One-Year Evaluation of Paliperidone Palmitate 6-Monthly: Satisfaction and Perceived Effectiveness Among Patients, Relatives, and Clinicians

Introduction

Treatment adherence is a critical component of positive therapeutic outcomes, significantly influencing the prognosis of severe and enduring mental disorders, such as schizophrenia and other psychotic disorders. To this end, the World Health Organization (WHO) has identified non-adherence as one of the most challenging aspects of the management of schizophrenia.¹ One major factor contributing to non-compliance in patients with schizophrenia is the complexity of the treatment regimen, which may include multiple daily medications and varying dosages.^2,3 Poor adherence to these medications remains a challenge, with studies indicating that retention rates can be as low as 50%.^4,5 Non-adherence can lead to increased relapses and hospitalizations, premature mortality, higher risk of suicide and increased healthcare costs, thereby highlighting the need to better understand and improve adherence among patients with a mental health illness.⁶

Other factors impairing treatment adherence are side effects, psychosocial support or lack thereof, perceived stigma, necessity of medication and the quality of the therapeutic relationship.^7,8 Interventions aimed at improving adherence, such as motivational interviewing and cognitive-behavioral strategies, have been effective in enhancing treatment persistence in these patients.⁹ Furthermore, the use of long-acting injectable (LAIs) antipsychotics has been associated with improved adherence rates, as these formulations reduce the frequency of dosing and the burden of daily medication management.¹⁰ LAIs offer additional advantages such as 1) sustained clinical stability leading to improved level of daily functioning, thus allowing more time for psychosocial and other recovery-oriented interventions, 2) patients who may struggle with memory problems and cognitive dysfunction do not have to remember to take daily medication and 3) the injectables are administered during visits by a mental health professional ensuring persistence and continuity as well as assertive follow up when and as needed.^11,12 As shown, with paliperidone 3-monthly (PP3), the first longer than one month acting antipsychotic that was made available, long dosage intervals mean less frequent injections and consequently less pain or fear of administration, less dependence on contacts with clinicians and a decreased necessity to travel for receiving an injection.¹³ More recently, a paliperidone palmitate formulation with stable therapeutic plasma levels for 6 months is the only LAI available to be administered twice a year. PP6M was approved for the treatment of adult patients with schizophrenia who previously were treated with either at least one injection of PP3M or with four consecutive injections of PP1M.¹⁴

The shared decision-making (SDM) process involves patients, their relatives, and clinicians working together to make informed decisions about treatment options, thereby fostering a sense of ownership, self-agency and responsibility in patients regarding their own care and enhancing treatment adherence.¹⁵ Given the stigma attached to antipsychotic injectable treatments, patients’ perspectives are vital in the discussion of LAIs and their incorporation into general treatment strategies.¹⁶ PP6M is introduced as a novel solution to address the need for longer-acting treatments in patients with chronic conditions. Nonetheless, to date research with PP6M is limited to clinical trials^17–19 and only two real world studies at 6²⁰ and 12 months.²¹ While data from clinical trials excluded patients with schizophrenia and comorbid psychiatric conditions such as substance misuse, real-world studies provide more diverse and representative data, capturing a wider range of patient characteristics, including comorbidities, age groups, and treatment adherence. This study aims to fill the gap in knowledge regarding patient preferences for treatment frequency, specifically exploring how PP6M compares to other long-acting injectable options in terms of convenience and satisfaction. We hypothesized that PP6M would show high satisfaction rates and perceived effectiveness compared to prior treatments of patients, their relatives and mental health professionals on the twice-yearly treatment with PP6M in usual clinical practice.

Methods

The cohort of patients derived from the P2Y study. This is a multicenter, prospective study across different urban sites in Europe. The protocol, inclusion and exclusion criteria were previously published.²⁰ Briefly, adults carrying a diagnosis of schizophrenia, schizoaffective, psychotic, delusional, bipolar or personality disorders, intellectual disability and autism spectrum disorders initiating PP6M treatment were included. Patients <18, pregnant women and those without medical records in the past 2 years were excluded. There were no exclusion criteria regarding comorbid substance use, treatment-resistant schizophrenia, comorbid affective disorders or other concomitant pharmacological treatments. Data collected extend from 2021 to 2024. Patients, relatives and psychiatrists were asked for satisfaction, by using the Medication Satisfaction Questionnaire (MSQ), and perceived effectiveness after completing one year of treatment with PP6M. The MSQ rates satisfaction on a 7-point Likert scale (1 = extremely dissatisfied; 7 = extremely satisfied), and has been validated for patients with psychotic disorders.²² Patients were also asked for their perceived effectiveness of PP6M compared to the previous treatment (1 = PP6M is inferior to previous treatment; 2 = PP6M is similar to previous treatment; 3 = PP6M is superior to previous treatment).

The sample size of the study (n = 233) was determined based on the characteristics of the real-world study, where the aim was to gather sufficient data to assess patient preferences and treatment outcomes. This sample size is comparable to the clinical trial for PP6M, which similarly had a robust cohort size to ensure statistical reliability and generalizability of the findings. Given the nature of the study, which aims to reflect real-world conditions rather than a controlled clinical trial environment, we believe this sample size provides an adequate representation of the patient population to achieve meaningful insights.

The study is conducted in accordance with International Conference on Harmonization Good Clinical Practice guidelines, the Declaration of Helsinki and approved by the corresponding Ethics Committee (ref. CEI.23–11_PY2_2022). Before study initiation, written informed consent covering retrospective, screening and prospective collecting data was obtained from participants (or their legal representatives, if appropriate). The protocol and consent forms were approved by the respective institutional ethics committee at each site.

Descriptive analyses (ie, frequencies, means and standard deviations) were used to describe the demographic characteristics and evaluate the outcomes of the questionnaires. Group analysis was performed using ANOVA or Mann–Whitney U-tests while Student’s t-test or Chi-square test were used for qualitative variables. All data were analyzed using IBM SPSS 22.0.

Results

In total, 233 patients were included in this study, of which 9 (4%) discontinued PP6M at 12 months. The patient characteristics are summarized in Table 1. Most patients were male (69%, 160 participants), with an average age of 41.7 years (±1.3) ranging between 18 and 78 years old. 66% (156 patients) carried a diagnosis of schizophrenia and 16% (38 patients) of comorbid substance use disorder. Furthermore, 22% (51 patients), 70% (164 patients) and 8% (19 patients) were treated with PP1M, PP3M and other oral/LAIs antipsychotics, respectively. It is worth noting that most 47% patients (110/233) preferred to be treated with PP6M as the main reason to discontinue the previous treatment.

Table 1 Demographic and Clinical Data

PP6M Satisfaction

The majority of patients (81.5%, n = 190/233), relatives/carers (81.1%, n = 189/233) and clinicians (90.9%, n = 212/233) were extremely satisfied, very satisfied or satisfied 1 year after switching from PP1M, PP3M and other antipsychotic to PP6M as demonstrated in Table 2 and Figure 1A. Between 7% and 21% of all three parties (37 patients, 40 relatives and 17 clinicians) stated they are neutral when comparing PP6M with the previous treatment. Only 2.6% of patients (n = 6), 1.7% of relatives (n = 4) and 1.7% of clinicians (n = 4) reported being somewhat unsatisfied with PP6M. No statistical differences were found in treatment satisfaction between patients, relatives and clinicians in both schizophrenia (p = 0.293) and no-schizophrenia (p = 0.149) subgroups. As outlined in Table 2, similar findings were reported between patients diagnosed with schizophrenia and other diagnoses with no differences when comparing both subgroups of patients (p = 0.150), relatives (p = 0.122) and clinicians (p = 0.388).

Table 2 Evaluation of PP6M Satisfaction by Participants Groups

Figure 1 Perceived satisfaction (A) and effectiveness (B) by patients, relatives and clinicians in patients treated with PP6M up to 12 months.

Perceived Effectiveness

As shown in Figure 1B, 42% of patients, 45% of their relatives and 40% of clinicians perceived PP6M as more effective compared to the previous treatment. In contrast, only 3% of patients, relatives and clinicians perceived PP6M as less effective. As shown in Table 3, the perceived effectiveness is higher, but not significant, in patients diagnosed with other diagnoses different from schizophrenia (40% vs 47%, p = 0.325) and their relatives/carers (43 vs 48%, p = 0.320) and similar proportion among their clinicians (40% vs 42%, p = 0.690). PP6M was perceived as more effective than PP3M in both patients with schizophrenia and other mental disorders (46% vs 42%). It is noteworthy that patients with schizophrenia previously treated with PP1M perceived PP6M as equally effective (71%) while most patients diagnosed with other mental disorders reported PP6M as superior (70%). Finally, the group of patients previously treated with other oral or LAIs antipsychotics perceived PP6M as equally effective compared to the previous treatment (63% and 64%). As outlined in Table 3, no statistical differences were found in perceived treatment effectiveness between patients, relatives and clinicians in the different subgroups.

Table 3 Evaluation of PP6M Perceived Effectiveness by Participants Groups

Discussion

To the best of our knowledge, this is the first study evaluating the patients’ and their relatives/carers and clinicians perspectives and preferences with PP6M. The overall experience of patients was that PP6M is preferable and confers advantages compared to the previous treatment, PP1M, PP3M and other oral and LAIs antipsychotics; these findings were mirrored by their carers/relatives and psychiatrists.

Specifically, our results demonstrated a high patient satisfaction rate (81%) with PP6M compared to previous treatments, although most patients switched over from PP3M or PP1M. Previous studies demonstrated high patient satisfaction with PP3M performing better across most studies following a switch from PP1M.^12,23,24 A recent study for example with PP3M showed that 10% of patients evaluated PP3M as being better than PP1M while higher rates were found for relatives and clinicians (15 and 26%).¹² In our study, almost half (41–44%) of patients, relatives and clinicians perceived PP6M to be superior to the previous treatment which is a considerable proportion considering that most patients are already stabilised on long acting treatments.

Perhaps the “less is more” principle can be applied in this case as the ultra-long-acting antipsychotic treatment may be associated with improved social functioning and less stigma.²⁵ Infact, a number of potential benefits and advantages have been recorded including the convenience and ease of access particularly in rural, under-resourced or deprived areas. Regardless, some patients with busy schedules prefer to visit their healthcare professionals or specialized nursing staff less frequently and often view frequent injections as a burden. Nonetheless, regular contact between patients and clinicians is crucial for maintaining treatment adherence and to assess patient symptoms and other needs. Thus, the time saved in administering injections can be dedicated to other therapeutic activities, such as rehabilitation and psychotherapy. Additionally, the PP6M administration schedule offers greater flexibility in dosing compared to PP3M and PP1M, helping to prevent missed maintenance doses up to 3 weeks later than the programmed administration. Greater flexibility and protection helps mitigate against partial adherence which has been shown to also affect patient outcomes adversely in the form of delays, treatment gaps and missed doses.²⁶ Therefore, long-acting treatments can significantly reduce the burden for patients, their families, caregivers, and healthcare providers.²⁷

In the past, studies have reported lower rates of patients choosing LAI treatment (3–12%)²⁸ though novel therapeutic options and shared decision making may aid choice and uptake. In this regard, different studies showed no differences in satisfaction between antipsychotics treatments or formulation but they found that patients who chose the treatment decided by consultation with physicians or matched their preferences had significantly higher satisfaction levels.^29,30

For instance, a study highlighted that patients and relatives who participated in SDM reported increased satisfaction with their treatment and a greater understanding of the risks and benefits associated with their medications.³¹ However, it is essential to balance family involvement with respect for the patient’s autonomy and preferences. Clinicians’ perspectives on shared decision-making are equally important. A systematic review has shown that when clinicians adopt a shared decision-making approach, it not only enhances patient satisfaction but also fosters a stronger therapeutic alliance, which is crucial for adherence.³² Overall, positive attitudes and experience of patients, relatives and clinicians with PP6M can help expand the use of long acting antipsychotic treatments and potentially improve the clinical outcomes. In this regard, recent data demonstrated that PP6M improved adherence and reduced hospital admissions compared to previous treatments.²¹ The main advantage of PP6M is that by reducing the number of administrations, it can also contribute to minimise the attached stigma as well as the dependency on health services whilst improving access to care particularly in rural or deprived areas. Previous studies with PP3M demonstrated that concerns that less frequent administrations could lead to increased relapse or discontinuation rates did not actually materialise in clinical practice.¹³ Conversely, less frequent treatments may be associated with higher treatment persistence and greater social acceptance, inclusion and promotion of rehabilitation which in turn can improve the overall patient experience and the collaborative process.^11,16 Future studies with a follow-up period of two years or longer are needed to assess whether patient satisfaction levels and perceptions of the treatment remain stable over time. Long-term evaluations could provide valuable insights into the durability of treatment preference, potential changes in patient experience, and factors influencing sustained adherence to PP6M.

Strengths and Limitations

To our knowledge, the present study is the first to evaluate the subjective perceptions from patients, relatives and clinicians after 1 year of treatment with PP6M in real world clinical practice. The study was independent from external funding and prospective to minimise bias but its cross-sectional design provides only a snapshot of patients’ perspectives and change in opinion overtime cannot be captured. The questionnaire was only administered to patients after 1 year, therefore patients who discontinued PP6M after 6 months may have had a different experience and are therefore not included. Furthermore, other potential confounding factors such as duration of illness, level of functioning and accommodation have not been accounted for. What is more, a significant drawback of this study is that widely employed validated scales were not employed for the evaluation of satisfaction which may reduce its generalisability and comparability with future research. Moreover, the potential for social desirability bias cannot be completely ruled out, as patient-reported satisfaction may be influenced by the tendency to provide favorable responses. To mitigate this, data were collected anonymously, and no incentives were provided to participants. Last, our study exclusively included patients from urban areas, limiting the generalizability of our findings to rural populations. Differences in healthcare access, treatment perception, and socioeconomic factors could influence satisfaction levels in rural settings.

Conclusions

Patients, their carers and relatives as well as mental health professionals reported a high satisfaction rate with PP6M, and equally good or even better perceived effectiveness compared to PP1M, PP3M or other oral or LAIs antipsychotics in the majority of cases. By improving patient satisfaction and experience, PP6M may reduce treatment discontinuation rates or improve quality of life. Further prospective studies are needed to examine overall effectiveness, side effects and satisfaction with PP6M, and whether an improved subjective experience can reduce schizophrenia relapse rates by improving adherence and patients’ quality of life.