Maryia Zhdanava,1 H Lynn Starr,2 Todor I Totev,3 Patrick Lefebvre,1 Aditi Shah,1 Kristy Sheng,4 Dominic Pilon1

1Analysis Group, Inc., Montréal, QC, Canada; 2Janssen Scientific Affairs, LLC, Titusville, NJ, USA; 3Analysis Group, Inc., Boston, MA, USA; 4Analysis Group, Inc., Menlo Park, CA, USA

Correspondence: Maryia Zhdanava, Manager at Analysis Group, Inc, 1190 Avenue des Canadiens-de-Montréal, Suite, 1500, Montréal, QC, H3B 0G7, Canada, Tel +1 514-394-4469, Email [email protected]

Purpose: To describe changes due to the COVID-19 pandemic in the prescribing of long-acting antipsychotics (LAI) for schizophrenia, patient outcomes, and patient and healthcare provider (HCP) attitudes regarding COVID-19 vaccination in the United States (US).
Methods: An anonymous online survey was administered to US-based LAI prescribers with a psychiatry specialty in May 2021. Information on prescriber and clinical practice characteristics, LAI prescribing, patient outcomes, and attitudes toward COVID-19 vaccination was collected and described.
Results: Of the 401 LAI prescribers meeting survey criteria, 64.6% reported that LAI prescribing remained unchanged (increase: 19.2%, decrease: 14.0%). The majority did not switch patients from LAIs to oral antipsychotics (OAP; 63.3%) or to LAI formulations with lower frequency of administration (68.1%); most prescribers switched the same number of patients from OAPs to LAIs during the pandemic as in previous practice (65.1%). Half of LAI prescribers (50.1%) reported antipsychotic adherence as unchanged among most patients; 44.6% reported symptom control/relapse frequency as unchanged. Most prescribers believed their patients with schizophrenia should be prioritized for COVID-19 vaccination (74.1%) and encouraged all patients to obtain a COVID-19 vaccine (84.0%). However, 64.1% of prescribers reported hesitancy among some patients about vaccines’ safety; 51.4% reported that some patients were willing to be vaccinated despite the hesitancy, 48.6% indicated that some patients perceived COVID-19 vaccines as safe, effective, and important.
Conclusion: LAI prescribing and prescriber-reported antipsychotic adherence in patients with schizophrenia remained largely unchanged approximately one year after the start of COVID-19. Focused efforts to overcome patients’ COVID-19 vaccine hesitancy are warranted.

Keywords: adherence, antipsychotics, COVID-19, physician survey, prescribing habits, schizophrenia

Introduction

Schizophrenia is a chronic, heterogenous psychiatric disorder involving various clinical dimensions, including positive symptoms (eg, delusions and hallucinations), negative symptoms (eg, anhedonia, social withdrawal, blunted affect), disorganized behavior, and impaired cognitive or executive function.1,2 The estimated prevalence of schizophrenia is between 0.25% and 0.64% in the United States (US), with an incidence of 1.5 per 10,000 people.3–5 Despite the relatively low prevalence, schizophrenia is associated with substantial health, societal, and economic burden, including high healthcare resource utilization6–8 and increased risk of premature mortality, disability, mental health comorbidities, and suicide.9–15 Furthermore, the difficult symptoms associated with schizophrenia profoundly decrease patients’ quality of life and daily functioning.16,17

As a result of confirmed cases of illness caused by a SARS-CoV-2 Novel Coronavirus (2019-nCoV or COVID-19), the US Secretary of Health and Human Services determined the existence of a public health emergency on January 27, 2020.18 The COVID-19 pandemic has placed at risk certain in-person encounters with healthcare providers that are essential for the stability of patients with schizophrenia,19,20 including the administration of long-acting injectable antipsychotics (LAIs). Antipsychotic therapy is a mainstay of care for schizophrenia,1 and LAIs have well-recognized clinical utility, partially due to their reduced frequency of administration compared with daily oral antipsychotics (OAPs).21–23 Previous evidence has demonstrated improved adherence to LAI therapy and symptom control relative to OAPs21–23 and reduced rates of hospitalization and relapse.24,25 The disruption of the continuity of care in schizophrenia, including LAI administration, might result in patient decompensation and relapse.26 In the context of a global pandemic, it could also place an additional strain on the healthcare system, further increasing emergency department visits and hospitalizations, as well as contributing to COVID-19 transmission.20 Given the benefits of prescribing LAIs on the one hand and the challenges of in-person care provision during the COVID-19 pandemic on the other, it is important to understand ways in which the pandemic has affected treatment decisions and treatment outcomes among patients with schizophrenia.

Besides disruptions to in-person healthcare provision, the COVID-19 pandemic may also directly affect health outcomes of patients with mental illness.27 People with schizophrenia may be at a higher risk of COVID-19 transmission due to factors such as cognitive impairment, lower awareness of risk, and barriers to adequate infection control including congregate living.28 Moreover, a higher risk of mortality has been observed in people with schizophrenia and COVID-19,29 underscoring the need for education on prevention and prompt access to safe and efficacious vaccines.30 In these circumstances, psychiatrists might have a critical role in moving patients, particularly the mentally ill, from hesitancy to vaccine confidence and acceptance.31

To this end, we conducted a survey among healthcare providers (HCPs) in the US who treat patients with schizophrenia with LAIs (ie, LAI prescribers) to assess changes in their prescribing habits and perceived patient health outcomes prior to and during the pandemic, as well as to understand their attitudes and perceptions of their patients’ attitudes regarding COVID-19 vaccination.

Methods Data Source Survey Instrument

De-identified, individual-level data was collected nationwide between May 10 and May 25, 2021, through an anonymous cross-sectional double-blinded online survey administered to US-based HCPs with a psychiatry specialty. Participants were recruited from an online physician panel via a third-party vendor (Dynata, LLC) and provided their informed consent prior to responding to the survey questions. All study materials were reviewed by the WIRB-Copernicus Group Independent Review Board, which granted an exemption determination on April 19, 2021 per Title 45 of CFR, Part 46.104(d)(2) as no personally identifiable information was collected.32

The survey collected information on characteristics of participating LAI prescribers, prescriber-reported changes in LAI prescribing habits and perceived patient outcomes during the COVID-19 pandemic, as well as prescriber and perceived patient attitudes toward COVID-19 vaccination. To facilitate survey completion, measures were taken to provide lists of potential response categories to all questions, with the option to select “other” and type in a free-text response if the provided categorical answers did not cover the intended response.

Quality control measures were implemented (ie, consistency and range checks) to resolve any conflicts in the data and presented survey respondents with prompts to allow for confirmation or revision of answers. The survey was tested prior to a full launch among a subset of LAI prescribers to ensure all questions were clear and correctly interpreted. The quality and accuracy of completed surveys were reviewed after de-identification, and data were cleaned, cross-checked, and aggregated. All completed surveys passed the quality checks, and no respondent was excluded because of data quality issue.

Study Participants

The participants in this study were US-based HCPs who met the following criteria: 1) had a specialty in psychiatry; 2) had practiced psychiatry for ≥2 years and were employed by the same clinical practice since January 2019; and 3) had treated patients with schizophrenia with LAIs since January 2019.

Statistical Analyses

All survey responses were categorical and as such were summarized descriptively using frequencies and proportions. Free-text responses given as “other” responses to categorical questions were reported in the tables either categorically or in the footnotes. Completed surveys did not contain missing data because answers to all questions were required. All analyses were conducted using SAS Enterprise Guide 7.1 (SAS Institute, Cary, NC).

Results Characteristics of LAI Prescribers and Their Clinical Practice

A total of 401 LAI prescribers met all study criteria and completed the online survey (Table 1). Most respondents were physicians (79.8%), 14.0% were nurse practitioners, 4.7% were physician assistants, and 1.5% were pharmacists. Half of the LAI prescribers (50.4%) had over 15 years of practice in psychiatry and over two-thirds (68.1%) had over 10 years of practice. The most common clinical practice settings were private practices (24.9%), community health centers (22.4%), and the outpatient clinics of hospitals (18.2%). Almost all surveyed LAI prescribers practiced in urban geographical settings (urban areas [67.8%] or urban clusters [26.7%]). The majority of practices provided individual, family, or group counseling (82.0%), LAI administration services (77.8%), and social work/referral services (68.6%). The survey respondents were generally evenly distributed across US geographic regions, with a slightly higher proportion in the South US (32.9%).

Table 1 Characteristics and Clinical Practice of LAI Prescribers

LAI Prescribing Patterns in 2019 and During the COVID-19 Pandemic Overall Prescribing of LAIs

Approximately two-thirds of LAI prescribers (64.3%) reported treating more than five patients with schizophrenia with LAIs per month in 2019 (Table 2). Most reported that LAI prescribing rates remained unchanged during the COVID-19 pandemic (64.6%), while 19.2% reported an increase and 14.0% reported a decrease in LAI prescribing rates. The most commonly prescribed LAIs both before and during the COVID-19 pandemic were reported to be 1-month paliperidone palmitate (84.0% and 80.9%, respectively), aripiprazole (83.8% and 77.8%), and haloperidol decanoate (74.6% and 65.8%). During an average prescribing encounter, most LAI prescribers (85.3%) reported spending between 11 and 30 minutes with each patient. For nearly two-thirds of LAI prescribers (64.6%), the COVID-19 pandemic did not impact the duration of time spent with patients.

Table 2 LAI Prescribing Patterns During the COVID-19 Pandemic

Switching Patients from LAIs to OAPs During COVID-19 Pandemic

Approximately two-thirds (63.3%) of LAI prescribers did not switch patients with schizophrenia from LAIs to OAPs during the COVID-19 pandemic, while 33.7% did (Figure 1A). Among those who switched patients to OAPs (n = 135), the most common reasons for the switch were concerns about patients skipping injections due to COVID-19 (59.3%) and requests from patients or their caregivers (58.5%) (Figure 1B).

Figure 1 Switching patients from LAIs to OAPs during COVID-19 pandemic. (A) Percentage of HCPs who reported switching patients from LAIs to OAPs during the COVID-19 pandemic (N=401). (B) HCP-reported reasons for switching from LAIs to OAPs among HCPs who reported switching (n=135).

Abbreviations: COVID-19, coronavirus disease of 2019; HCP, healthcare professional; LAI, long-acting injectable; OAP, oral antipsychotic.

Switching Patients from OAPs to LAIs During COVID-19 Pandemic

Approximately two-thirds of LAI prescribers (65.1%) switched the same number of patients from OAPs to LAIs during the COVID-19 pandemic as per their routine previous practice, while 19.7% switched more patients and 12.2% switched fewer patients (Figure 2A). Among those who switched more patients to LAIs (n = 79), the most common reasons for the switch were better adherence and symptom control with LAIs over OAPs (78.5%) and patients’/caregivers’ requests (53.2%) (Figure 2B). Among those who switched fewer patients to LAIs (n = 49), the most common reasons against making the switch were concerns with patients skipping injections due to COVID-19 (73.5%) and the risk of COVID-19 transmission (67.3%) (Figure 2C).

Figure 2 Switching patients from OAPs to LAIs during the COVID-19 pandemic. (A) HCP-reported changes in switching from OAPs to LAIs during the COVID-19 pandemic (N=401). (B) HCP-reported reasons for switching from OAPs to LAIs among HCPs who reported switching more patients (n=79). (C) HCP-reported reasons for switching fewer patients from OAPs to LAIs among HCPs who reported switching fewer patients (n=49).

Abbreviations: COVID-19, coronavirus disease of 2019; HCP, healthcare professional; LAI, long-acting injectable; OAP, oral antipsychotic.

Switching Patients to LAI Formulations with Lower Frequency of Administration During COVID-19 Pandemic

Over two-thirds (68.1%) of LAI prescribers did not switch patients to LAI formulations with lower frequency of administration during the COVID-19 pandemic, while 25.9% did (Figure 3A). Among those who did not switch patients (n = 273), the most common reason for the decision was the lack of medical need (58.6%) (Figure 3B). Among those who switched patients (n = 104), the most common reasons for the decision were reduced risk of COVID-19 transmission (75.0%) and better adherence and symptom control with lower frequency formulations (52.9%) (Figure 3C).

Figure 3 Switching patients to LAI formulations with lower frequency of administration during the COVID-19 pandemic. (A) Percentage of HCPs who reported switching patients to LAI formulations with lower frequency of administration during the COVID-19 pandemic (N=401). (B) HCP-reported reasons for not switching patients to formulations with lower frequency of administration among HCPs who reported not switching (n=273). (C) HCP-reported reasons for switching patients to formulations with lower frequency of administration among HCPs who reported switching (n=104).

Abbreviations: COVID-19, coronavirus disease of 2019; HCP, healthcare professional; LAI, long-acting injectable; OAP, oral antipsychotic.

Prescriber-Reported Antipsychotic Adherence and Treatment Efficacy During the COVID-19 Pandemic Changes in Patients’ Adherence to Antipsychotic Therapy During COVID-19 Pandemic

Half of LAI prescribers (50.1%) reported that antipsychotic adherence remained unchanged for the majority of patients during the COVID-19 pandemic and 22.2% reported no clear overall trend in adherence (eg, an increase in some patients and a decrease in others) (Figure 4A). On the other hand, a decrease in antipsychotic adherence in most patients was reported by 15.7% of LAI prescribers, while an increase in most patients’ adherence was reported by 5.7%.

Figure 4 Changes in antipsychotic adherence during the COVID-19 pandemic. (A) HCP-reported changes in antipsychotic adherence during the COVID-19 pandemic (N=401). (B) HCP-reported reasons for increased antipsychotic adherence among HCPs who reported an increase in some or the majority of patients (n=112). (C) HCP-reported reasons for decreased antipsychotic adherence among HCPs who reported a decrease in some or majority of patients (n=152).

Abbreviations: COVID-19, coronavirus disease of 2019; HCP, healthcare professional; LAI, long-acting injectable; OAP, oral antipsychotic.

Among LAI prescribers who reported improved antipsychotic adherence in some or most patients (n = 112), the most common reason cited was that increased use of telehealth improved the ability to reach patients (70.5%); other commonly cited reasons included shared decision-making with patients/caregivers (44.6%) and switching from OAPs to LAIs (42.9%) (Figure 4B). Among LAI prescribers who reported decreased antipsychotic adherence in some or most patients (n = 152), the most commonly cited reasons were patients’ social isolation (78.3%), lack of in-person contact with patients (64.5%), and patients’ fear of COVID-19 exposure (60.5%) (Figure 4C).

Changes in Symptom Control and Relapse Frequency During COVID-19 Pandemic

Slightly less than half of LAI prescribers (44.6%) reported that symptom control and relapse frequency remained unchanged for the majority of patients during the COVID-19 pandemic, while 22.2% reported no clear overall trend (ie, an increase in some patients and a decrease in others) (Figure 5A). However, 18.2% of LAI prescribers reported that symptom control and relapse frequency worsened in most patients while 8.5% reported an improvement in most patients (Figure 5A).

Figure 5 Changes in symptom control and relapse frequency during the COVID-19 pandemic. (A) HCP-reported changes in symptom control and relapse frequency during the COVID-19 pandemic (N=401). (B) HCP-reported reasons for increased symptom control among HCPs who reported an increase in some or majority of patients (n=123). (C) HCP-reported reasons for deteriorated symptom control among HCPs who reported a deterioration in some or majority of patients (n=162).

Abbreviations: COVID-19, coronavirus disease of 2019; HCP, healthcare professional; LAI, long-acting injectable; OAP, oral antipsychotic.

Among LAI prescribers who reported an improvement in symptom control and relapse frequency in some or most patients (n = 123), most cited it was due to the increased use of telehealth making patients easier to reach (68.3%) as well as due to the use of shared decision-making with patients/caregivers (52.0%) (Figure 5B). Among those who reported a decrease in symptom control and relapse frequency in some or most patients (n = 162), the reasons most frequently given were patients’ social isolation (77.8%), lack of in-person contact with patients (64.8%), and patients’ fear of COVID-19 exposure making them more symptomatic (52.5%) (Figure 5C).

Healthcare Provisions During the COVID-19 Pandemic

During the COVID-19 pandemic, most of the LAI prescribers (85.0%) reported using telehealth whenever possible; it was the most frequently used safety measure to protect patients and staff from COVID-19 exposure at their clinical practice (Table 3). Other commonly reported safety measures included screening patients for COVID-19 symptoms/exposure before appointment (73.6%), providing personal protective equipment to administer LAIs on site (68.3%), and minimizing contact between patients (ie, by staggering appointments, increasing waiting room capacity, installing physical barriers, etc. [62.6%]).

Table 3 Healthcare Provisions During the COVID-19 Pandemic

Among the LAI prescribers who used telehealth during the pandemic (n = 341), the most frequently named positive aspects of telehealth were maintaining contact with patients (84.8%), helping to monitor patients treated with LAIs between injections (53.7%), and allowing for visibility into patients’ living conditions and better understanding of patients’ treatment needs (53.4%) (Table 3). However, over half of the LAI prescribers (57.8%) experienced challenges maintaining contact with patients through telehealth due to patients lacking access to technology, which is the most commonly reported negative aspect of telehealth.

Nearly all LAI prescribers (92.1%) involved patients/caregivers in decision-making regarding the best treatment plan; 72.1% reported that patients/caregivers discussed and provided consent for treatment plans, 62.3% reported asking patients about including caregivers in treatment decisions, and 52.6% reported asking patients to approve treatment plans.

Attitudes of LAI Prescribers to COVID-19 Vaccination for Patients with Schizophrenia Prioritizing Patients with Schizophrenia for COVID-19 Vaccination

Approximately three-fourths of LAI prescribers (74.1%) believed that patients with schizophrenia should be prioritized for COVID-19 vaccination (Figure 6A). Among these respondents (n = 297), the most common reason for prioritization was concerns about the higher risk of severe consequences of COVID-19 for patients with schizophrenia (83.5%) (Figure 6B). Concerns about patients posing a higher risk of contracting (69.7%) or transmitting (63.0%) COVID-19 were also commonly cited as reasons for vaccine prioritization.

Figure 6 Attitudes of HCPs toward prioritizing patients with schizophrenia for COVID-19 vaccination. (A) Should patients with schizophrenia be prioritized for COVID-19 vaccination? (N=401). (B) Reasons for prioritizing patients with schizophrenia for COVID-19 vaccination (n=297).

Abbreviations: COVID-19, coronavirus disease of 2019; HCP, healthcare professional.

Encouraging Patients with Schizophrenia to Be Vaccinated Against COVID-19

Most of the surveyed LAI prescribers (84.0%) encouraged all their patients with schizophrenia to receive a COVID-19 vaccine, and additionally 10.7% stated that they encouraged some but not all patients to be vaccinated (Figure 7A). The most frequently cited reasons for encouraging vaccination were the belief that everyone should be vaccinated regardless of underlying conditions (among those who encouraged all patients [n = 337]: 68.2%; some patients [n = 43]: 58.1%) and concern of the higher risk of severe consequences from COVID-19 among patients with schizophrenia (67.7% and 48.8%, respectively) (Figure 7B and C). Among LAI prescribers who did not encourage certain patients to be vaccinated, the most common reasons were patients not meeting the criteria for the current phase of vaccinations (27.9%) and lack of contact with patients (25.6%) (Figure 7D).

Figure 7 Attitudes of HCPs towards encouraging patients with schizophrenia to be vaccinated against COVID-19. (A) Have you encouraged your patients with schizophrenia to be vaccinated against COVID-19? (N=401) (B) Reasons for encouraging all patients to be vaccinated against COVID-19 (n=337). (C) Reasons for encouraging some patients to be vaccinated against COVID-19 (n=43). (D) Reasons for not encouraging some patients to be vaccinated against COVID-19 (n=43). (E) Reasons for not encouraging all patients to be vaccinated against COVID-19 (n=9).

Abbreviations: COVID-19, coronavirus disease of 2019; HCP, healthcare professional.

Just 2.2% of LAI prescribers (1.9% of physicians, 5.4% of nurse practitioners, and no physician assistants or pharmacists) did not encourage patients to receive a COVID-19 vaccine (Figure 7A). Among these respondents (n = 9), the most common reasons for not encouraging vaccination were the lack of information about different vaccines and their impact on patients with schizophrenia (33.3%) and the belief that vaccination is a personal choice (33.3%) (Figure 7E).

Attitudes of Patients with Schizophrenia on COVID-19 Vaccination Reported by LAI Prescribers

Two-thirds of LAI prescribers (64.1%) reported hesitancy among some patients regarding COVID-19 vaccine safety, although half (51.4%) of the LAI prescribers reported that despite hesitancy regarding vaccine safety or efficacy, some patients were willing to be vaccinated to minimize the risks of COVID-19 (Figure 8). Approximately half of LAI prescribers (48.6%) indicated that some patients perceived COVID-19 vaccines as safe, effective, and important. However, a third of LAI prescribers (32.4%) reported that some patients were unwilling to be vaccinated and unconcerned with COVID-19 consequences.

Figure 8 Attitudes of patients with schizophrenia towards COVID-19 vaccines, according to HCPs (N=401).

Abbreviations: COVID-19, coronavirus disease of 2019; HCP, healthcare professional.

Discussion

This survey of US-based LAI prescribers treating patients with schizophrenia revealed that LAI prescribing habits and perceived patient adherence to antipsychotics remained largely unchanged during the COVID-19 pandemic. Telehealth and in-clinic safety measures were widely employed to maintain contact with patients and reduce infection risk. However, more LAI prescribers reported that their patients’ antipsychotic adherence and symptom control had deteriorated than improved. The LAI prescribers who switched patients to LAIs with lower frequency of administration or to OAPs aimed to reduce the risk of patients skipping LAI injections or COVID-19 transmission and prescribers who switched from OAPs to LAIs were primarily motivated by better adherence and symptom control with LAIs. Most LAI prescribers believed that patients with schizophrenia needed to be prioritized for COVID-19 vaccination and encouraged their patients to become vaccinated; very few LAI prescribers did not encourage vaccination. Additionally, while most LAI prescribers reported COVID-19 vaccine hesitancy among some of their patients, over half indicated that they had patients who expressed willingness to be vaccinated to minimize COVID-19 risks.

Our finding of largely unchanged LAI prescribing during the pandemic is consistent with the American Psychiatric Association’s (APA) COVID‐19 Pandemic Guidance encouraging healthcare facilities to include the ongoing use of LAIs for patients with high-risk chronic psychiatric illness as a necessary procedure.33 Further, it is consistent with a report by Gannon et al, who found that LAI prescribing largely remained stable before and after the implementation of social distancing and COVID-19 restrictions in March 2020 at a Pittsburgh ambulatory clinic.19

The surveyed LAI prescribers who switched more patients from OAPs to LAIs during the COVID-19 pandemic primarily did so because they expected better adherence and symptom control with LAIs. As a chronic disease, schizophrenia requires ongoing, long-term treatment to control symptoms and prevent relapse. However, a confluence of factors (ie, lack of insight or stability, cognitive impairment, bothersome medication side effects, etc.) create challenges for treatment that often result in suboptimal adherence to antipsychotic therapy.34–36 Prior studies have consistently demonstrated strong evidence of the clinical utility of LAIs in improving adherence and symptom control due in part to the lower frequency of administration compared with daily OAPs.21–23,37

This study revealed that both prescribers and patients/caregivers were mindful of strategies reducing the impact of COVID-19 on LAI treatment. About a third of the surveyed LAI prescribers reported switching patients from LAIs to OAPs during the COVID-19 pandemic, primarily due to concerns of patients skipping injections and as a result of patients’/caregivers’ request. Conversely, about one-fourth of LAI prescribers switched patients to LAI formulations with lower frequency of administration to reduce the risk of COVID-19 transmission from in-person healthcare visits. A recent Romanian study suggested that switching from LAIs to OAPs during COVID-19 was mainly requested by patients/caregivers to reduce the number of in-person visits to pharmacies, medical offices, or public mental health centers in the context of the pandemic.38 A patient’s individual living and/or caregiver situation may impact which medications are most convenient and have the lowest perceived risk to acquire.

Half of LAI prescribers reported that antipsychotic adherence stayed the same in the majority of patients, and close to a half reported that symptom control stayed the same; however, it is worth noting that more respondents reported their patients deteriorated during the COVID-19 pandemic than improved. The LAI prescribers listed a variety of reasons for the deterioration in antipsychotic adherence and symptom control, including patients’ social isolation. These results suggest that the COVID-19 pandemic may impact patient outcomes by disrupting patients’ support systems, as well as healthcare provisions, with potential increase in risks of mortality and morbidity.

In this study, the majority of the LAI prescribers used telehealth. As reported by the surveyed LAI prescribers, telehealth has potential advantages to promote antipsychotic adherence and symptom control among patients with schizophrenia via maintaining more convenient contact, enabling continuous monitoring between injections, and helping to understand patients’ living conditions and treatment needs. The positive impacts of telehealth among patients with severe mental illness on treatment adherence, symptom control, and reduced hospitalizations have been suggested in previous studies.39–41 However, prior research also reported that the lack of face-to-face interactions in telehealth may impact the ability to build therapeutic relationships, conduct nuanced assessments, or identify deteriorating mental health.42 In addition, over half of the LAI prescribers in this study reported experiencing challenges maintaining contact with patients via telehealth due to patients’ lack of access to technology.

The APA’s guidance as well as multiple articles has suggested that patients with schizophrenia and other severe mental illness face unique challenges during the COVID-19 pandemic.19,20,43–45 These issues include higher risks of contracting COVID-19 and serious complications, lower socioeconomic status limiting access to care, unstable access to or knowledge of pandemic resources, susceptibility to misinformation, and mistrust in healthcare systems.19,20,43–45 The consequences of vaccine hesitancy are greater among patients with severe mental illness, and historically, the access to preventative care and uptake of vaccines such as the influenza vaccine can be as low as 25% for these patients.44,46 Thus, the involvement of HCPs they trust and have established a treatment relationship with may be imperative for the timely vaccination of this patient population. Most of the LAI prescribers surveyed in this study believed that patients with schizophrenia needed to be prioritized for COVID-19 vaccination and encouraged their patients to become vaccinated, which aligns with the recently published APA recommendation supporting the equitable distribution of the COVID-19 vaccine among patients with serious mental illness by actively engaging with patients/caregivers and disseminating accurate information on vaccination.44 However, most LAI prescribers reported that at least some patients were hesitant about the vaccine safety and/or efficacy, which may be in line with the general trends of vaccine hesitancy in the US overall population (as high as 66.8%47). Therefore, focused strategies are needed to support patients with schizophrenia at risk of remaining unvaccinated to overcome vaccine hesitancy and prevent a severe course of illness.

This study benefits from several important strengths, including unique and recent data from a large sample of US-based LAI prescribers on their perceptions of the impact of the COVID-19 pandemic on LAI prescribing habits and outcomes of patients with schizophrenia. The survey design permitted the collection of data that are not available in secondary data sources (such as electronic medical records and claims databases). Additionally, this study is timely given the importance of understanding current disruptions in health care during the pandemic, particularly among vulnerable patient populations with critical needs for treatment maintenance like those with schizophrenia. The results may also have a broader impact on understanding the attitudes toward COVID-19 vaccination among HCPs (specifically, LAI prescribers in this study) and their perceptions of the degree of vaccine hesitancy among patients with severe mental illness.

The results of this study should be considered in the light of several limitations, some of which are inherent to survey studies. First, the data collected in this study were self-reported by the participating LAI prescribers and may be subject to recall bias. Furthermore, patients’ attitudes on COVID-19 vaccination were recalled and reported by the participating LAI prescribers, therefore may not fully represent the opinions of patients themselves. In addition, although attempts were made to minimize selection bias (eg, enrolling a relatively large number of participants from a nationwide panel), there remained a potential for bias since a LAI prescriber’s decision be on a panel and to contribute time to the survey was not random. While three vaccines had been approved for use at the time of the survey, availability and prioritization of patient populations varied greatly by geographic area. Additionally, most participating LAI prescribers practiced in urban geographical settings, which may limit the generalizability of the results to rural settings. Lastly, the timing of the survey largely pre-dated the propagation of the Delta variant of the COVID-19 virus as the dominant variant in the US, which may have resulted in additional changes in patients’ and LAI prescribers’ attitudes towards vaccination.

Conclusions

The results of this survey study contextualize the unique challenges that LAI prescribers and patients with schizophrenia have encountered during the COVID-19 pandemic and provide encouraging insights into the maintenance of LAI treatments and alignment of clinical practice with US treatment guidelines. During the COVID-19 pandemic, LAI prescription habits and LAI prescribers’ perceptions of their patients’ adherence to therapy were largely unchanged. Additionally, despite patients’ perceived vaccine hesitancy, the vast majority of LAI prescribers encouraged vaccination for COVID-19. Focused efforts to minimize barriers to and delays in COVID-19 vaccination of patients with schizophrenia, as well as to sustain the critical link between HCPs and patients for the maintenance of antipsychotic treatment, are recommended.

Abbreviations

APA, American Psychiatric Association; COVID-19, coronavirus disease of 2019; HCP, healthcare provider; LAI, long-acting injectable antipsychotics; OAP, oral antipsychotics; US, United States.

Data Sharing Statement

Due to the nature of this research, participants of this study did not agree for their data to be shared publicly, so supporting data are not available. Therefore, restrictions apply to the availability of these data, which are not publicly available.

Ethics Approval and Informed Consent

Study participants provided their informed consent prior to responding to the survey questions. All study materials were reviewed by the WIRB-Copernicus Group Independent Review Board, and the study was granted an exemption determination per Title 45 of CFR, Part 46.104(d)(2) as no personally identifiable information was collected.

Acknowledgments

The authors thank the prescribers who participated in this survey. We acknowledge Shelley Batts, PhD, of Analysis Group, Inc. for medical writing assistance, which was funded by Janssen Scientific Affairs, LLC. We also acknowledge Camilo Obando, MD, MBA, an employee of Janssen Scientific Affairs, LLC, and Sophia Monaghan, MS, an employee of Janssen Scientific Affairs, LLC during the study’s conduct, for support in study design and results interpretation.

Author Contributions

All authors have made significant contributions to the conception or design of the study, or the acquisition, analysis, or interpretation of data, drafting the manuscript and revising it critically for important intellectual content, have provided final approval of this version to be published, and agree to be accountable for all aspects of the work.

Funding

This work was supported by Janssen Scientific Affairs, LLC.

Disclosure

Maryia Zhdanava, Todor I. Totev, Patrick Lefebvre, Aditi Shah, Kristy Sheng, and Dominic Pilon are employees of Analysis Group, Inc., which provided consulting services to Janssen Scientific Affairs, LLC for the conduct of this study. H. Lynn Starr was an employee of Janssen Scientific Affairs, LLC and held stock in Johnson & Johnson, Inc. (the parent company of Janssen) during the conduct of this study.

References

1. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia; 2019. Available from: https://psychiatryonline.org/doi/pdf/10.1176/appi.books.9780890424841. Accessed December17, 2020.

2. Kahn RS, Sommer IE, Murray RM, et al. Schizophrenia. Nat Rev Dis Primers. 2015;1:15067. doi:10.1038/nrdp.2015.67

3. Desai PR, Lawson KA, Barner JC, Rascati KL. Estimating the direct and indirect costs for community-dwelling patients with schizophrenia. J Pharm Health Serv Res. 2013;4(4):187–194. doi:10.1111/jphs.12027

4. Kessler RC, Birnbaum H, Demler O, et al. The prevalence and correlates of nonaffective psychosis in the National Comorbidity Survey Replication (NCS-R). Biol Psychiatry. 2005;58(8):668–676. doi:10.1016/j.biopsych.2005.04.034

5. Wu EQ, Shi L, Birnbaum H, Hudson T, Kessler R. Annual prevalence of diagnosed schizophrenia in the USA: a claims data analysis approach. Psychol Med. 2006;36(11):1535–1540. doi:10.1017/S0033291706008191

6. Albert M, McCaig LF. Emergency department visits related to schizophrenia among adults aged 18–64: United States, 2009–2011. NCHS Data Brief. 2015;215:1–8.

7. Schoenbaum M, Sutherland JM, Chappel A, et al. Twelve-month health care use and mortality in commercially insured young people with incident psychosis in the United States. Schizophr Bull. 2017;43(6):1262–1272. doi:10.1093/schbul/sbx009

8. Zhang W, Amos TB, Gutkin SW, et al. A systematic literature review of the clinical and health economic burden of schizophrenia in privately insured patients in the United States. Clinicoecon Outcomes Res. 2018;10:309–320. doi:10.2147/CEOR.S156308

9. Vos T, Allen C, Arora M, et al. GBD 2016 disease injury incidence prevalence collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017;390(10100):1211–1259.

10. Olfson M, Stroup TS, Huang C, et al. Suicide risk in Medicare patients with schizophrenia across the life span. JAMA Psychiatry. 2021;78(8):876–885. doi:10.1001/jamapsychiatry.2021.0841

11. Olfson M, Gerhard T, Huang C, Crystal S, Stroup TS. Premature mortality among adults with schizophrenia in the United States. JAMA Psychiatry. 2015;72(12):1172–1181. doi:10.1001/jamapsychiatry.2015.1737

12. Simon GE, Stewart C, Yarborough BJ, et al. Mortality rates after the first diagnosis of psychotic disorder in adolescents and young adults. JAMA Psychiatry. 2018;75(3):254–260. doi:10.1001/jamapsychiatry.2017.4437

13. Correll CU, Solmi M, Croatto G, et al. Mortality in people with schizophrenia: a systematic review and meta-analysis of relative risk and aggravating or attenuating factors. World Psychiatry. 2022;21(2):248–271. doi:10.1002/wps.20994

14. Hjorthoj C, Sturup AE, McGrath JJ, Nordentoft M. Years of potential life lost and life expectancy in schizophrenia: a systematic review and meta-analysis. Lancet Psychiatry. 2017;4(4):295–301. doi:10.1016/S2215-0366(17)30078-0

15. Kokurcan A, Safak Y. Assessment of obsessive-compulsive disorder comorbidity and obsessive-compulsive symptom dimensions in patients with schizophrenia. Saudi Med J. 2020;41(3):275–282. doi:10.15537/smj.2020.3.24909

16. DeRosse P, Nitzburg GC, Blair M, Malhotra AK. Dimensional symptom severity and global cognitive function predict subjective quality of life in patients with schizophrenia and healthy adults. Schizophr Res. 2018;195:385–390. doi:10.1016/j.schres.2017.10.018

17. Dong M, Lu L, Zhang L, et al. Quality of life in schizophrenia: a meta-analysis of comparative studies. Psychiatric Quarterly. 2019;90(3):519–532. doi:10.1007/s11126-019-09633-4

18. Public Health Emergency. Determination that a public health emergency exists; 2020. Available from: https://www.phe.gov/emergency/news/healthactions/phe/Pages/2019-nCoV.aspx. Accessed December20, 2021.

19. Gannon JM, Conlogue J, Sherwood R, et al. Long acting injectable antipsychotic medications: ensuring care continuity during the COVID-19 pandemic restrictions. Schizophr Res. 2020;222:532–533. doi:10.1016/j.schres.2020.05.001

20. Kozloff N, Mulsant BH, Stergiopoulos V, Voineskos AN. The COVID-19 global pandemic: implications for people with schizophrenia and related disorders. Schizophr Bull. 2020;46(4):752–757. doi:10.1093/schbul/sbaa051

21. Alphs L, Benson C, Cheshire-Kinney K, et al. Real-world outcomes of paliperidone palmitate compared to daily oral antipsychotic therapy in schizophrenia: a randomized, open-label, review board-blinded 15-month study. J Clin Psychiatry. 2015;76(5):554–561. doi:10.4088/JCP.14m09584

22. Pilon D, Muser E, Lefebvre P, et al. Adherence, healthcare resource utilization, and Medicaid spending associated with once-monthly paliperidone palmitate versus oral atypical antipsychotic treatment among adults recently diagnosed with schizophrenia. BMC Psychiatry. 2017;17(1):207. doi:10.1186/s12888-017-1358-3

23. Pilon D, Tandon N, Lafeuille MH, et al. Treatment patterns, health care resource utilization, and spending in Medicaid beneficiaries initiating second-generation long-acting injectable agents versus oral atypical antipsychotics. Clin Ther. 2017;39(10):1972–1985.e. doi:10.1016/j.clinthera.2017.08.008

24. Kane JM, Schooler NR, Marcy P, et al. Effect of long-acting injectable antipsychotics vs usual care on time to first hospitalization in early-phase schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2020;77(12):1217–1224. doi:10.1001/jamapsychiatry.2020.2076

25. Kishimoto T, Hagi K, Kurokawa S, Kane JM, Correll CU. Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre–post studies. Lancet Psychiatry. 2021;8(5):387–404. doi:10.1016/S2215-0366(21)00039-0

26. Emsley R, Chiliza B, Asmal L, Harvey BH. The nature of relapse in schizophrenia. BMC Psychiatry. 2013;13(1):50. doi:10.1186/1471-244X-13-50

27. Druss BG. Addressing the COVID-19 pandemic in populations with serious mental illness. JAMA Psychiatry. 2020;77(9):891–892. doi:10.1001/jamapsychiatry.2020.0894

28. Yao H, Chen JH, Xu YF. Patients with mental health disorders in the COVID-19 epidemic. Lancet Psychiatry. 2020;7(4):e21. doi:10.1016/S2215-0366(20)30090-0

29. Nemani K, Li C, Olfson M, et al. Association of psychiatric disorders with mortality among patients With COVID-19. JAMA Psychiatry. 2021;78(4):380–386. doi:10.1001/jamapsychiatry.2020.4442

30. Mazereel V, Vanbrabant T, Desplenter F, De Hert M. COVID-19 vaccine uptake in patients with psychiatric disorders admitted to or residing in a university psychiatric hospital. Lancet Psychiatry. 2021;8(10):860–861. doi:10.1016/S2215-0366(21)00301-1

31. Freudenreich O, Van Alphen MU, Lim C. The ABCs of successful vaccinations: a role for psychiatry. Curr Psychiatry. 2021;20(3):48–50. doi:10.12788/cp.0108

32. U.S. Department of Health and Human Services. 45 CFR 46: pre-2018 requirements. Available from: https://www.hhs.gov/ohrp/regulations-and-policy/regulations/45-cfr-46/index.html#46.101. Accessed October16, 2020.

33. American Psychiatric Association. COVID-19 pandemic guidance document: use of long-acting injectables as a clinically necessary treatment. Available from: https://www.psychiatry.org/File%20Library/Psychiatrists/APA-Guidance-Long-Acting-Injectables-COVID-19.pdf. Accessed October29, 2021.

34. Higashi K, Medic G, Littlewood KJ, et al. Medication adherence in schizophrenia: factors influencing adherence and consequences of nonadherence, a systematic literature review. Ther Adv Psychopharmacol. 2013;3(4):200–218. doi:10.1177/2045125312474019

35. Valenstein M, Blow FC, Copeland LA, et al. Poor antipsychotic adherence among patients with schizophrenia: medication and patient factors. Schizophr Bull. 2004;30(2):255–264. doi:10.1093/oxfordjournals.schbul.a007076

36. Kokurcan A, Karadag H, Ercan Doğu S, Erid F, Orsel S. Clinical correlates of treatment adherence and insight in patients with schizophrenia. Archiv Clin Exp Med. 2020;5:95–99. doi:10.25000/acem.717027

37. Pietrini F, Albert U, Ballerini A, et al. The modern perspective for long-acting injectables antipsychotics in the patient-centered care of schizophrenia. Neuropsychiatr Dis Treat. 2019;15:1045–1060. doi:10.2147/NDT.S199048

38. Ifteni P, Dima L, Teodorescu A. Long-acting injectable antipsychotics treatment during COVID-19 pandemic - A new challenge. Schizophr Res. 2020;220:265–266. doi:10.1016/j.schres.2020.04.030

39. Basit SA, Mathews N, Kunik ME. Telemedicine interventions for medication adherence in mental illness: a systematic review. Gen Hosp Psychiatry. 2020;62:28–36. doi:10.1016/j.genhosppsych.2019.11.004

40. Lawes-Wickwar S, McBain H, Mulligan K. Application and effectiveness of telehealth to support severe mental illness management: systematic review. JMIR Ment Health. 2018;5(4):e62. doi:10.2196/mental.8816

41. Flaherty LR, Daniels K, Luther J, Haas GL, Kasckow J. Reduction of medical hospitalizations in veterans with schizophrenia using home telehealth. Psychiatry Res. 2017;255:153–155. doi:10.1016/j.psychres.2017.05.024

42. Liberati E, Richards N, Parker J, et al. Remote care for mental health: qualitative study with service users, carers and staff during the COVID-19 pandemic. BMJ Open. 2021;11(4):e049210. doi:10.1136/bmjopen-2021-049210

43. Cipriani A. COVID-19 vaccination programme: where do people with mental health difficulties lie within the order of priority? BMJ Opin; 2021. Available from: https://blogs.bmj.com/bmj/2021/02/16/covid-19-vaccination-programme-where-do-people-with-mental-health-difficulties-lie-within-The-order-of-priority/. Accessed, October29, 2021.

44. American Psychiatric Association. COVID-19 pandemic guidance document: the role of the psychiatrist in the equitable distribution of the COVID-19 vaccine. Available from: https://www.psychiatry.org/FileLibrary/Psychiatrists/APA-Guidance-Psychiatrists-Role-in-Equitable-Distribution-COVID-19-Vaccine.pdf. Accessed October29, 2021.

45. Moreno C, Wykes T, Galderisi S, et al. How mental health care should change as a consequence of the COVID-19 pandemic. Lancet Psychiatry. 2020;7(9):813–824. doi:10.1016/S2215-0366(20)30307-2

46. Lorenz RA, Norris MM, Norton LC, Westrick SC. Factors associated with influenza vaccination decisions among patients with mental illness. Int J Psychiatry Med. 2013;46(1):1–13. doi:10.2190/PM.46.1.a

47. Aw J, Seng JJB, Seah SSY, Low LL. COVID-19 vaccine hesitancy—a scoping review of literature in high-income countries. Vaccines. 2021;9(8):900. doi:10.3390/vaccines9080900