Secondary Schizophrenia (73 page)

30,
45, 46],
and some negative
[31, 32, 33, 34, 47, 48,

49].
Drugs with a prolonged half-life when used in the
Anticonvulsants

elderly can lead to high blood levels causing toxicity.

Anticonvulsants can cause toxic psychosis when it
Corticosteroids

reaches toxic blood levels
[37].
Inouye and colleagues
examined the risk associated with anticonvulsant med-Following a review of the literature on this topic, Sirios
ications and found an increased risk
[34].

and colleagues
[50]
suggested that two clinical profiles
have been reported: an affective profile and a toxic-organic profile. Toxic psychosis was reported in 13%

Antidepressants

of cases and pure psychosis in 11%
[51, 52].
An affective psychosis with normal cognition can occur that
Antidepressants are known to increase the risk of
may be very similar to a primary psychiatry condition.

toxic psychosis, especially in elderly subjects
[32].
It
The toxic-organic profile comprises delusions, hallu-is clearly known that tricyclic antidepressants have
cinations, thought disorder, confusion, agitation, and
anticholinergic properties, amitriptyline being the
perplexity. It has been shown that prednisone is better
strongest and nortriptyline the weakest. These groups
than high-dose cortisone or adrenocorticotropic hor-of drugs are particularly at high risk
[38].
Among SSRI
mone in causing toxic psychosis. However, high-dose
antidepressants, fluoxamine
[39]
and paroxetine
[40]

steroids and female gender have been associated with
can cause toxic psychosis in high-risk patients.

increased risk of toxicity
[53, 54].

Antiemetics

Histamine H2 receptor antagonists

One study that examined the risk associated with
Histamine H2 receptor antagonists are linked to toxic
antiemetics found a positive result
[34].

psychosis
[33, 55].
Others also reported that the drugs
cimetidine
[56],
ranitidine
[56]
, and famotidine
[57]

can induce a toxic psychosis.

Antipsychotics

Antipsychotics

with

anticholinergic

properties,

Opioids and nonsteroidal

alpha-receptor blocking abilities, and with prominent
antiinflammatory drugs

dopamine D2 receptor binding are particularly at
an increased risk of causing neurotoxicity
[41].
Two
Opioid and nonopioid medications have been

studies that examined the risk reported positive results
reported to cause toxic psychosis. Several studies have
with antipsychotics
[11,
32].
Some of the newer drugs
examined opioid analgesics and found a correlation
with minimal anticholinergic effects are probably
with toxic psychosis
[11,
45, 46, 58]
. Among opioids,
safer compared to the older generation drugs.

pethidine is found to be more problematic because of
its metabolite norpethidine, which has anticholinergic and central nervous system excitatory properties
Antiparkinsonians

[30].
Nonsteroidal antiinflammatory drugs (NSAIDs)
have also been associated with toxic psychosis
All antiparkinsonian drugs by their dopamine activat-

[59,
60].

ing property can induce delirium
[42, 43, 44].
However, one study that examined the risk reported negative results
[32].
Delirium is a dose-related side effect.

Antibiotics

Therefore, reduction of appropriate antiparkinsonian
Antibiotics in toxic concentration in the blood have
182

drugs is necessary to manage parkinsonian symptoms.

been reported to be associated with toxic psychosis
Chapter 12 – Toxic psychosis

[61].
It may be difficult at times to distinguish between
importantly, drugs that are well known to cause toxic
psychosis induced by an infectious disease and that
psychosis in high-risk patients should be avoided.

induced by the prescribed antibiotic.

Implications for clinical practice

Pathogenesis of drug-induced

A number of centrally acting drugs are associated with
toxic psychosis

brain toxicity that leads to a psychotic state with acute
cognitive impairment. This is often seen in clinical
Centrally acting drugs may be present in toxic
practice and is sometimes difficult to differentiate from
concentrations due to excessive intake or impaired
primary psychiatric conditions such as an affective
clearance. Elderly patients and patients with multiple
psychosis or schizophreniform psychosis. In an acute
medical problems and organ damage are particularly
setting, it may not always be possible to test the cog-vulnerable because of pharmacokinetic changes. A
nition of an acutely agitated patient. Recognition and
number of mechanisms involving various neurotrans-management of toxic psychosis are vital for saving the
mitters have been reported. Cholinergic hypoactiv-lives of such patients.

ity, dopaminergic hyperactivity
[62]
and involvement
of γ -amino-butyric acid (GABA) and glutamatergic
diffuse modulatory pathways
[63]
have been the foci
Summary and conclusions

of research in this area. Gaudreau and colleagues
[64]

Toxic psychosis is a medical emergency and a mani-proposed a model that suggested the central role
festation of an underlying serious insult to the brain,
of thalamus in the causation of toxic psychosis.

due to an excessive amount of commonly prescribed
According to this model, psychotic symptoms could
drugs in the blood. Often the causes are multifacto-originate from a transitory dysfunction of thalamus
rial with several risk factors operating at the same time.

leading to sensory overload and hyperarousal. Psy-Almost all classes of prescription drugs can cause toxi-choactive medications such as benzodiazepines and
city when consumed in large amounts. Therefore, clini-opioids could exert this effect by compromising the
cians should be aware of this condition when prescrib-thalamic gating functions by interfering with cen-ing to patients, particularly high-risk groups such as
tral glutamatergic, GABAergic, dopaminergic, and
the elderly and the medically compromised.

cholinergic pathways.

Future research directions

Management

Good-quality, well-controlled studies are lacking in
Management, including the identification and treat-this area and the studies examining the risk of drugs
ment of acute precipitants and implementation of sup-causing toxic psychosis often reported mixed results.

portive and restorative care, is most important. A thor-Therefore, more studies are needed in this area. Future
ough review of medications taken is crucial as this
studies should be large enough to find meaningful
is often the most common reversible cause of toxic
associations and individual drugs should be stud-psychosis. The review should include exploring the
ied separately. Instruments that are used to diagnose
temporal association between the drug and the onset
and monitor the progress of toxic psychosis (delir-of psychosis, a recent change in prescription or dose
ium) should be standardized to make comparisons
increase, and a history of over-the-counter medica-easy across different settings. Additionally, researchers
tions. Once a medication was found to cause the psy-should study all the potential confounders and should
chosis, it should be stopped as soon as possible. Most
control for these in their analyses.

183

Organic Syndromes of Schizophrenia – Section 3

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