Table 2.

The key findings and conclusions of studies included in the systematic review and meta-analysis (n = 46)

Author, country	Key findings (prevalence and associated factors)	Conclusion
Ibrahim et al., Nigeria [21]	MNA was 55.7%. Seeking for traditional treatment (OR, 6.5), male (OR, 3.3), low levels of insight (OR, 1.8), and low social support levels (OR, 1.5) were predictors	Psycho-education on adherence and the active involvement of the family has significant in the prevention of MNA.
Alene et al., Ethiopia [22]	The prevalence of MNA was 42.5%.	MA is low and associated with pill burden, side-effect, and exposure to social drugs.
Eticha et al., Ethiopia [23]	MNA was 26.5%. Positive attitude (AOR, 1.4), awareness of illness (AOR, 1.4), and relabel symptoms (AOR, 1.6). Khat (AOR, 0.2), illiteracy (AOR, 0.13), and older age (AOR, 0.03) were the predictors of MNA.	Schizophrenia patients were highly non-adherence to their medication. Intervention strategies focused on patient education can be helpful to improve adherence.
Kenfe et al., Ethiopia [24]	MNA was 41.2%. Forgetfulness was attributed to 78.2% of their MNA. Irregular follow-up, poor social support, and complex drug regimen were associated with MNA.	MNA among psychiatric patients in Southwest Ethiopia is high and revealed possible associated factors.
Hibdye et al., Ethiopia [25]	MNA was 51.2%. Poor social support (AOR, 5.2), stigmatized (AOR, 2.2), negative attitude (AOR, 4.6), medication frequency (AOR, 1.7), unemployment (AOR, 2.1), and Khat chewing (AOR, 2.1) were predictors.	MNA was found to be high. It has significant implications to enhance level of adherence by tackling factors through intervention program.
Anne et al., USA [26]	MNA was 28%. It was associated with perceived stigma (0.05), patient-rated severity of illness (0.05), interpersonal problems (0.02), and age 60 years or older (0.04).	Clinicians’ should give psychological support to improve adherence
Hill. et al., Ireland [27]	MNA was 24%. It was associated with less insight, negative attitudes toward medication, substance misuse, and treatment duration.	Longer treatment duration is associated with non-adherence
Moritz et al., Germany [28]	MNA was 20%. Side-effect, missing voices, feeling of power as a motive for non-compliance, stigma, mistrust against the physician, and rejection of medication were the most frequent reasons for drug discontinuation	Approximately 1-in-5 patient had discontinued antipsychotic treatment due to forgetfulness and ambivalence toward symptoms.
Mert et al., Turkey [29]	MNA for bipolar disorder, schizophrenia, and MDD was 12.1%, 18.2%, and 24.2%, respectively. Irregular follow-up (OR, 5.7) and diagnosis (OR, 1.5).	MNA is a serious problem. Ensuring regular follow-up appointments and improving their thoughts are needed.
Novick et al., Multi-country-European [30]	MA was higher in bipolar patients than in schizophrenia, which might be schizophrenic patients had lower insight than in bipolar. Better insight was associated with higher MA and had stronger therapeutic alliance, which reduce the clinical severity.	Insight and MA were found to be closely related. Insight impacts on the therapeutic alliance with mental health and associated to treatment outcomes.
Hillary, Nigeria [31]	Adherence varied from poor adherence (55.5%) through moderate (36%) to high adherence (8.5%).	More than half of the psychiatric out-patients had MNA.
Ibrahim et al., Nigeria [32]	MNA was 54.2% (schizophrenia = 62.5%, bipolar = 45.8%). Multiple dosing frequency (OR, 7.8), side-effects (OR, 6.8), cost of medications (OR, 4.1), and poly-therapy (OR, 2.3) were factors associated with MNA.	Encourage rational pharmacotherapy, consider routine lower dosing prescriptions, integrating side effects surveillance, and early intervention are recommended
Dibonaventura et al., USA [33]	MA was 42.5%. Medication side-effect and forgetfulness were 86.19% and 48.4%, respectively. Agitation (OR = 0.6), sedation/cognition (OR = 0.7), prolactin/endocrine (OR = 0.7), and side-effects (OR = 0.6) were significantly associated with MNA.	Medication side-effects and resource are associated with MNA. Prevention, early detection, and effective management of side-effects are crucial to avert it.
Gurmu, et al., Ethiopia [34]	MNA was 50.2%. Schizophrenia (75.7%), bipolar disorder (37.5%), and depression (52.6%). Factors were perceived recovery (26.7%), drug unavailability (18.1%), adverse effect (12.7%), forgetfulness (10.6%), and being busy (8.6%).	The observed rate of antipsychotic MNA in this study was high. Interventions to increase adherence are therefore crucial.
Magura et al., USA [35]	Lower social support, alcohol use, lower satisfaction with medication, side-effects, lower self-efficacy for avoidance and recovery, forgetfulness, unnatural to be controlled by medication, careless at times, and felt better were the reasons for MNA.	Health care providers should encourage to address patients’ adherence strategies via education about side-effects and benefits of the medication.
Kikkert et al., European countries [36]	Medication efficacy, external factors (such as patient support and therapeutic alliance), insight, side-effects, and attitudes had influence on MA.	Professionals, care-givers, and patients do not have a shared understanding of which factors are important.
Teferra et al., Ethiopia [37]	Inadequate availability of food, perceived strength of medications, social support and safety net, lack of insight, failure to improve, side effects, substance abuse, stigma, and poor attitude of the care provider were some of the main reasons for MNA.	Greater attention to provision of social and financial assistance will potentially improve MNA.
Sher et al., USA [38]	Caregivers’ attribution of depression to cognitive and attitudinal problems, which significantly predicted patients’ MNA. Perceived stigma was also another predictor of non-adherence.	Involving caregivers on the treatment plan, social support, and attitude may improve adherence.
Mohamed et al., USA [39]	Insight and drug attitudes were associated with declining schizophrenia symptoms but increasing levels of depression. Change toward more positive medication attitudes was associated with changes in insight, improve community functioning, and greater medication compliance.	Better insight, positive attitudes toward medication, and educational interventions can be an important part of psychosocial rehabilitation services.
Sava, Turkey [40]	MNA was 26.5% and associated with education, lack of insight, thought they had recovered, believed that treatment had no-effect on their disorder, thinking that had recovered, not taking medication, and thought of treatment not effective.	Lower education level, having thought of inadequate information about illness, and lack of insight about treatment were significantly associated with MNA.
Sirey, USA [41]	MNA was 82%. Elderly (24%) and younger (13%) patients discontinued treatment completely. Patients perceived more stigma than older patients, stigma predicted treatment discontinuation.	Patients’ perceptions of stigma at the start of treatment had influence their subsequent treatment behavior.
Sajatovic. USA [42]	MNA was 45.9%. Younger age, unmarried, homeless, substance abuse, or fewer outpatient psychiatric visits were predictors.	Almost half of the patients had MNA that reduce the effectiveness treatments in clinical settings.
Sajatovic. USA [43]	MA was 51.9%. Factors associated were younger age, comorbid substance abuse, and homelessness were the factors associated with MA level.	MNA is common in bipolar disorder medication.
John, USA [44]	MNA was 77%. Weight gain and cognitive effects of a medication most significantly affected patients’ likelihood of MA.	Patients’ satisfaction is seriously affect adherence. Health care providers can optimize prescribing patterns.
Iseselo et al., Tanzania [45]	Financial constraints, lack of social support, family disruption, stigma, discrimination, and disruptive behavior were some of the influencing factors for MNA.	A collaborative approach between the care providers, leader,and family is needed.
J.M. Olivares, Spain [46]	Minimize patients waiting stay was significantly associated with MA.	Treatment retention had greater improvement in clinical symptoms, reduce hospital stay, and increase efficacy.
Charlotte, Sweden [47]	Antidepressant MNA was 61.4%. Age (< 35 or > 64 years), having personality disorder, sensation-seeking traits, substance abuse, and unavailability of concomitant medications were predictors.	Patient and illness-related factors may imply an increased risk of MNA.
Adeponle, et al., Nigeria [48]	Half (50.6%) of patients were adherent with appointments.	Family support was significantly associated with appointment, which can improve MA.
Rashid, Malaysia [49]	The type of antidepressant medication prescribed, not given a choice to choose the treating doctor, and the preference to traditional medicine were significant risk factors.	Involvement of patients, caregivers, flexible schedule, place choice, drug, and doctor can help to prevent MNA.
Roy, Ranchi (India) [50]	Poor infrastructure and lack of proper information about mental illness to patients and caregivers were some of the reasons for MNA.	Develop community mental health care facilities and provide adequate information to patients and caregivers.
Omran, Iran [51]	Non-compliance was reported as a possible cause of admission in (88.2%) of the re-hospitalized cases. No insight to disease (59%) and feeling of cure (27.6%) were causes for MNA.	Providing a better insight about disease to patients to take their medications, even feeling of cure is important.
Tara et al., Canada [52]	MA was 73%. Forgetting, change in routine, side effect, had lower self-efficacy, female, and had not completed post-secondary education were the most frequently identified reasons for MNA.	Clinicians should be simple and easy to address medication efficacy, tolerability, and social moderator
Banerjee, India [53]	MNA was 66.9%. Women (OR 2.7), consume extra pills (OR 2.8), and had a considerably lower internal locus of control (OR 4.5) were predictors	Interventions focusing on individuals and intersectoral system-oriented approach to improve MA are needed.
Oliver, Spain [54]	MNA was 33.9%. Long-term treatment duration is a factor for MNA. Women were more adherent than men.	Designing proper drug collection at pharmacies can improve the MA of patients.
Dave, UK [55]	Discontinuation was 80%. Lower discontinuation in the first 6 months after initiation was associated with higher age, weight gain, and comorbid irritable bowel syndrome.	Lack awareness was a risk for discontinuation.
Mahaye, South Africa [56]	MNA was 50.8%. Age and race become predictors of MNA.	Age and race were significant predictors for MNA.
Sundell, Sweden [57]	MNA was 26.1%. It was less in women (OR, 0.8) and least 2 years of higher education (OR, 0.7), and those who received social assistance (OR, 1.3).	MNA occurred more commonly among social support recipient
Akincigil, [58]	MNA was 49%. Care from a psychiatrist and higher general pharmacy utilization were associated with better adherence. Younger age, substance abuse, and comorbidity were associated MNA.	Substance abuse is one of the main risk factor for MNA and needs to be targeted for intervention.
Taj, Pakistan [11]	MA among major depressive and bipolar disorders was 61.5% and 73.9%, respectively. Reasons were sedation (30%), cost (22%), forgetting (36%), and no explanation by doctors (92%).	MNA is a common and important issue. Treatment cost and co-morbidity are common factors
Prukkanone et al., Thailand [59]	MA was 41% but all patients who attended only once were non-adherent, adherence may be as low as 23%.	MA to antidepressant therapy for treatment was high.
Shigemur, Japan [60]	MNA was 33.1%. It was associated with lower age, unemployed (OR, 1.9), higher daily dosing frequency, low drug satisfaction, and poor doctor–patient dyad, and age (> 34 years) (OR, 1.6).	MNA was predicted by lower age and unemployment.
Bambouer et al., USA [61].	MNA was 75%. Rates of antidepressant non-adherence significantly increased over time were 40%.	Effectiveness of electronically triggered, patient-specific, and faxed feedback should be carefully evaluated.
Demyttenaere et al., Belgium [62]	MA was 70%, and it was decreased by 2.5% per month and more than three times more rapidly in drop-outs.	MA decreases with time is influenced by demographic and clinical variables.
Mascha C. Ten D [63].	MNA ranged from 39.7 to 52.7%. It did not significantly differ between intermittent ad continuation antidepressant users (37.2% versus 25%).	MNA is high on MDD. Doctors continuously have to be aware of this problem
Baldessarini et al., USA [64]	MNA was 33.8%. Prescribing psychiatrists considered only 6% as MNA. Alcohol, youth, comorbidity, side effects, obsessive-compulsive disorder, and recovering from mania-hypomania and drug-complexity were the predictors.	Underestimation of the problem may encourage increasingly complex treatment regimens of untested value, added expense, and risk of adverse effects
Nega et al., Ethiopia [65]	MNA was 61.2%. It was associated with female (AOR, 2.3), combined drug (AOR, 2.7), long treatment duration (AOR, 2.3), > 24 months (AOR, 2.5), substance use (AOR, 2.6), perceived stigma (AOR, 2.2), patient’s poor attitude (AOR, 3.0), and poor social support (AOR, 1.8).	Psychotropic MNA was high. We recommend the concerned bodies to design and implement programs focused on associated factors in order to improve MA.

AOR adjusted odds ratio, CI confidence interval, MA medication adherence, MNA medication non-adherence, SCID-I Structural Clinical Interview Diagnosis I, TDM therapeutic drug monitoring