Prescription patterns in patients with schizophrenia who discontinued long-acting injectable antipsychotics: A chart-review.

Abstract

Long-acting injectable (LAI) antipsychotics that provide reliable drug delivery to patients whose adherence to oral medication is suboptimal are considered to be a promising treatment option for patients with schizophrenia.1 While LAI antipsychotics are reportedly superior to, or at least as effective as, oral counterparts in preventing relapse of schizophrenia,2-4 some patients may eventually need to discontinue LAI antipsychotics. Since these patients who fail to continue LAI antipsychotics represent a more difficult-to-treat population than those who successfully continue them, it is critically important to characterize their demographic and clinical characteristics in order to improve our understanding of the psychopharmacological management of this illness. To this end, we conducted a systematic chart review of patients with schizophrenia who started but later discontinued LAI antipsychotics during the course of treatment. A systematic chart review was conducted for patients with schizophrenia, according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems, who commenced LAI antipsychotic treatment from January 2005 to December 2014 at Inokashira Hospital in Tokyo, Japan. This retrospective chart review study was approved by the Institutional Review Board of Inokashira Hospital and was exempt from informed consent because the study utilized de-identified data that had been acquired during routine clinical care. The information about this study was posted at the in-hospital bulletin board to provide the opportunity to opt out. Among these patients, those who discontinued LAI antipsychotics at least once during the study period were identified. The collected information included age, sex, duration of illness, duration of treatment, reasons for discontinuation of LAI antipsychotics, the details of prescriptions up until December 2016, and outcomes at the time of final follow-up. When two or more possible reasons were identified, the most relevant reason was chosen based on the descriptions of charts. Ninety-nine patients were included in the present study (inpatients, n = 89 [89.9%]; mean ± SD age, 47.5 ± 13.5 years; males, n = 48 [48.5%]; mean ± SD duration of illness, 20.9 ± 12.7 years; mean ± SD duration of treatment, 17.6 ± 13.1 years). Haloperidol decanoate, LAI risperidone, fluphenazine decanoate, paliperidone palmitate, and fluphenazine decanoate plus haloperidol decanoate were used as the first LAI antipsychotics in 37 (37.4%), 31 (31.3%), 29 (29.3%), 1 (1.0%), and 1 (1.0%) patients, respectively. The reasons for discontinuation were as follows: insufficient response (n = 35, 35.3%), side-effects (n = 13, 13.1%), patient's request (n = 12, 12.1%), unstable physical conditions (n = 8, 8.1%), loss to follow-up (n = 6, 6.1%), symptom improvement (n = 4, 4.0%), unknown reasons (n = 10, 10.1%), and others (n = 10, 10.1%) (Table 1). The most frequent treatment status at the final observation was inpatient treatment (n = 38, 38.4%), followed by outpatient treatment (n = 28, 28.3%), referral to other hospitals or clinics (n = 22, 22.2%), death (n = 7, 7.1%), and loss to follow-up (n = 4, 4.0%). Twenty-nine patients (29.3%) resumed LAI at least once later during the course of the treatment. At the time of final follow-up, 13 patients (13.1%) were using LAI antipsychotics (LAI risperidone, n = 5; paliperidone palmitate, n = 5; fluphenazine decanoate, n = 2; haloperidol decanoate, n = 1) and 51 patients (51.5%) were receiving antipsychotic polypharmacy (mean ± SD number of antipsychotics, 1.7 ± 0.9). The most frequently used oral antipsychotic was olanzapine (n = 36, 36.4%), followed by risperidone (n = 35, 35.4%). The present chart review of patients with schizophrenia who discontinued LAI antipsychotics showed that after discontinuation of their first LAI antipsychotic, approximately one-third of patients resumed LAI, and about half of them were receiving antipsychotic polypharmacy. These facts highlight the difficulties in treating treatment-refractory patients with schizophrenia without LAI antipsychotics even after discontinuation. The results showed that many of the patients were in middle age and had received treatment over a long period of time. As seen from the reasons for discontinuation of LAI antipsychotics, the patients comprised a relatively challenging group. The adherence of patients in such a challenging group tends to be particularly poor. If patients do not show a sufficient response to LAI antipsychotics, clozapine may be considered. In Japan, use of clozapine was not common at the time of this review because of strict rules in place regarding the use of clozapine.5 Thus, while only nine patients (4.5%) were able to continue the same LAI antipsychotics during the study period, many patients may have been resorted to reintroduction of LAI antipsychotics or antipsychotic polypharmacy. Limitations of this study included a small sample size, lack of use of any rating scales, absence of the information on former regimens, and predominance of first-generation LAI antipsychotics. In conclusion, the real-world data indicate that patients who discontinued LAI antipsychotics eventually needed to resume LAI antipsychotics or receive antipsychotic polypharmacy, which indicates that earlier use of clozapine may be useful.6 Dr Asano has received speaker's honoraria from Otsuka Pharmaceutical, Dainippon-Sumitomo Pharma, Janssen Pharmaceuticals, and Yoshitomi Yakuhin within the past 3 years. Dr Suzuki has received manuscript or speaker's fees from Astellas, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Elsevier Japan, Janssen Pharmaceuticals, Kyowa Yakuhin, Meiji Seika Pharma, Mitsubishi Tanabe Pharma, MSD, Novartis, Otsuka Pharmaceutical, Shionogi, Shire, Tsumura, Wiley Japan, and Yoshitomi Yakuhin, and research grants from Eisai, Mochida Pharmaceutical, Meiji Seika Pharma and Shionogi. Dr Mimura has received speaker's honoraria from Daiichi Sankyo, Dainippon-Sumitomo Pharma, Eisai, Eli Lilly, Fuji Film RI Pharma, Janssen Pharmaceutical, Mochida Pharmaceutical, MSD, Nippon Chemipher, Novartis Pharma, Ono Yakuhin, Otsuka Pharmaceutical, Pfizer, Takeda Yakuhin, Tsumura, and Yoshitomi Yakuhin within the past 3 years. Also, he received grants from Daiichi Sankyo, Eisai, Pfizer, Shionogi, Takeda, Tanabe Mitsubishi, and Tsumura within the past 3 years. Dr Uchida has received grants from Eisai, Otsuka Pharmaceutical, Dainippon-Sumitomo Pharma, and Meiji-Seika Pharma; speaker's honoraria from Otsuka Pharmaceutical, Dainippon-Sumitomo Pharma, Eisai, and Meiji-Seika Pharma; and advisory panel payments from Dainippon-Sumitomo Pharma within the past 3 years.