Keywords
pharmacoepidemiology, prescription, antipsychotics, trends,
schizophrenia
Introduction
Schizophrenia is a chronic psychiatric disorder that is associated with
positive and negative symptoms as well as cognitive dysfunction and a
significant decline in psychosocial functioning.1 The
combination of pharmacotherapy with antipsychotics and psychotherapy,
such as psychosocial rehabilitation, is considered to be a treatment
that can improve not only the psychiatric symptoms of patients with
schizophrenia but also their cognitive and social
functioning.1,2 Schizophrenia often requires long-term
treatment with antipsychotic drugs. Historically, treatment with a wide
variety of antipsychotics has had an uncertain impact on
patient-centered long-term outcomes such as stable employment,
maintenance of good interpersonal relationships, and maintenance of
independent living, and there are serious concerns about side effects
(such as tardive dyskinesia, weight gain, diabetes, and dyslipidemia)
with some treatments.3 Older first-generation
antipsychotics (FGAs), such as haloperidol, have proven effective, but
side effects such as extrapyramidal symptoms (EPSs) and, in some cases,
tardive dyskinesia often limit long-term adherence. Since the 1990s,
second-generation antipsychotics (SGAs), which are equally effective and
have fewer side effects than FGAs, have become
mainstream.4-6Second-generation antipsychotic
(SGA) are expected to be equally or more effective than FGAs, especially
for negative symptoms, and are expected to reduce EPSs and the risk of
tardive dyskinesia. However, SGAs also have potentially serious side
effects (e.g., cardiovascular and endocrine side effects), and the
overall risk-benefit profile is less clear than expected.
Many guidelines state that pharmacotherapy is important in the treatment
of schizophrenia, and from various perspectives in these guidelines,
monotherapy with an SGA is considered ideal.7-11Previous studies have shown that SGAs are more commonly used than FGAs;
an international study examined international trends in antipsychotic
use in 16 countries in 2005 and found an increase in SGA use in all
study populations in 2014, but the pattern of antipsychotic use varied
widely across countries.12 From the database of
prescription data of the international drug safety program, the
prescription data of inpatients with schizophrenia from 2000 to 2015
showed that the use of SGAs significantly increased from 62.8% to
88.9%, and the prescription rate of FGAs decreased from 46.6% to
24.7%.13 In Japan, 82.3% of adult patients with
schizophrenia were treated with monotherapy, and 17.8% were treated
with multidrug therapy, with risperidone being the most commonly
prescribed monotherapy (20.8%) between 2006 and
2012.14 Between
2006 and 2012, a year-to-year increase in the proportion of SGA
monotherapy was seen in adult and elderly patients, and a decrease in
antipsychotic doses was seen among adults.14 Up to
81% of a study cohort of Japanese patients with chronic schizophrenia
were taking daily antipsychotic medication at doses exceeding an average
of 1000 mg chlorpromazine equivalents (CPeq) per
day.15 In a study covering six East Asian countries
and regions, Sim et al. found that 17.9% of their sample was prescribed
high doses of antipsychotics.16
Such previous studies looking at trends in prescribing have been limited
to comparisons of cross-sectional data from period to period. Some of
these data may or may not include the same patients. However, there are
currently no studies that follow prescribing trends over a long period
of time for the same patients. In actual clinical practice, few patients
start treatment with FGAs.12 While a recent report
from a combination of FGA and SGA indicates that monotherapy improves
psychiatric symptoms and does not increase relapse, regardless of FGA or
SGA,17 easy monotherapy to SGA is believed to be
associated with the risk of relapse. Thus, once FGA treatment is
switched to SGA treatment in chronically ill patients who had been
treated for a long time with FGA, the mental state of the patient often
becomes unstable, and for many such patients, FGAs are continued. We,
therefore, hypothesized that patients whose symptoms stabilized on FGAs
would be less likely to switch to SGAs and that the proportion of
patients using SGAs would be lower than those in previous studies.
Therefore, in this study, we examined whether the medication regimens of
schizophrenia patients with available data for the past 20 years changed
over this time period.