1969; Achte
et al., 1991), there is often a considerable delay
between TBI and the onset of psychotic symptoms
(Fujii & Ahmed, 1996; Fujii & Ahmed, 2001;
Sachdev et al., 2001). Once psychosis develops, the
constellation of post-traumatic psychotic symptoms
may be difficult to distinguish from those of
schizophrenia (Sachdev et al., 2001), complicating
the determination of the relationship, where
such exists, between an often remote TBI and a
recent-onset psychosis.
Nonetheless, there are important clinical, epide-
miological, and neurobiological differences between
the post-traumatic psychoses and the primary
psychotic disorders (e.g., schizophrenia, schizoaffec-
tive disorder). The post-traumatic psychoses are
often ‘atypical’ with regard to age of onset (Fujii &
Ahmed, 2001; Sachdev et al., 2001; Fujii & Ahmed,
2002), symptom types (Goethe & Levin, 1984),
neuroimaging findings (Fujii & Ahmed, 2002), and
the presence of comorbid conditions such as epilepsy
associated cognitive impairment (Fujii & Ahmed,
2002) when compared to the primary psychotic
disorders. These differences between psychosis due
to TBI and the primary psychotic disorders suggest
that TBI may be more than a risk factor for the
development of the primary psychotic disorders;
it may in some cases be an etiology of psychosis in its
own right.
Understanding the clinical and neurobiological
features of post-traumatic psychosis may advance our
understanding of the nature of psychosis in general
as well as facilitate identification and treatment of
post-traumatic psychosis specifically. These latter
issues are particularly relevant for clinicians working
in general psychiatric settings, in which recognizing a
patient’s psychosis as post-traumatic will further
entail consideration and/or treatment of additional
neuropsychiatric problems (i.e., seizures, cognitive
impairment) that may affect that patient’s clinical
presentation and response to treatment.
In the service of assisting psychiatrists and other
mental health clinicians with the diagnosis and
treatment of persons with post-traumatic psychoses,
this article will review post-traumatic psychosis,
including definitions relevant to describing the
clinical syndrome, as well as epidemiologic, neuro-
biological, and neurogenetic factors attendant to
it. An approach to evaluation and treatment will
then be offered, emphasizing identification of the

Correspondence to: David B. Arciniegas, MD, Director, Neuropsychiatry Service, University of Colorado Health
Sciences Center, Campus Box C268-68, 4200 East Ninth Avenue, Denver, CO 80262, USA. Tel: þ1 (303) 315 5365;
Fax: þ1 (303) 315 5641; E-mail: David.Arciniegas@UCHSC.edu
ISSN 0954–0261 print/ISSN 1369–1627 online/03/040328–13 ß Institute of Psychiatry
DOI: 10.1080/09540260310001606719

syndrome of post-traumatic psychosis, conditions
relevant to its differential diagnosis, and selection of
pharmacotherapies.
Defining traumatic brain injury
At the outset, the first step in the evaluation of a
psychosis as potentially post-traumatic is deter-
mining whether the patient experienced an event
that can be characterized fairly as a TBI. Although
the Glasgow Coma Scale (GCS; Teasdale &
Jennett, 1974) is the most widely known system
for brain injury severity classification in the acute
injury period, a more recent definition of mild
traumatic brain injury (Mild Traumatic Brain
Injury Committee, American Congress of Rehabili-
tation Medicine (ACRM), Mild Head Injury
Interdisciplinary Special Interest Group, 1993) may
be of greater use to psychiatric and mental health
clinicians evaluating patients in the post-acute or
later period after TBI. This definition requires that
as a result of an external application of force to
the brain, the patient experiences at least one of the
following: any period of loss of consciousness, any
loss of memory for events immediately before or after
the accident (post-traumatic amnesia, or PTA), any
alteration in mental state at the time of the accident
(e.g., feeling dazed, disoriented, or confused), or
focal neurologic deficit(s) that may or may not be
transient. The ACRM definition of mild TBI
includes only those injuries in which loss of
consciousness is approximately 30 minutes or less,
the GCS score at 30 minutes after injury is 13–15,
and the duration of PTA is no longer than 24 hours.
Injuries exceeding these criteria are considered to be
of more than mild severity.
This definition suggests that interruption of
memory and/or other deficits in mental or centrally
mediated neurological function are to be understood
as evidence of physiological insult (i.e., injury) to the
brain. Additionally, it makes clear that loss of
consciousness is not a requisite feature of a clinically
significant TBI. Although these criteria are not
without criticism (Ruff & Jurica, 1999), they are at
present the most widely accepted definition of mild
TBI. In the absence of another universally accepted
minimum criteria set for this condition (Arciniegas &
Silver, 2001), the authors recommend using these
criteria to determine whether an event experienced
by a patient is characterized fairly as a TBI.
Clinical symptoms of post-traumatic psychosis
After determining that a patient experienced a TBI,
the next step in evaluating that patient’s psychosis
as potentially post-traumatic is deciding whether
the presentation of that psychosis is consistent
with that most often observed among patients
Psychosis following traumatic brain injury 329
with this condition. Delusions (usually persecutory)
are the most common symptoms of post-
traumatic psychosis, although combinations of delu-
sions and hallucinations (i.e., ‘schizophreniform’
or ‘schizophrenia-like’ conditions) occur as well
(Davison & Bagley, 1969; Achte et al., 1969; De
Mol et al., 1982; Cummings, 1985; Cutting, 1987;
Violon & De Mol, 1987). Achte et al. (1991) report
that delusional psychosis occurs at twice the fre-
quency of post-traumatic schizophrenia-like psycho-
sis (28% and 14%, respectively). Fujii and Ahmed
(2002) report a higher frequency of delusions (78%)
than hallucinations (47%) among persons with such
symptoms in the late period following TBI. Among
patients with post-traumatic delusions, persecutory
(38%), grandiose (15%), and/or somatic (15%) types
were most common. Similarly, Sachdev et al. (2001)
report that persecutory (56%), referential (22%),
control (22%), grandiose (20%), and/or religious
(15%) delusions are the most common types among
persons with post-traumatic psychosis.
When hallucinations occur in the context of post-
traumatic psychosis, these are most often auditory
(92%) rather than visual (32%) (Fujii & Ahmed,
2002), although the presence and type of hallucina-
tion vary as a function of time since TBI. Subjects
with relatively later onset of psychosis (> two years
following TBI) are more likely to experience halluci-
nations than those with earlier onset. Among subjects
with relatively earlier onset of psychosis, visual
hallucinations are more common than auditory
hallucinations. Delirium and other comorbid medical
issues, common in the early post-injury period, may
contribute to such differences. Clinicians should
be mindful of such conditions when evaluating
a patient whose post-traumatic psychosis occurs
early after injury and/or is predominated by visual
hallucinations.
Disturbances of thought process and ‘negative’
symptoms are neither necessary nor sufficient for the
diagnosis of post-traumatic psychosis. While deficit-
type symptoms (anhedonia, lack of spontaneity, and
loss of social contact) may occur in post-traumatic
psychosis (Thomsen, 1984), such symptoms are
less common and less prominent than post-
traumatic delusions and hallucinations (Sachdev
et al., 2001) and are substantially less common
than in schizophrenia (Fujii & Ahmed, 2002). In fact,
post-traumatic neurocognitive disturbances may
mimic the disturbances of thought and behavior of
schizophrenia and may be mistaken as such if
not otherwise identified properly. Some of the post-
traumatic aphasias resemble superficially the dis-
turbed thought process of schizophrenia, including
non-fluent speech with agrammatical (‘disorga-
nized’) structure and undue word finding pauses
(‘alogia’ and/or ‘thought blocking’). Word substitu-
tions, phonemic paraphasias, and/or neologisms may
result in apparently ‘disorganized’ speech (or even
jargon aphasia akin to ‘word salad’), but these will in
330 David B. Arciniegas et al.

many cases be better understood as symptoms of one
of the posterior aphasias (Goethe & Levin, 1984).
Additionally, post-traumatic dysfunction in frontal-
subcortical systems may produce impairments of
executive function (dorsolateral syndrome), social
and emotional regulation (orbitofrontal syndrome),
and volition or motivation (anterior cingulate
syndrome) (Arciniegas et al., 2002). As such, the
presence of disorganized speech, thought, or
behavior, catatonia, and negative symptoms should
not be used as the primary symptoms with which to
support a diagnosis of post-traumatic psychosis.
Their presence should prompt further evaluation of
the potential neurological (and post-traumatic) bases
for such symptoms or, alternatively, consideration of
a primary psychotic disorder.
The association between TBI and psychosis
After establishing the occurrence of a TBI and
determining that the patient’s psychotic symptoms
are consistent with those of post-traumatic psychosis,
the clinician must make an attempt to judge whether
there is an association between the medical condition
(i.e., TBI) and psychosis. Such an association has
been recognized since at least the early 19th century
(Proceedings on the Trial of James Hadfield, at the
Bar of the Court of the King’s Bench, for High
Treason, June 26:40 George III A.D. 1800) and is,
in the modern literature, well established (Shapiro,
1939; Davison & Bagley, 1969; Wilcox & Nasrallah,
1987; Malaspina et al., 2001). Conservative estimates
suggest that TBI increases the risk of psychosis at
least two- to three-fold over that of the general
population (Davison & Bagley, 1969; Thomsen,
1984; Violon & De Mol, 1987; Achte et al., 1991).
While these studies vary considerably with respect to
patient cohorts, diagnostic criteria used to define
post-traumatic psychosis, and the period of follow-
up over which such observations were made, they
consistently suggest that the TBI is associated with
psychosis.
However, the temporal relationship between TBI
and psychosis may not be immediately apparent in
an individual patient. Although psychosis may
develop shortly after TBI (Achte et al., 1969), this
condition in many cases develops only after a latency
of many months to years (Achte et al., 1969; Buckley
et al., 1993; Fujii & Ahmed, 1996; Feinstein & Ron,
1998; Fujii & Ahmed, 2001; Sachdev et al., 2001;
Fujii & Ahmed, 2002). The majority of these reports
suggest that latency periods between TBI and new-
onset psychosis of four or more years are not
uncommon. Because of this considerably long
latency period, establishing a temporal relationship
between TBI and psychosis is at best difficult and
will, in any individual case, most likely remain a
source of uncertainty for the treating clinician.
Nonetheless, in the absence of factors that better
account for the development of psychotic symptoms,
the present literature suggests that clinicians should
not dismiss TBI as an etiologic factor in the
development of psychotic symptoms based only on
a relatively long interval between these events. Quite
the contrary, clinicians should remain open to
considering a diagnosis of psychosis due to TBI
even in a patient whose psychotic symptoms first
develop many years after the initial injury.
Risk factors for post-traumatic psychosis
Further consideration of a individual patient’s
psychosis in the context of TBI, and in particular
determining whether that psychosis is a direct
physiologic consequence of TBI, may be made
more sophisticated by identifying pre-injury, injury-
related, and post-injury risk factors for post-
traumatic psychosis (Table 1). At the outset, it is
important to note that our understanding of these
risk factors remains uncertain and an area of active
investigation. Nonetheless, clinicians evaluating
patients with psychosis and TBI should be aware of
those factors about which there is published data.
Pre-injury factors
Male gender (Fujii & Ahmed, 2002), pre-injury
neurodevelopmental and neuropsychiatric problems
(Violon & De Mol, 1987; Fujii & Ahmed, 2001), and

Table 1. Pre-injury, injury-related, and post-injury risk factors for posttraumatic psychosis

Pre-injury factors Injury factors Post-injury factors

Male gender Greater severity of TBI
Neurodevelopmental disorders Neuroimaging abnormalities
Neurological disorders, including prior TBI Frontal injury
Psychiatric disorders Temporal injury
Substance disorders Generalized atrophy
Family history of schizophrenia Laterality of injury
Left or both hemispheres:
Schizophreniform symptoms
Right hemisphere:
Predominantly delusional
symptoms
Electroencephalographic abnormalities
Asymmetric temporal slowing
Intermittent spikes
Post-traumatic epilepsy
Cognitive impairments
Memory
Visuospatial function
Executive function
Other posttraumatic
psychiatric disorders
Substance use disorders

family history of schizophrenia (Malaspina et al.,
2001; Sachdev et al., 2001) are among the strongest
pre-injury risk factors for post-traumatic psychosis.
The nature of the association between these factors
and post-traumatic psychosis remains uncertain.
The findings of Fujii and Ahmed (2001) suggest
that there may be an interaction between male
gender and prior neurological or neurodevelopmen-
tal problems, and that this interaction may contribute
to the association between male gender and risk
of post-traumatic psychosis. However, pre-injury
psychiatric, neurodevelopmental, and neurological
conditions also appears to contribute to the risk of
developing post-traumatic psychosis irrespective
of gender (Violon & De Mol, 1987; Fujii &
Ahmed, 2001).
There may also be an interaction between family
history of schizophrenia and TBI in which family
history increases not only the likelihood of psychosis
after TBI but also the likelihood of TBI within these
families (Malaspina et al., 2001; AbdelMalik et al.,
2003). This interaction may reflect genetically
mediated cognitive (i.e., attentional, executive) dis-
turbances, propensity for risk-taking behaviors, and/
or other psychosocial factors among persons with
TBI and a family history of schizophrenia. However,
such interpretations are at best speculative and
require further investigation.
Injury factors
Severity and locus/laterality of injury appear to be
associated with risk of post-traumatic psychosis.
Greater severity of traumatic brain injury has been
associated with the development of post-traumatic
psychosis (Davison & Bagley, 1969; Sachdev et al.,
2001), varying from 2.8% among patients with
relatively more mild TBI to 14.8% among those
with severe TBI (Hillbom, 1960). Fujii and Ahmed
(2002) also observed a high rate (65%) of clinically
significant neuroimaging abnormalities (suggesting
relatively more severe TBI) among patients with
post-traumatic psychosis. However, the association
between TBI severity and post-traumatic psychosis is
not without controversy (Violon & De Mol, 1987;
Fujii & Ahmed, 2001; Malaspina et al., 2001).
Psychosis may develop after even a relatively mild
TBI and clinicians should not discount the possibil-
ity of a diagnosis of post-traumatic psychosis based
solely on a history of a relatively mild TBI.
Aggregating data from many published cases of
post-traumatic psychosis, Fujii and Ahmed (2002)
report that the temporal and frontal lobes appeared
to be the most commonly affected areas in the post-
traumatic psychoses, consistent with observations
among persons with psychosis in other neurological
conditions (Cummings, 1992; Edwards-Lee &
Cummings, 2000) and with primary psychotic
disorders such as schizophrenia (Thompson et al.,
Psychosis following traumatic brain injury 331
2001). Although Fujii and Ahmed (2002) report
comparable rates of focal abnormalities and general-
ized atrophy (62% and 60%, respectively) among
persons with post-traumatic psychosis, focal lesions
when present were most commonly frontal and
temporal.
Laterality of injury may also be relevant to the
development and type of post-traumatic psychosis.
Left hemispheric, and in particular left temporal,
or bihemispheric injury is most strongly associated
with the development of a schizophreniform post-
traumatic psychosis (Hillbom, 1960; Davison &
Bagley, 1969; Sachdev et al., 2001). By contrast,
right hemispheric injury is more commonly asso-
ciated with the development of delusions alone
(Cummings, 1992; Edwards-Lee & Cummings,
2000; Arciniegas et al., 2001).
Post-injury factors
Among the many post-injury factors potentially
relevant to the development of post-traumatic
psychosis, electroencephalographic (EEG) abnor-
malities, post-traumatic epilepsy, and cognitive
impairments appear to be most strongly associated
with this condition. Electroencephalographic abnor-
malities are observed in as many as 70% of persons
with post-traumatic psychosis (Fujii & Ahmed,
2002). Approximately half (55%) of these EEG
abnormalities are localized, with the modal abnor-
mality being asymmetric temporal slowing. Less
commonly, intermittent spikes are seen. While it is
tempting to posit causal relationships between EEG
abnormalities and ‘psychotic’ symptoms related to
the functions served by the areas in which such
abnormalities occur, the nature of the association
between such findings and post-traumatic psychosis
remains, at present, a matter of speculation.
Approximately 33–58% of patients with post-
traumatic psychosis also experience post-traumatic
seizures (Hillbom, 1960; Fujii & Ahmed, 1996),
which exceeds the frequency of post-traumatic
epilepsy more generally (1–12%) (Annegers et al.,
1980; McKenna et al., 1985). However, this
association is not without controversy (Sachdev,
2001), and the temporal relationship between TBI,
post-traumatic epilepsy, and post-traumatic psycho-
sis is in some cases indeterminable (Davison &
Bagley, 1969). Some will undoubtedly find it
tempting to suggest that subclinical or simple partial
seizures may underlie ‘psychotic’ (and particularly
hallucinatory) symptoms among persons with sig-
nificant post-traumatic EEG abnormalities and/or
post-traumatic epilepsy. However, it is possible that
the presence of clinically significant EEG abnor-
malities and post-traumatic epilepsy among persons
with post-traumatic psychosis merely reiterates the
association between severity of TBI and all of these
problems.
332 David B. Arciniegas et al.
Nonetheless, because the occurrence of psychotic
symptoms among persons with post-traumatic
epilepsy carries both diagnostic, and treatment impli-
cations, clinicians should make efforts to evaluate
patients for seizures and, when present, the relation-
ship of such to the psychotic symptoms. Psychotic
symptoms may occur during or immediately after the
seizure (peri-ictal), in which case they are episodic,
or they may occur inter-ictally, in which case they
tend to be more chronic (Trimble, 1991; McAllister
& Ferrell, 2002). Symptoms arising in the former
context suggests the need for more aggressive anti-
convulsant treatment, while those arising in the latter
context may require treatment with both anti-
convulsant and anti-psychotic agents (Arciniegas
et al., 2001).
Fujii and Ahmed (2002) report that approximately
88% of patients with post-traumatic psychosis
demonstrate clinically significant impairments on
neuropsychological testing, including deficits in
memory, executive function, and visuospatial func-
tion. As Cummings (1992) suggests, such dysfunc-
tion could then result in impaired assessment of
environmental information or misattribution of
internal information to the environment (hallucina-
tions, illusions), produce incorrect assignment of
danger to this information (delusions), or foster
inappropriate fear and threatened behavior (para-
noia). It is possible that remediation of cognitive
impairments following TBI may be a useful compo-
nent of the treatment of post-traumatic psychosis and
the functional impairments it produces.
Additional post-injury factors, including other
post-traumatic psychiatric and/or substance dis-
orders, may also contribute to the development of
post-traumatic psychotic symptoms. Evaluation of
these should be included in the assessment of persons
with psychosis following TBI, although both their
contribution to a patient’s psychosis and potential
relevance to the treatment of that psychosis will, for
the present, remain a matter of individual clinical
judgment.
Evaluation of the patient with
psychosis following TBI
The evaluation of a patient with psychosis following
TBI (Table 2) begins with a careful injury history
and determination that the patient experienced
an injury that is characterized fairly as a TBI.
The evaluation must also include a comprehensive
assessment of current symptoms, neurodevelopmen-
tal history, pre- and post-injury medical, neurologi-
cal, psychiatric, and substance disorders, and also a
family history. Obtaining collateral and corroborative
history is a necessity in these cases, since the brain-
injured patient may not recall accurately important
details of the history due to the neurocognitive effects
of the TBI, his or her psychosis, or both. Thorough
physical and neurological examinations and a
detailed mental status examination are requisite
elements of the clinical assessment.
With regard to the psychosis more specifically, the
evaluation should confirm that the symptom profile
is predominantly hallucinatory (usually auditory)
and/or delusional (usually persecutory), and that
thought disturbance, catatonia, and negative symp-
toms, if present at all, are not the predominant ones.
Additionally, the evaluation should support the
clinician’s judgment that these symptoms are not
accounted for by another medical or mental dis-
order, including a post-traumatic or other delirium.
Structural neuroimaging (i.e., preferably using
magnetic resonance imaging) may provide evidence
of a TBI, and the authors recommend undertaking
such studies following the first-onset of psychotic
symptoms in this or any other context. Additionally,
structural neuroimaging should be obtained if the
patient’s psychosis is atypical for a primary psychotic
disorder, and/or the clinical examinations demon-
strate any abnormalities in elemental neurological or
cognitive function. If the history suggests the
possibility of a seizure disorder, an EEG should
also be obtained. Neuropsychological testing should
be undertaken to clarify the types and severities of
cognitive impairments, as well as the potential for
their remediation through rehabilitative therapies
(Cicerone & Giacino, 1992; Cicerone et al., 1996;
Cicerone et al., 2000).
Findings from the evaluation serve not only to
characterize the patient and his or her psychosis, but
also to identify other cognitive, emotional, behav-
ioral, or neurological problems that may influence
diagnosis, treatment selection, expectation of
therapeutic response, and prognosis. Treatment
selection in this population requires consideration
of the reciprocal effects between such conditions and
Table 2. Essential elements of the neuropsychiatric evaluation
of a patient with psychosis and TBI
History of present illness/current symptoms
Patient account
Collateral/corroborative history
(i.e., witness accounts, medical records, etc.)
Injury history
Medical and neurological history (pre-/post-injury)
Psychiatric history (pre-/post-injury)
Substance use disorder (pre-/post-injury)
Neurodevelopmental history
Family history (psychiatric, neurological, and medical)
Social history
Mental status examination
General
Cognitive
Neurobehavioral (i.e., Neuropsychiatric Inventory,
Neurobehavioral Rating Scale, etc.)
Physical examination
Neurological examination
Structural neuroimaging (MRI preferable)
Laboratory testing (if indicated clinically)
Electroencephalogram (if indicated clinically)
Neuropsychological testing (if indicated clinically)

the patient’s psychosis, the beneficial and potentially
adverse effects of treatments offered for each, and the
integration of anti-psychotic medications with other
rehabilitative, neuropharmacologic, behavioral, and
social interventions.
Differential diagnosis of psychosis due to TBI
Post-traumatic psychosis may develop in the context
of several other post-traumatic syndromes, including
post-traumatic amnesia (or post-traumatic confu-
sional state), post-traumatic epilepsy, post-traumatic
mood disorders, and medication or substance
intoxication or withdrawal states (Table 3). The
occurrence of psychotic symptoms that are best
accounted for by any of these conditions precludes a
diagnosis of psychosis due to TBI. However,
psychotic symptoms that first manifest in one of
these other conditions (e.g., during post-traumatic
amnesia) may persist after resolution of that condi-
tion, in which case the clinician might judge the
symptoms to reflect an emerging post-traumatic
psychotic disorder.
Post-traumatic amnesia (PTA) refers to the period
of dense impairment of new learning (anterograde
amnesia, with or without retrograde amnesia) sur-
rounding the acute injury (Russell & Smith, 1961).
Post-traumatic amnesia is best regarded as one of
several features of the post-traumatic confusional
state, or post-traumatic delirium (Trzepacz, 1994).
This condition is quite distinct from post-traumatic
psychosis in which sensorium is typically normal and
memory impairments (to the extent that such are
present) are not generally as dense as during the
period of PTA. Although hallucinations and delu-
sions may occur during the period of post-traumatic
amnesia/delirium, hallucinations in this context are
usually visual and delusions are generally less well
organized than in post-traumatic psychosis (Goethe
& Levin, 1984; Trzepacz, 1994).
As noted above, psychotic symptoms may develop
immediately after a seizure or inter-ictally. The
occurrence of psychotic symptoms during only
Table 3. The differential diagnosis of post-traumatic psychosis
Delirium, including posttraumatic
amnesia/confusional state
Post-traumatic epilepsy
Post-ictal psychosis
Interictal psychosis
Idiopathic major depression with psychotic features
Post-traumatic depression disorder with psychotic features
Idiopathic mania with psychotic features
Post-traumatic mania disorder with psychotic features
Substance intoxication
Substance withdrawal
Adverse effect of prescribed medication
Pro-dopaminergic drugs
Anti-cholinergic drugs
Schizophrenia and other idiopathic psychotic disorders
Psychosis following traumatic brain injury 333
post-ictal periods is most consistent with a diagnosis
of post-ictal psychosis, precludes a diagnosis of
psychosis due to TBI, and should prompt aggressive
treatment with an anticonvulsant agent. Psychotic
symptoms arising inter-ictally may merit an addi-
tional diagnosis of psychosis due to TBI; however,
this diagnosis is probably best reserved until maximal
treatment with anticonvulsant agents is undertaken
and it becomes clear that the psychotic symptoms
persist despite such interventions.
Depression and/or mania may develop following
TBI, and in some cases psychotic symptoms may
be a feature of these conditions (Achte et al.,
1991). Although depression is the more common of
these post-traumatic neuropsychiatric disturbances
(Hibbard et al., 1998), mood disorder-related
psychotic symptoms appear to be more prominent
among persons with mania following TBI (Clark &
Davison, 1987; Bracken, 1987; Reiss et al., 1987;
Pope et al., 1988; Nizamie et al., 1988). Without
question, consideration of a separate diagnosis of
psychosis due to TBI should be deferred pending full
treatment of the post-traumatic mood disorder and
re-evaluation of residual, if any, psychotic symptoms
thereafter.
Pre- and post-injury substance use disorders occur
with considerable frequency among persons with
TBI (Hibbard et al., 1998). As with any diagnosis of
psychosis, clinicians should assiduously evaluate
patients for these conditions, including both intox-
ication and withdrawal states. The occurrence of
psychotic symptoms in either setting precludes a
diagnosis of psychosis due to TBI and should
prompt treatment appropriate to these conditions
before considering further this diagnosis.
Distinguishing between post-traumatic psychosis
and schizophrenia is perhaps the most challenging
consideration in the differential diagnosis of psycho-
sis due to TBI given the possibility of considerable
phenotypic similarity between these conditions
(Achte et al., 1991; Sachdev et al., 2001). As noted
previously, patients with psychosis due to TBI must
have hallucinations, delusions, or both. However,
these patients are much less likely to manifest
thought disorder, catatonia, or negative symptoms
than patients with schizophrenia. When any of these
latter problems are the predominant feature of a
patient’s psychosis, a diagnosis of psychosis due to
TBI is unlikely to be the most accurate one. Mean
age of onset of post-traumatic psychotic symptoms
ranges between 26 to 33 years (Fujii & Ahmed, 2001;
Sachdev et al., 2001; Fujii & Ahmed, 2002), which is
approximately 5–10 years later than the generally-
accepted mean age of onset of schizophrenia
(Norquist & Narrow, 2000). Atypical age of onset
may therefore be of some use in distinguishing
between these conditions. Evidence of focal lesions
on clinical neuroimaging, particularly when
consistent with the kinds of findings typical of
TBI (i.e., skull fractures, focal contusions and/or
334 David B. Arciniegas et al.
encephalomalacia, gray-white junctional injuries,
or diffuse axonal injury), may favor a diagnosis of
psychosis due to TBI. Prominent and/or lateralized
EEG abnormalities, and/or the presence of a post-
traumatic seizure disorder, may also favor a diagnosis
of post-traumatic psychosis, notwithstanding the
caveats regarding these issues described above.
Diagnosing psychosis due to TBI
Even when a thorough evaluation is performed and
differential diagnosis considered, establishing a
diagnosis of psychosis due to TBI is challenging on
at least two levels. First, the definition of this
condition is in the literature highly variable and
often imprecise. Early definitions included ‘loss of
ego boundaries’, ‘gross impairment in reality testing’
and/or ‘impairment that grossly interferes with the
capacity to meet ordinary demands of life’ (Flaum &
Amador, 2000), reflecting the prevailing theoretical
frameworks at the times during which such defini-
tions were offered. Relatively more modern studies at
times define psychosis more restrictively to denote
conditions that are ‘schizophrenia-like’ or ‘schizo-
phreniform’ in character (Achte et al., 1969; Achte
et al., 1991; Sachdev et al., 2001), presumably based
on the evolving diagnostic criteria for the comparable
primary psychiatric condition bearing these names.
Such historical discrepancies in the published
definitions of this condition make difficult the
application of the information they contain to the
diagnosis and treatment of patients with post-
traumatic psychosis (Smeltzer et al., 1994).
The Diagnostic and Statistical Manual of Mental
Disorders, 4th Edition-Text Revised (DSM-IV-TR;
Flaum & Amador, 2000) provides a modern frame-
work in which to begin clarifying the diagnosis of
psychosis due to a medical condition, and in this case
psychosis due to TBI. Specifically, the criteria
offered therein for psychotic disorder due to a
medical condition include:
.
Prominent hallucinations or delusions (the more
prominent of which serves as a qualifier of the
diagnosis, such as ‘with delusions’ or ‘with
hallucinations’).
.
Evidence from the history, physical examination,
or laboratory findings that the disturbance is the
direct physiological consequence of a medical
condition.
.
Lack of evidence suggesting that the disturbance is
better accounted for by another mental disorder.
.
Lack of evidence suggesting that the disturbance
occurs exclusively during the course of a delirium.
These criteria represent the most clearly articulated
framework for the study and clinical care of persons
with psychosis and TBI published to date.
However, they are at best provisional and may be
criticized on several points. The first criterion
emphasizes symptom type, either prominent hallu-
cinations or delusions, and its inclusion in this set
of diagnostic criteria is well founded based on the
literature in this area. Nonetheless, it appears to
suggest that a patient’s psychosis may be predomi-
nantly hallucinatory or predominantly delusional,
but not both. This may not characterize accurately
the symptoms commonly experienced by patients
with TBI, and may not exclude with sufficient
clarity those symptoms not characteristic of psycho-
sis due to TBI (i.e., thought disorganization,
catatonia, and/or prominent negative symptoms).
The third and fourth criteria, which seek to exclude
other possible explanations for the psychosis, are
both reasonable and useful guides for the clinician’s
effort to sort through the differential diagnosis of
psychosis following TBI (discussed in the next
section of this review). However, a patient with
post-traumatic psychosis may present with addi-
tional neuropsychiatric (i.e., cognitive) or neuro-
logic (i.e., seizure) conditions that may be the cause
of, a contributor to, or simply comorbid with that
patient’s psychosis. When such conditions are
present, clinicians may not be able to exclude the
possibility that another mental or neurological
disorder better accounts for the psychosis.
Nonetheless, clinicians may recognize all of these
problems as post-traumatic and may, despite
uncertainty regarding the possible contributions of
the other sequelae of TBI, choose to offer the
patient a diagnosis of psychosis due to TBI.
The second of the DSM-IV-TR criteria for
psychotic disorder due to a medical condition is at
present the most problematic. Our understanding of
the pathophysiological mechanisms of psychosis—
even in the primary psychiatric disorders—is at best
incomplete, and in the context of traumatic brain
injury there are only anatomic and functional
associations with psychosis. There is speculation
that psychosis may arise as a function of injury to
frontal systems resulting in impaired information
processing, injury to limbic-paralimbic areas result-
ing in aberrant threat signaling, or some combination
of both (Cummings, 1992; Edwards-Lee &
Cummings, 2000). Laterality of injury may influence
types of psychotic symptoms, with left hemisphere or
bilateral injuries producing a more ‘schizophreni-
form’ psychosis (i.e., hallucinations and delusions)
and right hemisphere injuries resulting in delusions
alone (Hillbom, 1960; Davison & Bagley, 1969;
Cummings, 1992; Edwards-Lee & Cummings,
2000; Arciniegas et al., 2001; Sachdev et al., 2001).
Approximately 70% of patients with post-traumatic
psychosis demonstrate significant EEG abnormal-
ities (typically slowing and/or intermittent spikes),
about half of which (55%) are localized to one of the
temporal areas.
However, the relevance of these findings to the
pathophysiology of psychosis due to TBI is uncer-
tain. The influence of injury location and/or laterality
 Psychosis following traumatic brain injury 335

on symptom type is not strict, and the meaning of
electroencephalographic findings as regards the
pathophysiological basis of psychotic symptoms is
at best speculative. Additionally, very few studies
apply neuroimaging and none apply post-mortem
neuropathological examination to the study of post-
traumatic psychosis. Consequently, very little is
known about the pathophysiology of post-traumatic
psychosis that can be applied to the clinical diagnosis
of this condition. When patients demonstrate
traumatically induced lesions or electroencephalo-
graphic abnormalities consistent in both type and
location with those most strongly associated with
post-traumatic psychosis, clinicians may be more
confident in their diagnosis of psychosis due to TBI.
However, establishing a pathophysiological mechan-
ism by which TBI may cause psychosis is at present
and will be for the foreseeable future a source of
considerable uncertainty for both neuroscientists and
clinicians.
As a function of these issues, making a diagnosis
of psychosis due to TBI using the DSM-IV-TR
criteria is not straightforward and may leave
clinicians wanting for a clearer definition of this
disorder. Unfortunately, there is no published
consensus regarding the diagnostic criteria for
psychosis due to TBI other than those offered in
the DSM-IV-TR. Pending the development of
alternative frameworks for diagnosing this condi-
tion, such as Lyketsos and Treisman (1996) offer
for depression due to a general medical condition,
these diagnostic criteria will remain the standard
with which clinicians make the diagnosis of psy-
chosis due to TBI. Nonetheless, the authors regard
that standard as difficult to meet in most cases.
Therefore, we suggest for the present a relatively
conservative diagnostic approach in which first-
onset psychosis occurring after a clinically signifi-
cant TBI is simply referred to as a post-traumatic
psychosis, and the diagnosis of psychosis due to
TBI is offered only in those cases in which the
clinician judges the clinical evidence as unreservedly
supportive of that diagnosis.
Treatment of post-traumatic psychosis
Treatment of the post-traumatic psychoses (Table 4)
is predicated on careful consideration of the differ-
ential diagnosis and determination of the condition
most likely responsible for the psychotic symptoms.
When delirium, seizure disorder, mood or substance
disorders, or other conditions etiologically relevant
to the psychotic symptoms are present, treatment
must first be directed towards resolutions of these
conditions. If these disorders are not present,
if psychotic symptoms persist despite treatment of
such conditions, or if psychotic symptoms are life
threatening, treatment with an anti-psychotic medi-
cation may be warranted concurrent to definitive
treatment of comorbid or contributing conditions.
Prior to initiating treatment with any medication,
reduction or elimination of medications that may be
exacerbating psychotic symptoms and/or related
behavioral disturbances (including benzodiazepines)
should be attempted, and use of non-essential
medications should be discontinued (Silver &
Yudofsky, 1994; Arciniegas et al., 2000). Character-
ization of the psychosis using standardized scales
such as the Neuropsychiatric Inventory (Cummings
et al., 1994) or the Neurobehavioral Rating Scale
(Levin et al., 1987) should be used to define clearly
the baseline symptom types and their severity, and
to provide a standardized and repeatable method by
which to assess the effects of treatment. Additionally,
since these measures require input from caregivers
or others familiar with the patient’s condition, they
may also serve as a means by which to educate those
individuals about the nature, severity, and target
symptoms of the therapeutic intervention offered to
the patient.
When patients are already engaged in treatments
for other problems arising from TBI, psychiatrists
and other mental health clinicians should integrate
their treatments with those provided by the multi-
disciplinary care team serving that patient. Given
the complexity of these patients, communication
between providers and coordination of services are

Table 4. Treatment principles for the treatment of posttraumatic psychosis

Treatment of comorbid or contributing medical conditions
Discontinuation of non-essential medications
Reduction and/or elimination of medications that may exacerbate psychosis or related behavioral
disturbances (i.e., benzodiazepines)
Use of standardized scales to characterize baseline symptoms and severity of psychosis (i.e. Neuropsychiatric Inventory,
Neurobehavioral Rating Scale)
Education of patient/family about nature and severity of illness, target symptoms for treatment and interventions
Cautious dosing of anti-psychotic medications (start-low, go-slow)
a. Atypical anti-psychotic medications are first-line therapy
b. Start at one-third to one-half of usual starting dose
c. Careful monitoring for adverse events and/or drug–drug interactions
d. Continuous symptom reassessment using standardized scales
Medication augmentation with second agent using different mechanism of action before switching to a different
anti-psychotic medication
Communication between treatment providers and coordination of services for multidisciplinary approach to treatment
and rehabilitation
336 David B. Arciniegas et al.
essential to the development and implementation of
the treatment plan.
When medications are prescribed, cautious dosing
(i.e., a start-low, go-slow approach) is recom-
mended, and initial treatment should begin using
one-third to one-half the starting dose used in
comparably ill non-injured psychiatric patients
(McAllister, 1998). While this guide to treatment
initiation is useful, it is important to recognize that in
some cases standard therapeutic doses may be
required to effect remission or control of post-
traumatic psychotic symptoms and related behavioral
disturbances. In the process of gradual dose titration,
both assiduous symptom reassessment using the
types of standardized scales noted above and careful
monitoring for drug-drug interactions are essential
(Silver & Yudofsky, 1994; Arciniegas et al., 2000).
When a single medication provides only partial relief
of symptoms and/or cannot be tolerated at therapeu-
tic doses, it may be useful to augment the effect of
that medication using a second low-dose agent with a
different mechanism of action before switching to
another anti-psychotic agent (Silver & Yudofsky,
1994; Arciniegas et al., 2000).
With regard to medication therapies for the
neuropsychiatric sequelae of TBI, there are at
present no randomized, double blind, placebo-
controlled studies with which to guide treatment
selection. Consequently, medication selection is at
present predicated on clinician judgment based on
understanding the neuropharmacology relevant to
TBI and may be guided further by the few case
reports available describing the benefits and side
effects of anti-psychotic agents in this population.
As a general rule, medications with potent anti-
dopaminergic, anti-cholinergic, and anti-histaminic
properties should be avoided given their tendency to
produce significant adverse effects in this population
(Arciniegas et al., 2000). Anti-psychotic medications
that strongly antagonize dopamine appear to delay
neuronal recovery after brain injury (Feeney et al.,
1982; Goldstein, 1995). Consistent with this obser-
vation, Rao et al. (1985) found that patients treated
with haloperidol in the acute period following TBI
experienced significantly longer periods of post-
traumatic amnesia, although the acute rehabilitation
outcome was not ultimately different from those not
treated with this medication. Similarly, Stanislav
(1997) demonstrated that two common typical anti-
psychotic medications, thioridazine and haloperidol,
adversely affected cognitive performance in brain-
injured patients and that discontinuation of these
medications, and particularly thioridazine, effected
cognitive improvements. Hypotension, sedation, and
confusion occur commonly during treatment of post-
traumatic psychosis with typical anti-psychotics.
These side effects are themselves potentially danger-
ous and also may exacerbate cognitive and physical
impairments in these patients. Paradoxical effects
from medications in this population are also of
concern; for example, Sandel et al. (1993) observed
new-onset delusions in a TBI patient receiving
chlorpromazine for the treatment of agitation follow-
ing TBI, an effect attributed to the significant
anti-cholinergic properties of this agent.
Clinicians should also be aware that patients with
brain injuries are particularly susceptible to dysto-
nias, akathisias, and other extrapyramidal side effects
produced by typical anti-psychotic medications, even
when relatively low doses are prescribed (Yassa et al.,
1984a; Yassa et al., 1984b; Rosebush & Stewart,
1989; Wolf et al., 1989). Neuroleptic malignant
syndrome (NMS) may also develop shortly after
initiating treatment with typical anti-psychotics such
as haloperidol (Vincent et al., 1986; Wilkinson et al.,
1999). The development of seizures is also of
concern during treatment with typical anti-psychotic
agents. If patients with TBI are treated with typical
anti-psychotic medications, the development of any
of these side effects or serious adverse reactions (and
especially NMS) should prompt discontinuation of
these agents. Given this literature and the availability
of several atypical anti-psychotic medications, the
authors strongly discourage the use of typical,
and particularly the low-potency, anti ¼ psychotic
medications among persons with TBI.
Atypical anti-psychotic medications should be
regarded as first-line treatments for psychosis due
to TBI in light of their several potentially significant
advantages over conventional neuroleptic medica-
tions in this context, including reduced risk of
extrapyramidal symptoms and/or tardive dyskinesia.
Presently, there are six atypical neuroleptic medica-
tions from which to choose, including clozapine,
risperidone, olanzapine, quetiapine, ziprasidone, and
aripiprazole. However, there is at present a dearth of
reports with which to guide selection of atypical anti-
psychotic agents in this population.
Michals et al. (1993) used clozapine to treat nine
brain-injured patients with psychotic symptoms or
outbursts of rage and aggression that had failed to
respond to other medications. Three of these
patients demonstrated marked improvements in
aggression and/or psychosis, three demonstrated
decreased agitation and auditory hallucinations,
and an adequate duration of treatment was not
achieved in three patients. Two of nine patients
experienced seizures during treatment. Burke et al.
(1999) also report improvement in refractory psy-
chotic symptoms after TBI during treatment with
clozapine.
While these reports suggest that clozapine may be
useful in the treatment of psychosis and aggressive
behavior after brain injury, this treatment carries a
relatively high risk of adverse effects including
seizures. Clozapine treatment is associated with a
significant dose-related incidence of seizures,
ranging from 1% to 2% of patients who receive
doses below 300 mg/day, and 5% of patients who
receive 600–900 mg/day (Lieberman et al., 1989).

The observation of Michals et al. (1993) suggests that
this risk may be increased among patients with TBI,
although the very small number of patients described
in that report makes this cautionary note preliminary
at best. The effect of clozapine on post-traumatic
cognitive impairments in this population is also not
clear from these reports, but its substantial anti-
cholinergic properties are worrisome in this regard.
This possibility, combined with the non-trivial risk of
agranulocytosis associated with its use and cumber-
some treatment-monitoring regimen, limit the
usefulness of this agent for the treatment of post-
traumatic psychosis. If this agent is prescribed to
persons with post-traumatic psychosis, its use should
be undertaken with due caution. The authors
recommend that use of clozapine be reserved for
the treatment of psychotic symptoms refractory to
other atypical anti-psychotic medications.
The literature regarding the usefulness and poten-
tial side effects of the other atypical anti-psychotics,
including risperidone, olanzapine, quetiapine,
ziprasidone, and aripiprazole, is disappointingly
meager. Schreiber et al. (1998) report a case in
which risperidone was an effective and well tolerated
treatment for delusions and sleep disturbance
following TBI. The authors have used this medica-
tion in two patients that developed psychosis
(paranoid delusions, auditory hallucinations) after
TBI in both the post-acute and late post-injury
periods. One of these patients, a 45-year-old male
without significant prior neurological, psychiatric, or
substance problems suffered a severe TBI with
bifrontal contusions and scattered white matter
lesions in bifrontal and bitemporal areas, and
developed psychotic symptoms (auditory hallucina-
tions, persecutory and referential delusions) approxi-
mately two months post-injury. These symptoms
interfered with his ability to participate in acute
inpatient rehabilitation. He was treated with risper-
idone in an A-B-A-B fashion over approximately six
weeks. His psychosis was reduced substantially and
his participation in rehabilitative therapies improved
during treatment with risperidone 4 mg per day, but
the patient relapsed during reduction of risperidone
below 3 mg per day. He did not develop significant
motor or cognitive impairments during the period of
this treatment.
The authors treated another patient successfully
with risperidone. This patient was a 55-year-old male
without significant prior neurological, psychiatric, or
substance problems who suffered a severe TBI
resulting in bifrontal and bitemporal contusions,
severe bifrontal diffuse axonal injury, and marked
cognitive impairments. He developed persistent
post-traumatic psychosis, characterized by promi-
nent auditory hallucinations and persecutory delu-
sions, approximately two years after TBI. These
symptoms resulted in significant behavioral distur-
bances, including agitation and intermittent aggres-
sion. He failed to respond to treatment with
Psychosis following traumatic brain injury 337
haloperidol, up to 5 mg per day, prescribed over a
period of approximately six months by his primary
care physician. Following neuropsychiatric consulta-
tion, haloperidol was discontinued and treatment
with risperidone was initiated and gradually titrated
to 2 mg twice daily over a three-month period.
This treatment effected remission of his psychotic
symptoms and related behavioral disturbances with-
out significant adverse effects. While these observa-
tions are at best anecdotal, they suggest that
risperidone may be in some patients a useful and
well-tolerated treatment for post-traumatic psychosis.
There are no published reports of improvement in
psychosis following TBI during treatment with
olanzapine, quetiapine, ziprasidone, or aripiprazole.
Among these agents, olanzapine may be of particular
interest because of its facilitation of cholinergic
function via antagonism of 5HT3 and 5HT6 recep-
tors, an effect that may in part offset its otherwise
considerable anti-muscarinic properties (Callaghan
et al., 1997). This effect may in part explain the
relatively greater degree of cognitive improvements
observed during its use when compared to risper-
idone and/or haloperidol (Purdon et al., 2000).
In light of those observations, the authors preferen-
tially use olanzapine (2.5–15 mg per day) for the
treatment of post-traumatic auditory and visual
hallucinations and persecutory delusions in the
acute inpatient rehabilitation setting, particularly
among patients experiencing such symptoms during
the period of PTA. In our experience, olanzapine,
generally offered as a single bedtime dose, affords
substantial reductions in psychotic symptom sever-
ity, as well as improvements in sleep continuity and
participation in acute rehabilitative therapies. To
date, we have not observed significant adverse effects
(treatment-emergent hyperglycemia, hyperlipidemia,
hypertriglyceridemia, orthostasis, weight gain) as a
function of this treatment during the period of
inpatient rehabilitation. However, further investiga-
tion of the therapeutic benefits and risks of this and
the other atypical anti-psychotic agents among a
larger number of persons with post-traumatic psy-
chosis is needed before formal recommendations
regarding their use in this population can be offered.
Conclusion
Psychosis is a relatively infrequent but potentially
serious and debilitating consequence of TBI.
The role of TBI in the genesis of psychosis is a
complex matter, but there appear to be substantial
clinical, epidemiological, and neurobiological differ-
ences between the post-traumatic psychoses and the
primary psychotic disorders. Traumatic brain injury
is associated with an increased risk of psychosis, and
that risk appears to extend over many years after the
initial injury. Delusions, hallucinations, or both are
the most common symptoms of post-traumatic
338 David B. Arciniegas et al.
psychosis, while formal thought disorder, catatonia,
and negative symptoms are relatively uncommon.
Pre-injury variables that increase risk of post-
traumatic psychosis include male gender, prior
neurodevelopmental problems (including prior
TBI), prior psychiatric disorders, and family history
of psychotic illnesses like schizophrenia. Post-
traumatic psychosis appears to be more common
after relatively severe injuries, though this condition
may develop in some mildly injured individuals as
well. Laterality of injury may influence the types of
psychotic symptoms, with right hemisphere injury
more commonly associated with delusions and left
hemisphere (particularly left frontotemporal) injuries
associated with schizophrenia-like presentations.
Among the many post-injury factors potentially
relevant to the development of post-traumatic
psychosis, EEG abnormalities, post-traumatic
epilepsy, and cognitive impairments appear to be
most strongly associated with this condition.
Understanding these issues and considering them
in the context of the DSM-IV-TR criteria for
psychosis due to a medical condition (TBI) guides
usefully the evaluation and treatment of patients with
this condition. The evaluation entails establishing
that a patient’s history provides reasonable evidence
of a TBI, determining that patient’s psychotic
symptoms are consistent with the types commonly
seen in the post-traumatic psychoses, and careful
consideration of differential diagnosis for post-
traumatic psychotic symptoms. After making a
diagnosis of post-traumatic psychosis, treatment
with atypical anti-psychotic agents in the context
of a multidisciplinary rehabilitation program is
recommended.
Acknowledgements
The authors gratefully acknowledge the assistance of
Thomas W. McAllister, MD, in the preparation of
this manuscript. Support for the preparation of this
manuscript was provided by the Spalding Rehabilita-
tion Hospital, Aurora, CO, USA.
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