Secondary Schizophrenia (154 page)

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389

Section

Treatment

5

Section 5

Treatment

Michael D. Jibson and Rajiv Tandon

Facts box

tive symptoms refer to active psychosis, as manifested
r

by hallucinations, delusions, suspiciousness, and dis-Treatment of a primary disorder with
organized thought or behavior. Negative symptoms
secondary psychosis may improve, have no
include blunted affect, reduced-speech production,
effect on, or complicate treatment of the
loss of interest in personal relationships, lack of moti-psychotic symptoms.

vation or volition, anhedonia, and social inattention.

r
Antipsychotic medications are nonspecific
Cognitive impairments involve the full range of atten-agents that improve hallucinations,
tion, memory, language, and executive function. Mood
delusions, and thought disorganization
symptoms include aberrations in affective expression
irrespective of cause and without addressing
as well as a predilection for depression associated par-underlying pathology.

ticularly with acute episodes of illness.

r
Clozapine has significantly greater efficacy
Each of these domains is likely to be involved to
for primary psychotic disorders than other
some degree in all schizophrenia patients, but none
antipsychotics, but also carries greater risk.

is pathognomonic for the illness. Thus, the diagnosis
r
Antipsychotics other than clozapine may
of primary schizophrenia is made by the exclusion of
have minor differences in efficacy, but these
other diagnosable conditions that give rise to a sim-are overshadowed by major differences in
ilar cluster of symptoms. The length of the differen-side effects.

tial diagnosis, and the rarity of many of the conditions
r

to be considered, make it impractical to systematically
Treatment selection among the

eliminate every possible medical diagnosis. Evaluation
antipsychotics will usually be determined by
instead focuses on general screening procedures and
side-effect risk for individual patients, rather
the observation of symptoms atypical for the primary
than by efficacy differences for specific
disorder.

disorders.

Among the findings that would suggest the presence of a medical condition giving rise to psychotic
symptoms are a positive drug screen, focal neurological signs, seizure activity, a history of brain injury,

endocrine abnormalities, evidence of infection or
Schizophrenia is characterized by psychosis and long-inflammatory process, or a family history of a genetic
term functional impairment, generally accompanied
disorder such as Huntington’s or Wilson’s Disease.

by affective disturbance, loss of volition, interper-More ambiguous is the presence of a movement disor-sonal deficits, and cognitive dysfunction. Secondary
der, which might suggest a neurologic condition, but
schizophrenia is the occurrence of these symptoms
could also be the result of antipsychotic treatment or
as a direct result of a diagnosable medical condition,
may simply be associated with primary schizophre-such as seizure disorder or drug intoxication. Primary
nia. Clinical features and diagnostic tests for the
schizophrenia refers to a condition in which these dis-more common causes of secondary schizophrenia are
ease manifestations cannot be directly explained by
beyond the scope of this chapter and are described
identifiable medical pathology or intoxicants.

elsewhere in this book; the appropriate treatment of
The symptoms of schizophrenia may be concep-secondary schizophrenia begins with a comprehensive
393

tualized as falling into four basic categories. Posi-diagnostic assessment.

Treatment – Section 5

disorder must be carried on in parallel with treatment
General principles of drug treatment

of the psychosis.

Drug treatment of primary schizophrenia is symp-Parkinson’s Disease is an idiopathic degeneration
tomatic, without the expectation of improvement in
of motor pathways within the brain. In its advanced
underlying core pathology. Medications are judged on
stages, it may be associated with psychosis and cog-their efficacy in each symptom domain, with their
nitive decline, as well as its characteristic tremor and
greatest effect on positive symptoms. They affect the
bradykinesia
[5].
Treatment of the primary disor-overall course of illness primarily by managing these
der is symptomatic, focusing on relief of rigidity and
symptoms and reducing their impact on the patient’s
other motor symptoms by augmentation of endoge-functional ability and quality of life.

nous dopamine with dopaminergic medication. As is
Treatment of secondary schizophrenia, in contrast,
generally true of dopamine agonists, these agents may
may include drug therapy directed at the primary
initiate or worsen psychotic symptoms
[6],
placing the
pathology: this may be curative of both medical and
treatment of the primary diagnosis in direct conflict
psychiatric symptoms, may alleviate psychosis by con-with that of the secondary psychosis. Conversely, use
trolling medical symptoms, may be required for con-of antipsychotic medications with even a low risk of
trol of medical symptoms and have little impact on
motor side effects may worsen the parkinsonian symp-the secondary psychiatric disorder, or may be in direct
toms
[7].

conflict with treatment of the psychotic symptoms. The
Generally, in cases in which underlying pathology
following examples illustrate these possible interac-is identified and is treatable, treatment should focus
tions between treatment of the primary disorder and
on the primary diagnosis. Antipsychotic medications
the secondary psychosis.

should be brought to bear whenever these treatments
In 1900, approximately 5% of institutionalized
are not adequate to address the secondary psychiatric
mental patients were diagnosed with general paresis
symptoms or when they may worsen such symptoms.

of the insane
[1].
Symptoms included active psychosis
accompanied by progressive dementia and characteristic motor signs. With the identification of Treponema
pallidium as the causative agent, the diagnosis was
Antipsychotic medications

changed to tertiary syphilis and the focus of treatment
A large body of evidence demonstrates the efficacy of
shifted from psychosis to the underlying central ner-antipsychotic medications in the treatment of primary
vous system infection. Definitive antibiotic treatment
schizophrenia, schizoaffective disorder, and bipolar
in the form of penicillin cured the primary illness and
mania. The primary effect of the medications is reduc-alleviated psychosis and dementia in 80% of patients
tion of delusions, hallucinations, disorganization, and
with mild disease. Although patients with advanced
acute agitation associated with any of these disor-disease continued to experience symptoms associated
ders. In bipolar disorder, the medications have demon-with neuronal damage, 30% of patients who had suf-strated broad efficacy against the elevated mood symp-fered psychiatric symptoms for several years recov-toms of manic episodes, and to a lesser extent against
ered from those symptoms sufficiently to return to the
bipolar depression. They are often helpful for the
community and even resume employment
[2].
In this
depressive symptoms associated with schizophrenia.

context, penicillin might be considered the first, and
There is little evidence that they are effective for
among the most successful, psychiatric medications.

depression in contexts other than schizophrenia or
Temporal lobe epilepsy is among the most com-bipolar disorder. They have modest benefits for the
mon causes of partial complex seizures and has a high
negative symptoms of schizophrenia and minimal
correlation with intermittent or chronic psychosis. It
benefit for its cognitive symptoms. They do not appear
is not known if the seizure activity of the disorder or
to address underlying pathology in any of these disor-the underlying brain lesion is associated with develop-ders but are limited entirely to symptom reduction.

ment of psychosis
[3].
Surgical resection of the tempo-Antipsychotics are widely used for primary and
ral lobe brings about remission of seizures in a major-secondary psychotic symptoms in other contexts, such
ity of cases, but rarely leads to improvement of the
as brief psychotic disorder, dementia, drug-induced
psychosis, and may even result in an increase in these
states, and major depression. Most data support the
394

symptoms
[4]
. In this case, treatment of the underlying
use of the medications as nonspecific agents effective
Chapter 32 – Drug treatment of secondary schizophrenia

for psychosis irrespective of the clinical situation. In a
of this class
[9].
In the schizophrenic CATIE study
few cases, specific studies support such use.

population, perphenazine was as effective as newer
Antipsychotic medications will be reviewed briefly,
antipsychotics, but resulted in more treatment discon-followed by specific evidence of their efficacy in
tinuation because of EPS. Although TD was not a
selected types of secondary schizophrenia.

problem with perphenazine in the study, it should be
noted that patients with pre-existing movement dis-Conventional antipsychotic medications
orders were not randomized to the drug, thus limiting the predictive value of the study for these side
Older drugs with higher risk of extrapyramidal side
effects. Perphenazine carries a slightly lower risk of
effects (bradykinesia, rigidity, tremor, and akathisia;
EPS than the other drugs of this class, but there are
EPS) and tardive dyskinesia (TD) are classified as
few other substantive differences among them. Many
conventional antipsychotics, neuroleptics, or first-members of this class (including fluphenazine, per-generation antipsychotics (FGAs). These drugs show
phenazine, and haloperidol) are available in a long-good efficacy against psychotic symptoms such as
acting injectable (depot) formulation.

delusions and hallucinations, but less benefit for
the negative symptoms and functional deterioration that often accompany these symptoms. They
Atypical antipsychotic medications

remain important because of their widespread avail-Newer drugs with lower risk of EPS and TD are clas-ability, low cost, and useful routes of administration,
sified as atypical or second-generation antipsychotics.

including oral, intramuscular, intravenous, and depot
With the exception of clozapine, which will be dis-formulations.

cussed separately, they are not more effective than the
The risk of movement disorders with these drugs
older drugs, but have a more benign side-effect profile
is relatively high. Tardive dyskinesia occurs at a rate of
with regard to abnormal movements. Tardive dyskine-5% of patients per year of exposure to the conventional
sia risk with the newer drugs is estimated at 0.5% per
drugs. TD risk also rises with age, such that patients
year of exposure, and patients over 70 years old have a
over 70 years old have a 25%–30% risk of TD after 1