Health Science Journal

Keywords

Schizophrenia; Non adherence; Antipsychotic drugs

Abbreviations

AMSH: Amanuel Mental Specialized Hospital; AOR: Adjusted Odds Ratio; CI: Confidence Interval; DIA: Drug Inventory Attitude; EPS: Extra Pyramidal Side Effect; MMARS: Morisky Medication Adherence Rating Scale

Introduction

Background

Non communicable diseases, mental health disorders, HIV/ AIDS and tuberculosis combined represented 54% of the burden of all illness worldwide [1] and predicted to rise to 65% of the global burden of disease in 2020 [2].

Schizophrenia is one of the serious mental health problem characterized by clinical syndrome of variable, but profoundly disruptive, psychopathology that involves cognition, emotion, perception, and other aspects of behavior. The classic course of schizophrenia is one of exacerbations and remissions and patient usually relapse [3]. Antipsychotic medications are the mainstay of the treatment for schizophrenia and have reduced the number of recurrent psychotic episodes among persons with schizophrenia [4].

Advancements in the treatment of psychiatric disorders are limited by non-adherence, which steal power from even the most beneficial medications [5]. WHO defined non adherence as “a case in which a person’s behavior in taking medication does not corresponds with agreed recommendations from a health care provider”. Medication non adherence, either willful or inadvertent and can include: Failing to initially fill or refill a prescription, discontinuing a medication before the course of therapy is complete, taking more or less of a medication than prescribed and taking a dose at the wrong time [1].

Patients with psychiatric disorders show a greater degree of non-adherence to treatment than those with physical disorders. The adherence rates range from 40 to 70% to 60-92% in the respective disorders [6]. Among different psychiatric illnesses patients suffering from psychotic disorders are the most likely not to adhere to treatment followed by those suffering from depressive disorders and bipolar disorder [5].

Study done in Kenya on 100 psychiatric outpatients discharged from mental hospital to estimate the treatment compliance or adherence after 3 months; patients were interviewed to assess treatment adherence and 55 percent of them fail to adhere to their treatment for certain reason [7]. Similar studies were done in different part of Africa to determine magnitude of antipsychotic drug non adherence on schizophrenia patients. Study done in Nigeria on 313 schizophrenia patients to examine medication adherence among outpatients in relation to their subjective quality of life and other socio demographic, clinical and service related factors indicated that 40.3% of the respondents were medication non adherent [8]. Related study done on 217 schizophrenia patients to assess factors associated with relapse in Johannesburg; South Africa indicates that more than one third of patients (35.8%) were non adherent to their treatment [9].

Factors influencing non-adherence may be broadly categorised into factors related to the treatment, patientrelated factors, health care, and socio-economic circumstances [10]. There are certain studies which were undertaken by scholars regarding factors associated with antipsychotic drug non adherence. Study done in Pakistan came across the following common self-reported personal factors of the patients as cause of non-adherence: 'I forgot to take medication'(36%) and 'I thought I am better now and do not need to take medication' (32%) [5].

Pilot study done in Uganda indicated that non adherence was correlated significantly and negatively with need for treatment and insight. In the same study no demographic factors were correlated with non-adherence [11]. Study done in India to assess reason for drug non adherence showed that 35% of patients were non adherent because they were not able to come for medicine due to long distance that was inconvenient. Additionally 28% patients due to improvement in symptoms, 41% because of financial problem, 16% because of side effects and 15% because of lack of care givers discontinued their treatment [12].

Failure to adhere to antipsychotic regimens is associated with exacerbation of psychotic symptoms, increased aggression against self and others, worse prognosis, increased use of inpatient and acute outpatient services and increased costs. Importantly, non-adherence to medication has been suggested to be the most important modifiable factor contributing to psychotic relapse [13] which leads to rehospitalization [14].

Data regarding the prevalence and associated factors of non-adherence among psychiatric patient particularly schizophrenia from developing countries, especially Ethiopia is scarce. To the knowledge of the present researcher although certain study was done on non-adherence of chronic medical illness there is no study done on this regard in Ethiopia. This study attempts to bridge the gap and information in this regard and helps to design effective interventions and therapeutic techniques for enhancing adherence behavior among schizophrenia patients.

Methods

Study design and subject

Over a month period, we performed institutional based cross-sectional study on 403 schizophrenia patient at Amanuel mental specialized hospital. Amanuel mental specialized hospital is the only mental hospital in the country which engaged in giving core mental clinical services, conducting research and trainings of professionals. There were about 41,583 schizophrenia patient who had regular follow in the year 2012 at outpatient; the majority are male (24,154). The hospital has 300 beds in 11 case teams (wards) which serves patient from the whole country. Eligible patients were age 18 and above, had given informed consent and had DSM-IV diagnosis of schizophrenia. However patients who were acutely agitated and cannot be able to communicate with data collectors were excluded from study.

Measurements

Structured, pre tested and pre coded questionnaire was used to collect socio-demographic characteristics and nonadherence related factors by face to face interview of the participants. Data regarding the type of schizophrenia, the type of drug/s, frequency of drug taken, drug regimen and presence of co-morbid depression were reviewed from patient document. Drug non-adherence was assessed using the 4-item version of self-reporting questionnaire of Morisky Medication Adherence Rating Scale (MMARS) [15], patient attitude towards treatment was assessed by 10-item Drug Inventory Attitude (DIA) [16].

Statistical analysis

Data were entered and cleaned using EPI Info version 2002 and exported to SPSS version 20 for analysis. Descriptive statistics were used to summarize the data. Multiple logistic regressions were used to identify associated factors of drug non adherence with several independent variables. Odds ratio, 95% confidence interval and p-value were used to identify associated factors. A p-value of <0.05 was considered to indicate statistical significance association and p-value of Hosmer and Lemeshow test was found to be 0.394. Ethical clearance was obtained from university of Gonder ethical review board and AMSH. Informed consent was obtained from Participants and Participation was on voluntary bases and had full right to withdraw at time of need during the interview process.

Results

Patient characteristics

Four hundred three respondents were participated in the study with the response rate of 95.3%. 268(66.5%) male were participated in this study. The mean age of participants was 32.7(SD+9.59 years) and age ranged from 18 to 57. 250(62.0%), 313(77.7%) and 226(56.1%) participants were Orthodox Christians, never married and jobless respectively. As to income, 270(67%) by participants earn less than 30 USD (Table 1).

Table 1 Distribution of patients by socio-demographic factors attending at AMSH; March, 2013 (n=403).

Variables	Categories	Number	Percent
Sex	Male	268	66.5
	Female	135	33.5
Age	18-27	142	35.2
	28-37	138	34.2
	>38	123	30.5
Marital Status	Never married	313	77.7
	Ever married	90	22.3
Religion	Orthodox	250	62
	Muslim	94	23.3
	Protestant	59	14.6
Ethnicity	Amhara	168	41.7
	Oromo	91	22.6
	Gurage	87	21.6
	Tigrae	57	14.1
Educational Status	Above Secondary School	151	37.5
	Secondary School	147	36.5
	Primary School	92	22.8
	No Formal Education	13	3.2
Occupation	Jobless	226	56.1
	With job	177	43.9
Monthly Income	< 570	270	67
	> 570	133	33

Regarding treatment related factors of participants 375(93.0%) were on conventional antipsychotic drug, 269(66.7%) were on mono therapy, 210(52.1%) took their medication on daily bases (Table 2). 109(27.0%), 45(11.2%) and 29(7.2%) of the participants reported extra pyramidal, psychic and anti-cholinergic side effects respectively (Table 2).

Table 2 Distribution of patients by treatment related factors attending at AMSH; March, 2013 (n=403).

Variables	Categories	Number	Percent
Type of schizophrenia	Paranoid	226	56.1
	Disorganized	62	15.4
	undifferentiated	85	21.1
	Catatonic	30	7.4
Type of drug	Low potency	250	62
	High potency	125	31
	Atypical	28	7
Drug regimen	Mono therapy	269	66.7
	Poly therapy	113	33.3
Frequency of drug	Once every day	210	52.1
	Twice daily	193	47.9
Duration of being on treatment	< 6 months	115	28.5
	6 months to 2 years	166	41.2
	> 2 years	122	30.3
Experienced side effects	Yes	181	44.9
	No	222	55.1

Table 3 Distribution of patients by health care and patient related factors; March, 2013 (n=403).

Variable	Categories	Number	percent
Time taken to reach hospital	< 2 hours	235	58.3
	> 2hours	168	41.7
Psychiatric co-morbidity	Yes	110	27.3
	No	293	72.7
Insight during treatment initiation	Yes	158	39.2
	No	245	60.8
Perceived stigma	Yes	199	49.4
	No	204	50.6
Family encouragement	Yes	352	87.3
	No	51	12.7
Substance use	Yes	256	63.5
	No	147	36.5
Health information	Yes	317	78.7
	No	86	21.3
Attitude towards drug	Positive	355	88.1
	Negative	48	11.9

Of the respondents, 370(91.8%) had free access to drugs and 51(12.7%) had no family encouragement (Table 3). Concerning substance, 108(26.8%) used alcohol and 41(10.2%) were used khat/chat use since initiation of treatment. As measured by MMARS, the overall prevalence of antipsychotic drug non adherence in the study population was found to be 48.4%.

Table 4 Factors associated with antipsychotic drug non adherence among patients attending at AMSH; March, 2013 (n=403).

Explanatory variables	Drug non adherence		COR(95% CI)	AOR(95% CI)
	Yes	No
Sex
Male	141	127	1	1
Female	54	81	0.60(0.39, 0.91)	0.79(0.44, 1.41)
Monthly income
Less than 570	139	131	1	1
> 570	56	77	0.69(0.45, 1.04)	0.82(0.46, 1.47)
Type of drug taken
Low potency	120	130	1	1
High potency	69	56	1.34(0.87, 2.05)	1.96(1.09,3.52)
Atypical	6	22	0.29(0.12, 0.75)	1.03(0.34, 3.16)
Co-morbiddepression
Yes	83	27	3.75(2.28, 6.18)	2.23(1.12, 4.45)**
No	112	181	1	1
Drug regimen
Mono therapy	102	167	1	1
Poly therapy	93	41	2.38(1.52, 3.73)	2.37(1.21, 4.65)**
Extra pyramidal side effects
Yes	75	34	3.19(2.01, 5.10)	2.66(1.44, 4.91)**
No	120	174	1	1
Duration of treatment
< 6 months	46	69	1	1
6 months to 2 years	85	81	0.60(0.36, 1.01)	1.69(0.87, 3.28)
>2 years	64	58	0.95(0.59, 1.52)	1.72(0.66, 4.47)
Perceived stigma
Yes	123	76	2.97(1.98, 4.45)	3.35(1.94, 5.81)**
No	72	132	1	1
Family encouragement
Yes	156	196	1	1
No	39	12	4.08(2.07, 8.06)	2.99(1.31, 6.86)**
Attitude towards drug
Positive	159	196	1	1
Negative	36	12	3.69(1.86, 7.34)	3.79(1.56, 9.23)**
Khat use
Yes	66	42	2.02(1.29, 3.17)	2.01(1.11, 3.65)**
No	129	166	1	1
Alcohol use
Yes	31	10	3.74(1.78, 7.86)	4.7(1.79,12.46)**
No	164	198	1	1
Cannabis use
Yes	32	9	4.34(2.01, 9.36)	4.5(1.64,12.12)**
No	163	199	1	1

Factors associated with drug non adherence

During bivariate analysis of antipsychotic drug non adherence in relation to each explanatory variable: sex, monthly income, Type of drug taken, duration of treatment, co-morbid depression, drug regimen, extra pyramidal side effects, perceived stigma, having family encouragement, attitude towards drug, alcohol use, khat/chat use and cannabis use were variables that fulfilled the minimum requirement (0.2 level of significance in this study) and were further analyzed by multivariate logistic analysis.

On the other hand age, marital status, religion, ethnicity, educational status, occupation, type of schizophrenia, anticholinergic side effect, psychic side effect, frequency of drug taken, time taken to reach hospital and cigarette use were not fulfilled the minimum requirement i.e., 0.2 level of significance and were excluded from further analysis.

During the multivariate analysis, co-morbid depression, drug regimen, extra pyramidal side effects, perceived stigma, alcohol use, khat/chat use, family encouragement and attitude towards treatment were found to be statistically significant.

Patients who had co-morbid depression were about two times more likely to be non-adherent as compared with patients who had no co-morbid depression (AOR=2.23, 95%CI (1.12, 4.45). As to drug regimen patients who were on poly therapy were about twice more likely to be non-adherent as compared to patients who were on mono therapy (AOR=2.37, 95%CI (1.21, 4.65).

Regarding antipsychotic drug side effects among study participants, patients who had EPS were about three times more likely to be non-adherent to their antipsychotic drug when compared to patients who had no EPS (AOR=2.66, 95%CI (1.44, 4.91). Similarly study participants who had felt stigmatized were about three times more likely to be nonadherent to their drug as compared to patients who hadn’t felt stigmatized (AOR=3.35, 95%CI (1.94, 5.81).

Concerning substance use patients who were using khat/ chat, cannabis and alcohol after treatment initiation were found to be two times, about four times and about five times more likely non adherent than patients who had no history of those substance use with (AOR=2.01, 95%CI (1.11, 3.65), (AOR=4.46, 95%CI (1.64, 12.12) and (AOR=4.72, 95%CI (1.79, 12.46) respectively.

Absence of family encouragement (AOR=2.99, 95%CI (1.31, 6.86), negative attitude towards treatment (AOR=3.79, 95%CI (1.56, 9.23), were factors remained to be statistically significant. On the other hand sex, monthly income, duration of treatment and type of drug found to have no statistically significance association with antipsychotic drug non adherence (Table 4).

Discussion

The overall prevalence of antipsychotic drug non adherence in the current study area was found to be slightly higher than study done in Nigeria and India which were 40.3% [8] and 35.5% [17] respectively. Meta-analysis of published literature indicated that the prevalence of antipsychotic drug non adherence in schizophrenia ranged from 40% to 50% [18]. The possible reason for the difference in the magnitude of prevalence can be due to the socio cultural difference in the study population and clinical related factors. Almost all (93%) of study subjects in the current study area were taking conventional antipsychotic. The other possible factors that cause higher non adherence in this study area might be the higher substance uses and the difference in the sample size and inclusion criteria.

During bivariate analysis no socio-demographic factors were found to be statistically associated with drug non adherence. This finding was consistent with many previous studies [19,20]. Type of antipsychotic drugs was not found to have statistical significance. Contrary to this study done in France indicated that Individuals prescribed atypical antipsychotic drugs were more likely to be adherent than those prescribed typical antipsychotics [21]. The possible reason can be since participant in the current study area had less availability of atypical antipsychotic over typical antipsychotics which resulting in taking their medication unless they developed extra pyramidal side effects which is difficult for patient to tolerate side effects. Additionally small numbers of participant were on atypical antipsychotic in the current study area.

Regarding the drug regimen, study participants who were on poly therapy were about two times more likely to be nonadherent than those on mono therapy which is in line with study done in Nigeria in which participants who took significantly fewer number of medications were independently and negatively associated with antipsychotic drug non adherence [8].

Study done by Hamburg indicated that patients presenting with side effect compared with patients without side effect had a significantly more negative general attitude toward antipsychotics and were less likely to be encouraged to take such a medication in case of need [22]. Similarly another study indicated patient having extra pyramidal and psychic side effects and sedation were found to be statistically significantly associated with non-adherence [23]. Current study also found out that side effect is highly associated with non-adherence. Patient experiencing EPS has to about three fold risk of being non adherent; while this study didn’t appreciate anti cholinergic side effects and psychic side effect as a reason of non-adherence.

Alcohol use, cannabis use and khat/chat use were independently and significantly associated with nonadherence. Participants who used alcohol and cannabis were four to five times more likely to be non-adherent than those who didn’t used. This finding coincides with study done in France which reported non adherence was associated in patients with substance use [24]. Possible reasons includes the specified substance use can have negative impacts on a person's internal state causing increased cognitive anomalies and unpleasant withdrawal symptoms. In addition to the physical consequences there are a number of long term social and clinical consequences associated with drug and alcohol use. Substance users also tend to report greater extra pyramidal symptoms than abstinent patients and are at greater risk of tardive dyskinesia. Other consequences of those substances are increased risk of social exclusion and ultimately, homelessness or lack of family support which can end up with medication non-adherence.

Current study also found out perceived stigma and attitude towards treatment were the other factors which were identified to have statistical significance; which coincides with study done in Nigeria and Uganda [11,25].

The present study has some limitations: In this study drug non adherence was measured using self-report which tends to underestimate drug non adherence and also raises the question of patients' ability to recall events. Additionally the study did not consider the degree/ severity of drug non adherence.

Conclusion

In the current study area about half of study participants were non-adherent to their drug. In the final adjusted multivariate analysis drug regimen, co-morbid depression, attitude towards treatment, extra pyramidal side effect, alcohol use and khat use were found to have statistical significance with antipsychotic drug non adherence.

Factors such as duration of being on treatment, income and gender in the final adjusted model were not shown any significant relationship with antipsychotic drug non adherence in this study. Concerned body should consider the accessibility of drugs having lower extra pyramidal side effects. Furthermore investigations that combine self-report with other methods should be conducted.

Competing Interests

There is no financial and non-financial competing interest.

Authors’ Contributions

All authors contributed to the design of the study. S G. participated in the design of the study, performed the statistical analysis, and drafted the manuscript EA Participated in the design of the study, statistical analysis, and helped to draft the manuscript, TF participated in the design and statistical analysis. All authors have reviewed and approved the manuscript.

Acknowledgements

This study was supported by university of Gondar and Amanuel Mental Specialized hospital, Addis Ababa, Ethiopia. We would like to express our appreciation to all the participants who agreed to be interviewed. We also thank those who provide technical support, and the physicians and nurses for their assistance and efforts.

20133

References

1. World Health Organization (2003) Adherence to long-term therapies. WHO, Geneva.
2. Kaplan HI, Sadock BJ (2010) Synopsis of psychiatry (10th edn.). Lippincott Williams and Wilkins, Baltimore. pp:489-495.
3. Stephen M (2000) Essential psychopharmacology: Neuroscientificbasis and practical applications (2nd edn.). Cambridge university press, Cambridge.pp:401-405.
4. Taj F, Tanwir M, Aly Z, Khowajah AA, Tariq A, et al.(2008) Factors associated with non-adherence among psychiatric patients at a tertiary care hospital. JPMA 58:432-6.
5. Cramer JA, Rosenbeck R (1998) Compliance with medication regimens for mental and physical disorders. PsychiatrServ 49: 196-201.
6. Okonji M, Dhadphale M (2005) Treatment compliance among psychiatric outpatients inKenya. ActaPsychiatricaScandinavica 75: 240-242.
7. Adelufosi AO, Adebowale TO, Abayomi O, Mosanya JT (2011) Medication adherence and quality of life among Nigerian outpatients with schizophrenia. Gen Hosp Psychiatry 34: 72-79.
8. NGB Kazadi, MYH Moosa, FY Jeenah (2008) Factors associated with relapse schizophrenia.S Afr J Psychiatr14:53-58.
9. American Society on Aging (2006) Improving medication adherence in older adults. American Society, America.
10. Richard G, Judith L, Alice M (2007) Pilot study of adherence with antipsychoticmedications in people with schizophrenia and schizoaffective disorders inUganda.
11. Rekha R, Masroor J, Sushma K, Prashant KC (2005) Reasons for drug non-compliance of psychiatric patients. J Indian AcadApplied Psychol 31: 24-28.
12. MasandPS, Roca M, Turner MS, Kane JM (2009) Partial adherence to antipsychotic medication impacts the course of illness in patients with schizophrenia. J ClinPsychiatr 11:147-154.
13. Sullivan G, Wells KB, Morgenstern H, Leake B(1995) Identifying modifiable risk factors forrehospitalization: A case-control study of seriously mentally ill persons inMississippi. Am J Psychiatry152:1749-1756.
14. Morisky DE, Green LW, Levine DM (1986) Concurrent and predictive validity of a self- reported measure of medication adherence. Med Care 24: 67-68.
15. Sharma S, Kumar N, Chakraborti S, Sinha S, Kumari S, et al. (2012) Prevalence and factors associated with medication compliance in Indian patients suffering from mental disorders. Trop Doct 42: 28-31.
16. Hudson TJ, Owen RR, Thrush CR, Han X, Pyne JM, et al. (2004) A pilot study of barriers to medication adherence in schizophrenia. J Clin Psychiatry 65: 211-216.
17. Lacro JP, Dunn LB, Dolder CR, Leckband SG, Jeste DV (2002) Prevalence of and risk factors for medication non adherence in patients with schizophrenia. J Clin Psychiatry 63: 892-894.
18. Weiss KA, Smith TE, Hull JW, Piper AC, Huppert JD (2002) Predictors of risk of non-adherence in outpatients with schizophrenia and other psychotic disorders. Schizophrenia Bull 28: 341-349.
19. Dassa D, Boyer L, Benoit M, Bourcet S, Raymondet P, et al. (2008) Factors associated with medication non-adherence in patients suffering from schizophrenia: A cross-sectional study in a universal coverage health-care system.Aust N Z J Psychiatry 44: 921-928.
20. Lambert M, Conus P, Eide P, Mass R, Karow A, et al. (2004) Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence. Eur Psychiatry 19: 415-422.
21. Dibonaventura M, Gabriel S, Dupclay L, Gupta S, Kim E (2012) A patient perspective of the impact of medication side effects on adherence: results of a cross sectional nationwide survey of patients with schizophrenia. BMC Psychiatry 12: 20.
22. Misdrahi D, Petit M, Blanc O, Bayle F, Llorca PM (2012) The influence of therapeutic alliance and insight on medication adherence in schizophrenia. Nord J Psychiatry 66: 49-54.
23. Adewuya AO, Owoeye OA, Erinfolami AR, Coker AO, Ogun OC, et al. (2009)Prevalence and correlates of poor medication adherence amongst psychiatric outpatients in south western Nigeria. Gen Hosp Psychiatry 31: 167-174.