Development and acceptability testing of a decision aid for considering whether to reduce antipsychotics in individuals with stable schizophrenia

Abstract Aim Continued antipsychotic treatment is the key to preventing relapse. Maintenance antipsychotic monotherapy and optimal dose use are recommended for individuals with stable schizophrenia because of their undesirable effects. Decision aids (DAs) are clinical conversation tools that facilitate shared decision‐making (SDM) between patients and health‐care providers. This study aimed to describe the development process and results of acceptability testing of a DA for individuals with stable schizophrenia, considering (i) whether to continue high‐dose antipsychotics or reduce to the standard dose and (ii) whether to continue two antipsychotics or shift to monotherapy. Methods A DA was developed according to the guidelines for the appropriate use of psychotropic medications and International Patient Decision Aid Standards (IPDAS). First, a DA prototype was developed based on a previous systematic review and meta‐analysis conducted for identifying the effects of continuing or reducing antipsychotic treatment. Second, mixed‐method survey was performed among individuals with schizophrenia and health‐care providers to modify and finalize the DA. Results The DA consisted of an explanation of schizophrenia, options to continue high‐dose antipsychotics or reduce to the standard dose, options to continue two antipsychotics or shift to monotherapy, pros and cons of each option, and a value‐clarification worksheet for each option. The patients (n = 20) reported acceptable language use (75%), adequate information (75%), and well‐balanced presentation (79%). Health‐care providers (n = 20) also provided favorable overall feedback. The final DA covered six IPDAS qualifying criteria. Conclusion A DA was successfully developed for schizophrenia, considering whether to reduce antipsychotics, which can be used in the SDM process.


| INTRODUC TI ON
Schizophrenia is a psychiatric disorder characterized by repeated relapse of psychotic episodes. 1 Approximately 0.3%-0.7% of individuals worldwide are diagnosed with schizophrenia. 2 Individuals with schizophrenia suffer from significant distress and impairment in personal, family, social, educational, occupational, and other important areas of life. 3 Therefore, continued improvements in the treatment for schizophrenia are crucial, and maintenance treatment using antipsychotics is particularly important to prevent relapse. 4,5 Although continued antipsychotic treatment is essential for preventing relapse, antipsychotics have undesirable effects, including extrapyramidal symptoms, 6 neurocognitive impairments, [7][8][9] and sudden cardiac deaths, 10 which are at least partially dose dependent. 11 Accordingly, it is clinically important to minimize long-term antipsychotic use. Several trials have been conducted to reduce the use of antipsychotics. For example, a meta-analysis of six randomized controlled trials (RCTs) examining a switch from antipsychotic polypharmacy to monotherapy and remaining on antipsychotic polypharmacy showed a significant difference in study discontinuation due to all causes, whereas no significant differences in relapse, psychopathology, neurocognition, extrapyramidal symptoms, or body weight/ body mass index (BMI) between the two groups were noted. 12 Another meta-analysis of 18 RCTs investigating antipsychotic dose reduction in schizophrenia revealed that the relapse rate was significantly higher in the reduction group than in the maintenance group, whereas neurocognition was significantly improved. 13 The result from these meta-analyses raises another clinical question: how should we apply the evidence from these metaanalyses to clinical practice? Understanding how individuals receiving treatment perceive these results is important. This indicates that sharing treatment decisions with patients is essential. This is because even if there is a proven intervention, without shared decision-making (SDM), evidence-based medicine can turn into evidence tyranny. 14 SDM has gained attention in psychiatric disorders and other physical disorders. 15 Decision aids (DAs) are decision-support tools that help stakeholders, including patients and health-care providers, participate in the SDM process. Thus, DAs help clarify health-care decisions that need to be considered, show relevant information and outcomes of related options, and explore patients' own preferences and values. 16 Some DAs for schizophrenia have been developed, such as a booklet used in a psychiatric acute ward 17 and a digital tool for first episode of psychosis, 18 which aimed to facilitate SDM in the initial phase of treatment. However, to the best of our knowledge, no DA is currently available for individuals with stable schizophrenia who are considering reducing antipsychotics in maintenance treatment.
This study aimed to describe the development process and results of the acceptability testing of a DA for individuals with stable schizophrenia, considering (i) whether to continue high-dose antipsychotics or reduce to the standard dose and (ii) whether to continue two antipsychotics or shift to monotherapy.

| Study design
We developed a DA according to the guidelines for appropriate use of psychotropic medications, 19 Ottawa Decision Support Framework, 20 and International Patient Decision Aid Standards (IPDAS) 21 ( Figure 1). The IPDAS are an evidence-based criteria that provide the development process and contents of DAs. 21 The process of DA development includes (1) clarifying the target population and their decisional needs, (2) gathering a steering committee of specialists, (3) reviewing previous studies to determine the treatment options and its outcomes, (4) developing a prototype of the DA, (5) acceptability testing (alpha test) of the prototype among stakeholders who are not involved in the DA treatment. Second, mixed-method survey was performed among individuals with schizophrenia and health-care providers to modify and finalize the DA.

Results:
The DA consisted of an explanation of schizophrenia, options to continue high-dose antipsychotics or reduce to the standard dose, options to continue two antipsychotics or shift to monotherapy, pros and cons of each option, and a valueclarification worksheet for each option. The patients (n = 20) reported acceptable language use (75%), adequate information (75%), and well-balanced presentation (79%).
Health-care providers (n = 20) also provided favorable overall feedback. The final DA covered six IPDAS qualifying criteria.

Conclusion:
A DA was successfully developed for schizophrenia, considering whether to reduce antipsychotics, which can be used in the SDM process.

K E Y W O R D S
acceptability, antipsychotics, decision aid, schizophrenia, shared decision-making development, (6) improving the prototype following the results of the acceptability testing to finalize the DA, and (7) field testing (beta test) of the DA to determine its effectiveness in actual clinical settings. 22

| Target population
In this study, the DA targeted individuals with schizophrenia whose conditions are stable with undergoing antipsychotic treatment: (i) high-dose antipsychotic monotherapy (chlorpromazine-based dose ≥600 mg/day) or (ii) combined use of two antipsychotic drugs. The DA did not target those who were receiving antipsychotic treatment but still suffered from active symptoms of schizophrenia.
Furthermore, the DA excluded those receiving more than two antipsychotics as combined therapy.

| Steering committee
A steering committee consisting of experts on schizophrenia treatment (all listed as authors) and DA methodology was gathered. The committee included 12 psychiatrists who regularly attend to individuals with schizophrenia and a psychiatric nurse with sufficient knowledge about SDM for those with mental health conditions 15,23 and experience developing DAs in psychiatry.

Clarifying target population
Individuals with schizophrenia whose mental conditions are stable and are receiving high-dose antipsychotic monotherapy (chlorpromazine-based dose ≥ 600 mg/day) or combined use of two antipsychotic drugs.

Assembling steering committee
Twelve psychiatrists and one psychiatric nurse Literature review Treatment options: A: For those who are receiving antipsychotic monotherapy:

| Determining related outcomes of the options
First, regarding the consequences of the two options for monotherapy-to continue high-dose antipsychotics or reduce to the standard dose-we cited the results of an additional subgroup analysis of previously conducted meta-analysis. 13 The subgroup analysis focused on trials that compared study discontinuation due to all causes between those who continued high-dose antipsychotics and those who reduced it to the standard dose. 13 Second, regarding the consequences of two options for the combined use of two antipsychotics-to continue polypharmacy or shift to monotherapy-we referred the results of a previous systematic review and meta-analysis. 12 The meta-analysis focused on trials that compared study discontinuation due to all causes on those who continued polypharmacy (two antipsychotic drugs) and those who shifted to monotherapy. 12

| Prototype development
Based on the results of our literature review, we developed a DA prototype according to the IPDAS criteria. 21 The prototype was written in Japanese.

| Alpha acceptability test
Alpha acceptability testing of the DA prototype was conducted among stakeholders, including individuals with schizophrenia and health-care providers. The test consisted of DA assessments in terms of length, content, balanced information presentation, and decision-making ability. 27 This is a common process of DA development using stakeholders' feedback to finalize the DA. The committee developed a mixed-method survey according to the validated DA acceptability assessment questionnaires. 27 Individuals with schizophrenia who were receiving antipsychotic treatment and health-care providers who were routinely caring for those individuals were asked to review the prototype and complete the survey. Twenty individuals were approached from each group.
The sample size was determined according to previous DA development studies, in which participants' acceptability was examined. 28,29 Results of acceptability test were then used to revise and improve the contents of the DA that would be suitable for use in actual clinical settings.

| Assessment of the developed DA based on the IPDAS criteria
Finally, the developed DA was assessed using the IPDAS. 21 Beta testing to examine its effectiveness was not performed be-

| Development of the DA prototype
The of previously conducted meta-analysis were referred. 13 In the group that reduced high-dose antipsychotics to the standard dose, 30 out of 151 (19.9%) discontinued study participation due to all causes. In comparison, 12 out of 117 (10.3%) in the group that continued with high-dose antipsychotics discontinued study participation due to all causes. 13 The subgroup analysis showed no significant differences in study discontinuation due to all causes between the two groups: to continue high-dose antipsychotics and reduce to the standard dose (N = 5, n = 268, RR = 1.59, 95% CI = 0.85-2.94, p = 0.14). 13 In addition, the DA described options for combined treatment of two antipsychotic drugs: to continue polypharmacy or shift to monotherapy, the pros and cons of the options, and a value-clarification worksheet for each option. Regarding the outcomes of the options, the results of a previous meta-analysis were cited. 12 In the group shifting to monotherapy, 57 out of 177 (32.2%) discontinued study participation due to all causes, whereas 24 out of 154 (14.6%) discontinued study participation due to all causes in the group of continuing polypharmacy. 12 This meta-analysis found that study discontinuation due to all causes was lower in the option to continue polypharmacy (two antipsychotic drugs) than in the option to shift to monotherapy (N = 6, n = 341, RR = 2.28, 95% CI = 1.50-3.46, p = 0.0001). 12 To describe these outcomes for each option, pictorial diagrams of 100 faces were used, where shaded faces represented the proportion of individuals predicted to experience each outcome (Figures 2 and 3).
In the Appendices of the DA prototype, useful information such as chlorpromazine-equivalent doses for antipsychotics, side effects of antipsychotics, concept of recovery, and coping strategies to promote recovery were provided. Appendix S1 presents the content and rationale of the DA prototype.

| Patients
Twenty individuals with schizophrenia who were undergoing antipsychotic treatment reviewed the DA prototype and completed the survey. The mean age of the participants was 47.7 years, and 12 (60%) were women. Table 1 shows the results of the four-point Likert scale used to assess how well the information is described

| Health-care providers
A total of 20 health-care providers, including psychiatrists, nurses, pharmacologists, and psychologists, completed the questionnaire.
The mean age was 34.6 years; six were women, five were men, and one was unknown. Overall, the perceptions of the DA prototype were favorable ( Table 2).

TA B L E 2
Health-care providers' perceptions of the DA prototype (n = 20).

Mean SD
It will be easy for me to use 3.95 0.69 It is easy for me to understand 3.55 0.76 It will be easy for me to experiment with using the strategy before making a final decision to adopt it 3.65 0.67 The results of using the strategy will be easy to see There is a high probability that using this strategy may cause/result in more benefit than harm 4.15 0.75 Note: Scores ranged from 1 (strongly disagree) to 5 (strongly agree).
Health-care providers' positive feedbacks were described below: "The information seems to be understandable for patients and their families, as the text is large and generally easy to read." "I like that the patient can write their own ideas in the booklet." "We can follow the steps, which can proceed decision-making." "The information in the Appendix allows patients to check whether the amount of medication they are receiving is correct." "Using this booklet, health-care providers arrive at a common perspective regarding antipsychotic medication treatment without personal bias."Furthermore, several suggestions were also provided: "The sentence 'Continuation of antipsychotic medication treatment is important to prevent relapse' should be emphasized in bold." "Terms related to side effects, such as extrapyramidal symptoms and autonomic nervous system, should have furigana (way of pronunciation) as well." "Doctors who use the information in the booklet need to be properly familiar with how to use the booklet beforehand." "For each type of decision-making, it may be useful to prepare two types of DA, which would be simple and easy."

| Development of the final DA
The final DA, which is available in both Japanese and English (Appendix S3), attained a high-quality as determined by international DA criteria (Appendix S4). Our DA covered all IPDAS qualifying criteria (six of six), which was essential to be considered a DA.
Our DA also met all IPDAS certification criteria (six of six

| DISCUSS ION
This is the first study on the development and acceptability testing of DA for individuals with stable schizophrenia, considering the reduction in the current antipsychotic treatment. The results suggest that the developed DA, a conversation and treatment decisionsupport tool, was acceptable to stakeholders, particularly individuals with schizophrenia and health-care providers.
Patient participation has gained attention in the mental health field 15 similar to other somatic areas. 16 In addition, the majority of individuals with schizophrenia desire to participate in their own treatment decisions. 31

ACK N OWLED G M ENTS
We sincerely thank the patients and health-care providers for their participation in this study.

FU N D I N G I N FO R M ATI O N
This study was supported by research grants from the Ministry of Health, Labor, and Welfare of Japan (21GC1016) and Grants-in-Aid for Scientific Research (20K10792).

DATA AVA I L A B I L I T Y S TAT E M E N T
The data supporting the results reported in the article is available in the supplementary information.