PSYCHOTIC DISORDER DUE TO A

GENERAL MEDICAL CONDITION1

SUBSTANCE iNDUCED PSYCHOTIC
DISORDER

1. INTRODUCTION
Psychotic disorders are a group or a
spectrum of illnesses that alters a
persons perception, thought, affect,
and behavior. Among all the psychiatric
diseases psychosis represents perhaps
the most dramatic and clinically
captivating condition. Three in every I 00
people will experience a psychotic
episode. Psychosis and substance abuse
co-occur more frequently than can be
explained by a chance. Psychosis
secondary to general medical conditions
or substance abuse is most unpredicted
and devastating condition. The

evaluation of a patient with psychotic

disorders requires consideration of the
possibility that the psychotic symptoms
result from a general medical condition
or the ingestion of a substance.

? PSYCHOTIC DISORDERS
Emil Kraepelin (1856 to 1926) first
delineated separate psychotic
conditions. The most generalized
definition of psychosis is descnbed as a
loss of ego boundaries or a gross
impairment of reality testing. A broader
psychosis definition includes other
positive symptoms of schizophrenia
(i.e.., disorganized thought process,
grossly disorganized or catatonic
behavior) An excess in dopaminergiC1
and a deficit in glutaminergic
(specifically NMDA) signaling

correspond to positive and negative

symptoms of psychosis.
Currently, DSM-IV-TR adheres to
narrower definition of psychosis that
includes only hallucinations and
delusions. Psychotic disorders can be
primary or secondary.
Primary Psychotic Disorders indudes
Schizophrenia related Disorders and
affective psychosiSSecondary Psychotic Disorders includes,
Dementia: Alzheimers, Vascular, other
dementias, Substance-Induced and
General Medical Conditions induced
psychosis.

;3 PSYCHOTIC DiSORDER DUE TO A

GENERAL MEDICAL CONDITION

Karl Bonheoffer, (1909), one of the

fathers of organiC psychiatry,
recognIzed 100 years ago that the
psychiatric clinical picture produced by
a medical condition was rather uniform
and unspecific.

3.1. Definitiofl
DSM-IV states that, Psychotic Disorder
Due to a General Medical Condition
includes prominent hallucinations or
delusions that are directly secondary to
a medical disorder or physiological
effects of a general medical condition.

3.2. EpidemiOIOV
Prevalence rates of Psychotic Disorder
due to a General Medical Condition are
difficult to estimate in the given wide
variety of underlying medical etiologies.
The lifetime

prevalence of all psychotic disorders was

3.06% and rose to 3.48% but, psychotic disorders
due to a general medical condition is only 021%

3.3. Etioloqw
Potential etiologies of general medical
disorder of psychosis described in
acronym as MINES;

M-Metabotic

I- Infections

N- Neurologic
E- Endocrine
S- Sensory disorders and other
Hypocalcaemia, hyponatremia.
hypoglycemia, uremia:
hepaticencephalopatF , porphyria.

Alzheimers disease, Picks disease,

Huntingtons disease, calcification,
multiple sclerosis.
Although other psychiatric problems
are quiet common in general medical
disorders, psychosis in medical
disorders are limited. The noteworthy
disorders are;

331. Metabolic disorders

Acute intermittent porphyria(AlffJ is an
autosomal dominant disease of heme
synthesis that results from defects in
the enzyme
phorphobilinogendeamiflaSe(PBGD). A
diagnosis of AlP is suggested by an
excess of porphobilinogen in urine and
a concomitant decrease in
porphobilinogendeaminase. Therefore
the excess of porphyrine molecule
affects the brain, results in
neuropsychiatric problem. Among the
metabolic disorders, only acute
intermittent porphyria is sufficiently
common to be routinely considered in
patIents with psychosis, particularly if
the abdominal complaints (colicky
pain, severe constipation) and
peripheral neuropathy are present.
Antipsychotic drugs should be
cautiously used because which
increase the acute attacks. Tay-sachs

disease is rare storage disorder,

psychosis is one of the possible
symptoms.
Metabolic disorder
Sensory disorders
Vascular disorder
Psychosis secondary to hallucinations
and delusions.
deafness
Vitamin deficiencies
and blindness,
Atherosclerotic vascular disease.
Neurodegenerative
are associated
wtl
Vitamin B12 deficiency, folate
deficiency, thiamine deficiency.

basal gang
1;

3
Infecti
HIV/A1DS,
ous
encephalitis
disease
lethargica,
CreutzfeldtJacob
disease,
syphil
Neurolo
gical
disord
ers

malaria,
acute
viral
encepha
htis,terti
ary
syphilis.
Brain
tumors,

especiall
y
temporal
lobe and
deep
hemisph
eric
tumors;
epilep
Endocr
ine
disord
ers

especially
complex
partial
seizure
disorder
head
trauma,
anoxic
brain
injury.
Addisons
disease,
Cushing

s
disease,
hyper- or
hypothyr
oidism,
pan hy
pituitaris
m.

33.2. Infectious disorders:

I

HIV patients are vulnerable to a variety

of psychiatric disturbances. The range
wide from states
of acute distress on becoming aware of HIV
status to profound depression/psychotic
illnesses.
Acute psychological reactions:
Acute stress reactions are most
commonly observed at the time of
notificatior of a positive serological test
result. The principal manifestations are:
I Acute shock
i Bewilderment and
! Anxiety, typically lasting for several
weeks.
Major depression may be precipitated,
with depersonalizatIon, insomnia and
suicidal ideation. A preoccupation with
bodily symptoms is thought to be
indicative of comencing disease.
Other reactions include
a

Anger
Despair
Guilt
: Increased use of alcohol or drugs
Social withdrawi or denial.
Longer-term psychiatric disorder:
Longer-lasting psychiatric disorders may
emerge during the asymptomatic or
symptomatic stages of infection, but it
is uncertain whether this is more
common than in patients with other
serious medical conditions.
Anxiety presents in 4-9% of patients (Justice
et al.2004). Somatic symptoms of
anxiety are sometimes Interpreted as
evidence of progression to further
stages of the disorder, giving rise to an
escalating vicious circle. Alcohol or drugs
may be abused in attempts to selfmedicate for the symptoms of anxiety.
Depression has a varied reported
prevalence, ranging from 2% to 48% of
patients in different surveys ( perkins et

al,1994, Fernandez 2002, Chander et al,

2006). Depression and withdrawal can
significantly interfere with the
procedures required for management of
the illness. Care in identifying
depression is particularly important and
especially in the context of overlap of
somatic symptoms such as fatigue, pain
appetite loss and sleeplessness that
may be present throughout the
infection with HIV. Anhedonia and
diurnal variation may be useful
discriminating symptoms suggestive of
depression. Suicide presents a
considerable risk in both the early and
late stages of the disorder.
Obsessive compulsive disorder : This can occur
with or without depressed mood, commonly
involving repeated bodily scrutiny for
evidence of progression of disease.
4

Psychoses: New-onset psychosis in

HIV-positive patients has been
reported in range from 0.5% to I 5%.
Many pictures have been reported.
some seemingly typical of psychoses
occurring in other settings, while
others have shown special features.
Sometimes however, organic
symptomatology remains absent
throughout the illness which presents
as a purely functional psychosis.
Alternatively the psychosis may reflect
HIV brain infection, especially in
patients with no previous history of
psychiatric illness and who are
unaware of their seropositivity.
The variety of pictures encountered;
which include
Delusions
Hallucinations
Bizzare behaviour
Thought disorder

Lability of mood and

Major affective disorder mayfeature
prominantly, with or without organic
accompaniments in the mental state.
Treatment; AntIpsychotic medication
should always be used at the lowest
possible dose for the shortest possible
duration to avoid interaction (extra
pyramidal side effects) with ART.
Typical antipsychotic; Haloperidol (0.52.5 mg) and chiorpromazine (25-50
mg), atypical antipsychotic;
Risperidone (1-4 mgld) have proven
effective and safe.
> CreutzfeldtJacob disease typically occurs
later in life (mean age, 60 years), and
manifests with a rapidly progressive
course characterized by cerebellar
ataxia, dementia, myoclonus,
seizures, and psychiatric symptoms
progressing to akinetic mutism and
complete disability within months
after disease onset. Psychiatric

symptoms such as personality

changes, anxiety, depression,
paranoia, obsessive-compulsive
features, and psychosis occur in about
80% of patients during the first 100
days of illness (Wall et al., 2005).
About 60% present with symptoms
compatible with a rapidly progressive
dementia.
> New-variant CJD 1s a new form of
acquired spongiform encephalopathy
in which patients have a different
course characterized by younger age
at onset (mean age, 29 years),
prominent psychiatric and sensory
symptoms, and a longer disease
course. Spencer and colleagues, 2002
reported that 63% demonstrated
purely psychiatric symptoms at onset
(dysphoria, anxiety, anhedonia), 15%
had purely neurological symptoms,
and 22% had features of both.

> Neurosyphilis-Manifestations of late

neurosyphilis indude tabes dorsalis, a
rapidly progressive dementia with
psychotic features, or general paresis,
or both. Presenting psychiatric
symptoms of neurosyphilis can include
personality changes, hostility,
confusion, hallucinations,
expansiveness, delusions, and
dysphoria.. Symptoms also reported in
association with neurosyphilis include
explosive temper, emotional lability,
anhedonia, social withdrawal,
decreased attention to personal
affairs, unusual giddiness,

histrionicity, hypersexuality, and

mania. A significant incidence of
depression has been associated
with general paresi&
:3.3.3. CNS disorder:
TRA UMA TI C BRA IN INJUR Y (TB!)
Psychotic Disorder Due to Traumatic Brain
Injury is the current DSM-IV diagnosis given
to individuals who develop a psychosis
after a traumatic brain injury
(TB!). According to DSM IV- TR
the criteria include
Presence of hallucinations or
delusions
evidence (history, physica, or
laboratory) that the psychosis is a
direct physiological consequence
of TBI
psychosis is not better accounted for
by another mental disorder; and
4)

Psychosis does not occur

exclusively during a state of
delirium.
Approximately 1 .5% of TBI
(traumatic brain Injury) patients develop
psychotic symptoms. Psychotic features
can be transient or persistent and
may follow either an acute or
chronic course. Following head
injury the clinical features of
delirium include confusion,
inattention, cerebral
disorganization and psychotic
symptoms incorporated into this
context. When the patient emerges
from delirium, more discrete
psychotic features might become
evident and characterIstic
symptoms include delusional
disorientation, delusional
misidentification and
confabulation. Confabulations may
become chronic, especially in the

context of associated global cognitive

impairment and lack of insight. The
longer term clinical presentation
has considerable overlap with
primary schizophrenic disorder,
with a prominence of persecutory
and other delusions and auditory
hallucinations.
The onset is often gradual, with a
sub-acute or chronic course.The
absence of first-rank symptoms
distinguishes TBI psychosis from
schizophrenia; shows better
response to neuroleptics, less need
for maintenance medication with
better improvement. Although nondelirium associated hallucinations
can occur in post-TB!, in some
patients, post-TBI psychosis may be
an ictal-related process.
Pathology: Some studies suggest
that psychosis is related to left
sided and temporal injuries but

others find no relatjonship to the

type or location of the injury.
Treatment; for post-TB! psychosis wIth
neuroleptics should be initiated at
one third to one half of the usual
doses because of potential adverse
reactions. There is some evidence
that neuroleptics may impede
cognitive recovery. Atypical
neuroleptic, is effective (except for
Clozapine which lower the seizure
threshold). Benzodiazepines should
be sparingly used.
Other problems related to TB!:
Changes in personality:

The severity of the brain injury usually

correlates reasonably well with the
development of personality and
behavioural changes.
Common symptoms include;
Apathy

Loss of spontaneity and drive

4> Labile mood
+ Self-centred behaviour

Disinhibition
4> Irritability and
4 Reduced control over aggressive
impulses.
Personality changes are frequently
associated with cognitive impairment
and accompanied by a Jack of insight
and poor awareness of safety and
personal hygiene.
Pathology: During TBI the medial
orbital surface of the frontal lobes and
the anterior, inferior surface of the

temporal lobes are particularly

vulnerable to developing contusions.
These regions play a major role in
social behaviour with injury resulting
in changes in personality.
Treatment: Appropriate treatment
includes providing emotional support
and education for the patient and
family members. A cognitive
behavioural approach to the
symptoms may also be useful.
Pharmacological interventions, such
as selective serotonin reuptake
inhibitors (SSRIs) and mood
stabilizers, can be used to target
specific symptoms, including
aggression and emotional instability.
Cogn itive disorders:
Cognitive impairment has been
described at prevalence rates of 2570% post-TB! (Vaishnavi et a!. 2009)
Immediately after TBI, loss of
consciousness or coma may ensue,

followed by a variety of cognitive and

behavioural abnormalities including
agitation, confusion, disorientation,
altered psychomotor activity and both
retrograde and anterogracle amnesia.
In some cases permanent cognitive
deficits result which typically include
difficulties with attention,
concentration, memory, language,
executive functions and reduced
speed of information processing. TBI
may increase the risk of disinhibition
in patients with dementia.
Treatment Cognitive disorders are
treated through a multidisciplinary
approach focusing on neurorehabilitation. Specific cognitive
deficits may improve through
occupational therapy, physiotherapy,
speech therapy, vocational training,
cognitive rehabilitation and
pharmacological interventions.
. Aggression:

Between 35 and 96% of post-TB1

patients are reported to have
exhibited agitated behaviour during
the acute recovery period (Reeves &
Panguluri, 201 1 ). Displays of
aggression are somewhat varied
among patients with TB! but are often
consistent for an individual patient.
Aggression is usually impulsive, out of
proportion to the stimulus and short
lived (known as Episodic Dyscontrol
Syndrome). Anger and impulsive
verbal outbursts seem to be the main

characteristics of aggression post-TBI.

Pathology: Lesion location has been less readily
associated with outcomes, although frontal
lesions are associated with early
agitation, aggression and behavioural
problem&
Treatment: Environmental
interventions rather than drug
therapies are often the preferred means
of managing agitation in the acute post-TBI
phase. Anticonvulsants such as
Carbamazepine and Vaiproate have
been reported to be effective in
clinical practice Atypical
antipsychotics, antidepressants,
Buspirone, lithium and Amantadine
have also been used to manage posttraumatic aggression.
Mood disorders: Depression:
Depression is recognized as a
common complication of TBI but
estimations of its frequency vary.

Prevalence rates for major depressive disorder

have been described between 15 to
61%. Diagnosing depression is
complicated because the cognitive,
emotional and somatic symptoms of
depression can overlap with direct
symptoms of TBI. For example, sleep
disturbance, concentration difficulties
and apathy are common symptoms in
TBI survivors both with and without
mood disorders. The symptoms of
post-TBI depression do not differ from
those with depression without
associated head injury although they
are more frequently characterized by
irritability, anger and aggression than
by sadness.
Pathology: Lateral frontal lesion
locations are associated with an
increased risk of developing
depression compared to medial
lesIons, with right lateral lesions
increasing the risk of anxious

depression and left anterior lesions

increasing the risk of major
depression.
Treatment: The treatment of post-TB1
depression is similar to that of
depression in primary psychiatric
practice and includes psychological
interventions, antidepressants and
ECT. SSRIs are considered first line as
they are usually safe and well
tolerated. Tricyclic antidepressants
have a lesser role both because of the
higher incidence of anticholinergic
side effects that can adversely affect
cognition and due to evidence of
possible reduced efficacy. MAOIs are
not recommended due to lack of
efficacy data and potentially serious
side effects, particularly when dietary
restrictions are not adhered to in a
population with a high rate of
cognitive difficulties.
3) Epjlepsy:

Nearly 30% to 50% of the epileptic

populations have some type of
psychiatric co-morbidity, Psychosis is
common in temporal lobe epilepsy
(TLE) and several patients have
psychosis of epilepsy (POE). This is
classified according to the temporal
relation of ictal events, Post ictai
psychoses are short lasting of good
prognosis. Dopaminergic systems get
extremely sensitive in the chronic
phase of epilepsy, therefore chronic
sub cortical discharges impaired in
frontal functions probably may explain
the development of psychosis in
epilepsy.
Temporal lobectomy is a safe and
effective procedure in treatment
resistant psychotic epileptic patients,
which may increase risk of
neurobiological changes. All
Antipsychotics reduce the
epileptogenic threshold (ET) and may

cause epileptic seizures. This

phenomenon is called
8

alternative psychosis. or forced

normalization. Space-occupying
lesions like temporal lobe lesions are
thought to increase the likelihood of
psychosis. Conditions like increased intracranial
pressure, (hydrocephalus) been
associated with psychosis. Rarely
psychosis can be the presenting
symptom of a stroke. In some cases,
stroke related seizure activity is
responsible for the psychosis.
S

Postictal psychosis is probably the most

common psychotic disorder seen in epilepsy.
The onset of psychotic symptoms then
often sudden and dramatic
accompanied by marked agitation and
behavioral disturbance. The
phenomenology is pleomorphic with a
mixed picture including paranoid,
grandiose and religious delusions, auditory,
visual and somatic hallucinations, and
prominent variable affective changes.

Treatment; Typical heuroleptics, such as

phenothiazines, and Haloperidol are
undoubtedly safest antipsychotic to
treat psychosis of epilepsy (POE),
Atypical neuroleptics, can be indicated
for all types of psychoses in epilepsy
(except Clozapine). Benzodiazepines
have a limited use, and seem to be
optimal during acute situations.
Electroconvulsive therapy (ECT) is
acknowledged as potentially beneficial.
C) Parkinsons disease:
Psychosis in untreated Parkinsons
disease is rare. Psychotic symptoms
may be secondary to a prescribed
dopaminergic agent, but some patients
experience visual halluinations before
any medications are started. Symptoms
include; confusion, excitement,
agitation, paranoid delusions, hallucinations
and suicidal intentions. Education and
support should be offered to all patients
with these symptoms. Treatment:

caution with use of an antipsychotic

medication because it worsens the
parkinsonian symptoms. Atypical
antipsychotics; Quetiapine 12.5-75 mg/d
or Olanzapine 25-5 mg/d may be
beneficial. Some patients require
Clozapine 12.5-75 mgld.
D) Demyelinatinq diseases:
Diseases that disrupt the integrity of
white matter tracts in the brain can lead
to psychosis, likely to be caused by the
functional disconpectivity of critical
brain regions. Multiple sclerosis, the
most common demyelinating disease, is
associated with psychosis more often
than can be expected by chance.
E) Tumours: A variety of neoplasms
cause cognitive and behavioral
disorders. The number of patients
presenting with a primary psychiatric
diagnosis secondary to an unidentified
brain tumor is likely to be less than
5%.Limbic encephalitis, associated with

small-cell lung cancer (SCLC) and

testicular cancer, produces a significant
amnestic syndrome and
neuropsychiatric symptoms including
agitation, depression, personality
changes, apathy, delusions,
hallucinations, and psychosis

E) Psychiatric seguelae of CVA

A range of psychiatric problems may
occur following stroke. These include:
a

*cognitive disorders

. Vascular

dementia (see pp. 144, 145)

. Subcorticai
. Amnestic

dementia (see p. 133)

disorder (see pp. 148, 149)

*personality changes
These tend to involve a constriction in
the range of interests and a loss of

intellectual flexibility. Irritability is

common and catastrophic reactions
may occur in response to stress or
change in routine. Emotional flexibility
may be reduced and affective
responses often become shallow and
stereotyped.
*

Pathological emotionalism

May occur 4 6 weeks post- CVA,

especially following left frontal infarcts.
Presentation involves outbursts of
unprovoked and uncontrollable emotion
and distress, with disinhibition a major
feature.
-

*poststroke depression
Depressive illness after stroke is
extremely common, occurring in up to
60% of cases. Its onset is usually
between 3 and 24 months following the

stroke. It was a neglected phenomenon

until recently and many cases are misor under-diagnosed with symptoms
being attributed to the cognitive insult.
S Biological factors direct physiological
effects of the brain injury, with location
(e.g. left anterior frontal), large size,
increased age and female gender being
risk factors.
Psychological factorssudden
dependency; disability; premorbid
personality traits (especially neurotic or
highly independent individuals). Social
risk factorsbeing alone; lack of social
support; financial worries.

Irm

Antidepressants: SSRIs are

considered safe following stroke but
some evidence suggests that TCAs are
more efficacious.

*psych oses
Manic, hypomanic, and paranoid
psychoses may result from a CVA,
especially right hemisphere infarcts.
Peduncular hallucinosis is an uncommon
psychosis characterised by visual and
auditory hallucinations and is
associated with infarcts involving the
pons and midbrain.

F) Chronic subclural haematoma

(SDH)
An insidious and fluctuating organic
syndrome may result from an
undetected chronic subdural
haematoma. A SDH results from rupture
of the bridging veins between the dura
and arachnoid mater and tends to occur
over the frontal and/or parietal cortices.
In 30% of cases there is bilateral SDH.

SDH should be suspected where there is

a changing pattern in cognitive
function, especially if risk factors