Medication nonadherence and its associated factors in psychiatric patients in India: A systematic review and meta-analysis : Indian Journal of Psychiatry

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Medication nonadherence and its associated factors in psychiatric patients in India: A systematic review and meta-analysis

Ramamurthy, Parthasarathy; Jayasree, Arya1; Solomon, Susan; Rudravaram, Vishnu V.2; Menon, Vikas3; Thilakan, Pradeep

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Indian Journal of Psychiatry 65(5):p 506-525, May 2023. | DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_249_22
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One in seven Indians suffers from one or more mental disorders of varying severity.[1] Disability from such mental disorders adversely affects the socio-economic status of the family.[2] About half of the patients with major psychiatric disorders are nonadherent to their psychotropic medications.[3] Various patient-related factors, therapy-related factors, disease-related factors, clinician/healthcare system-related factors, and social and economic factors that contribute to medication nonadherence (MNA) in psychiatric patients have been identified.[4] MNA in patients with psychiatric disorders leads to a greater risk of relapse, hospitalization, and suicide.[5,6] Thus, MNA has an overall detrimental effect on the patient’s recovery and functioning.

Globally, MNA and its associated factors have been extensively studied. Semahegn et al.[3] systematically reviewed 46 studies and reported that 49% of patients with major psychiatric disorders were not adherent to their prescribed medications. Individual patient behaviours and lack of social support were the factors most commonly associated with MNA. Only two Indian studies were included in the previous review. Banerjee and Varma[7] reported a prevalence of 66.9% MNA in patients with unipolar depression. Female gender and lower internal locus of control were reported to predict MNA in this population. There are several other Indian studies that have been conducted in this field and varying prevalence values were reported.[8–11] Varying prevalence values and different factors associated with MNA were reported in these studies.

MNA and the factors associated with it among psychiatric patients in India are likely to be different from the west considering the different healthcare systems, poor mental health awareness, inadequate mental health infrastructure, wide treatment gap, and various socio-cultural factors. Indian studies on MNA have not been systematically reviewed. In this context, the present systematic review and meta-analysis were undertaken to determine the prevalence of MNA among patients with psychiatric disorders in India and to identify the factors associated with MNA in these patients.


Search strategy and study selection

The study protocol was developed following Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols guidelines and registered in the International Prospective Register of Systematic Reviews (PROSPERO Registration number CRD42021256116).

Eligible articles were obtained by searching PubMed, Google scholar, and Directory of Open Access Journals. Then, the reference lists of the selected articles were hand-searched to identify other relevant articles. Articles published in peer-reviewed journals before May 15, 2021 were retrieved. Grey literature including dissertations and databases for conference proceedings were excluded.

The search phrases were used in different combinations to conduct the literature search in the various databases mentioned above. The following search string was used for PubMed search:

((((((((medication nonadherence[MeSH Terms]) OR (medication noncompliance[MeSH Terms])) OR (medication adherence[MeSH Terms])) OR (medication compliance[MeSH Terms])) OR (patient nonadherence[MeSH Terms])) OR (patient adherence[MeSH Terms])) OR (patient noncompliance[MeSH Terms])) OR (patient compliance[MeSH Terms])) OR (medication persistence[MeSH Terms]) AND (((psychotic disorders[MeSH Terms]) OR (bipolar affective psychosis[MeSH Terms])) OR (depressive disorders[MeSH Terms])) OR (anxiety disorders[MeSH Terms]) Filters: Adult: 19+ years and English language.

To be included in this systematic review, the study had to fulfil the following criteria. The study participants should have been recruited from India. The study participants should have been adult patients aged 18 years and more with a diagnosis of psychotic disorders, mood disorders, and/or anxiety disorders. The study should have reported the prevalence of MNA and/or factors associated with MNA. The study should have been observational (cross-sectional, case-control, and cohort studies) and published in the English language in a peer-reviewed journal before May 15, 2021.

Studies assessing MNA in patients with a primary diagnosis of substance use disorders were excluded. Interventional studies that assessed the effectiveness of strategies to improve medication adherence were also excluded from this review.

Two authors (P.R. and A.J.) conducted the literature search independently. After a literature search from various sources, the citations were downloaded to Zotero software. Duplicate citations were removed from the collection. Subsequently, two authors (P.R. and A.J.) screened the titles to identify those that were related to MNA in psychiatric patients. Subsequently, the abstracts of the selected articles were reviewed to identify the articles that assessed MNA in adult psychiatric patients in India. The full texts of the selected articles were reviewed independently by the same two authors for eligibility in the present review based on the abovementioned criteria. Differences of opinion were sorted through mutual discussion and inputs from S.S. and P.T.

Data extraction

From the included articles, the relevant data were extracted using a predesigned proforma by two authors (P.R. and A.J.). The name of the author, year of publication, state/region of India from where the participants were recruited, diagnosis, sample size, tool (s) used to assess MNA, the prevalence of MNA, and factors associated with MNA were abstracted and entered in a table created in a word document. From studies that reported only the numbers, the prevalence of MNA was calculated from the data provided in the article. In studies that used more than one method to assess the prevalence of MNA, the value obtained from the self-report instrument (since it was the most commonly used method) was chosen for meta-analysis. The factors associated with MNA were qualitatively described as per the classification suggested by Jin et al.[4] In this classification, factors affecting medication adherence were divided into five categories: patient-related (e.g., demographic factors, patient knowledge, etc.), therapy-related (e.g., medication side effects, treatment complexity, etc.), healthcare system-related (e.g., Long waiting time, lack of accessibility, etc.), social and economic factors (e.g., cost and income, social support), and disease factors (e.g., disease symptoms and severity of disease).

Quality appraisal

Appraisal tool for cross-sectional studies (AXIS tool)[12] was used to critically appraise the included articles. P.R. and S.S. conducted the critical appraisal independently and differences of opinion were resolved through mutual discussion and inputs from P.T.

Statistical analysis

R version 4.1.2[13] was used for data analysis. The pooled prevalence of MNA was computed using the inverse variance method and a 95% confidence interval (CI) for pooled prevalence was calculated. Heterogeneity was assessed using I2 statistics. A forest plot was constructed to represent the prevalence of MNA in the included studies. Subgroup analysis of the prevalence of MNA among psychotic disorders, bipolar disorders, and depressive disorders were conducted and the results were summarized using forest plots. The factors associated with MNA were qualitatively synthesized and described under the headings: patient-related, therapy-related, disease-related, healthcare/system-related, and social and economic factors. Publication bias was assessed by Egger’s test and a visual assessment of the funnel plot.


The flowchart for study selection and inclusion in the review has been presented in Figure 1. A total of 42 studies[7–11,14–50] with a pooled sample size of 6,268 patients were included in the systematic review. Among them, 32 studies[7–11,15,17,18,20–22,24–26,28,29,32,34–42,45–50] with a pooled sample size of 4,964 were included in the meta-analysis.

Figure 1:
PRISMA flow diagram for study selection

Among the studies included in the systematic review, the study participants were patients with schizophrenia/psychotic disorders in 14 studies, multiple psychiatric diagnoses in 14 studies, bipolar affective disorders in eight studies, depression in five studies, and obsessive compulsive disorder in one study. Self-rated instruments were the most common method used to assess MNA (17 studies). Five studies defined MNA based on the proportion of days the patient took medications. Nine studies used multiple methods and 11 studies used various other definitions for assessing MNA [Table 1].

Table 1:
Prevalence of Medication nonadherence among psychiatric patients: study characteristics

Since I2 was greater than 75%, substantial heterogeneity was assumed and hence random-effects model was used for estimating the pooled prevalence. The pooled prevalence of MNA in psychiatric patients was found to be 0.44 (95% CI, 0.37-0.52). A high degree of heterogeneity was noted (I2 = 94%) [Figure 2]. Among studies conducted on schizophrenia and other psychotic disorder patients, the pooled prevalence of MNA was found to be 0.37 (95% CI, 0.28-0.46) [Figure 3]. Similarly, the pooled prevalence of MNA in bipolar disorder and depressive disorder patients were 0.47 (95% CI, 0.23-0.72) and 0.70 (95% CI, 0.60-0.78), respectively [Figures 4 and 5, respectively].

Figure 2:
Forest plot of medication nonadherence among psychiatric patients in India
Figure 3:
Forest plot of medication nonadherence among patients with schizophrenia and other psychotic disorders in India
Figure 4:
Forest plot of medication nonadherence among patients with bipolar disorder in India
Figure 5:
Forest plot of medication nonadherence among patients with depressive disorders in India

Meta-regression analysis was carried out to identify the source of heterogeneity. For MNA, type of assessment (self-report vs. clinician-rated), decade of publication, and sample size had P values less than. 20 and were included in the multivariable model. The final multivariable model with decade of publication and type of assessment was able to explain 16.2% of the between-study variability in the prevalence of MNA.

Factors associated with MNA

The findings of various studies on the factors associated with MNA are summarized in Annexure 1.

Annexure 1:
Factors associated with medication nonadherence (MNA) in psychiatric patients

Patient-related factors

Most studies did not find any association between age and MNA.[7,10,14,20,33,36,37,39–41,47,49] Younger-age group had better adherence in one study,[21] while a lower age was associated with poorer adherence in two studies.[24,35] Several studies did not find any association between gender and MNA.[10,15,17,20,21,24,36–38,40,41,46,47] Four studies found that compliance was better in females,[25,26,33,35] while one study found that female gender was associated with MNA.[7] Most studies did not find any association between education and MNA.[7,10,15,17,21,24,33,35,37,39,40,46] Lower education was associated with noncompliance in some studies[20,26] and greater literacy was associated with better compliance in one study.[41] Marital status did not associate with MNA.[7,10,17,20,21,24,26,33,35–37,41,49]

Negative attitude toward medications,[19] lower internal locus of control,[7] fear regarding taking medication,[9] and pharmacophobia[29] were shown to be associated with MNA. Patient trust and patient expectation from the psychiatrist were not associated with MNA.[27] Lithium-related knowledge was associated with better medication adherence to lithium therapy in bipolar patients.[40] Poor knowledge about the nature of depression was associated with MNA[9] and depression literacy was associated with better antidepressant adherence.[31]

Ansari and Mulla[25] and Rao et al.[33] found that substance abuse was associated with MNA, while a few other investigators reported no association between the two factors.[20,21,35,36] Singh et al.[40] reported that comorbid alcohol dependence and hypothyroidism were associated with medication adherence, while comorbid hypertension and diabetes were not associated with medication adherence.

Therapy-related factors

Side effects of medications, polypharmacy, drug availability, supervision of medications, and treatment duration were the therapy-related factors evaluated for association with MNA by various studies. Medication side effects were associated with MNA in one study,[9] while two studies did not find such an association.[20,41] Polypharmacy was found to be associated with MNA in a few studies.[9,35] Shah et al.[41] found that compliance was better in monotherapy and once-daily regimen in patients with schizophrenia. However, polypharmacy was not associated with MNA in some studies.[17,20,36] It was also found that drug availability and supervision of medications were not associated with MNA.[20] Conflicting results were reported regarding the association between treatment duration and MNA.[7,15,38]

Disease-related factors

Greater severity of illness was associated with MNA in nearly all the studies that evaluated this association.[8,20,21,24,25,35,38,39,47] Several studies did not find any association between the duration of illness and MNA.[20,33,35–37,40,41] Two other studies found a positive association between the duration of illness and MNA.[17,46] Some studies found an association between insight and MNA,[20,24,35,42] while others did not find any association.[14,37,41] Age at onset of illness was found to be associated with MNA in some studies,[24,38] while not in others.[36,37,39,41] In bipolar disorder, the number of lifetime episodes, the number of lifetime manic episodes, and residual mood symptoms were not associated with medication adherence, whereas a less number of lifetime depressive episodes showed a positive association with high medication adherence.[36] Presence of depressive symptoms and global cognitive deficits were associated with MNA in patients with schizophrenia.[10]

Healthcare provider or system-related factors

A good doctor-patient relationship was found to be associated with better compliance.[33]

Social and economic factors

Warikoo et al.[8] showed that higher income was associated with better medication adherence and Chaudhari et al.[35] found that low household income was associated with low adherence. However, a few other studies[20,21,24,37,47] did not find any association between income and MNA. Nonaffordability of medications was associated with MNA.[9] One study found that cost of medications was associated with MNA,[21] while two other studies did not find any such association.[20,41] Three studies evaluated the impact of social support on MNA with conflicting results.[17,18,37]

Reasons for MNA

Several studies have enquired about the common reasons for MNA from the patients and/or the caregivers using Rating of Medication Influences scale or other checklists. The most common reasons for MNA reported were side effects of medicines,[10,16,17,24,26,3,35,46] financial obstacles,[17,18,20,24,26,35,46] no perceived benefit from medications,[18,20,26,35,41] and medicines not perceived as necessary.[18,20,26,35,41] Embarrassment and stigma related to treatment[10,20,35,41] and lack of knowledge and awareness about the course of illness[10,21,26] were other commonly stated reasons for MNA.

Publication bias

A visual inspection of the funnel plot indicated an absence of smaller studies and that the study findings were symmetrically distributed [Figure 6]. The results of Egger’s test (P =0.21) did not reveal any evidence of publication bias.

Figure 6:
Funnel plot of the studies included in the meta-analysis

Risk of bias assessment

As noted in Annexure 2, most studies did not categorize and address nonresponders and did not provide any information on nonresponders. Also, information on the selection process of the participants was not readily available from the studies.

Annexure 2:
Risk of bias assessment using appraisal tool for cross-sectional Studies (AXIS tool)


The present review found that the prevalence of MNA among psychiatric patients in India was 44%. This finding is remarkably similar to that found by another recent meta-analysis (studies included from across the world) which reported that 49% of major psychiatric disorder patients were nonadherent to their psychotropic medication.[3] MNA in schizophrenia patients in India was found to be 37% in the present study. This is clearly lower than the 56% reported in the earlier study.[3] A recent meta-analysis of studies using electronic adherence monitoring in schizophrenia revealed that the proportions of patients with oral antipsychotic adherence ranged from 50% to 80% for the 70% threshold for satisfactory adherence.[51] There was a variability in the methods adopted to assess MNA. Self-rated instruments were the most preferred method probably because of the low cost and ease of administration. None of the Indian studies included in the present review used electronic adherence monitoring which is considered to be the gold standard among the available options to assess MNA. MNA of 47% in bipolar disorder patients in the present study is comparable to the rate reported in the previous study.[3] The 70% prevalence of MNA in depressive disorder patients is significantly higher than that of 50% reported in the previous study.[3] In contrast to serious mental illnesses, depression may not be considered a medical illness needing pharmacological treatment in India and this may contribute to the high rate of MNA in these patients.

Among the patient-related factors, age, gender, education, and marital status were not found to be associated with MNA in the present review. Previous systematic reviews found inconsistent associations between these socio-demographic factors and MNA.[3] More pertinently, negative attitudes toward taking medication and fear of taking medication were associated with MNA in this review. This finding is consistent with previous reports that showed that medication beliefs[5] and health beliefs[52] were related to medication adherence.

Among the therapy-related factors, polypharmacy was found to be associated with MNA in some studies. This finding assumes importance as this is a potentially modifiable factor. Not surprisingly, complex polypharmacy was associated with lower treatment adherence in bipolar disorder[53] and schizophrenia.[54] Among the disease-related factors, greater severity of illness was consistently associated with MNA. Patients with poor adherence likely had poor outcomes and hence a greater severity of illness was found during cross-sectional assessments in most included studies. An insight was associated with MNA in some studies in the present review. That lack of insight should be associated with MNA is not surprising and this has been reported in several previous reviews.[5,56,56]

Among the healthcare/system-related factors, good doctor-patient relationship was associated with better adherence. Previous reviews[5,55,56] also found a similar relationship between therapeutic relationships and medication adherence. Among the social and economic factors, the cost of medications and nonaffordability were associated with MNA in some studies. Earlier, low socio-economic status was found to be an important risk factor for MNA in schizophrenia spectrum and bipolar disorder.[56] Patients from low socioeconomic status may find it difficult to take time from their regular work to visit the hospitals regularly to collect their medications and also may find it difficult to afford the travel and medication cost. The present review found that the most common reasons for MNA reported were side effects of medicines, financial obstacles, and no perceived benefit from medications. Similar findings were reported in a recent review[57] which reported that poor insight and medication side effects were among the most common reasons for nonadherence in severe mental illness. Wade et al.[58] also reported that side effects and economic difficulties were among the common reasons for nonadherence.

Considering the high prevalence of MNA in patients with psychiatric disorders, mental health professionals can consider the use of standard instruments to assess MNA as part of routine follow-up care in their patients. Medication adherence should not be taken for granted particularly in situations where there is less than optimal treatment response. Evaluating and addressing the common reasons for MNA in patients with psychiatric disorders will benefit the clinicians and the patients. Addressing the modifiable factors associated with MNA (for instance, polypharmacy, medication side effects, cost of medications, negative attitude toward and fear of medications, and doctor-patient relationship) is likely to improve medication adherence and the long-term outcome in these patients.

A few challenges with meta-analysis of observational studies have been described.[59] Selection bias and confounding are the major factors that introduce bias in the summary effect. Greater methodological heterogeneity and clinical heterogeneity are commonly encountered during meta-analysis of observational studies. It is difficult to assess the risk of bias both within and between studies.


Our systematic review and meta-analysis should be interpreted keeping the following limitations in mind. Other databases like Scopus were not searched for retrieving the relevant articles and that may be considered as a limitation. None of the studies used electronic medication adherence monitoring which is considered a gold standard by many. Varying tools and definitions were used to assess MNA and the validity of some of these methods is not proven. Selection bias and nonresponder bias could not be ruled out in most of the included studies. Interventional studies that evaluated the effectiveness of adherence enhancing interventions were not included in the present review.

Future directions

Longitudinal studies that evaluate MNA during various phases of psychiatric treatment will provide valuable information to clinicians. The use of multiple methods to assess MNA is likely to capture its complex nature and provide a deeper understanding of its various facets. Developing low-cost adherence enhancing interventions will go a long way in addressing this common problem.


About half of the patients with psychiatric disorders in India are nonadherent to their psychotropic medications. Negative attitude toward taking medications, polypharmacy, greater severity of illness, lack of insight, and cost of medications were associated with MNA. Side effects, financial obstacles, and no perceived benefit were the commonly reported reasons for MNA. Evidence-based interventions to improve medication adherence in these patients need to be developed and implemented proactively keeping in mind the factors associated with MNA.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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Anxiety disorder; depressive disorder; medication nonadherence; medication noncompliance; mental disorder; psychotic disorder

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