Clinician differences in attitudes and perceptions on the use of long-acting injectable antipsychotic agents in treating patients with schizophrenia: results from the US DECIDE survey

Introduction

Prevention of relapse is a key treatment goal for schizophrenia, as relapses are associated with decreased brain volume, resistance to further treatment, financial costs, increased risk of hospitalization, increased risks of violence toward self and others, and reduced functionality [1]. Poor adherence or nonadherence to oral antipsychotic (OA) medications is a major modifiable risk factor for relapse that has been reported in approximately 40–60% of patients with schizophrenia [2–6]. Challenges to adherence with daily OA treatments include disrupted cognition and insight, lack of perceived benefit, adverse events, lack of social support, concomitant substance abuse, chaotic environments, and lack of daily routines [1, 2, 5–8]. Furthermore, clinicians and patients often overestimate adherence with OAs [2, 9, 10].

Compared with OAs, which must be taken daily, long-acting injectable antipsychotic (LAI) medications are associated with greater adherence [11–17] and, in turn, lower rates of relapse/hospitalization [15–26]. LAIs are also associated with lower rates of mortality and suicidal behavior [25–27] and lower inpatient/emergency department visit costs than OAs [14–16]—a possible reflection of higher rates of adherence. Despite these benefits, < 15% of patients with schizophrenia in the US are prescribed LAIs [1, 28]. Although this low rate (compared to oral OA use) is partly attributable to differing purchase costs and inadequate service infrastructure for the provision of LAIs, limited use of LAIs also reflects lack of knowledge and misconceptions among physicians, as well as patients and caregivers [29]. Many psychiatric clinicians reserve LAIs for patients with more severe symptoms or adherence issues [30–32]. However, expert opinion and guidelines suggest that LAI use should be expanded [33–35].

Several surveys have investigated antipsychotic (AP) treatment goals and preferences as well as barriers to LAI use [30–32, 35, 36]. Limited knowledge and lack of confidence in prescribing LAIs are consistently reported as barriers to clinicians implementing LAIs in their practice, particularly if patients are perceived as doing well on their current OA [30, 31, 37]. In addition, clinicians are concerned about the logistics of administering an injectable medication, such as medication storage and having staff available to administer injections [31, 32]. Some patients fear needles, want to avoid injections, or associate injectable medications with being stigmatized; moreover, clinicians may hesitate to recommend LAIs if they anticipate the patient will perceive the treatment negatively [30, 31, 37, 38]. Additional barriers include concerns about cost and uncertainty about the place of LAIs in therapy [30–32, 37]. Surveys have also noted that clinician experience with LAI-associated adverse events, patient and caregiver involvement, and having staff available to administer LAIs were important factors impacting LAI prescribing, with clinicians preferring to have flexible options for administration and dosing [32, 36].

Psychiatric clinicians have shown heterogeneity in terms of LAI use [32, 39]. Although surveys have described barriers to LAI use, limited information is available on why some clinicians are more motivated or able to successfully navigate these barriers, and data are lacking on different subgroups of prescribers. The DEtermining Clinician factors for Implementing LAIs and DEfeating barriers (DECIDE) study was designed to assess environmental/demographic factors, attitudes, motivation, and knowledge/confidence related to LAI use for the treatment of schizophrenia among United States (US)-based psychiatric clinicians. In the present analysis, we report findings regarding attitudes, practices, and perceptions from the DECIDE study in the overall study population, among subgroups of clinicians reporting high and low LAI use, and among subgroups of clinicians with differing mindsets toward the use of LAIs.

Methods

In collaboration with a clinical expert and a team of researchers, a draft survey was developed to assess environmental/demographic factors, attitudes, motivation, knowledge/confidence, and barriers related to the use of LAIs among US clinicians with patients with schizophrenia. After cognitive interviews and a walkthrough of the key messages with 4 practicing clinicians, the survey was revised; the final version included 44 questions and was estimated to take approximately 15 min to complete. The survey largely consisted of multiple choice and Likert-based questions, as well as some rating scales, supplemented with a few open-ended questions. Clinicians were asked to estimate their prescribing practices (e.g., proportion of patients with schizophrenia taking an LAI [either as monotherapy or as part of combination therapy] vs. proportion taking an OA) and the characteristics of their patients with schizophrenia (e.g., race, insurance coverage). In addition, two hypothetical case studies were included to investigate treatment practices.

The survey was reviewed and approved by the sponsor, Teva Branded Pharmaceutical Products R&D, Inc. The Western Institutional Review Board (Puyallup, WA) exempted the research project from institutional review board oversight under the Common Rule 45 CFR § 46.104(d)(2) (research only included interactions involving survey procedures, and there were adequate provisions to maintain participant privacy and confidentiality).

The survey was distributed by CE Outcomes via email to US-based psychiatrists, psychiatric nurse practitioners (NPs), and psychiatric physician associates (PAs) from commercial lists and clinician databases. Respondents provided informed consent and were given a monetary incentive ($50–$60) to complete the survey. Eligible clinicians managed ≥ 1 patient with schizophrenia per month and indicated psychiatry as their specialty. Survey responses were collected via an online survey platform. The survey could not be submitted unless all questions were answered (respondents were prompted to answer unanswered questions).

Based on power calculations using the number of known clinicians in this specialty in the US and a margin of error of less than ± 5%, 380 completed surveys were targeted. Therefore, 1168 clinicians were invited to participate. Quotas were set to collect responses from 295 psychiatrists and 85 NPs/PAs. Separate quotas were set based on clinician self-reported view of LAIs (“mindset”). Mindset was identified based on responses to the question “Which of the following best fits the current way you view your use of [LAIs] for your patients with schizophrenia?” The “early-use mindset” consisted of clinicians who selected “I actively use LAIs as early as possible for my patients.” The “severity-reserved mindset” was based on the response “LAIs are reserved for patients with more severe symptoms, or later in the patient journey when other treatments have failed.” The “adherence-reserved mindset” was based on the response “LAIs are reserved for patients with identified adherence issues to oral medication.” Finally, the “LAI-hesitant mindset” included clinicians who selected “I’m hesitant to recommend LAIs due to a concern or barrier (lack of experience, access, etc.) but would consider using them more” or “LAIs do not offer a significant advantage versus OAs for my patients or are not worth ‘the work.’” The goal was to have equal enrollment in each mindset subgroup.

The first respondents to complete the survey were analyzed. Once a quota was reached, the system would not accept additional responses for that clinician or mindset category. Responses were analyzed in subgroups defined according to LAI use based on the clinician-estimated proportion of patients taking APs from their practice who were using LAIs: low (1st − 33rd percentile; ≤14% of patients taking APs using LAIs), mid (34th − 67th percentile; 15–30% using LAIs), and high (68th − 100th percentile; ≥31% using LAIs). However, due to the number of participants who reported rates that were at the cutoff points for each grouping, the groups were not equal in size. The mid LAI use subgroup was not included in this analysis to increase the chances of detecting differences. In addition, responses were analyzed in subgroups defined according to LAI mindset (as described previously); responses from clinicians categorized as “mid LAI users” were included in the mindset subgroup analysis.

Data were summarized using descriptive statistics. Chi-square tests and t-tests comparing the clinician subgroups were conducted on all survey items using Qualtrics (Provo, UT) and SPSS 27 (IBM: Armonk, NY).

Results

Discussion

This study is, to our knowledge, the most comprehensive examination of environmental/demographic factors, attitudes, motivation, and knowledge/confidence toward LAI use among different subgroups of clinicians treating patients with schizophrenia. Overall, US clinicians estimated that 25% of their patients with schizophrenia used LAIs, and few felt their use was too high. More than half of clinicians participating in DECIDE indicated low confidence with aspects of managing LAIs, and the confidence domain was the only one to show a separation across LAI use/mindset subgroups (Fig. 8). Differences between the high and low LAI use subgroups and between mindset subgroups in this and other domains may guide future educational efforts supporting LAI use.

Clinicians in the high LAI use and early-use mindset subgroups tended to have similar survey responses, in part because of the overlap of physicians in both subgroups (i.e., 70% of the high LAI use subgroup and 60% of the early-use mindset subgroup). Clinicians in these subgroups reported significantly greater confidence in treating patients with LAIs than clinicians from the low LAI use/other mindset subgroups. They disagreed with reserving LAIs for patients with severe symptoms or adherence issues and were more likely to report aggressively pursuing LAI treatment for their patients (i.e., using “any means necessary”). Although clinicians with high LAI use and/or an early-use mindset managed a greater number of patients with schizophrenia each month, they were less likely to report feeling stressed by managing these patients, perhaps due to their confidence with using LAIs.

Clinicians with low LAI use and/or adherence- or severity-reserved mindsets tended to have similar survey responses, suggesting a confidence with LAIs that was greater than that of clinicians with an LAI-hesitant mindset but less than that of clinicians with high LAI use and/or an early-use mindset. Interestingly, clinicians with severity- and adherence-reserved mindsets differed in their responses regarding satisfaction with their LAI:OA use ratio. A higher proportion of those with severity-reserved mindsets were LAI-motivated, expressing dissatisfaction with their LAI:OA use ratio (feeling that their OA use was too high). In comparison, a higher proportion of those with an adherence-reserved mindset reported satisfaction with their LAI:OA use ratio.

While most (82%) clinicians from the LAI-hesitant subgroup were categorized as having low LAI use, only 35% of clinicians in low LAI use subgroup also had an LAI-hesitant mindset, showing that multiple mindsets contributed to low LAI use. Clinicians with an LAI-hesitant mindset had the lowest levels of confidence with LAIs and were also more likely to report increased stress or feelings of burnout associated with managing patients with schizophrenia. Clinicians in the low LAI use and LAI-hesitant mindset subgroups reported fewer educational triggers than clinicians in the high LAI use/early-use mindset subgroups, and significantly lower proportions reported a change in their perception of the use of LAIs over their careers than clinicians in the high LAI use and early-use mindset subgroups, respectively. Interestingly, clinicians from the low LAI use and LAI-hesitant mindset subgroups also showed motivation to use LAIs, with significantly larger proportions reporting dissatisfaction with high OA use than clinicians in the corresponding subgroups (34–46% vs. 15–28%). Although these clinicians report limited current use of LAIs, they may be motivated to consider using LAIs more often if their confidence and knowledge increased.

Some perspectives were consistent across subgroups. Clinicians were aligned on starting patients on an OA before an LAI to ensure effectiveness and tolerability of the medication, consistent with expert consensus and prescribing information recommending a trial of oral medication of less than 6 weeks duration [34, 37, 40–42]. Across LAI use and mindset subgroups, 53–68% of clinicians agreed that most patients taking OAs eventually relapse or have adherence issues. Indeed, schizophrenia is largely characterized by recurrent relapses and, even in the setting of confirmed continuous AP exposure, relapse or symptom worsening is observed in more than 20% of individuals over 1 year of follow-up [43].

Clinicians participating in DECIDE estimated lower rates of nonadherence within their own practice (26%) than for the population nationwide (53%). This finding was observed across LAI use and mindset subgroups, and clinicians with less frequent use of LAIs estimated lower rates of nonadherence. Clinicians are known to overestimate medication adherence in AP-treated patients with schizophrenia [2, 9, 10, 30, 44–46]. Our results suggest that clinicians are aware of the challenges of nonadherence among patients with schizophrenia, particularly clinicians using LAIs more frequently, but that it is difficult for them to assess adherence within their own practice.

Results from the present survey build on those from an earlier survey by Citrome et al. that indicated clinicians were reluctant to switch patients from OAs to LAIs if the patient was perceived as doing well [31]. In addition, and similar to the present survey, adherence issues were reported as a major barrier to managing schizophrenia and a notable reason for considering LAIs [31]. Investigators reported lower clinician confidence related to administering injectable therapy and transitioning a patient from an OA to LAI and that confidence and familiarity with newer therapies may predict use of LAIs [31]. In DECIDE, clinicians in the high LAI use and early-use mindset subgroups reported significantly higher levels of confidence with such topics than those in the low LAI use/other mindset subgroups.

Similar to DECIDE, Zhdanava et al. reported that approximately 60% of clinicians who frequently prescribe LAIs (≥ 1 patient per month with schizophrenia treated with LAIs) had > 10 years of practice in psychiatry, and that those with higher LAI use tended to have a larger caseload of patients with schizophrenia [32]. Psychiatrists practicing in India estimated that they prescribed LAIs to 9% of patients in the acute phase of their illness and 18% of those in the stabilization/stable phase; interestingly, 59% considered themselves to underuse LAIs [47]. When surveyed, French psychiatrists estimated that they prescribed a second-generation LAI to 30% of their patients with schizophrenia; an association between caseload and LAI prescription was found, with clinicians who work with a greater number of patients with schizophrenia being more likely to use LAIs [48]. In addition, 36% of clinicians who frequently prescribed LAIs reported that they recommended LAIs to patients with early-stage schizophrenia [32].There is growing support for use of LAIs earlier in the disease course [34, 35]. Earlier use, within the first 3 years of treatment or following a first episode of psychosis, has been associated with improved AP adherence, decreased relapse rates, and reduced long-term mortality and may reduce the progressive decline in functioning associated with disease recurrence [25, 35]. In DECIDE, clinicians in the high LAI use and early-use mindset subgroups reported high levels of agreement (73–86%) that LAIs are a good early option for patients. Although lower proportions of clinicians from the other subgroups agreed with this approach, their agreement level was still over 40%.

In the survey by Zhdanava et al., clinicians who frequently prescribed LAIs also reported having frequent training and/or education, primarily online CME, peer-reviewed literature, and attending conferences/congresses [32]. Likewise, Citrome et al. concluded that educational initiatives are needed to address attitudinal drivers related to a clinician’s decision to discuss or recommend LAIs and to address specific issues related to LAI use [31]. In DECIDE, training, peer-review publications, continuing education, and colleagues were motivators for LAI use, particularly among clinicians in the high LAI use and early-use mindset subgroups. Given the gap between knowledge and clinical practice, educational activities and peer-review publications that focus on the adherence benefits of LAIs (and, in turn, relapse) and that provide guidance on switching patients to LAIs, including how to broach the subject, may motivate and facilitate real-world use of LAIs.

Overall, this report is exploratory and descriptive in nature. The survey included only a select sample of US-based psychiatric clinicians, which may limit generalizability to the whole of the US and to regions outside of the US. Moreover, selection bias may have arisen through the self-selection of clinicians most likely to respond to such surveys and the fact that respondents were screened out once “clinical role” and “mindset” quotas were reached (thereby capturing clinicians who completed the survey sooner rather than later). As such, these data may not provide a population-wide estimate of the proportion of clinicians meeting criteria for high LAI use or who have a mindset open to early use of LAIs. As in surveys of this type, self-reported data reflect subjective opinions, which are, by definition, inexact and susceptible to recall bias. Clinicians may have overestimated LAI use, if such use is considered desirable, or underestimated nonadherence. In addition, it was not possible to ask follow-up questions, which could have provided additional information (i.e., the direction of a “change” in perception of LAIs). Furthermore, this is not an exhaustive survey and there were some variations in clinical practice that could not be explained. Last, these data represent the attitudes and perceptions of clinicians towards LAIs, not their patients’. Investigations into the sentiments of different patient populations, such as those defined by disease severity and medication adherence, are warranted. To that end, a recent multinational survey study investigated the perceptions, utilization and experience of HCPs, patients, and caregivers with LAIs [49, 50] and will provide insights into different perspectives about LAIs.

Conclusions

To our knowledge, DECIDE is the first study to compare attitudes and factors surrounding LAI use among subgroups of psychiatric clinicians, and these results showed key differences between clinicians based on their level of LAI use and their mindsets related to LAI use. Implementation of LAIs may require logistical changes within a practice, such as training staff to give injections or having medications available in office; some clinicians may be better equipped to make such changes or are more engaged in treating patients with schizophrenia. DECIDE showed that some clinicians (i.e., high LAI use or early-use mindset) have incorporated LAIs into their management of schizophrenia, and significant proportions of those with low LAI use or LAI-hesitant mindset show motivation to use LAIs. Together, these results highlight a need for continuing education to increase awareness of AP nonadherence and the value of LAIs and to help clinicians identify opportunities to improve patient outcomes.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Author contributions

DV, GDS, EB, KRF, MS, and RTH contributed substantially to the conception and design of this study. GDS and EB acquired and analyzed the data. All authors (DV, GDS, EB, KRF, MS, ST, and RTH) participated in the interpretation of the data, critically reviewed and revised the manuscript, approved the final document to be submitted, and agree to be accountable for all aspects of the work.

Funding

This study was supported by funding from Teva Branded Pharmaceutical Products R&D, Inc. Medical writing and editorial support were funded by Teva Branded Pharmaceutical Products R&D, Inc.

Data availability

Qualified researchers may request access to patient-level data and related study documents, including the study protocol and the statistical analysis plan. Requests will be reviewed for scientific merit, product approval status, and conflicts of interest. Patient level data will be deidentified and study documents will be redacted to protect the privacy of trial participants and to protect commercially confidential information. Please email USMedInfo@tevapharm.com to make your request.

Declarations