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.