Effect of LAI Antipsychotics on Relapse Frequency and Adverse Drug Events of Schizophrenia Patients

Introduction: Non-adherence to oral antipsychotic medication is common in schizophrenia patients, and it is very likely to lead to recurrence. Whereas the frequency of recurrence in schizophrenia is associated with poorer long-term outcomes and disease progression. The use of long-acting injectable (LAI) antipsychotics has become a favorable approach in the management of schizophrenia, especially to reduce relapse rates and minimize treatment-related side effects. The aim of this study was to evaluate the effect of using LAI antipsychotics, specifically fluphenazine decanoate, on the relapse rate of schizophrenia patients as well as to assess the potential associated side effects. Methods: This study was a quantitative analytical study design with a retrospective cohort approach involving 1102 schizophrenia patients in RSJ Prof. Dr. Soerojo Magelang who received LAI therapy (fluphenazine decanoate) in various administration frequencies and time intervals. Data on relapse frequency and adverse drug events were obtained from medical records and adverse drug events yellow forms. The bivariate test used was a Wilcoxon signed rank test. Results: The results showed that 77.86% of respondents received LAI with an administration interval ≥ 180 days, and 92% received LAI with low administration frequency (1–5 times). There was a significant decrease between the frequency of relapse in schizophrenia patients and the incidence of drug side effects before and after the administration of antipsychotic LAI. Conclusions: In this study, it was found that the use of antipsychotic LAI (fluphenazine decanoate) can significantly reduce the frequency of relapse and the incidence of adverse drug events in schizophrenia patients.

Introductions

Mental disorders rank as the fifth most disabling disease globally, at 14.4%[1]. Among these mental disorders, schizophrenia is one of the disorders that most affects the quality of life of individuals. Schizophrenia is chronic and is considered a life-shortening disorder, with life expectancy 15-20 years shorter than the average population[2]. In addition, schizophrenia is one of the most prevalent mental disorders, affecting an estimated 23.6 million people worldwide in 2019[3].

Schizophrenia is a complex condition with a multiple combination of symptoms that can be categorized into negative, positive, and cognitive symptoms[4]. Among adults, schizophrenia affects 1 in 222 people, or 0.45%. The most common age of onset of schizophrenia is during late adolescence and the twenties, but in males it often occurs earlier than in females[5]. The prevalence of relapse among individuals with schizophrenia ranges from 50 to 92% worldwide[6]. Even around 80% of schizophrenia patients experience repeated relapses[7]. Relapse is defined as when a patient who has been in remission experiences acute psychotic exacerbation again[8].

Relapse could result in major consequences, such as the risk of the patient endangering either themselves or others, deteriorating personal relationships, education, or employment status[9]. The most significant factors related to schizophrenia relapse include the frequency of psychotic episodes, non-adherence to treatment, comorbid psychiatric diseases, side effects of therapy, substance abuse, layoffs, stressful life circumstances, and psychotic stress[7].

Initiating long-acting injectable (LAI) was primarily recommended by current guidelines among patients with a history of inconsistent and inadequate compliance[10]. Furthermore, LAI is also often associated with lower relapse rates compared to oral antipsychotics[11]. This is because long-acting injectable (LAI) antipsychotics have been shown to improve continuity of therapy and strengthen adherence due to their longer pharmacokinetic half-life and less frequent administration[12].

Fluphenazine is a typical antipsychotic used for the symptomatic management of psychosis in patients with schizophrenia. Long-acting injectable (LAI) formulation of fluphenazine decanoate is used predominantly as maintenance therapy for chronic schizophrenia along with associated psychotic disorders in patients who are unable to tolerate oral formulations or for whom adherence to medication is of concern[13]. However, due to dopaminergic antagonism, fluphenazine can cause extrapyramidal symptoms, including acute dystonic reactions, akathisia, parkinsonian features such as resting tremor and shuffling gait, tardive dyskinesia, opisthotonos, and oculogyric crises[13].

In Indonesia, the prescription of injectable long-acting antipsychotics is highly prevalent among patients with schizophrenia, especially in mental health care facilities such as mental hospitals. However, no studies have been conducted on the effects of using long-acting injectable (LAI) antipsychotics in schizophrenia patients in Indonesia. Therefore, this study aims to investigate the effect of using long-acting injectable (LAI) antipsychotics on the frequency of relapse and the incidence of adverse drug events in schizophrenia patients at RSJ Prof. Dr. Soerojo Magelang.

Methods

The research design used in this study was a quantitative analytical study design with a retrospective cohort approach. This study was conducted at RSJ Prof. Dr. Soerojo Magelang in the period from January 2020 to December 2023. The population in this study were patients diagnosed with schizophrenia according to DSM V criteria in the age range of 19-59 years who received antipsychotic therapy LAI (fluphenazine decanoate) 25 mg injected intramuscularly with a total of 1727 people. Exclusion criteria are patients with schizophrenia with comorbid organic mental disorders and comorbid physical diseases. The sampling technique used in this study was total sampling; based on the restriction criteria, a sample size of 1102 people was obtained.

Data collection was sourced from patients' medical records and drug side effect forms, including data on patient characteristics (age, gender, diagnosis, type of comorbid disease, and history of drug use), number of rehospitalizations, and number of adverse drug events reported. The side effect of LAI (fluphenazine decanoate) identified in this study was extrapyramidal syndrome with the main symptoms of hypersalivation, body stiffness, and oculogyric crisis. Statistical analysis in this study was performed with the Wilcoxon signed rank test using SPSS. The ethical approval for this research was obtained from Soerojo Hospital Ethical Clearance and Law Commission with reference number DP.04.03/D.XXXVI.12/10/2024.

Results

The characteristics of the respondents in this study were grouped by age and gender, as listed in the following table:

Table 1.Patient criteria

Characteristics	n	%
Age
19 - 44 years	852	77.31
45 - 59 years	250	22.69
Gender
Man	690	62.61
Woman	412	37.39
Total	1102	100

The administration of LAI antipsychotics in the respondents of this study was categorized based on the frequency and mean interval of administration, as listed in the following table:

Table 2.Number of antipsychotic LAI administered

Frequency of administration	n	%
1 - 5 times	1018	92.38
6 - 10 times	39	3.54
11 - 15 times	18	1.63
16 - 20 times	3	0.27
21 - 25 times	6	0.54
26 - 30 times	3	0.27
31 - 35 times	5	0.45
36 - 40 times	3	0.27
41 - 45 times	2	0.18
46 - 50 times	5	0.45
Total	1102	100

Table 3.Interval of

Interval	n	%
≤ 30 days	73	6.62
31 - 60 days	94	8.53
61 - 90 days	26	2.36
91 - 120 days	19	1.72
121 - 150 days	16	1.45
151 - 180 days	16	1.45
> 180 days	858	77.86
Total	1102	100

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