Authors: Perminder S. Sachdev

Secondary Schizophrenia (156 page)

BOOK: Secondary Schizophrenia

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397

year at 900 mg/day. In contrast to other antipsychotic
chosis and behavioral disturbances in dementia
[61].

Treatment – Section 5

Parkinson’s Disease

useful as adjunctive agents or in treatment-refractory
Studies of Parkinson’s Disease have examined both
cases
[78].
No single antipsychotic drug has emerged
antipsychotic efficacy and the effect of the drugs on
as uniquely effective, and survey data indicate that all
movement symptoms. Clozapine has proven effec-agents are widely used with equally fair results
[79].

tive in reducing psychotic symptoms and has not
Complicating the diagnostic and therapeutic
shown a risk of worsening parkinsonian symptoms
approach to psychosis in SLE is the risk of psychosis
[62, 63].
Quetiapine has received attention because of
with steroid treatment, one of the standard therapies
its low risk of movement disorders in schizophrenia
of the disorder. Recommended approaches to differ-patients, and has generally proven effective in Parkin-entiate SLE-related psychosis from steroid-induced
son patients
[64, 65, 66].
Some studies, however, show
symptoms are manipulation of the dose of corti-it to be less effective than clozapine,
[67, 68]
and one
costeroid to determine if the psychosis improves or
study found no efficacy for quetiapine
[69].
Risperi-worsens with increased doses of the drug
[79].
Because
done
[70]
and olanzapine
[71]
have been the subject
psychotic symptoms respond promptly to effective
of fewer and smaller studies, and have generally been
treatment of the underlying disorder, they should
found to carry higher risk of parkinsonian symptoms.

improve with more aggressive steroid treatment
[80].

Ziprasidone and aripiprazole are represented only by
case studies.

Human immunodeficiency virus

Current recommendations for antipsychotic use in
Psychosis and negative symptoms similar to those seen
Parkinson’s Disease favor quetiapine or clozapine as a
in primary schizophrenia have long been noted in
first-line agent, and clozapine for treatment-refractory
human immunodeficiency virus (HIV) patients. The
cases.

differential diagnosis of these symptoms is complicated by the increased risk of individuals with pre-

Seizure disorder

existing psychotic disorders to contract HIV. As with
Antipsychotics have shown benefit in small, open-other forms of schizophrenia, psychotic symptoms
label, and retrospective studies of psychosis in the con-respond more favorably to antipsychotic treatment
text of various seizure disorders. The largest of these
than do negative symptoms.

studies involved 21 children and adolescents treated
HIV patients are particularly at risk for extrapyra-with risperidone and showed a response rate com-midal side effects from antipsychotic medications
[81].

parable to that seen for primary psychotic disorders
Atypical antipsychotics in general are recommended
[72].
Although the antipsychotic clozapine is known
on that basis for this population
[82].
Thus far, no sin-to lower seizure threshold, there was no increase in
gle agent has demonstrated unique efficacy or tolera-seizure activity in a series of six patients treated for
bility in this population.

severe psychosis unresponsive to other interventions
As in the case of SLE, certain treatments of HIV

[73].
Perhaps most intriguing have been studies show-infection may place patients at increased risk of psy-ing normalization of brain function in epilepsy-related
chosis. Specifically, antiretroviral agents have been
psychosis with antipsychotic medications
[74, 75].

associated with onset or worsening of psychosis
[83].

More common, however, is the finding that the psy-In these cases, alteration of the antiretroviral regimen
chosis can only be adequately treated after the seizures
is the preferred approach.

have been controlled
[76].

Antipsychotics for schizophrenia secondary to

genetic disorders

systemic disorders

Huntington’s Disease

Systemic lupus erythematosus

Huntington’s Disease is a genetically acquired degen-Psychosis is among the more common and severe
erative disorder of the basal ganglia
[84].
As in the
symptoms of systemic lupus erythematosus (SLE),
case of Parkinson’s Disease, patients may manifest psy-sometimes presenting as the initial manifestation of
chosis, choreoform movements, and cognitive decline.

the disease and always requiring intervention
[77].

Because there is no effective treatment for the under-Although the preferred approach to treatment is to
lying disorder, antipsychotic medications are the first-

398

address the underlying disorder, antipsychotics may be
line therapy for psychotic symptoms and may be
Chapter 32 – Drug treatment of secondary schizophrenia

useful for other symptoms of the disease. A recent crit-known risk of psychosis. Several antipsychotic agents
ical review of treatments found modest support for
have been reported to be effective in these cases,
the use of antipsychotics to treat psychotic symptoms,
though only a few have been the subject of carefully
behavioral disturbance, and choreoform movements
conducted studies. The emphasis in these cases is on
[85].
Specifically, studies are available on the use of
reduction of psychosis without exacerbation of the
risperidone for psychosis, olanzapine for behavioral
movement disorder. Consequently, agents with low
disturbance and movement disorder, and haloperidol
risk of parkinsonian side effects, particularly clozapine
for psychosis and chorea. Current thinking regard-and quetiapine, have been the focus of most studies.

ing the increased risk of extrapyramidal symptoms
Clozapine has been shown to improve psychotic
with conventional drugs suggests the preferential use
symptoms induced by levodopa treatment of Parkin-of atypical agents. For this reason, clozapine has been
son’s patients, with complete amelioration of psychosis
widely used to control both psychosis and motor
in about half of patients
[89, 90, 91].
Clozapine doses
symptoms
[86]
, but with the availability of other, more
in these studies were well below those used in pri-benign, antipsychotics with low risk of EPS, clozap-mary schizophrenia, typically around 50 mg/day. More
ine should be considered only one of several viable
recently, low to moderate doses of quetiapine have
options.

shown similar efficacy
[92, 93, 94, 95].
Neither of these
agents caused a worsening of the movement disorder
Wilson’s Disease

or dementia. In contrast, both olanzapine
[96]
and
A rare flaw in copper metabolism gives rise to the
ziprasidone
[97]
have been reported in small studies
deposition of metallic copper in brain, liver, and other
to reduce the effectiveness of levodopa treatment in
tissues, leading to the psychiatric and medical mani-Parkinson’s patients, thus limiting their utility in these
festations of Wilson’s Disease. Because psychosis is so
cases.

often an early manifestation of the disease, many of
these patients are diagnosed with schizophrenia and
Corticosteroids

treated with antipsychotic medications, with limited
Glucocorticoids are a rare, but well-established cause
benefit
[87]
. Definitive treatment involves chelation
of psychosis, often in conjunction with mood elevation
of excess copper. Psychotic symptoms may improve
[98].
No controlled studies of individual antipsychotics
as copper levels normalize, especially in cases treated
are available in this population, but numerous case
early in the course of illness. A specific role for antipsy-reports support the use of risperidone
[99, 100, 101]

chotic medications has not been established with for-or conventional antipsychotics
[102, 103]
. The mood-mal studies, and there are few data to guide clinicians
stabilizing agent valproic acid has also been used pro-in this area.

phylactically against both psychosis and mood disturbance
[104].

Antipsychotics for substance-induced schizophrenia

Drugs of abuse

Implications for clinical practice

Most studies of antipsychotic treatment of substance-The pattern that emerges in these cases is sufficient to
induced psychosis focus on the pharmacology of both
recommend the use of antipsychotic medications for
the precipitating and the treating agents. Hallucino-control of hallucinations, delusions, and thought dis-gens and psychostimulants have been used extensively
organization irrespective of the origin of the symp-in human and animal models to provoke or stimu-toms. Although in a few cases other symptomatic treat-late psychotic symptoms for study. Despite this inter-ments may be useful, antipsychotics remain the agents
est from a research perspective, few studies of clinical
of choice in most cases. In those conditions for which
efficacy are available. Expert guidelines recommend
medical treatment of the primary disorder is possible,
the use of antipsychotics and benzodiazepines to con-antipsychotics may be used in addition to, but never in
trol symptoms until detoxification from the offending
place of, treatment of the underlying pathology.

agent is complete
[88].

Dopaminergic drugs

Antipsychotic treatment selection

Dopaminergic agents used to treat movement disor-Although limited efficacy studies are available for some
399

ders, such as in Parkinson’s Disease, carry a well-of these conditions, in most instances they are not
Treatment – Section 5

Table 32.1
Comparison of antipsychotic side effects
Anticholinergic

Prolactin

qTc

symptoms

EPS

Hypotension elevation

prolongation Sedation

Wt gain

Aripiprazole

+
/
−

Olanzapine

+
/
−

+ + +

Quetiapine

+
/
−

+ + +

Risperidone

+
/
−

Ziprasidone

+
/
−

Clozapine

+ + +

+
/
−

+ + +

Low Potency Neuroleptics

+ + +

High Potency Neuroleptics
+
/
−

+ + + +

+
/
−

\+
/
−
: Rarely significant or encountered only at high doses
+
: Mild severity or low frequency at average doses
++
: Moderate severity or frequency at average doses
+++
: Often clinically significant across the entire dose range
sufficient to dictate drug choice. To an even greater
patient in maintaining sufficient weight. Despite its
degree than with primary schizophrenia, selection of
superior efficacy, clozapine may need to be avoided
an antipsychotic requires attention not only to effi-because of seizure risk. In each case, awareness of side-cacy data, but more particularly to side-effect pro-effect risks is a primary consideration of treatment
files. In contrast to the paucity of information on
choice.