INTRODUCTION:

Substance abuse is both a social and public health problem with a substantial burden to society. Opioid dependence, with an estimated prevalence of 16.5 million in 2013 worldwide¹ carries a high cost to society by resulting in unemployment, crimes and family disruption² not to mention transmission of diseases such as HIV and Hepatitis C. In Malaysia, there is an estimated 400 000 to 800 000 drug users³, with 234 000 heroine abusers⁴. Harm reduction approach against HIV/AIDS in this country was introduced and approved by the government in 2003. Methadone Maintenance Therapy (MMT) was introduced as part of the harm-reduction approach in 2005⁵.

Methadone is a synthetic opiate receptor agonist used in the treatment of opioid drug addictions. Usage of methadone as a therapy prevents opiate users from injecting and sharing needles, which are vehicles for the spread of HIV and other blood borne viruses⁶, and also cause other harms such as damaged veins, local abscesses and endocarditis. This is one of the main aims of the MMT done in government clinics, other than reducing crime rates done by illicit-substance abusers. Other benefits is that the clients are able to work and be employed, as methadone at appropriate doses does not hinder a patient’s intellectual capacities or abilities to perform tasks⁷ and it corrects the compulsive use of heroin and other opiates⁸. Thus, it improves the clients’ quality of life and enables for a normal life. This has been proven in numerous studies where there were improvements in the physical and psychosocial domain in their quality of life^{9, 10}.

Many factors contribute towards the success of MMT. The capacity of different programmes to achieve significant reduction in illicit drug use varies greatly according to the treatment centers and across countries¹¹. In Malaysia, the indicator used to gauge the success of the methadone programme is the retention rate, which ranges from 54.7 to 95%^6,9 and urine positivity indicating relapse. Some studies have highlighted the importance of the organization and the characteristics of the treatment being delivered to ensure success of the programme. For example, although treatment outcome was shown to be influenced negatively by age at first use of heroin, length of drug use, use of cocaine before treatment, and race, but these patient characteristics had less impact on outcome than did programme characteristics¹². The more effective clinics were characterized by higher doses of methadone prescribing¹³, having a treatment goal of successful ongoing maintenance rather than abstinence, and having better quality counseling, more medical services, better staff-patient relationships, low staff turnover rates, and better management^{11, 14}.

It is crucial to incorporate the local and cultural norms and practices in the MMT programme strategy, given the objectives to tackle the drug dependence problem in the society. These treatments need to be evaluated by identifying determinants of successful outcomes such as abstinence of heroin in order to carry out a more effective intervention. Some studies have been done in Malaysia regarding MMT, but the focus of the previous studies was more on the retention rate and quality of life and factors affecting them. To ensure the success of therapy, it is important that we can determine what are the factors significantly influence the opioid addicts undergoing MMT to relapse into taking of heroin despite being in the therapy. Relapse occurs when a person returns to drug use after a period of abstinence.¹⁵ There is also lack of resemble studies here in Malaysia, which include programme characteristics such as the goals and specific psychological interventions. Therefore, this study was done to determine the prevalence of relapse to injecting behaviour and the factors associated with relapse among opioid addicts compliant to MMT in Kuala Nerus, Terengganu.

MATERIALS AND METHODS:

This is a cross-sectional study done from June to July 2016. Samples were recruited from opioid addicts undergoing MMT at three primary care outpatient treatment centers in Kuala Nerus district, Terengganu, which is situated in the northeastern Peninsular Malaysia.

Sample size calculation to determine the prevalence relapse among clients involved in methadone maintenance therapy was done using single proportion formula.

n= (Z/Δ)²P(1-P)

n= Minimum required sample size

Z= Value of standard normal distribution=1.96

D= Precision=0.05

P= Prevalence of relapse from literature.

The prevalence of relapse was 8%⁷ hence minimum required sample size was 113. Considering non response rate of 10%, the sample size calculated was 124.

All subjects who came for treatment within the study period who fulfilled the criteria of i) 6 months in therapy ii) a period of abstinence of more than a month; and consented were interviewed face-to-face using a semi-structured questionnaire.

Subjects were defined as having current relapse when they admit of taking any illicit heroin for the past one month or have the evidence of positive urine for heroin or new injection mark; with previously being abstinent of heroin during therapy of at least one month by having a negative urine test for heroin.

Quantitative data were entered and analyzed using Predictive analytics software (PASW) Statistics version 22.0 (SPSS Inc., Chicago, IL, USA). Data were checked and cleaned before analysis. Descriptive analysis was used to determine the prevalence of relapse. Simple and Multiple Logistic Regression confirmatory analysis were used to determine the factors associated with relapse. Dependent variable was relapse and independent variables were age, gender, working status, type of work, income, level of education, race, home arrangement, marital status, personal history of opioid use, usage of other substances, presence of co-morbid illnesses, client’s expected goal of therapy and history of urine positivity.

Ethical clearance was obtained from National Medical Research Ethics Committee (NMRR Reference Number: 5-2307-27817).

RESULTS:

All respondents were males of Malay race and of Islamic religion. Mean age was 36.2. Mean duration in MMT was 1.4 years. Demographic characteristics are shown in Table 1. Majority of the respondents (52.7%) were single (Table 1). The proportion of patients who were married increased from 28.7% to 33.6% after being in the programme. Majority (95.1%) of them had only up to secondary school education. About 66.4% of the patients were employed currently, compared to 54.1% at the time of treatment initiation and most were labourers fishermen, had small business and a few were drivers.

Current relapse, defined as any episode of intake of heroin for the past one month after a period of abstinence was 34.4% (Fig. 1).

Table 2 shows the descriptive statistics of the factors influencing relapse in the respondents. The majority of those who had a duration of MMT treatment more than two years had no relapse (76%) compared with a minority of those who had a duration of less than two years. Majority of respondents have a correct goal of being in MMT, which is abstinence from heroine (59.8%). There were almost as many respondents having heroin addiction duration less than 15 years and respondents with 15 years and more. Majority of those with addiction duration of less than 15 years had no relapse (72.3%). However, this factor is not significant after logistic regression analysis (Table 3).

Table 3 shows the significant factors of relapse in MMT clients. Those clients taking of methamphetamine during therapy had 5.99 times higher odds to relapse compared to those who did not. The clients who had parents who were divorced or had a single parent before the start of addiction were at 8.96 higher odds to have relapse.

Table 1: Demographic Characteristics of Respondents.

		n	Percent
Marital Status
	married	41	33.6
	single	64	52.7
	divorced	17	13.9
Educational status
	postsecondary	6	4.9
	form 4/5	78	63.9
	Form 3 and below	38	31.1
Working status prior to MMT
	working	66	54.1
	no stable work	24	19.7
	no work at all	32	26.2
Current working status
	working	81	66.4
	no stable work	24	19.7
	no work at all	17	13.9
Income
	0-1000	78	63.9
	1000-3000	44	36.1
living status
	with family	111	91.0
	with friend	1	.8
	alone	10	8.2

Table 2: Descriptive Statistics of Factors Influencing Relapse

Variables		No Relapse n(%)	Relapse n(%)
Goals of treatment	Abstain from heroine	64 (87.7%)	9 (12.3%)
	Stop from all substance including methadone	9 (22.5%)	31 (77.5%)
	To reduce heroine	1 (11.1%)	8(88.9%)
Duration of treatment	More than 2 years	57 (76%)	18 (24%)
	One to two years	12 (36.4%)	21 (63.6%)
	Less than one year	5 (35.7%)	18(64.3%)
Duration of heroine abuse	Less than 15 years	47 (72.3%)	18 (27.7%)
Duration of heroine abuse	15 years and more	27 (47.4%)	30 (52.6%)

Table 3: Significant Associated Factors of Relapse in MMT clients

Variable	Regression coefficient (b)	Adjusted Odds Ratio ^a(95% CI)	Wald Statistic	p-value
Status of parents prior to addiction	2.19	8.96(1.13, 71.10)	4.31	0.038
Duration of therapy	2.48	11.99 (2.62, 54.89)	10.23	0.001
Goal of therapy	4.10	60.24 (12.12, 299.29)	25.10	<0.001
Taking of metamphetamine during therapy	1.79	5.99 (1.45, 24.75)	6.10	0.013

^aForward LR Multiple Logistic Regression model was applied

Multicollinearity and interaction term were checked and not found

Hosmer-Lemeshow test, (p=0.980), classification table (overall correctly classified percentage=84.7%) and area under the ROC curve (91.6%) were applied to check the model fitness.

Fig. 1: Prevalence of current relapse in respondents.

DISCUSSION:

The baseline characteristics of the respondents for this study were quite similar to previous studies being done in Malaysia in terms of age¹⁶, level of education and marital status^{16, 17}. There was increased in rate of employment after being started on MMT from 54 to 66 %. This is similar to a study done in Kuantan, Malaysia showed an increase from 70 to 77% in employment¹⁷. Although the increase in this study was quite large, the final employment proportion was still lower compared to the other studies. This is may be due to the lower employment baseline. This is one factor, which should be looked into as improvement in employment may be one of the measures indicating effectiveness of this programme.

Previous research has shown that addiction was associated with significant brain changes, in particular, related to brain reward circuitry. Areas of limbic system governing emotions and prefrontal cortex governing cognition and social behaviours were directly affected which affect the employability of the addicts. As the treatment instituted and continued, the person showed improved behaviours and better thinking process¹⁸. Therefore, those who have a good response to MMT should have no problem in getting a job to secure their income. As can be seen, they were in the lower socioeconomic group with the majority of them earning less than RM1000 per month.

Relapse in MMT:

Most studies have suggested that relapse is common after treatment for drug addiction. A ten-year prospective follow-up study have shown that approximately one-third of clients who were in full remission relapsed in the first year¹⁴, which is similar with the results for this study. A few other studies show a much less relapse rate^{19, 20} and some studies show a much higher relapse of 64%¹⁶. However, comparing relapse between studies must take into account the definition of relapse used in the study as it may indeed be the cause of discrepancy.

Associated Factors of Relapse in MMT Clients:

The main significant factor for relapse was the clients’ goal for treatment (p<0.001) where clients’ who intended to stop all substance, including methadone at the start of treatment had the highest risk for relapse (OR 60.24). Several reports suggest that abstinence from all drugs, including methadone, may not be an appropriate treatment goal for many patients. Ball and Ross found that the most successful clinics had successful maintenance on methadone rather than abstinence as their goal of treatment. Patients were less likely to relapse if they had a goal of successful ongoing maintenance rather than abstinence and better counselling¹³. The reason being that the nature of methadone treatment is avoiding the clients from continuing abuse of the heroine. This harm-reduction approach avoids the prevents opiate users from injecting and sharing needles, which are vehicles for the spread of HIV and other blood borne viruses⁶, and also cause other harms such as damaged veins, local abscesses and endocarditis. This is one of the main aims of the MMT done in government clinics, other than reducing crime rates done by illicit-substance abusers.

This aim needs to be communicated effectively to the MMT clients at the start of the therapy in order that the clients do not have an unrealistic expectation which will only trigger untoward frustration towards the therapy. This weakness of MMT providers who did not provide proper counseling to convey the aim of MMT is very important to be detected as it is a factor which can be remedied. However, further studies need to be conducted whether this fact is indeed miscommunication or there is resistance in acceptance of the clients towards the counseling given.

Those clients taking of methamphetamine during therapy were almost at 6 times higher odds to relapse compared to those who did not. Some other studies also show taking methamphetamine as a risk for relapse^{21, 22,
23} which may indicate the non-serious intention of the clients to quit abusing illicit drugs. Therefore, there is a need to emphasize to the clients who want to enroll in the programme that they need to be seriously intended to quit all illicit substances in order to be successful in their therapy.

Previous study finding that the dose of methadone correlated with urine positivity⁶ was not found in this study. However, there were findings from previous more recent studies which also did not find this correlation^17,
22. This shows that the methadone doses should be individualized and is increase in higher doses, e.g. more than 65 mg to prevent relapse is not a blanket rule to everyone.

The status of parents who were divorced or had a single parent before the start of clients’ addiction was found to be significantly associated with higher relapse rate in this study. This factor shows that the coping mechanism of those who had a stressful childhood may be poorer compared to those with intact family. This may be the cause of the start of their addiction themselves. It may also indicate lesser social support during therapy. This finding underscores the importance of the psychosocial cause of addiction itself and identification of the stressors which may cause someone to start addiction and relapse in therapy. There were studies which found a significant correlation drug use among daughters living with single fathers compared of daughters living with single mothers, while gender of parent was not associated with sons’ usage²⁴. This factor needs to be studied more deeply. It is recommended that a further study needed to validate this and a qualitative study regarding the underlying factors for starting addiction and relapse in therapy be carried out.

This study limitations includes a cross-sectional design, relying on recall information by the respondents which is subjected to recall bias and non-adjustment of probable confounding factors towards religious practice and knowledge scores.

CONCLUSION:

Relapse in opioid addiction remains high in those receiving MMT in Terengganu, Malaysia. Further effort should be taken to inculcate the appropriate goals of therapy in MMT clients and further intervention is needed in MMT effective to prevent relapse, which may contribute towards achieving more successful therapy outcomes.

CONFLICT OF INTEREST:

The authors declare no conflict of interest.

ACKNOWLEDGEMENT:

This study has been funded by short term grant by University Sultan Zainal Abidin (UniSZA/2016/ DPU/13). The support is greatly appreciated.

REFERENCES:

1. United Nations Office on Drugs Crime. World Drug Report 2013 May 2013, UNODC, Vienna, Austria. Available from: http://www.unodc.org/wdr/index.html

2. World Health Organization, United Nations Office on Drugs and Crime, Joint United Nations Programme on HIV/AIDS. WHO/UNODC/UNAIDS position paper: Substitution maintenance therapy in the management of opioid dependence and HIV/AIDS prevention 2004.

3. Ministry of Health, Malaysia. National clinical guidelines and procedures for the use of buprenorphine and buprenorphine/naloxone in the treatment of opioid dependence in Malaysia, 2006.

4. Ruger JP, Chawarski M, Mazlan M, Luekens C, Ng N, Schottenfeld R. Costs of addressing heroin addiction in Malaysia and 32 comparable countries worldwide. Health Serv Res 2012; 47 (2): 865-87.

5. Gill JS, AH S, Habil MH: The first methadone programme in Malaysia: overcoming obstacles and achieving the impossible. Asean J Psychiatry 2007; 8:64-70.

6. Mohamad et al. Better retention of Malaysian opiate dependents treated with high dose methadone in methadone maintenance therapy. Harm Reduction Journal 2010; 7:30

7. Gordon NB, Appel PW: Functional potential of the methadone maintained person. Alcohol Drugs and Driving 1994; 11: 31-37.

8. Dole VP: Implications of methadone maintenance for theories of narcotic addiction. JAMA 1988; 260:3025-3029.

9. A. Norsiah et al Can Primary Care Clinic run MMT service well? Malaysian Family Physician 2010; Vol 5 No1

10. LinXiao et al, Quality of Life of Outpatients in Methadone MaintenanceTreatment Clinics. Acquir Immune Defic Syndr 2010; Vol 53, Supplement 1

11. M Farrell, J Ward, R Mattick, W Hall, G V Stimson, D des Jarlais, M Gossop, J Strang. Fortnightly Review: Methadone maintenance treatment in opiate dependence: a review BMJ 1994; 309:997

12. Ball JC, Ross .The effectiveness of methadone maintenance treatment: patients, programs, services, and outcome.New York:Springer-Verlag,1991.

13. Latowsky M: Methadone death, dosage and torsade de pointes: riskbenefit policy implications. J Psychoactive Drug 2006; 38: 513-519.

14. Hunt, William A Bespalec, Dale A. Relapse rates after treatment for heroin addiction. Journal of Community Psychology, Vol 2 (1), Jan 1974; 85-87

15. National Institute on Drug Abuse. Drugs, Brains, and Behaviour. The Science of Addiction 2014.

16. Jacob SA, Mohammed F, Hassali MAA, Malays J Med Sci Profile of Clients Attending a Methadone Clinic 2015; Jan-Feb; 22 (1): 58–69.

17. M Ramli, A B A Zafri, M R Junid, S Hatta. Associated Factors to Non-Compliance in Methadone Maintainence Therapy. Med J Malaysia Vol 67 No 6 December 2012.

18. Volkow ND, Baier RD and Goldstein RZ. Neuron, 2011; 69, 599-602

19. Xie H, McHugo GJ, Fox MB, Drake RE. Substance abuse relapse in a ten-year prospective follow-up of clients with mental and substance use disorders. Psychiatr Serv 2005; 56: 1282-1287.

20. George P Outcomes from the Malaysian Arm of The International Survey Informing Greater Insights in Opioid Dependence Treatment (INSIGHT) Project. Med J Malaysia 2015; Vol 70 No 2 April

21. Ruger JP, Chawarski M, Mazlan M, Luekens C, Ng N, Schottenfeld R. Costs of addressing heroin addiction in Malaysia and 32 comparable countries worldwide. Health Serv Res 2012; 47 (2): 865-87.

22. Kaur, S., Mohd, H. B., and Mohamed, M. N. Projek Perintis Program Rawatan Terapi Gantian (RTG) Menggunakan Methadone di Pusat Khidmat AADK. Journal Antidadah Malaysia 2008; 5 (1), 1-30

23. Mohammadpoorasl A, Fakhari A, Akbari H, Karimi F, Arshadi Bostanabad M, et al. Addiction Relapse and Its Predictors: A Prospective Study. J Addict Res Ther 2012; 3:122. doi:10.4172/2155-6105.1000122

24. Hemovich V, Crano WD. Family Structure and Adolescent Drug Use: An Exploration of Single-Parent Families. Substance use & misuse. 2009; 44 (14): 2099-2113. doi:10.3109/10826080902858375.

Received on 24.11.2017 Modified on 15.05.2018

Research J. Pharm. and Tech 2018; 11(7): 2724-2728.

DOI: 10.5958/0974-360X.2018.00503.6