Secondary Schizophrenia (72 page)

current evidence related to the occurrence of toxic
worsening, and presence of delusions,

psychosis (delirium) caused by commonly prescribed
hallucinations, and thought disorder.

r

drugs consumed in excessive amounts. The most com-It is sometimes difficult to differentiate
mon presentation is clearly that of delirium. Therefore,
between toxic psychosis and primary

the clinical features of this are discussed briefly, fol-psychiatric conditions.

lowed by a discussion of the literature relevant to the
r
General risk factors include older age,

association between commonly prescribed drugs and
underlying dementia, and severe physical

delirium.

illness.

r
Several classes of drugs have been implicated.

r

Clinical features of delirium

Pathogenesis of toxic psychosis is poorly

Without careful assessment, delirium can easily be
understood. However, current knowledge is

mistaken for a number of primary psychiatric disor-that there is dysfunction of a number of
ders such as dementia, depression, and psychosis. The
neurotransmitters such as acetylcholine,

key characteristics of delirium are a disturbance in the
dopamine, GABA, and glutamate.

r

level of consciousness, an impairment of cognition and
Management includes the identification and

perception, acute onset and fluctuating course, a med-treatment of the underlying cause, which is
ical history of illnesses or toxic exposure to drugs, and
often multifactorial.

r

presence of other features such as a reversal of the
Common clinical situation: clinicians should
sleep-wake cycle
[2].
Table 12.1 sho
ws the DSM-IV cribe able to correctly identify this state to
teria for the diagnosis of delirium.

reduce mortality.

An important challenge for the clinician is to differ-r
Current research is flawed by methodological
entiate delirium from other conditions such as depres-issues. Future research should include a large
sion, dementia, and functional psychoses. However,
number of patients, use standardized

certain signs and symptoms can assist clinicians to dis-measurements, study individual drugs, and
tinguish between delirium and other conditions
[3].

control confounders.

Table 12.2
provides the salient features of delirium,
179

dementia, and psychosis. Electroencephalography can
Organic Syndromes of Schizophrenia – Section 3

Table 12.1
DSM-IV diagnostic criteria of delirium
a) Disturbance of consciousness (that is, reduced clarity of awareness of the environment, with reduced ability to focus, or shift
orientation)
b) A change in cognition (such as memory deficit, disorientation, language disturbance) or the development of a perceptual
disturbance that is not better accounted for by a pre-existing established or evolving dementia.

c) The disturbance developed over a short period of time (usually hours to days) and tends to fluctuate during the course of the day.

d) Where the delirium is due to a general medical condition-there is evidence from the history, physical examination, or laboratory
findings that the disturbance is caused by the direct physiological consequences of a general medical condition. Where the delirium
is due to substance intoxication-there is evidence from the history, physical examination, or laboratory findings of either 1 or 2:
1) The symptoms in criteria (a) and (b) developed during substance intoxication
2) Medication use – etiologically related to the disturbance
Where the delirium is due to substance withdrawal-there is evidence from the history, physical examination, or laboratory findings
that the symptoms in criteria (a) and (b) developed during or shortly after the withdrawal syndrome. Where delirium is due to
multiple etiologies-there is evidence from the history, physical examination, or laboratory findings that the delirium has more than
one aetiology (for example: more than one etiological general medical condition, a general medical condition plus substance
intoxication, or medication side effects).

(e) Delirium not otherwise specified: this category should be used to diagnose a delirium that does not meet criteria for any of the
specific types of delirium described. Examples include a clinical presentation of delirium that is suspected to be due to a general
medical condition or substance use but for which there is insufficient evidence to establish a specific aetiology, or where delirium is
due to causes not listed (for example, sensory deprivation)
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Text Revision, Fourth Edition (Copyright 2000).

American Psychiatric Association.

be useful in differentiating delirium from other con-hospital patients suffer from delirium at any time and
ditions, particularly primary psychiatric states such as
the rate increases with age.

schizophrenia.

General risk factors

Burns and colleagues
[10]
suggested that the risk fac-

Epidemiology

tors could be categorized into predisposing factors,
such as older age, underlying cognitive impairment,
A number of methodological shortcomings are

or physical illnesses; precipitating factors, such as an
reported to be associated with the studies on the
infection, or even a combination of these two factors.

prevalence of delirium. These include under-reporting
Even though physical frailty is a major confounding
due to short duration in some cases, lack of consensus
factor in ageing, Schor and colleagues reported that
in the definition, use of different screening tools, sam-age more than 80 years was an independent risk factor
ple bias, and study settings. As a result, the reported
for the occurrence of delirium
[11]
. It has been noted
prevalence and incidence rates of delirium varied
that alterations in the metabolism of drugs with age
significantly in different studies.

may cause increased vulnerability to side effects. Other
In general hospital patients, Hodkinson
[4]
has
reported risk factors include dementia
[12],
poor phys-reported a prevalence of 35% in patients older than
ical health
[13],
and depression
[12].
One of the most
65 years of age. O’Keefe and Lavan
[5]
reported a
common biochemical abnormalities associated with
prevalence of 18% at admission and an additional
delirium is hypoalbuminemia. This is a very impor-24% during hospital stays in an acute geriatric setting.

tant risk factor for drug-induced delirium, because low
Chisholm and colleagues
[6]
reported a rate of more
albumin level can enhance brain toxicity by making the
than 50% in a mixed group of medical and surgical
blood concentration of the unbound, centrally acting
patients over the age of 60 years. Most studies found a
drug higher
[14].

higher prevalence in surgical patients
[7, 8].
A higher
prevalence has also been found in oncology settings
[9].
Most published data on prevalence and incidence
General etiological factor

are restricted to hospitalized, medically ill elderly. In
Delirium is viewed as a potential medical emergency.

180

general, 10%–15% of medical and surgical general
Several causes of delirium have been identified, but
Chapter 12 – Toxic psychosis

Table 12.2
Differentiating characteristics of delirium, dementia, and psychosis
Salient features

Delirium

Dementia

Psychosis

Onset

Acute

Gradual

Acute

Course

Fluctuates, worse at night

No change

No change

Level of consciousness

Altered

Clear sensorium

Clear sensorium

Attention and

Reduced

Generally intact, but may be

Generally intact, but may be impaired

concentration

impaired

Orientation

Usually disorientated in time

Often impaired

May be impaired

Delusions

Usually paranoid in nature,

May occur in some cases

Multiple systematized delusions or

fleeting and poorly systematized

singe well formed

Hallucinations

Usually visual

Often absent, but may be

Usually auditory, but can occur in any

present in Lewy body

modalities

Dementia

Psychomotor activity

Increased, reduced, or shifting

Often normal

Sometimes varies

Speech

Often incoherent (formal thought

Nominal dysphasia and

Normal, or formal thought disorder in

disorder)

sometimes perseveration

disorganized patients

Physical findings

Present in some conditions such

Often absent

Often absent

as metabolic encephalopathy

Medical conditions or

Usually present

Often absent

Usually absent

drug toxicity

the links between this condition and the underly-

Table 12.3
Classes of drugs reported to cause
ing mechanisms are poorly understood. The list of
delirium

conditions associated with delirium include intracere-1. Anticholinergics
bral infections, drug and alcohol withdrawal, acute
2. Anticonvulsants

metabolic encephalopathy from renal or hepatic fail-3. Antidepressants
ure, head injury, brain tumors, epilepsy, brain hypoxia,
4. Antiemetics

thiamine, vitamin B12 and folate deficiencies, various
endocrine disorders, acute cerebrovascular episodes,
5. Antipsychotics

toxins or drugs, and heavy metal poisoning
[15].

6. Antiparkinsonians

7. Benzodiazepines

Delirium (toxic psychosis) due to

8. Corticosteroids

commonly used drugs

9. Histamine H2 receptor antagonists

10. Opioids and Nonsteroidal antiinflammatory drugs
Several classes of drugs have been reported to cause
delirium and toxic delirium, especially in elderly
11. Antibiotics

patients.
Table 12.3
shows the common classes of drugs
that cause delirium. Review of every single agent is
dementia, infection, and metabolic abnormalities. Psy-beyond the scope of this chapter, because nearly every
chotropic medications are reported to cause delirium
class of drug has been associated with neurotoxicity in
often, as they were involved in 15%–75% of delirium–
susceptible individuals. Interested readers should read
cases
[9, 21, 22, 23, 24, 25, 26, 27].
However, only 2%–
the Medical Letter
[16, 17],
which publishes an updated
14% of cases were accounted for delirium exclusively
list biannually. Additional lists can also be found in
due to drugs
[21, 22, 23, 24, 25, 26, 27].

other sources
[18, 19, 20].
Literature on drug-induced
delirium is mainly based on case reports and uncontrolled case series. Delirium is usually multifactorial in
Anticholinergics

etiology and there is often an interplay of several fac-Pure anticholinergics or drugs with anticholinergic
tors such as the effect of a particular drug or drugs in an
properties are well known to cause toxic psychosis,
181

elderly patient with multiple medical problems such as
especially in older patients
[28, 29].
However, this
Organic Syndromes of Schizophrenia – Section 3

effect has not been confirmed in several other clinical
Benzodiazepines

studies
[11, 21, 30,
31, 32, 33, 34].
Nonetheless, serum
Benzodiazepines are commonly prescribed drugs and
anticholinergic activity measured using a radioactive
they are associated with toxic psychosis. Several stud-assay gives a more accurate estimate of anticholiner-ies have examined the associated risk and reported
gic activity, and did show a robust relationship to toxic
mixed results; with some reporting positive results
[11,

psychosis
[35, 36].