Review of clinical medication adherence in patients with schizophrenia

Abstract

Medication adherence in patients with schizophrenia is essential for managing symptoms, improving prognosis, and enhancing the quality of life. Despite the importance of adherence, it remains a global challenge. It is influenced by various factors, including symptom severity (e.g., excitement and impulse control disorders), attitudes towards medication (e.g., pharmacophobia), lack of social support, and the communication efficacy of healthcare teams. Regarding assessment tools, self-report questionnaires, such as the Morisky Scale, are common but subject to recall bias. Electronic monitoring devices (e.g., Medication Event Monitoring System) and pharmacy refill data offer more objective measures of adherence, whereas biomarkers, such as blood drug concentration monitoring, show promise under specific conditions but require further validation. Long-acting injectable antipsychotic medications have shown greater adherence benefits than oral medications. Psychological interventions such as motivational interviewing and mindfulness training, along with multidisciplinary team efforts, including psychiatrists, pharmacists, and psychotherapists, can significantly improve patient outcomes. Future research should integrate innovative drug formulations (e.g., long-acting, low-side-effect medications), digital health technologies (e.g., medication reminder apps and wearable devices), and supportive policies (e.g., community-based free medication services) as well as patient education to enhance disease awareness. However, the ethical and legal dilemmas (e.g., balancing patient autonomy with involuntary medication) and privacy concerns in technological applications require further exploration. In conclusion, enhancing medication adherence in patients with schizophrenia requires a personalized, multifaceted approach, and collaborative efforts across various sectors to achieve optimal clinical results and social functioning.

Key Words: Medication adherence; Schizophrenia; Long-acting injectable antipsychotics; Psychological interventions; Digital health technologies; Ethical-legal challenges

Core Tip: Medication adherence is critical for managing symptoms, improving prognosis, and enhancing quality of life in patients with schizophrenia. This article examines the multifaceted factors influencing adherence, including symptom severity, attitudes toward medication, social support, and healthcare team communication. It evaluates assessment tools such as the Morisky Scale, electronic monitoring devices, and biomarkers, while highlighting effective strategies like long-acting injectable antipsychotics, psychological interventions, and multidisciplinary team efforts. Future directions emphasize innovative drug formulations, digital health technologies, and supportive policies. However, ethical, legal, and privacy challenges require further exploration.

INTRODUCTION

Medication adherence among patients with schizophrenia is far from satisfactory globally. Research in various medical domains has indirectly highlighted this issue. For example, a study of 195 patients with type 2 diabetes in Cameroon found a 54.4% nonadherence rate to antidiabetic medication[1]. In the context of human immunodeficiency virus, an analysis of 13667 patients across 65 primary studies revealed that self-reported adherence was, on average, 3.94% (individual adherence) and 16.14% (group adherence) higher than that measured using indirect methods, showing significant discrepancies between the different tools[2].

In cardiovascular disease, a study within a large healthcare network indicated that over one-third of patients eligible for statins did not actually receive them. Among those treated, it took approximately two years to reach guideline-directed statin intensity. Moreover, non-adherence to these guidelines has been linked to increased rates of cardiovascular events and mortality[3]. These findings demonstrate that medication adherence is a challenge across various health conditions, suggesting that patients with schizophrenia are likely to face similar obstacles.

Medication adherence varies regionally among patients with schizophrenia. A large prospective cohort study in western China involving 207569 patients found that 15.7% of those non-adherent to medication exhibited violent behavior compared to 8.3% of adherent patients. Additionally, there are notable differences in the risk of engaging in public security-related violent behavior between urban and rural patients[4]. A study in Spain showed that increased drug cost-sharing leads to reduced adherence to prescribed antipsychotic medications and a higher risk of hospitalization among patients with schizophrenia[5].

Research across different regions has also shown that the social and treatment characteristics of patients are linked to medication adherence. In a Chinese community study, a survey of 601 outpatients with schizophrenia revealed that those in the nonadherent group had a longer duration of untreated psychosis, lower body mass index, higher proportion of rural residents, and lower average monthly household income[6]. India’s National Mental Health Programme (NMHP) has had a dual impact on people with mental disorders. By expanding its coverage, the NMHP has enabled more patients, particularly those in remote areas, to gain access to basic mental healthcare services. To some extent, this has enhanced the rates of diagnosis and treatment of mental disorders, improved patient prognoses, and boosted quality of life. However, the effectiveness of the NMHP is constrained by factors such as insufficient funding, shortage of human resources, social perception, and cultural stigma associated with mental disorders. Consequently, some patients struggle to obtain adequate treatment and support services[7].

Therefore, these regional variations highlight the need for strategies to improve medication adherence in patients with schizophrenia and to be tailored to regional characteristics and individual patient differences. Medication adherence is critical for the prognosis of patients with schizophrenia, particularly from the perspective of symptom control. A study involving 64 patients with first-episode schizophrenia indicated that high adherence to antipsychotic medications is generally associated with reduced reality distortion symptoms. Furthermore, during the first three months of treatment, higher adherence correlated with decreased levels of avolition-apathy and poverty of speech[8]. Another study involving 154 patients found a significant positive correlation between patients’ medication adherence and their psychosocial adaptation concerning body weight, image, and self-esteem; higher adherence was associated with better psychosocial adaptation[9].

In terms of healthcare resource utilization, a study on community-dwelling patients with schizophrenia found that those who fully adhered to their medication regimens had significantly lower rates of hospitalization for mental and non-mental health reasons and fewer emergency department visits for mental health issues[10]. In a randomized controlled trial involving patients with multiple episodes of schizophrenia, motivational interviewing (MI) did not significantly enhance overall medication adherence. However, in subgroups such as female patients, non-cannabis users, younger individuals, and those with shorter disease durations, MI was effective in reducing hospitalization rates[11]. These findings highlight the positive effect of improved medication adherence on the prognosis of patients with schizophrenia.

THEORETICAL BASIS OF MEDICATION ADHERENCE IN PATIENTS WITH SCHIZOPHRENIA

Pathological mechanisms of schizophrenia and pharmacological treatment

Schizophrenia is a severe mental disorder characterized by complex pathological mechanisms. Neurotransmitter abnormalities play a crucial role in its pathogenesis, particularly the abnormal transmission of monoamine neurotransmitters, such as dopamine, serotonin, and norepinephrine. Positron emission tomography studies have demonstrated that dopamine D1 and D2/D3 receptors, dopamine transporters, and dopamine synthesis capacity are linked to cognitive function in patients with schizophrenia[12]. Additionally, 5-hydroxytryptamine receptor 1A and 5-hydroxytryptamine receptor 2A receptors in the serotonergic system are associated with cognitive abilities. Moreover, metabolic disorders are prevalent in these patients, potentially attributed to symptom-related effects, etiological factors, and antipsychotic medications. For instance, some antipsychotics influence weight by affecting receptors in the hypothalamus that regulate appetite. Antagonistic actions on 5-hydroxytryptamine receptor 2C, dopamine D2 receptors, histamine H1 receptors, and muscarinic M3 receptors may also contribute to this effect[13].

Antipsychotic drugs remain the cornerstone of schizophrenia treatment, and exhibit varying degrees of efficacy and side effects. An analysis of 17 randomized trials comparing haloperidol with low-potency first-generation antipsychotics found no significant difference in the clinical response between the two groups. However, the haloperidol group experienced more movement disorders, whereas low-potency drugs were associated with increased sedation, postural issues, and weight gain[14]. Similarly, another study comparing fluphenazine with low-potency first-generation antipsychotics found no significant difference in treatment efficacy between the two groups; however, the fluphenazine group had a higher incidence of movement disorders, whereas the low-potency group exhibited more pronounced sedative effects[15].

Definition and assessment methods of medication adherence

Medication adherence refers to the extent to which patients follow medical advice regarding their medication regimens. Among the various assessment methods, self-report questionnaires like the 8-item Morisky Medication Adherence Scale (MMAS) are frequently used. This scale evaluates adherence through the patients’ self-reported medication-taking behaviors. For instance, a study involving 103 patients with type 2 diabetes and systemic arterial hypertension used this scale and found that after pharmaceutical education, the rate of adherence in the intervention group increased significantly from 8.7% to 43.5% at 6 months[16]. However, self-report questionnaires are subject to limitations, such as recall bias.

In addition to self-reporting, other methods have been employed. In renal transplant recipients, the Basel Assessment Scale for Immunosuppressive Therapy Adherence self-report questionnaire was used to measure adherence, and revealed that 36.3% of patients were nonadherent[17]. Additionally, electronic monitoring devices, such as the Medication Event Monitoring System, which records when a medication bottle is opened, provides a more objective assessment of adherence. In a schizophrenia study, the non-adherence rate measured by the Medication Event Monitoring System was 41.2%, which was significantly higher than that assessed by pill counting (7.8%), clinician-rated scales (7.8%), and self-reports (25.5%)[18]. Each assessment method has strengths and weaknesses, and combining multiple methods can yield a more accurate evaluation of medication adherence.

Factors affecting medication adherence in patients with schizophrenia

Numerous factors affect adherence to medication in patients with schizophrenia. Among patient-related factors, symptom severity plays a significant role. Research indicates that symptoms such as excitement, impulse control, and delusional thoughts are more pronounced in nonadherent patients. For example, a study involving 51 schizophrenic patients showed that those who were nonadherent scored higher on these symptoms than their adherent counterparts[18]. Additionally, patients’ attitudes toward medication are crucial; for instance, those with pharmacophobia exhibit significantly lower adherence to medication than those with pharmacophilia. In a study of 176 patients, the average adherence score for those with pharmacophobia was 2.9, whereas it was 6.98 for those with pharmacophilia[19].

External factors were equally critical. For example, social support influences adherence to medication. A study in Thailand found that factors such as therapeutic alliances and experiences with medication side effects enhanced patients’ disease perception, which in turn influenced adherence, whereas social support did not directly affect disease perception or adherence behavior[20]. The role of the healthcare team is also pivotal, because therapeutic alliances are significantly correlated with adherence. In a study of 38 hospitalized patients, the correlation coefficient between therapeutic alliances and adherence was 0.663 (P < 0.0001)[21]. Moreover, factors such as the inconsistent appearance of drugs may affect adherence, although findings in this area are conflicting since one study found no significant association between the inconsistent appearance of antipsychotic drugs and reduced patient adherence[22].

DIAGNOSIS AND ASSESSMENT TECHNIQUES FOR MEDICATION ADHERENCE IN PATIENTS WITH SCHIZOPHRENIA

Comparative analysis of medication adherence assessment tools

Various tools are available to assess medication adherence in patients with schizophrenia, each with distinctive characteristics. The MMAS is a commonly used self-report scale that has been widely applied to different diseases. For instance, a study on patients with inflammatory bowel disease (IBD) using the MMAS-8 to assess adherence found that its accuracy in identifying non-adherent patients was relatively low, with an area under the curve of 0.6 (confidence interval: 0.5-0.7), a specificity of 34%, and a negative predictive value of 57%[23].

When compared with objective methods, such as pharmacy refill indices, differences in consistency emerged between the self-report scales and pharmacy refill indices. In a study involving patients with kidney disease, the MMAS self-report scale, pharmacy refill-based medication possession ratio, and proportion of days covered showed moderate consistency in classifying and quantifying adherence. Notably, the MMAS did not overestimate adherence, and the adjusted covariance analysis indicated a significant association (P < 0.001)[24].

Disease-specific assessment tools were developed for this purpose. For example, the IBD Medication Adherence Tool, designed specifically for IBD patients, demonstrated a moderate correlation with the MMAS-8 (r = 0.56, P < 0.001). This tool effectively assesses the adherence to oral medications in IBD patients[25]. In summary, although individual assessment tools may have limitations, employing multiple tools in combination can enhance the accuracy of medication adherence assessment.

Application of electronic health records in medication adherence monitoring

Electronic health records (EHRs) have a significant potential for monitoring medication adherence in patients with schizophrenia. EHRs enable access to data on patients’ medication prescriptions and pharmacy refills, which facilitate the calculation of indicators such as the (proportion of days covered) to assess adherence. For example, a study involving American Indian adults with type 2 diabetes used EHR data from 2018 to 2021 to explore the relationship between medication adherence and cardiometabolic control indicators. This analysis included details on medication prescriptions, patient demographics, and comorbidity information[26].

Furthermore, EHRs support the implementation and evaluation of interventions. In a study on patients with opioid use disorder, EHR data were used to assess the impact of collaborative care models on medication treatment days and acute healthcare utilization. This model featured components such as nurse care manager support for medication treatment, and the study analyzed administrative data, electronic medical records, and insurance claims data from EHRs[27]. However, the widespread integration of medication adherence assessments into routine EHR systems has not yet been fully utilized. In particular, the transplant community has advocated for such integration to enhance patient outcomes and strengthen the physician-patient relationship[28].

Potential of biomarkers in medication adherence assessment

Biomarkers have a potential value in the assessment of medication adherence in patients with schizophrenia. Although research in this field is relatively limited, various studies have explored its potential from different perspectives. Mennickent et al[29] analyzed serum samples from 26 patients with schizophrenia who were taking clozapine for six months to five years. They found a link between sub-therapeutic serum concentrations and medication non-adherence. Comparison of adherence assessments via serum drug levels and indirect tools, such as the the Positive and Negative Syndrome Scale, revealed discrepancies. This study showed that monitoring clozapine serum levels offer a more objective adherence assessment method and a new tool for tackling medication nonadherence in patients with schizophrenia.

Research in other medical fields has offered insights into the use of biomarkers to assess medication adherence. In the context of human immunodeficiency virus treatment, studies have investigated the use of drug concentration biomarkers to monitor adherence to antiretroviral therapy. Patients have expressed a strong preference for monitoring adherence through pharmacokinetic testing, believing that it could enhance their treatment adherence[30]. These findings suggest that biomarkers could provide a more objective and accurate method for assessing medication adherence in patients with schizophrenia; however, further research is necessary to validate and refine this approach.

TREATMENT STRATEGIES FOR MEDICATION ADHERENCE IN PATIENTS WITH SCHIZOPHRENIA

Optimization and individualization of drug treatment plans

Optimizing and individualizing drug treatment plans are both essential for enhancing medication adherence in patients with schizophrenia. When selecting an antipsychotic medication, it is important to consider the varying efficacies and side effects of the different drugs as well as the specific needs of each patient. For instance, a study comparing aripiprazole once-monthly (AOM) with paliperidone palmitate found that AOM might offer advantages over paliperidone palmitate in the short-term treatment of schizophrenia, demonstrating a significant difference in the primary efficacy endpoint in favor of AOM [odds ratio (OR) = -6.4; 95% confidence interval: -11.402 to -1.358][31].

Dose adjustment is another critical element for treatment optimization. Some studies have tailored drug doses based on genetic polymorphisms. For example, a study involving Chinese Han patients with venous thromboembolism treated with warfarin showed that variables such as CYP2C9 and VKORC1 genotypes, age, and weight were associated with warfarin dose requirements. These factors accounted for 37.4% of the variability in dosing. A pharmacokinetic dosing algorithm created from these variables could accurately predict the maintenance dose, with 64.5% of the predicted doses falling within an acceptable range (-1 mg/day ≤ Δ warfarin dose ≤ 1 mg/day) in the validation cohort[32]. This approach of treatment individualization plans based on unique patient characteristics can significantly improve medication adherence and outcomes in patients with schizophrenia.

Promoting medication adherence through psychological interventions

Psychological interventions are pivotal in enhancing medication adherence in patients with schizophrenia. MI is widely used in this context. In a study involving patients with multiple episodes of schizophrenia who experienced medication nonadherence leading to psychotic relapse, MI did not significantly enhance overall medication adherence but did reduce hospitalization rates in specific subgroups, including female patients, non-cannabis users, younger individuals, and those with shorter disease durations[22]. In another study focusing on adolescent psychotropic medication adherence, two sessions of MI significantly increased adherence scores from 63.7% at baseline to 80.6% at the end of the study (17% mean change, P < 0.0001)[33].

Other psychological intervention methods have also been proven beneficial. For instance, a study on patients with schizophrenia implemented a mindfulness-based psychoeducation program that notably improved participants’ cognitive insight and medication adherence. Post-intervention, the average scores on the Beck Cognitive Insight Scale and medication adherence rating scale in the intervention group were significantly higher than those in the control group (P < 0.05)[34]. These findings suggest that carefully selected psychological interventions can effectively promote medication adherence in individuals with schizophrenia, when tailored to various patient demographics and characteristics.

The role of multidisciplinary teams in medication adherence management

Multidisciplinary teams are crucial in managing medication adherence in patients with schizophrenia. They are typically comprised of psychiatrists, nurses, pharmacists, psychotherapists, and other healthcare professionals. In a study involving patients with heart failure, a nurse-supervised multidisciplinary management program that included multidisciplinary visits, telephone follow-ups, and educational booklets significantly enhanced medication adherence. The MMAS scores of the intervention group increased notably from pre-intervention to 8 weeks pot-intervention (P < 0.001)[35].

In cancer care, a multidisciplinary team-based clinical care pathway improves treatment adherence. In one study, 82 patients with cancer were randomly divided into control and observation groups, with the latter receiving care through a multidisciplinary education team-based pathway. Compared to the control group, the observation group demonstrated significantly better treatment adherence at one day before discharge and at two months after discharge (P < 0.05)[36]. Additionally, in pediatric hematopoietic stem cell transplant patients, strategies implemented by multidisciplinary treatment teams, such as personalized and multicomponent medication adherence support, are believed to enhance adherence and reduce the burden on caregivers[37].

CONTROVERSIES AND CHALLENGES IN MEDICATION ADHERENCE OF PATIENTS WITH SCHIZOPHRENIA

Comparison of long-acting injectables and oral medications

The comparison between long-acting injectables (LAIs) and oral medications for the treatment of schizophrenia has been area of (Table 1). Various studies have indicated that LAIs improve medication adherence as shown in a study involving patients with schizophrenia or bipolar disorder, those using LAIs demonstrated 5% higher medication adherence and a 20% lower risk of discontinuation than those switching to different oral antipsychotic monotherapies over a one-year follow-up period[38].

Table 1 Comparative effectiveness of long-acting injectable vs oral antipsychotics.

Ref.	Population	Key outcomes (LAI vs OAP)	Effect size/statistical significance	Key limitations
Greene et al[38], 2018	Schizophrenia (n = 5638)	Adherence (PDC ≥ 0.8): 33.9% vs 25.5%	Adjusted mean PDC: + 5% (LAI superior, P < 0.001)	Unmeasured clinical differences (e.g., baseline severity) may bias results; medicaid-only population
		mean PDC: 0.55 vs 0.50
		Discontinuation: 63.2% vs 72.0%	Discontinuation risk: 20% lower for LAI (HR = 1.20, P < 0.001)
		Time to discontinuation: 196 vs 123 days
	Bipolar disorder (n = 11344)	Adherence (PDC ≥ 0.8): 30.9% vs 21.5%	Adjusted mean PDC: + 5% (LAI superior, P < 0.001)	Same limitations as schizophrenia cohort
		mean PDC: 0.51 vs 0.45
		Discontinuation: 67.9% vs 77.4%	Discontinuation risk: 19% lower for LAI (HR = 1.19, P < 0.001)
		Time to discontinuation: 149 vs 99 days
Bossie et al[40], 2015	Schizophrenia (meta-analysis of 11 studies)	Pragmatic trials: Consistently favored LAI for relapse prevention, hospitalization reduction, and adherence. Explanatory trials (RCTs): Often showed no significant difference in efficacy	ASPECT-R score (pragmatism): LAI-superior studies: 31.6 ± 6.4	Limited representation of 1st-gen LAIs; ratings based on published reports (not protocols)
			Non-superior studies: 11.9 ± 1.9, P = 0.007
			Most differentiating domain: Participant compliance assessment (P = 0.005)

LAI: Long-acting injectable; OAP: Oral antipsychotics; PDC: Proportion of days covered; HR: Hazard ratio; RCTs: Randomized controlled trial; ASPECT-R: A study pragmatic-explanatory characterization tool-rating.

However, other studies have reported contradictory results. In a retrospective study examining the impact of LAIs and oral antipsychotics on restoring competency-to-stand trials, LAIs were not significantly associated with an increased likelihood of restoring competency[39]. These variations in findings might be attributed to factors such as study design and characteristics of the patient population. Therefore, the applicability of study designs can affect outcomes, as more practical designs might better highlight the benefits of LAIs, whereas exploratory studies could downplay these benefits by introducing specific variables[40].

Leucht et al[41] utilized a Bayesian framework for a multi-treatment meta-analysis to compare the effects of 15 antipsychotic drugs and a placebo in the acute treatment of schizophrenia. The results demonstrated that all medications were more effective than the placebo. Drugs, such as chlorpromazine, amisulpride, olanzapine, and risperidone, have shown superior efficacy. Additionally, this study suggests that LAIs may offer certain advantages in enhancing patient adherence to medication, which can reduce relapses caused by missed doses. On the other hand, oral medications have advantages in terms of convenience of administration and flexibility in dosage adjustment; however, they rely on patient self-administration according to their schedule, and poor adherence can compromise treatment effectiveness.

The relationship between medication adherence and quality of life

Medication adherence is closely related to the quality of life in patients with schizophrenia. A long-term follow-up study of patients with chronic schizophrenia found that medication adherence positively correlated with global outcomes and life satisfaction. Specifically, in a study involving 20 patients, medication adherence showed positive correlations with global outcomes rated by blinded clinicians (P = 0.049) and overall functioning (P = 0.021). In the ratings by non-blinded clinicians, medication adherence was positively correlated with global outcomes (P = 0.001) and patient-reported life satisfaction (P = 0.028)[42].

Studies of other health conditions have also supported this relationship. In a research involving patients with type 2 diabetes, treatment satisfaction is significantly related to medication adherence and quality of life, with higher treatment satisfaction linked to better medication adherence and improved quality of life[43]. These findings suggest that enhancing medication adherence in patients with schizophrenia not only helps manage the condition but also improves their quality of life. Emphasizing this link in clinical practice is crucial, and efforts should be made to enhance medication adherence, thereby improving quality of life.

In my daily work at a psychiatric outpatient clinic, I witnessed the shocked impact of stigma on patients’ medication adherence. A survey of 127 patients with relapsed mental health conditions revealed that 68% had reduced or stopped their medication on their own due to the “fear of exposing their condition”. A typical case involved a university student who concealed olanzapine tablets in a vitamin C bottle and his roommate mistakenly ingested them. Subsequently, the student panicked and stopped taking the medication. This led to worsening of his symptoms and forced him to take a leave of absence from school. These real-life cases highlight negative impact of stigma by creating a psychological shackle of "taking medicine equals shame" and also leading to complex strategies of hiding medication (such as grinding tablets and mixing them into food) and avoidance of medical care.

The impact of cultural factors, ethics and law on medication adherence management

Traditional concepts related to medicine are deeply rooted in many cultures and significantly influence treatment choices and medication behaviors of patients with mental disorders. In some low- and middle-income countries, traditional complementary medicine is widely used to treat mental disorders. For example, studies in Sudan have shown that a significant number of patients with mental disorders have a history of receiving traditional treatments, and in most cases, treatment decisions are made by the family on their behalf[44]. Ethics and laws significantly influenced medication adherence in patients with schizophrenia. From an ethical standpoint, respecting patient autonomy and ensuring informed consent are paramount. In the medical decision-making process, it is crucial that patients’ rights to choose their treatment options are fully honored and that they are well-informed about the benefits and risks of their drug treatments. For instance, in discussions about assisted dying for patients with mental illnesses, the necessity of rigorously assessing patients’ autonomous decisions and desires to meet ethical standards has been emphasized[45].

Various policies and regulations affect the implementation of medication adherence management as seen how community-free medication service policies in some areas have positively affected medication adherence. A study conducted in Beijing communities found a significant positive correlation between participation in these policies and medication adherence (OR = 1.557)[46]. However, regional variations in the enforcement of laws and policies can lead to different levels of support for the enhancement of medication adherence. In the Netherlands, the Coercive Care Act, which became effective from January 1, 2020, replaced the he Bijzondere Opnemingen in Psychiatrische Ziekenhuizen Act. It permits coercive treatment both inside and outside hospitals, while prioritizing patients’ opinions on such measures. Since its implementation, studies have indicated a notable decrease in seclusion time, yet involuntary medication incidents have increased in 2020[47]. In contrast, seclusion and mechanical restraints are used more frequently in Germany and data obtained in 2014, revealed that among 15832 hospital admissions, only 78 (approximately 0.5%) involved involuntary medication. This might stem from the 2013 legal amendments that imposed stricter restrictions, leading to a more cautious use of involuntary medication[48]. Furthermore, legal regulations governing medical practices also influence how healthcare professionals manage medication adherence, ensuring that medical actions are lawful and compliant, and protect patients’ rights.

CONCLUSION

The potential impact of new drugs on medication adherence

The development of new drugs offers hope for improving medication adherence in patients with schizophrenia. Advances in drug development technology have led to the development of medications with improved pharmacokinetic properties, which can simplify treatment regimens and boost adherence. For instance, in the treatment of chronic hepatitis B, nucleos(t)ide analogs have demonstrated high rates of sustained medication use and adherence, at 81% ± 3.8% and 87.8% ± 19.1%, respectively[49]. This indicates that the development of similar user-friendly drugs with clear efficacy and fewer side effects for patients with schizophrenia could significantly improve adherence.

Moreover, new drugs may offer better tolerability, thus reducing non-adherence caused by adverse drug reactions. Many patients discontinue treatment because of intolerable side effects associated with antipsychotic drugs. By minimizing these side effects, new medications can substantially enhance patient adherence. Additionally, innovations in drug formulations such as the development of long-acting injections can reduce the daily medication burden on patients, improve convenience, and potentially increase medication adherence.

Nonetheless, new drugs like long-acting injections, raise issues regarding medication adherence and accessibility for patients with mental disorders. A study found that Drug reimbursement policies can be a major barrier to the use of LAI antipsychotics for recurrent schizophrenia[50]. Health insurance coverage also significantly affects drug accessibility for these patients. In the United States, the Affordable Care Act’s dependent coverage expansion in 2010 allowed young adults to stay under their parents’ health insurance, which increased insurance coverage and improved health outcomes for patients with mental disorders[51].

Personalized intervention

Personalized intervention strategies can effectively improve medication adherence, thereby enhancing overall treatment outcomes. In fact, patients with chronic schizophrenia require more comprehensive intervention strategies, including an integrated model combining pharmacological, psychological, social, and skill-based approaches. This model improves patients’ cognitive abilities and reduces both positive and negative symptoms, thereby enhancing their social functioning[52]. LAIs can reduce adherence issues caused by forgetfulness or reluctance to take medication, particularly in patients with first-episode schizophrenia and comorbid substance use disorders[53].

The application prospects of digital health technologies in medication adherence

Digital health technologies offer vast potential for improving medication adherence in patients with schizophrenia. Mobile applications are particularly valuable because they enable timely medication intake through reminder functions. A systematic review of patients with tuberculosis highlighted that digital health interventions such as short message service reminders and video directly observed therapy effectively enhance medication adherence. Some studies have reported Ors and relative risks for treatment completion rates ranging from 1.10 to 7.69 with short message service reminders[54].

Additionally, integrating wearable devices with digital health technologies allows for real-time monitoring of patients’ medication behaviors and physiological indicators. For instance, a study on patients with Parkinson’s utilized a digital health system comprising smartphones, smartwatches, and inertial measurement units to track the patients’ self-reported medication adherence and monitor their real-world activities, which aided in the optimization of treatment regimens[55]. However, the application of digital health technologies also faces challenges, including issues related to data security and privacy protection as well as variability in patients’ acceptance of technology. These issues must be addressed to promote and apply these new technologies.

Implementing APP interoperability with EHR systems via the the health level seven fast healthcare interoperability resources protocol can boost data standardization and interoperability. This ensures accurate and timely information exchange, promotes data sharing across healthcare settings, and supports continuous and comprehensive patient care[56]. Blockchain technology, owing to its decentralized and immutable nature, can encrypt and secure patient medication data. Preventing unauthorized access and ensuring data integrity increase patient trust in the EHR systems[57].

The role of policies and education in improving medication adherence

Policies and education are crucial to enhance medication adherence in patients with schizophrenia. At the policy level, governments and relevant agencies can foster a supportive medication environment by implementing helpful policies. For instance, community-free medication service policies implemented in certain regions have significantly boosted patient adherence to medication regimens[58]. Moreover, policies can facilitate the involvement of multidisciplinary teams in patient management, enhance the integration and optimization of medical resources, and offer more comprehensive support to patients.

In terms of education, it is vital to inform patients about their condition and medications. A study of newly diagnosed patients with tuberculosis demonstrated that those with a better understanding of tuberculosis exhibited higher medication adherence[59]. In addition, training healthcare professionals in medication adherence management is essential. A study involving internal medicine residents found that after participating in a two-hour interactive seminar, residents’ confidence and practices in assessing and advising patients, including those with low health literacy, improved markedly. This included more frequent evaluations of patients’ comprehension of their medications and barriers to adherence[60]. By reinforcing policy support and educational initiatives, the goal is to improve medication adherence in patients with schizophrenia.

Collaboration within multidisciplinary teams is cost-effective for improving medication adherence in patients with mental disorders. On the one hand, optimizing HR allocation via communication and coordination can reduce hospitalization costs and enhance outpatient service efficiency. On the other hand, specialized training programs can improve team members’ communication and collaboration in complex situations, thereby reducing medical errors and improving patient safety[50,51,61].