Background

Psychiatric disorders have been a global public health challenge. Almost 450 million people are affected by psychiatric disorders worldwide. It contributes 14% of the overall global burden of diseases, and 30% of the non-fatal diseases burden, which is worsened by medication non-adherence [1,2,3]. Psychiatric disorders cost approximately US$2.5 trillion in 2010 and are expected to rise up to US$6.0 trillion by 2030. Lost resources and production, unemployment, absences from work, and premature mortality are some of the indirect economic costs [3]. The World Health Organization (WHO) has designed a comprehensive strategic action plan (2013–2020) to promote mental well-being, prevent psychiatric disorders, and provide care and support to reduce morbidity, disability, and mortality [4].

Nearly one third (31.7%) of people who suffer major psychiatric disorders end up with a long-term disability and dependency [5]. Psychiatric disorders are associated with individual factors as well as community social support, cultural, social protection, living standards, and other environmental factors [4]. Compliance to medication is essential but challenging in the management of major psychiatric disorders [6,7,8]. The WHO defines medication non-adherence as, “a case in which a person’s behavior in taking medication does not correspond with agreed recommendations from health personnel” [9]. Patients with major psychiatric disorders are most likely to be non-adherent to medication due to poor reasoning and lack of insight about their illness and treatment [8, 10, 11].

Psychotropic medication non-adherence can lead to exacerbation of their illness, reduce treatment effectiveness, or leave them less responsive to subsequent treatment. Other consequences of non-adherence include re-hospitalization, poor quality of life or psycho-social outcomes, relapse of symptoms, increased co-morbid medical conditions, wastage of health care resources, and increased suicide [7, 8, 12,13,14,15]. Research evidence on the level of psychotropic medication non-adherence and its associated factors among patients with major psychiatric disorders is essential to design appropriate interventions to achieve desired treatment goals for both patients and health care providers. Although several primary studies have been conducted on this issue, there has not been any systematic review and meta-analysis carried out to inform policy. Thus, a systematic review and meta-analysis on the level and factors associated with psychotropic medication non-adherence is useful to inform policy makers and program planners. Therefore, the main aim of this systematic review and meta-analysis was to summarize available findings of primary studies to determine the level of psychotropic medication non-adherence and associated factors.

Methods

Protocol development and registration

This systematic review and meta-analysis has been registered in the international Prospective Register of Systematic Reviews (PROSPERO 2017:ID:CRD42017067436) [16] and written in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statements guidelines [17] (see Additional file 1). The detail of this systematic review and meta-analysis protocol has been published elsewhere [18].

Search methods for identification of studies

The Medical Subject Headings (MeSH) and keywords were constructed based on the review question. Studies were searched using search engines, from the main electronic databases (PubMed (Medline), EMBASE, CINAHL, Web of Science, and PsycINFO), and other sources (Google Scholar, reports, thesis, or dissertation). Search strings were constructed using a combination of MeSH terms such as psychotropic non-adherence, non-compliance, compliance, adherence, determinants, barriers, associated factors, risks, correlates, influencing factors, and major psychiatric disorders (see Additional file 2). The search strings were modified to suit to the corresponding database interface. All of the identified studies were exported to the EndNote citation manager [19], and duplicates were removed.

Eligibility criteria

Studies were included in the systematic review and or meta-analysis if they fulfill the following eligibility criteria. The criteria were as follows:

  • Studies had been conducted among adult patients (18 years and older);

  • Studies had been conducted on one or more of the major psychiatric disorders (major depressive disorders, schizophrenia, or bipolar disorder) were eligible;

  • Studies reported psychotropic medication non-adherence or adherence and or factors associated with medication non-adherence;

  • Studies conducted at community and/or facility-based;

  • Studies used observational study designs (cross-sectional, case-control cohort, and or survey);

  • Studies were written in English before December 31, 2017;

  • Documents (both published and unpublished studies, survey reports, thesis, or dissertations) which were accessible with full text.

Selection of studies into systematic review

Studies were systematically selected using predetermined eligibility criteria. Studies’ title and abstract that clearly mentioned either patients with major psychiatric disorder psychotropic medication non-adherence or adherence were selected for the subsequent evaluation. Then, to minimize bias during screening, two authors (AS and GT) independently screened the title and abstract of the studies to proceed to the next step of the studies selection. Studies overview such as aim of the study, design of the study, participants, and main outcome of the study were screened. In this stage, the studies potentially eligible for the full text were selected based on the title and abstract. The full text of the studies selected based on the title and abstract were re-assessed independently by two of the authors (AS and GT) for details. The body of the studies’ (aims, mainly design, participants, sampling method, findings, conclusions, and recommendations) were assessed. Finally, studies have reported the medication adherence or non-adherence among major psychiatric disorders patients (schizophrenia, major depressive, or bipolar disorders) and associated factors and fulfill the eligibility criteria were selected for the systematic review and meta-analysis. All studies that consider psychiatric disorders as a factor for medication non-adherence were excluded, because studies that consider psychiatric disorders as predictor for the non-adherence to treatment for other illness may not fully assess the adherence level of psychotropic medications. Overall, the studies’ selection process was adhered to the PRISMA flow diagram [17] (Fig. 1). Any difference during studies selection process was resolved through consensus.

Fig. 1
figure 1

Diagrammatic presentation of the selection process of studies for systematic review and meta-analysis

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Measurement of outcome and exposure

According to the WHO, medication non-adherence is defined as “a case in which a person’s behavior in taking medication does not correspond with agreed recommendations from a health personnel”. It can be either intentional or unintentional, including failing to initially fill or refill a prescription, discontinuing a medication before completing the course of therapy, taking more or less of a medication than prescribed, and taking a dose at the wrong time [9]. Thus, the main outcome of interest for this systematic review was the level of psychotropic medication non-adherence. Medication non-adherence was measured either as direct report from studies or indirectly by subtracting adherence report from total observations (sample size). Studies’ reported non-adherence in another way such as medication non-compliance, non-persistence, dropout, discontinuation, missing, and other alternatives was considered. Moreover, exposure or explanatory variables for the medication non-adherence were measured using synonymous terms such as determinants, predictors, barriers, associated factors, risk factors, and influencing factors.

Quality assurance of the systematic review

We searched both published and non-peer reviewed studies comprehensively for the systematic review and meta-analysis to minimize publication bias. The electronic or computerized, manual, and email searching methods were applied to have comprehensive search. Eligibility criteria, selection method, quality assessment, data extraction template, and regular meeting for discussion schedule were pre-designed by authors to assure the quality. The studies’ methodological quality critical appraisal was carried out using the Newcastle-Ottawa Scale [20] (see Additional file 3).

Data abstraction, synthesis, and statistical analysis

The two authors (AS and GT) abstracted the data from the included studies and recorded in the data extraction template. Studies’ detail descriptions such as an author, study area or country, aim, design, sample size, sampling procedure, and response rate were presented on the table using Microsoft Word (2013) (Table 1). Meanwhile, the raw data of medication non-adherence and total sample size were extracted and stored using Microsoft Excel (2013) template (see Additional file 4). All the meta-analysis were carried out using Stata SE-64 version 14.2 (Stata Corporation, College Station, TX) [66] and based on the recommendation for the meta-analysis of observational studies [67]. Heterogeneity between studies was assessed and substantial heterogeneity was anticipated when I2 greater than 75% [68, 69]. The pooled prevalence (proportion) was estimated using the inverse variance method [66]. The 95% confidence interval for pooled and sub-group proportion of patients’ medication non-adherence was computed. Moreover, the sub-group-pooled proportion of patients’ medication non-adherence was performed for schizophrenia, major depressive disorder, and bipolar disorders separately. Random effects model [70] was used for the overall pooled estimate and sub-group meta-analysis.

Table 1 Description of studies included for systematic review and meta-analysis (n = 46)
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Publication bias

Potential publication bias was assessed by inspecting the funnel plot [71]. The funnel plots were constructed using the plot-observed studies only and plot standard error with logit event rate (see Additional file 5). In addition, statistical tests Egger’s regression test (one-tailed test), p = 0.683, and Begg’s rank correlation (one-tailed), p = 0.831, were computed to make sure that there is no evidence of publication bias on studies included in this systematic review and meta-analysis. In addition, the tests confirmed that there are no small-study effects in the meta-analysis.

Results

A total of 46 studies were included in this systematic review and meta-analysis. Each study’s key findings and conclusion has summarized in detail (Table 2).

Table 2 The key findings and conclusions of studies included in the systematic review and meta-analysis (n = 46)
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Magnitude of psychotropic medication non-adherence

Thirty-five studies were used for meta-analysis to compute the pooled proportion of the psychotropic medication non-adherence. In 35 studies with 63,957 cases from a sample of 120,134, the pooled prevalence of medication non-adherence among major psychiatric disorders was 49% (95% CI 44%, 55%). In addition, the psychotropic medication non-adherence was 48%, 48%, 49%, and 57% in Africa, North America, Europe, and Asia, respectively (Fig. 2).

Fig. 2
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Pooled estimate of medication non-adherence (n = 35)

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Medication non-adherence among schizophrenia patients

Sub-group analyses were conducted for studies that reported medication non-adherence among schizophrenia patients. From nine studies with 2643 participants, the medication non-adherence among schizophrenia patients was 56% (95% CI 48%, 63%). The prevalence in the sub-group analysis was relatively consistent with the overall pooled prevalence (Fig. 3).

Fig. 3
figure 3

Pooled estimate of medication non-adherence of the schizophrenia patients (n = 9)

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Major depressive disorder medication non-adherence

From 16 studies with 42,255 participants, medication non-adherence among patients with major depressive disorders was 50% (95% CI 40%, 59%). The prevalence in the sub-group analysis was relatively consistent with the overall pooled prevalence, but a bit lower in Europe (Fig. 4).

Fig. 4
figure 4

Pooled estimate of medication adherence of the major depressive disorders patients (n = 16)

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Bipolar disorder patients’ medication non-adherence

From 10 studies with 73,250 study participants, medication non-adherence among patients with bipolar disorders was 44% (95% CI 43%, 45%) (Fig. 5).

Fig. 5
figure 5

Pooled estimate of medication non-adherence of bipolar disorder patients (n = 10)

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Determinants of psychotropic medication non-adherence

Medication non-adherence is influenced by various factors. We systematically mapped the factors that affect medication non-adherence among patients with major psychiatric disorder into individual patient, social support, clinical or treatment and illness, and health system-related factors based on the review of 46 studies.

Factors related with individual behaviors

Patient’s socio-demographic factors

Some psychiatric patients’ socio-demographic characteristics were associated with medication non-adherence. However, the association was inconsistent across studies. In four studies, unemployment was one of the factors associated with medication non-adherence [25, 31, 56, 60]. On the other hand, the nature of the job (for example, engaging in farming activities, being busy) influenced patients’ adherence to their medication [50]. Educational status was one of the influencing factors of medication non-adherence. In six studies, psychiatric patients having lower education level (lower than secondary education) were more likely to be non-adherent to their psychotropic medication compared to those patients having higher educational level [23, 40, 44, 52, 56, 57]. Patients’ non-adherence to their psychotropic medication was associated with some non-modifiable demographic factors such as age and gender) [28]. In three studies, patients aged 60 years and older were more likely to be non-adherent to their medication [23, 55, 58]. Nevertheless, one study [60] reported that young age (less than 34 years) patients were also more likely to have medication non-adherence. In three studies, the relationship of gender and medication non-adherence was inconsistent. Being female was a factor associated with medication non-adherence [52, 53, 65], but in two studies, being male also linked with medication non-adherence [21, 54].

Patients’ substance abuse

In eight studies, both psychostimulant and psycho-depressant substances misuse were associated with psychotropic medication non-adherence [23, 27, 29, 37, 42, 43, 58, 65]. In three studies, psycho stimulants (e.g., cigarette smoking) was a factor associated with psychotropic medication non-adherence among major psychiatric patients [23, 25, 65]. Likewise, three studies conducted in Ethiopia [23, 25, 65] have reported that “Khat” chewing was a factor associated with psychotropic medication non-adherence among psychiatric patients. In addition, in six studies, having a history of concurrent alcohol dependency was the main factor associated with psychotropic medication non-adherence [23, 25, 37, 47, 64, 65].

Patient attitude toward medication

In four studies, patients’ attitude toward medication was a crucial factor affecting treatment adherence and therapeutic alliance. Patients having negative attitude towards their medication was a factor associated with psychotropic medication non-adherence [23, 25, 39, 65]. Moreover, in two studies, patients having negative attitudes toward the psychotropic medication were more likely to seek alternative treatment such as traditional or religious treatment practices [21, 24]. Likewise, where patients were suspicious about the medication, believes that the medication would harm them, heard voices telling them not to take the medication, and taking medication is unnatural were less likely to adhere [36]. In three studies, psychiatric patients may also attribute to antipsychotic medication non-adherence due to the alterations in cognitive and attitudinal functioning and therefore be unwilling to use the medication [29, 37, 38].

Patients’ perceived stigma

In eight studies, the perception or the feeling of psychiatric patients being stigmatized by their families, neighbors, health professionals, and other community members was a factor associated with medication non-adherence [24, 25, 28, 36, 37, 41, 45, 65]. In one study, both internal and external triggering factors caused the patients to feel being stigmatized. Some of these included patient believe that they can get better without medicine were afraid of medication dependency and felt too embarrassed to take the medicine [24]. On the other hand, patients perceived the effects of the medication to be unnatural and reported feeling better after terminating them were the factors associated with medication non-adherence [35]. Similarly, in two studies, those patients who perceived that the treatment had no effect on their illness were more likely to be non-adherent to their medication [26, 40]. In seven studies, behavioral factors such as forgetting the right dose and right time of taking medication were the factors associated with medication non-adherence [11, 22, 24, 28, 34, 35, 52]. In six studies, patients and caregivers reported being busy with daily routines, careless about the timing, forgetting to remember medication time, and irregular follow-up were associated with medication non-adherence [11, 22, 24, 34, 35, 52]. In the worst scenario, patients’ complete rejection of the medication was a main cause of discontinuation and non-adherence to their medication [28].

Clinical factors

The clinical factors of medication non-adherence were re-categorized into medication side-effect, lack of insight about their illness and treatment, comorbidity, medication efficacy, long treatment duration, and complexity of the prescribed medication.

Medication side-effects

In several studies, psychotropic medication non-adherence was associated with medication-related side-effects [11, 22,23,24,25, 28,29,30, 32,33,34,35,36,37, 39, 44, 50, 52, 55, 64, 65]. In seven studies, patients feeling dizziness, fatigue, tiredness, sedation, lethargy, and sleepiness were the most frequently reported side-effects that contributed to medication non-adherence [11, 33, 36, 37, 50, 52, 65]. In two studies, sleepiness during day time (medication dose time) and potentially life-threatening or distressing side-effects seriously affected patients’ medication non-adherence [37, 44]. Another two studies, feeling of powerlessness, insomnia, difficulty thinking or concentrating, restlessness, or feeling jittery were found to be associated with medication non-adherence [28, 37]. Likewise, in five studies, weight gain was another medication-related side-effect that associated with medication non-adherence and patients’ perception toward their medication [25, 33, 36, 44, 55].

In two studies, side-effects such as decreased sexual interest and having a symptom of sexual dysfunction were associated with patients’ medication adherence [33, 36]. Moreover, patients and caregivers’ perceived medication adverse drug reaction was a factor associated with psychotropic medication non-adherence [34, 36]. Likewise, extra pyramidal symptoms or agitation [33], other medication-related side-effects such as cognitive deterioration or impairment [44], missing voice [28], paralysis of body parts, twisting of the neck, drooling, weakness, appetite stimulation [37], severe depressive symptoms and episodes [39, 44], salivation, dry mouth, and memory problem [50] were common factors associated with medication non-adherence.

Lack of insight about illness and medication

In seven studies, patients’ lack of insight (level of awareness or understanding) about their illness and medication was a common factor associated with psychotropic medication non-adherence [21, 23, 28, 39, 40, 50, 51]. Likewise, misunderstanding about the treatment consequences, lack of awareness of their illness and or mental disorder in general, and sometimes appreciating subjective relief symptoms [30, 36, 37] were the factors associated with medication non-adherence among major psychiatric disorder patients.

Medication efficacy

The pharmacological management of psychiatric disorders needs safe and efficacious medication to achieve desired treatment goals. The fact that lower medication efficacy and patient self-rating of efficacy were also factors associated with psychotropic medication non-adherence. Taking lower potent concomitant psychotropic medications [47, 65], recovery from illness [34], felt better [24, 52], and failure to improve with medication [37] were the factors associated with medication efficacy related with psychotropic medication non-adherence. Likewise, patients’ or caregivers’ perceived medication efficacy such as subjective relief of symptoms, patients’ feel drugs have no effect on the illness, not helpful, being ineffective [36, 46, 50], and feeling of cured [51] were side-effect-related factors associated with medication non-adherence.

Medication duration

In five studies, long treatment duration (6–12 months and longer) was an associated factor for medication non-adherence [22, 25, 37, 43, 65]. Similarly, having long-term medication prescriptions, long duration maintenance therapy [29, 54], and irregular follow-up [29] were associated with psychotropic medication non-adherence.

Treatment complexity

In three studies, multiple dose, frequency and drug combinations, or complex drug regimen were seriously linked with medication non-adherence [24, 32, 64]. In two studies, pill burden or consuming extra pills was also one of treatment-related factors that negatively influenced patients’ adherence to their psychotropic medication [22, 53]. In another two studies, taking medication twice per day was a negative factor for medication adherence [46, 49]. In addition, the route of medication administration had a significant effect on medication non-adherence. The patients on injectable medication were more likely to be adherent than the patient taking drugs orally [46].

Co-morbidity

In three studies, psychotropic medication adherence was compromised where there were co-morbidities of mental illness and other physical illnesses. Studies [11, 43, 64] reported that medication non-adherence was associated with patients having co-morbidities with their current psychiatric disorders. Of these, affective morbidity, obsessive-compulsive disorders, recovering from mania-hypomania [64], personality disorders and sensation of seeking personality traits [47], and alcohol abuse disorders [61] were negatively associated with medication adherence. Irritable bowel syndrome as a co-morbidity was also significantly associated with medication non-adherence [55].

Lack of social support

In seven studies, poor or lack of social or family support was associated with psychotropic medication non-adherence [21, 24, 25, 35, 37, 45, 65]. In two studies, limited or inadequate patient information, weak professional or family support, therapeutic alliance, social involvement, and low education were some of the social support-related factors [36, 37]. Cohesiveness, family reminding, and transport to hospital [37], lower family harmony or lack of resilient family support, discrimination by nearby people, disruption of family functioning or household routine and religious practices [45], weak community functioning [39], homelessness [42, 43], had old age caregivers or lack of caregivers [50], lack of family compliance of follow-up [51], lack of advice about their medication intake from friends and relatives [28], not receiving social assistance [57], and caregivers’ attribution of depression to cognitive and attitudinal problem [38] were the factors associated with psychotropic medication non-adherence.

Health system-related factors

The health system-related factor was the crucial area for getting quality mental health service. In three studies, medication non-adherence was associated with lack of free access to medicine due to inadequate or unavailability of psychotropic drug supplies in health facilities [24, 25, 34]. In one study, although psychotropic medications were normally provided free of charge in the government health facilities, patients were suffering unavailable of medication in the government pharmacies. Thus, patients need to buy from private pharmacies which are very expensive and lead to interruption of the medication. In addition, health care provider sometimes changes the drug but it may not be found in the government hospital pharmacy [45]. Therefore, the lack of alternative drug or therapy affects psychotropic medication adherence [39]. On the other hand, the lack of sufficient and quality health education to psychiatric patients and or their caregivers/relatives/families about the medication and illness influenced patients’ adherence to their prescribed medication [22, 36, 39, 40, 51].

In three studies, patient-physician or therapist relationship was crucial for better medication adherence. Consequently, unfriendly, judgmental behavior, inflexible appointment systems, mistrust, and having negative patient-physician relationships were the factors associated with patients’ psychotropic mediation non-adherence [28, 30, 60]. In one study, health care providers’ negative attitude had influenced patients’ adherence to the medication and their follow-ups [37]. Similarly, in two studies, health professional shortages had also affected medication adherence [49, 58]. Patient preference for traditional/complementary medicine was another cause of medication non-adherence [49]. Medication non-adherence was affected by the number of hospitalizations [28], irregular hospitalization and frequently discharge of patients, length of stay [42, 46], lack of patients’ satisfaction with health care services [44], and long distance to access the health service/recollect medications [50]. In three studies, health care providers would be unable to explain and optimize prescribing pattern, timing, and dose benefit of medication. In addition, the lack of friendly deal with medication complexity, tolerability, efficacy, and health belief issues were critical factors influence medication adherence [11, 44, 52]. Furthermore, the health care system has also associated with medication non-adherence. These factors were poor service structure and cumbersome purchasing procedure (affect access), availability and timely use or collection of psychotropic medication during follow-up visit, and patients not covered by health insurance scheme [58].

Medication cost

In seven studies, psychiatric patients and their caregivers having financial constraints to buy medicines were factors associated with medication non-adherence. In addition, the lack of money for transportation, to purchase proper food, and to buy medications were the factors associated with patients’ adherence to their medication. Psychotropic medications had an appetite stimulation that has been increasing food demand which incurs an additional economic burden [11, 24, 32, 37, 42, 45, 50] and contribute for medication non-adherence.

Discussion

This systematic review and meta-analysis determined the pooled proportion of psychotropic medication non-adherence and synthesized the associated factors with medication non-adherence among major psychiatric disorder patients. Almost half (49%) of patients with major psychiatric disorders did not adhere to their psychotropic medication. Medication non-adherence among patients with schizophrenia, major depressive disorder, and bipolar disorder were 56%, 50%, and 44%, respectively. Medication non-adherence is influenced by various factors such as patients’ individual behavior, social or family support, clinical or illness and treatment-related, and overall health care system-related factors.

Previous systematic reviews have indicated that medication non-adherence is a common challenge in the treatment of psychiatric disorders [72, 73]. This meta-analysis finding is consistent with a systematic review revealed an overall medication adherence level of 58% (ranged from 24 to 90%), and medication adherence to antidepressants was 65% [6]. Another earlier systematic review has shown that the level of medication non-adherence was 60% [74]. The present systematic review and meta-analysis finding is consistent with a finding from a comprehensive systematic review on schizophrenia which reported that a mean rate of non-adherence was 41.2%. The sub-group analysis indicated that a mean non-adherence rate was 49.5% [14], and another systematic review has shown that psychotropic mediation non-adherence was 44% [75]. Nevertheless, the present meta-analysis finding is a bit lower than a finding from a systematic review which revealed that adherence in psychiatric patients ranged from 10.7 to 38% [76].

This systematic review of factors influencing psychotropic medication non-adherence which is consistent with other systematic reviews [14, 72, 73, 77] has shown that medication adherence is mainly affected by patients’ negative attitude toward their medication, lack of insight, negative health belief, and perceived stigma. Similarly, medication non-adherence is consistently associated with patients behavioral practices (e.g., substance abuse) [14, 74] and also patients’ socio-demographic characteristics (such as educational status, age, gender, and employment) [14, 72]. The present systematic review has identified that the lack of social support is associated with medication non-adherence among major psychiatric disorder patients. This is similar with other reviews, which have reported that the lack of family involvement, care/dyad support, and other social supports are strongly negatively associated with poorer therapeutic alliance [14, 72, 75, 76]. In addition, medication non-adherence is associated with clinical- or medication-related factors [14, 72,73,74, 77]. This finding is supported by another systematic review which revealed that psychiatric disorder comorbidities with other physical disorders influence medication adherence and increase re-admission of psychiatric patients [73, 78, 79].

In the present systematic review, medication non-adherence is associated with poor functioning of the health system such as lack of psychotherapy, lack of information, long treatment duration with little health personnel follow-up, inadequate discharge planning, increased hospitalizations, poor support and care environment, experiencing access barriers to high-quality care and health care providers unable to provide elicit information on adherence, inadequate medication coverage, and poorer therapeutic alliance [14, 72, 74,75,76, 79]. Financial factors seriously affected medication adherence. These included unaffordability of medication, increased health care cost [73, 74], lack of health insurance [75], patients’ poor capacity, and limited resources [73].

A large amount of heterogeneity in the definition and measurement methods used to assess medication adherence have been reported in some reviews. The heterogeneity of factors related to non-adherence calls for individually tailored approaches to promote adherence [80, 81]. Non-adherence contributes enormously to poor health outcome and needs substantial work to improve treatment outcomes [80]. Evidence showed that improving adherence to psychotropic medications could have a positive impact on patients and society. Non-adherence issues need to be looked at from many angles and taking a multifaceted approaches with patients and healthcare providers to address identified challenges [81].

Conclusions

Almost half of patients with major psychiatric disorder did not adhere to their psychotropic medication. Patients’ individual behavior, lack or poor social/family support, treatment and illness-related clinical conditions, and the health system barriers are influencing factors of psychotropic medication non-adherence among patients with major psychiatric disorders. Therefore, multifaceted intervention is needed to create supportive environment for patients and caregivers to minimize psychotropic medication non-adherence. Additionally, supportive social and health care system programs should be designed to alleviate major psychiatric disorder patients’ medication non-adherence. Comprehensive approaches targeting the factors that affect medication non-adherence can bring tremendous positive outcomes. This systematic review and meta-analysis finding can be helpful to inform policy-makers, clinicians, and other caregivers to undertake necessary decisions to establish an integrated approach to boost therapeutic alliance and improve medication adherence.