1Department of Psychology, Medical Humanities Research Center, Binzhou Medical University, Yantai, 264003 China

2Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, 100191 China

3National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191 China

4NHC Key Laboratory of Mental Health (Peking University), Beijing, 100191 China

2Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, 100191 China

3National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191 China

4NHC Key Laboratory of Mental Health (Peking University), Beijing, 100191 China

5The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, Henan 453100 China

1Department of Psychology, Medical Humanities Research Center, Binzhou Medical University, Yantai, 264003 China

1Department of Psychology, Medical Humanities Research Center, Binzhou Medical University, Yantai, 264003 China

1Department of Psychology, Medical Humanities Research Center, Binzhou Medical University, Yantai, 264003 China

1Department of Psychology, Medical Humanities Research Center, Binzhou Medical University, Yantai, 264003 China

2Peking University Sixth Hospital, Peking University Institute of Mental Health, Beijing, 100191 China

3National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, 100191 China

4NHC Key Laboratory of Mental Health (Peking University), Beijing, 100191 China

5The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, Henan 453100 China

6PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871 China

7Chinese Institute for Brain Research, Beijing, 102206 China

Medication adherence of schizophrenic patients is a growing public health problem. We conducted a meta-analysis on the influencing factors of medication compliance in schizophrenic patients. We searched PubMed, Embase, Cochrane Library, and Web Of Science for relevant articles published up to December 22, 2022. Combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess influencing factors. Egger’s test, funnel plot, the trim and fill method, and meta-regression analysis were used to assess publication bias. A total of 20 articles were included in the analysis. Twenty influencing factors were divided into seven categories: drug factors (OR = 1.96, 95% CI: 1.48–2.59), problem behavior (OR = 1.77, 95% CI: 1.43–2.19), income and quality of life (OR = 1.23, 95% CI: 1.08–1.39), personal characteristics (OR = 1.21, 95% CI: 1.14–1.30), disease factors (OR = 1.14, 95% CI: 1.98–1.21), support level (OR = 0.54, 95% CI: 0.42–0.70), and positive attitude and behavior (OR = 0.52, 95% CI: 0.45–0.62). This meta-analysis found that drug factors, disease factors, problem behavior, low income and quality of life, and factors related to personal characteristics appear to be risk factors for medication adherence in people with schizophrenia. And support level, positive attitude and behavior appear to be protective factors.

Schizophrenia is a common severe mental disease with a lifelong prevalence rate of 1%, which is mainly manifested in the disorder of mental and psychological processes such as thinking, perception, self-experience, cognition, will, emotion and behavior, and has the characteristics of high disability rate, repeated illness and prolonged course1,2. The pathogenesis of schizophrenia is complex and not clear at present. Genetic susceptibility, abnormal neurotransmitter function and external factors may all contribute to the development of schizophrenia3.

The current treatment of schizophrenia is based on the administration of antipsychotic medication. Medication can control the condition of schizophrenic patients, which has been effective in the alleviation of positive symptoms, prevention of relapse, and extension of life expectancy4–6. The extent to which patients follow the prescribed time intervals and dosage requirements is defined as medication adherence3,7,8. A Low degree is considered as poor medication adherence. Medication non-adherence behaviors include not taking medication on time, not taking more or less medication according to the dose, stopping the medication and reducing medication by themselves.

Good medication adherence is the key to the effectiveness of drug treatment. Poor medication adherence will cause many problems in schizophrenic patients9,10. First, low medication compliance will lead to low efficacy and high relapse. Some articles pointed out that the symptoms of schizophrenia developed the fastest in the five years before the onset of schizophrenia, dosing on time and at the right dose is an important factor in the effectiveness of treatment, irregular medication is the key risk factor for relapse11. In a retrospective analysis of 419 psychiatric inpatients readmitted to hospital, Barnett et al. found that patients’ medication non-adherence significantly increased the risk of readmission compared to other factors, with an OR of 3.3312; data from Verdoux et al. show that the most common cause of relapse and readmission in adult studies is the discontinuation of prescription drugs. Patients who do not insist on medication are six times more likely to be admitted to the hospital again than those who insist on medication13,14. Furthermore, many studies have shown that poor medication adherence is associated with problematic behaviors such as violence, self-harm, and suicide. Buchanan et al. found that there was a significant positive correlation between low drug compliance and harmful violence through 18-month follow-ups of 1435 schizophrenic patients15; Díaz-Fernández et al. pointed out that the lack of treatment compliance of schizophrenic patients is a risk factor for the increase of suicidal behavior16; the results of a multicenter clinical trial in China also show that the aggression risk of schizophrenia patients is related to non-adherence to medication17.

Through a review of medication non-adherence behavior in schizophrenia patients, Lacro et al. noted that current medication non-adherence in schizophrenia patients is as high as 40–50%18. Fenton et al. reported a median non-adherence rate of 55% for oral antipsychotics19 and other data in the literature on medication non-adherence in schizophrenia patients ranging from 20 to 89%20–22. In recent years, many studies have been reported on the phenomenon of poor medication adherence in patients with schizophrenia, while the factors influencing medication adherence have also become a subject of scholarly interest. Available clinical observations and cohort studies suggest that patients’ age, gender, marital status, insight, other physical illnesses, economic conditions, etc. all have an impact on medication adherence18,23–25.

However, the current research lacks uniform predictors and has no clinical implications for interventions for medication adherence in patients with schizophrenia. Understanding the factors that influence medication adherence has practical implications for the identification of patients with low adherence and may assist in the development of clinical interventions for medication adherence. The aim of this study was to analyze the influencing factors of medication adherence of schizophrenic patients, to provide information for the formulation of intervention strategies for medication adherence, and to help patients recover better and reduce recurrence.

We conducted a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The initial study protocol was preregistered at PROSPERO (CRD42023388661). We searched PubMed, Embase, Cochrane Library, and Web of Science for relevant literature up to 22 December 2022.

The search consisted of the following terms as Medical Subject Headings (MSH) and different databases have corresponding modifications. The following search strategy was used: (schizo*) AND (adherence OR compliance OR non-adherence OR non-compliance) AND (relative OR risk*) AND (cohort OR “cohort study”).

Two researchers independently assessed the title and abstract that met the potential qualifications of the above search strategy to exclude the following articles: (i) use of long-acting injectable (LAI) antipsychotics; (ii) no relevant diagnosis of schizophrenia; (iii) review articles, comments, case reports, editorials, animal studies, and meta-analysis; (iv) data unextractable or incomplete; (v) language not English. The full text was then further assessed to determine whether the article met the inclusion criteria. The final articles included met the following criteria: (i) patients diagnosed with schizophrenia who are receiving at least one antipsychotic drug, and excluded patients with major medical conditions (such as liver or kidney dysfunction in relationship to cardiovascular disease organic brain disorders), with a history of substance use disorders; (ii) the study was designed as a cohort study or a cross-sectional study; (iii) the hazard ratios (HR), relative risks (RR), and odds ratios (OR) were reported.

All data were extracted independently by two investigators and the following data were collected for all articles: author, year of publication, country, sample size, sample age, diagnostic criteria, and influencing factors for medication adherence.

In terms of quality assessment, we used the Agency for Healthcare Research and Quality Checklist26 to assess the cross-sectional studies, and The Newcastle Ottawa Scale (NOS)27 was used to assess the cohort study. For each score, 1 indicates that the study meets this criterion and 0 indicates that the study does not meet this criterion. A total score of no less than 5 will be included in this meta-analysis.

In this meta-analysis, Stata 14.0 was used for data analysis28. We used the Q-test and I-squared (I2) values to assess heterogeneity. P  75% was considered significant heterogeneity. I-squared (I2) values close to 0% and P > 0.1 indicate that heterogeneity is small. Sensitivity analysis was carried out for the parts with large heterogeneity. Given the expected heterogeneity, we adopted the random effect model in advance. The odds ratio (OR) was used as the main index, and a 95% confidence interval (95% CI) was used to reflect the uncertainty of point estimation, with ORs = 1 indicating that the factor was not associated with medication adherence, ORs  1 as risk factors.

For publication bias, we used funnel plots for rough qualitative analysis combined with Egger’s test for quantitative analysis, significant Egger’s test result (P  75%, Q-test: P = 0.01