4. INTRODUCTION
Where there is poor
response to an
initial medication,
switching to another
antipsychotic drug is
recommended
Clozapine and all
long-acting injectable
antipsychotic
medications (LAIs)
were associated with
the lowest rates of
treatment failure
Antipsychotic
polytherapy
(augmentation with
two antipsychotics)
was reportedly
associated with the
second lowest rate of
treatment failure.
These findings
suggest that, in
contrast to the
findings from RCTs,
antipsychotic
augmentation is no
less efficacious than
clozapine in actual
practice.
As a strategy for the
treatment of
schizophrenia with
antipsychotics,
monotherapy is
clearly optimal when
both effective and
tolerated.
5. INTRODUCTION
From a perspective of true
endpoints such as
rehospitalization and
treatment failure, thus, LAIs
seem to be recommended,
and clozapine is
recommended for patients
with treatment-resistant
schizophrenia.
In addition, antipsychotic
polytherapy seems to be an
option for patients who have
not responded to either an
initial or a second
antipsychotic drug.
The objective of the study
was to determine the
effectiveness of antipsychotic
treatments focusing on LAI’s
and antipsychotic
polytherapy for the
prevention of treatment
failure in patients with
schizophrenia.
13. On univariate analysis, several covariates were
associated with treatment failure, including age,
diagnosis, time since onset, previous psychiatric
hospitalization, duration of hospital stay,
PANSS-8 at discharge, and switching to LAIs
Of the various antipsychotic combinations, only
olanzapine and paliperidone were significantly
associated with a lower risk of treatment failure
than monotherapy . Of them (32 patients), 14
patients (43.8%) received LAI paliperidone. In
contrast, aripiprazole and olanzapine were
significantly associated with a higher risk of
treatment failure than monotherapy.
In the adjusted model, time since onset, duration
of hospital stay ,CGI-I at discharge , and APEC
at discharge were associated with treatment
failure, but switching to LAIs was not
As for the secondary outcomes, on univariate
analysis, several covariates were associated with
treatment failure, including age , involuntary
admission , time since onset, duration of hospital
stay, CGI-I at discharge ,and switching to LAIs
Main Results
15. The objective of the present study was to determine the effectiveness of
antipsychotic treatments focusing on LAIs and APEC for patients with
schizophrenia.
In the adjusted model, switching to LAIs and APEC at discharge were
associated with treatment failure, but switching to clozapine was not.
These results suggest that the risk of treatment failure is about 19% lower
in patients with LAI treatments compared to patients without them and
about 17% lower in patients with APEC compared to patients without it
The present study showed a significant benefit of LAIs even in acutely
hospitalized patients with schizophrenia, which has never been investigated
before.
DISCUSSIONS
16. Similarly, the addition of a second antipsychotic reportedly had
advantages in mortality and psychiatric hospitalizations in a non-
interventional, retrospective-prospective, parallel arm study from the
Hungarian National Health Insurance Fund’s database
The present findings from acutely hospitalized schizophrenia patients
with no issue regarding the selection of patients showed the benefit of
APEC more clearly, and they are also consistent with the findings
from nationwide databases.
Another remarkable present finding is that APEC resulted in a
significantly lower risk of treatment failure.
DISCUSSIONS
18. As for specific antipsychotic combinations, only
the combination of olanzapine and paliperidone
was significantly associated with a lower risk of
treatment failure than monotherapy
This result suggests that the risk of treatment
failure is about 48% lower in patients with the
combination compared to patients with
antipsychotic monotherapy.
Nearly half of patients with the combination
received LAI paliperidone, again suggesting
the benefit of LAIs.
Combining aripiprazole and clozapine was
reportedly associated with the lowest risk of
rehospitalization , but combining any
antipsychotics with clozapine is not allowed in
Japan
From the findings of nationwide databases,
combining risperidone and olanzapine was
reportedly associated with a lower risk of
rehospitalization than monotherapy.
There was also a tendency for an association
between the combination of aripiprazole and
brexpiprazole and a lower risk of treatment
failure compared with antipsychotic
monotherapy, but other types of combinations
were not beneficial in the present study.
DISCUSSIONS
20. Conclusions
In conclusion, switching to LAIs or APEC in early
nonresponders seems to be beneficial for the prevention of
treatment failure in acutely hospitalized patients with
schizophrenia.
The risk of treatment failure was about 19% and 17%
lower in patients treated with LAIs and APEC,
respectively, compared to patients treated without them
As for specific antipsychotic combinations, only the
combination of olanzapine and paliperidone was
significantly associated with a lower risk of treatment
failure than monotherapy.
