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. Author manuscript; available in PMC: 2026 Oct 6.
Published in final edited form as: Schizophr Res. 2025 Aug 7;284:160–166. doi: 10.1016/j.schres.2025.08.004

Positive symptoms and medication adherence in response to oral versus long-acting injectable risperidone in Black, Latino, and White first-episode psychosis patients

Derek M Novacek 1,2, Kenneth L Subotnik 3, Joseph Ventura 3, Laurie R Casaus 3, Fiona Whelan 3, Catherine A Sugar 1,3,5, Keith H Nuechterlein 3,4
PMCID: PMC13637436  NIHMSID: NIHMS2204236  PMID: 40779812

Abstract

Black and Latino Americans are more likely to be diagnosed with psychotic disorders compared to White Americans. Furthermore, there are well documented ethnoracial disparities in access to second-generation antipsychotics including long-acting injectables (LAIs). LAI medications have the potential to help attenuate disparities by improving adherence and thus reducing relapse. Given this knowledge, a more concerted effort is needed to examine the clinical response and adherence to these medications in the early stages of psychosis. The present study examined positive symptoms and medication adherence in response to oral versus LAI risperidone in a sample of Black (N = 24), Latino (N = 34), and White (N=17) first-episode psychosis patients. Participants were recruited from local psychiatric hospitals and enrolled in a randomized controlled trial. Participants were randomly assigned to receive oral or LAI risperidone. Findings suggest that Latino patients were less likely to benefit from LAI risperidone and also had higher rates of nonadherence across medication conditions. Both Black and White patients benefited from LAI in terms of positive symptoms and medication adherence. Future studies should examine sociocultural factors that could be influencing the acceptability of LAIs for Latino first-episode patients as well as develop culturally responsive interventions to improve medication adherence and clinical outcomes. In addition, greater advocacy and equitable policies are likely needed to ensure access to LAIs for minoritized populations.

Keywords: first-episode, psychosis, long-acting injectable, risperidone, race and ethnicity

1. Introduction

It is well-documented that Black and Latino Americans are more likely to be diagnosed with a psychotic disorder compared to White Americans (Bresnahan et al., 2007; Kendler et al., 1996; Kessler et al., 2005; Schwartz & Blankenship, 2014) . In addition to higher incidence rates, Black and Latino Americans have also been found to endorse greater severity of positive symptoms compared to White Americans (Adebimpe, 1981; Minsky et al., 2003; Mukherjee et al., 1983; Strakowski et al., 1996), even when assessed by ethnicity-blinded clinicians (Arnold et al., 2004). Although there is evidence suggesting that the disparity in rates of psychotic diagnoses may reflect racial bias in diagnostic practices, several lines of research demonstrate that diagnostic bias cannot fully explain the higher prevalence rates (Gara et al., 2012; Selten & Hoek, 2008; Veling, 2013). Furthermore, Black and Latino Americans in the general population are more likely to endorse experiencing psychotic-like experiences (Cohen & Marino, 2013) . Although there has been much debate in the literature regarding the determinants of racial/ethnic disparities in psychosis (Anglin et al., 2021), a more concerted effort is needed to understand the efficacy of evidence-based first-episode interventions for Black and Latino Americans with psychotic disorders.

Antipsychotic medications are the first line of treatment for positive symptoms (Lieberman & First, 2018). However, some patients struggle with adhering to their prescribed medication regimen. Nonadherence to antipsychotic medications is predictive of relapses in psychotic symptoms in recent-onset psychosis (Morken et al., 2008; Subotnik et al., 2011). Long-acting injectable (LAI) antipsychotics have been shown to improve treatment adherence due to the need of less frequent administration compared to daily prescribed oral medications (Marcus et al., 2015). In line with this, in a randomized controlled trial, LAI risperidone controlled positive symptoms better than oral risperidone through a 12-month follow-up period in patients with first-episode psychosis (Subotnik et al., 2015). Moreover, two recent meta-analyses found that LAI antipsychotics were associated with lower relapse rates, reduced ER visits, and less frequent hospitalizations compared to oral antipsychotics (Kishimoto et al., 2021; Lin et al., 2021).

Ethnoracial Disparities in Access to Antipsychotic Medications

Ethnoracial disparities in antipsychotic medication practices have long been documented. Past studies demonstrated that Black and Latino Americans, compared to White Americans, are less likely to receive second-generation antipsychotic medications such as clozapine and risperidone, as opposed to first-generation antipsychotics (Cook et al., 2015; Kreyenbuhl et al., 2003; Kuno & Rothbard, 2002; Opolka et al., 2004). Similarly, Black Americans are less likely to be prescribed second generation LAIs compared to White Americans (Caballero et al., 2023; Li et al., 2023; Pesa et al., 2023). Less is known about access to second generation LAIs among Latino Americans. These inequities in access to second-generation antipsychotics, including LAIs, negatively impact patients. They also limit our understanding of the potential benefits of LAIs for Black and Latino Americans, including whether these medications improve adherence and treatment outcomes.

Ethnoracial Disparities in Medication Adherence

To compound the complexities described above with inequities in access to antipsychotic medications, Black and Latino Americans are also less likely to adhere to their medication regimen when prescribed antipsychotics (Gilmer et al., 2004; Opolka et al., 2003). Medication nonadherence is associated with higher rates of psychotic symptom relapse and rehospitalization (Alvarez-Jimenez et al., 2012) and thus an important treatment engagement target. Lower medication adherence may be due to various sociocultural factors such as cultural mistrust, health literacy, stigma, and differences in beliefs about psychosis (e.g., misconceptions regarding etiology and treatment), among other factors (Diaz et al., 2005; Hall & Heath, 2021; Kane et al., 2013; Lanouette et al., 2009; McQuaid & Landier, 2018). The lower burden inherent to LAIs may help improve acceptability and reduce disparities in medication adherence for Black and Latino patients. Data from a multi-state Medicaid database suggest that Black Americans are no more likely to discontinue LAIs compared to other ethnoracial groups (Caballero et al., 2023). Thus, LAIs show promise with improving treatment adherence and clinical outcomes for minoritized groups. However, further investigations are warranted.

The present study sought to build on the existing literature to examine ethnoracial differences in positive symptom response and medication adherence in a 12-month randomized controlled trial comparing oral risperidone to LAI risperidone in a sample of Black, Latino, and White first-episode patients enrolled in a coordinated specialty care program. To our knowledge, this is the first time ethnoracial differences in positive symptoms and medication adherence have been examined in the context of an RCT comparing modality of medication administration, and thus the analyses are exploratory in nature. We hypothesized that Black and Latino patients would benefit in particular from LAI risperidone, showing greater positive symptom control and better medication adherence compared to their counterparts on oral risperidone.

2. Method

2.1. Participants

The sample consisted of individuals recruited from psychiatric hospitals and clinics, outpatient treatment centers, and private practices in the greater Los Angeles area. Participants received outpatient mental health treatment at our first episode clinic between March 16, 2005 and September 27, 2012, as part of two simultaneous randomized controlled trials (ClinicalTrials.gov Identifiers NCT00333177 and NCT00330551). Entry diagnostic criteria included (1) a recent illness onset, with the first major psychotic episode occurring in the past two years (2) a diagnosis of schizophrenia, schizoaffective disorder (depressed type), or schizophreniform disorder based on DSM-IV criteria, (3) 18 to 45 years of age, (4) no evidence of a known neurological disorder, (5) treatment with risperidone was not contraindicated, (6) no premorbid intellectual disability, (7) sufficient English language skills to avoid invalidating measures, and (8) residence within commuting distance to the UCLA medical center. Participants who identified as either non-White, Black/African American, or Latino were included in the present analyses. More details regarding the full sample are published elsewhere (Subotnik et al., 2015).

2.2. Procedures

Participants received psychiatric treatment with antipsychotic medications and weekly individual case management from master’s and doctoral-level therapists. Participants were prescribed oral risperidone as the sole antipsychotic medication for at least three weeks before completing baseline assessments and being randomly assigned to either continue oral risperidone or switch to LAI risperidone. Participants were simultaneously randomly assigned to receive either cognitive remediation (CR) or health behaviors training (HB) in a fully crossed 2x2 randomized-controlled trial design. Those assigned to CR participated in a computer-assisted cognitive training program for six months at two hours per week followed by another six months of one hour per week. Those assigned to HBT received instruction in healthy eating habits, relaxation skills training, and light exercise for an equal number of hours per week. For more details regarding study enrollment and randomization refer to Subotnik and colleagues (2015). Note that because it was not one of the original study aims, the randomizations were not stratified by ethnoracial group. Study procedures were approved by the local institutional review board.

2.3. Measures

Psychotic Symptoms.

Positive psychotic symptoms were assessed with the expanded 24-item Brief Psychiatric Rating Scale (Ventura et al., 1993).The BPRS assesses a range of psychiatric symptoms rated by clinicians on a 1 (not present) to 7 (extremely severe) scale based on participant report and observation by the clinical interviewer. The BPRS was administered by case managers to each participant every two weeks during the study period. An aggregate score of positive symptoms items including unusual thought content, suspiciousness, and hallucinations was calculated. This aggregate score is referred to as reality distortion (RD) in the analyses.

Medication nonadherence.

Nonadherence to oral or LAI risperidone was rated by treating psychiatrists using a Likert scale ranging from 1 (excellent adherence) to 5 (very poor adherence). These ratings were determined based on a combination of the following considerations: timeliness of injections for long-acting injectable risperidone, pill counts for oral risperidone, patient report, clinician judgement, plasma levels, and Medication Event Monitoring System (MEMS™) data. Nonadherence ratings covered six-month windows.

2.4. Statistical Analysis

Analyses were conducted in SAS software, Version 9.4 (TS1M7) (Copyright © 2016, SAS Institute Inc, Cary NC, USA). To assess the shapes of the reality distortion trajectories by ethnoracial group and time, we applied LOESS (locally estimated scatterplot smoothing; Jacoby, 2000) to the biweekly BPRS data (see Figure 1). These plots suggested non-linear trends with a change in slope roughly around the 6-month point. Therefore, our primary analyses consisted of linear mixed models (LMMs) with medication (oral vs LAI risperidone) and ethnoracial group (Blank, Latino, White) as the primary between-subjects factors and time in days as the primary (continuous) within-subjects factor, allowing for a change in slope at 180 days. Random intercepts were included to account for the correlations induced by repeated measurements within-subjects. While the focus of this analysis is on medication adherence and its impact on reality distortion, participants were also assigned to a psychological treatment condition. Since the randomizations were not stratified by race/ethnicity, we controlled for this in the reality distortion model by including psychological treatment assignment (CR vs. HB) and its interactions with medication group and time as additional covariates to minimize the potential for confounding caused by any imbalances. The model for adherence was fit unadjusted since that is a medication-specific outcome.

Figure 1.

Figure 1.

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Loess plots of reality distortion by medication condition across the three ethnoracial groups

3. Results

3.1. Sample Characteristics

Demographic and clinical characteristics of the sample are presented in Tables 1 and 2. Participants in the present analyses included 34 Latino, 24 Black, and 17 White patients. There was a significant difference in education across the three ethnoracial groups, p = 0.01. White participants had highest number of years of education followed by Black and then Latino participants. Maternal and paternal years of education were also higher for Black and White participants compared to Latino participants, both p-values < 0.001. There were three participants in the Latino group who identified Spanish as their primary language, with the rest having English as their primary language. All of the White and Black participants reported English as their first language. The proportion of each ethnoracial group that reported substance use in clinical interviews at some point during the study period is reported in Table 1. There were no significant differences among ethnoracial groups in the proportion of participants who reported substance use. There were also no significant differences in the average number of cigarettes smoked per day among smokers across ethnoracial groups.

Table 1.

Means/standard deviations (or frequencies/proportions) and test statistics for demographic and clinical characteristics for Black, Latino, and White patients

Black (B)
(N=24)		 Latino (L)
(N=34)		 White (W)
(N=17)		 Statistic
(X2, F)		 Model p-
value
Age (M + SD) 21.75±4.12 20.41±2.26 22.18±3.75 F(2,72) = 2.04 0.14
Gender M, F (%) 17,7
(70.8,29.2)		 27,7
(79.4,20.6)		 14,3
(82.4,17.7)		 X2(2) = 0.91 0.64
Education (Years) (M + SD) 12.33±1.20 11.74±1.29 13.00±1.94 F(2,72)=4.53 0.01
Maternal Education (Years) (M + SD) 14.16±1.86 10.78±3.65 15.18±2.77 F(2,68)=14.89 0.0001
Paternal Education (Years) (M + SD) 14.10±3.54 10.92±4.16 15.76±2.56 F(2,58)=4.53 0.0002
Primary Language: English 24 (100%) 31 (91%) 17 (100)% -- --
Alcohol Use (Freq, %) 15 (63%) 25 (74%) 11 (65%) X2(3) = 1.07 0.78
Smoking: Frequency with Current Use (Freq, %) 5 (21%) 12 (35%) 9 (52%) X2(3) = 6.99 0.14
Average Number of Cigarettes Daily among Users 7.90 2.42 6.11 F(2,26) = 2.69 0.09
Marijuana Use (Freq, %) 4 (17%) 10 (29%) 4 (24%) X2(3) = 3.68 0.30
Oral risperidone dosage (mg) at randomization 3.19 ± 1.09 3.62 ± 1.13 3.78 ± 1.97 F(2, 75) = 0.64 0.54
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Table 2.

Means, standard deviations, and test statistics for psychiatric symptoms at baseline for Black, Latino, and White patients.

Symptom Ethnoracial
Group		 Mean Standard
Deviation		 Test Statistic Model p-
value
Reality Distortion Black 1.59 0.79 F(2, 73) = 3.52 p = 0.04
Latino 2.66 1.67
White 2.22 1.85
Suspiciousness Black 1.61 1.27 F(2, 73) = 1.03 p = 0.36
Latino 2.15 1.67
White 2.25 1.84
Grandiosity Black 1.30 0.70 F(2, 73) = 0.84 p = 0.44
Latino 1.74 1.42
White 1.50 1.41
Anxiety Black 2.09 1.04 F(2, 73) = 0.45 p = 0.73
Latino 2.32 1.27
White 2.13 1.20
Depression Black 1.91 1.08 F(2, 73) = 0.93 p = 0.40
Latino 1.59 0.92
White 1.94 1.24
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As described in the method section, all participants were on oral risperidone prior to randomization. There were no significant differences in the dosage of risperidone during this period, F(2, 75) = 0.64, p = 0.54. There were also no significant differences by ethnoracial group in medication side effects (i.e., akathisia and dyskinesia).

3.2. Reality Distortion

There was a significant group difference in reality distortion at baseline, F(2, 73) = 3.52, p = 0.04, with Latino patients demonstrating a greater severity of reality distortion compared to Black patients. Linear mixed models to examine effects on reality distortion showed a significant three-way interaction of ethnoracial group, medication condition and time, with differences in LAI vs oral risperidone effects over the initial 6-month intensive treatment period, F(2, 974) = 10.46, p < 0.0001). There were also significant differential changes in slope over the 6-12-month period demonstrated by a significant three-way interaction with ethnoracial group and medication condition, F(2, 974) = 4.45, p = 0.012. Table 3 shows the test of all the model components while Figure 2 shows the estimated marginal mean trajectories for each ethnoracial group over time by medication. The estimates are calculated based on an equal mix of CR and HB assignment, adjusting for any imbalance by ethnoracial category in the original assignments. These plots highlight the significant differential trajectories of reality distortion. Black participants appear to benefit from LAI risperidone compared to oral risperidone, maintaining their lower symptom levels following initial stabilization, while participants on oral medication gradually worsened over the first 6 months and leveled off. Latino participants overall showed a greater severity of reality distortion and did not appear to benefit from LAI risperidone compared to oral. Although White patients in the LAI condition started off with a greater severity of reality distortion, they appeared to benefit more (i.e. show a greater decrease in RD symptoms) than the White patients in the oral condition, although they did not achieve the same level of symptomatology as their Black counterparts. There were significant interactions of medication, psychosocial treatment (CR vs. HB) and time over both 0-6 and 6-12 months (F(2, 974) = 10.52, p = ,0012 and F(2,974) = 4.95, p = .0263), highlighting the importance of controlling for these factors in the models. However, tests for three-way interactions of race, psychosocial treatment and time were not significant.

Table 3.

Test statistics and significance values for linear mixed models of reality distortion and medication nonadherence

Reality Distortion Model Nonadherence Model
Model Term F (df) p-value F(df) p-value
TimeSlopeInitial 1.57 (1, 974) 0.2104 13.64 (1, 116) 0.0003
Race 1.87 (2, 67) 0.1619 1.18 (2, 69) 0.3129
Medication 0.00 (1, 67) 0.9994 0.90 (1, 69) 0.3473
Race x Med 5.22 (2, 67) 0.0078 1.28 (2, 69) 0.2843
Race x TimeInit 3.33 (2, 974) 0.0363 0.06 (2, 116) 0.9374
Med x TimeInit 4.73 (1, 974) 0.0299 8.52 (1, 116) 0.0042
Race x Med x TimeInit 10.46 (2, 974) <0.0001 2.78 (2, 116) 0.0665
TimeSlopeChange 4.26 (1, 974) 0.0393 3.10 (1, 116) 0.0808
Race x TimeCh 0.57 (2, 974) 0.5646 0.18 (2, 116) 0.8377
Med x TimeCh 5.42 (1, 974) 0.0201 1.79 (1, 116) 0.1834
Race x Med x TimeCh 4.45 (2, 974) 0.0119 1.63 (2, 116) 0.2002
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Figure 2.

Figure 2.

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Estimated marginal mean trajectories of reality distortion across time by ethnoracial group and medication assignment

3.3. Medication Nonadherence

Parallel models were fit for medication nonadherence, except those ratings covered 6-month intervals instead of biweekly. The tests of the model components are shown in in Table 3 and the estimated trajectory plots in Figure 3. These models revealed a significant two-way interaction between the initial time term and medication condition, F(1,116) = 8.52, p = 0.004. There was no significant main or interactive effect of ethnoracial group. However, the three-way interaction between the initial time term, ethnoracial group, and medication group was trending, F(2,116) = 2.78, p = 0.067. As depicted in Figure 3, the slopes from 0-6 months appear to differ by ethnoracial group. Both Black and Latino patients on oral risperidone appear to have an increase in medication nonadherence in the first 6 months. In contrast, Black and White patients on LAI risperidone show a decrease in medication nonadherence whereas Latino patients have an increase in the first 6 months. The change in slope at 180 days term was also trending, F(1,116) = 3.10, p = 0.081, suggesting that the trends seen from 0-6 months appear to level off from 6-12 months, consistent by both ethnoracial group and medication condition.

Figure 3.

Figure 3.

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Estimated marginal mean trajectories of medication nonadherence by ethnoracial group and medication condition (oral vs. LAI risperidone)

4. Discussion

The present study sought to examine positive symptoms and medication adherence in response to oral versus LAI risperidone in a sample of Black, Latino, and White patients with first-episode psychosis. Findings showed that Black patients tended to benefit from LAI compared to oral risperidone in terms of medication adherence and positive symptom control. Black patients taking oral risperidone had an increase in reality distortion over time whereas the LAI group remained stable. Latino patients showed better medication adherence with LAI than with oral risperidone, but this did not translate into more improvement in reality distortion over time in LAI compared to oral risperidone treatment. White patients had better medication adherence with LAI than with oral risperidone and a significant reduction in reality distortion in the LAI compared to oral group.

These results suggest that the benefits of LAI compared to oral antipsychotic medication are clear for improving medication adherence and psychotic symptom control for both Black and White first-episode psychosis patients. Latino first-episode psychosis patients showed higher overall levels of psychotic symptoms throughout the 12-month RCT period and, in the oral antipsychotic condition, higher medication nonadherence. A greater severity of psychotic symptoms is consistent with a previous study which found higher levels of psychotic symptoms in Latinos compared to both Black and White Americans (Minsky et al., 2003). More severe symptomatology at the start may have hindered Latino patients’ ability to benefit from LAI risperidone in addition to their increased medication nonadherence during the first 6 months. A systematic review of factors associated with nonadherence to psychotropic medications in Latinos identified factors such as experiencing barriers to high-quality care, lacking health insurance, and language barriers (Lanouette et al., 2009). Other relevant correlates of medication nonadherence in psychosis patients include poor insight, negative attitudes toward medications, substance use, and cognitive impairment (Higashi et al., 2013; Velligan et al., 2017). Family support and trust of a provider have been identified as protective factors for medication adherence in Latino and Black Americans respectively (Lanouette et al., 2009). It will be important for future randomized controlled trials of antipsychotic medications to simultaneously examine predictors of medication nonadherence to better determine causality. Moreover, psychosocial interventions are likely needed to address patients’ concerns regarding antipsychotic medications.

To our knowledge, this is the first study to examine whether there were ethnoracial differences in response to LAI antipsychotics. Previous research investigating the response to antipsychotics have not found any significant differences among ethnoracial groups ((Horvitz-Lennon et al., 2013; Storosum et al., 2023). More research is needed to understand the benefits across minoritized populations.

Although the focus of this study is on response to medication, we must acknowledge that this occurred in the context of a coordinated specialty care program in which participants also received psychotherapy, case management, and skills training. Two previous studies examined ethnoracial differences in NAVIGATE, a coordinated specialty care program for first-episode psychosis (Mueser et al., 2015). Both studies showed that Black and Latino patients benefited from NAVIGATE compared to community care as usual (Nagendra et al., 2023; Oluwoye et al., 2018). However, Black patients did not show the same level of improvement in positive symptoms compared to White patients (Nagendra et al., 2023). In contrast, Oluwoye and colleagues (2018) did not find evidence of any ethnoracial differences in psychiatric symptoms throughout the 24-month study period. Due to the limited sample size, we were not able to examine the contributions of other services patients received. Future research should continue to investigate the benefits of both psychotropic and psychosocial first-episode interventions for minoritized populations to help the field achieve health equity.

Limitations.

The primary limitation of the present study is that the original study design did not stratify the sample by ethnoracial group across treatment conditions. This led to relatively small sample sizes by ethnoracial group in each medication condition. Thus, our findings should be interpretation with caution and viewed as preliminary. This also limited our ability to fully examine ethnoracial differences in the 2x2 RCT treatment design. Thus, we focused on medication response while adjusting for the psychosocial treatment condition. Additionally, we were not able to examine patients of Asian or Indigenous backgrounds due to their limited representation in the study sample. Future studies should aim to have larger sample sizes with adequate representation of each ethnoracial group to fully examine the benefits of treatment components.

Conclusion.

The current study demonstrated mixed benefits of LAI risperidone compared to oral risperidone for positive symptoms and medication adherence in Black, Latino, and White first-episode psychosis patients. Although Black and White patients appeared to have benefited from LAI risperidone, Latino patients did not show the same benefit. Future research should continue to investigate the acceptability of LAI antipsychotic medications for Latino Americans. Relevant sociocultural factors such as language, immigration status, acculturation, health literacy, and cultural mistrust should be targeted in culturally responsive interventions to improve treatment outcomes. Additionally, the structural barriers limiting access to second generation LAIs for minoritized populations carry policy implications and warrant advocacy on behalf of impacted patients. Insurance companies and prescribing providers must be made aware of these disparities and address any ethnoracial biases in their practices or policies.

Footnotes

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