{'fraction_non_alphanumeric': 0.030275059996307918, 'fraction_numerical': 0.0203987446926343, 'mean_word_length': 4.825, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Opioid Dependence And Methadone Maintenance Treatment (MMT) Programme In Nepal In Three Different Decades: An Exploratory/Comparative Study

Introduction: First Methadone Maintenance Programme (MMTP) in Nepal was started in the year 1994. This study was done to study and explore/compare findings of the present study with that of studies published in Nepal in the new millennium. Material And Method: Study was conducted at the Mental Hospital, Lalitpur, Kathmandu, Nepal from 1994 to 2002. Data was collected for the initial 5 years from 1994 to 1998. These patients were followed up for the next five years till 2002. Data thus obtained are presented in a tabulated form, in terms of frequencies and percentages. Results: A total of 204 patients were put on Methadone Maintenance Treatment Programme (MMTP) during the scheduled period. One-hundred-and-twenty-two (60%) of them were abusing buprenorphine. Severity of buprenorphine abuse was between 1-6 ampoules (2 ml per ampoule) per day. Approximately 40% (81) of them were sharing the injecting equipment. Seventy-seven (38%) of them had been in police custody in the past, for various reasons like theft, cheating, possessing, trafficking, violence and other antisocial behaviours. Forty-five percent (92) clients were retained at the end of 5 years. Sixty-nine family members (spouses, mothers, brothers) from these 92 regular methadone clients were interviewed. Eighty-six percent (79) of the interviewed family members reported significant improvement in clients’ health. Eighty-one percent (75) of the family members reported significant improvement among the methadone users’ family in financial responsibilities and interest in work. Overall, MMTP was found to have reduced the amount of illicit drug abuse significantly in these patients. These results are compared with the data of the subsequent published data on MMTP from Nepal in the new millennium. Conclusion: Though the present study data may appear to be of historical value, we are presenting these data, in the light of the findings of the newer studies published of late from Nepal. Till date, our study remained the largest MMT Programme in Nepal, in terms of number of patients studied, number of years of study and number of years of follow up of these patients.


INTRODUCTION
Drug Abuse Scenario in Nepal from1960s to 1990s: In Nepal by mid-seventies cases of drug dependency on opiates, especially heroin began to appear. Both official and unofficial estimates indicate that from virtually no cases in 1976, there were over 10,000 and even as high as 20,000 heroin addicts a decade later, concentrated in the Kathmandu Valley. Drug abuse was mostly reported in young adults between the ages of 15-30 years of age [1][2][3] . Heroin (Brown sugar) was the most important drug of abuse reported. Mode of administration was mostly through smoking (71-78 % cases) and intravenous use in 22-29 % of cases [3][4][5] . Drug Abuse Scenario in 1990s: Buprenorphine Injection was introduced in the year 1989. Mainly young adults between the age of 15-30 years were reported to abuse buprenorphine [6][7][8] . Types of drugs that were abused were Buprenorphine (65-90%), Heroin (15%), Nitrazepam, combination of codeine and ORIGINAL ARTICLE ephedrine, combination of alcohol and nitrazepam, and sporadic abuse of Inhalants 7 . Mode of administration of drugs was through smoking (4-40 % cases) and Intravenous abuse in 60-75 % cases. About 40-65 % of IDUs were found to be sharing their Injecting equipment 3,7,9 . Following WHO SEARO's recommendation received in the year 1992 and approval from Ministry of Health, and Department of Drug Administration, HMG Nepal, and permission received from the Ministry of Home Affairs, Narcotic Control Division, HMG, Nepal, Methadone Maintenance Treatment Programme (MMTP) was introduced in the year 1994 at the Mental Hospital, Lalitpur, Nepal. At that time MMT programme was the only one of its kind, not only in Nepal but also for the entire SAARC countries.

Drug Abuse Scenario in the new millennium:
There are 92,436 people who use drugs (PUDs) in Nepal as per report published by Central Bureau of Statistics (2018). MMTP programme that was started in 1994, was stopped in 2002 due to some administrative problems [10][11][12]

MATERIAL AND METHOD
Mental Hospital, Lalitpur, Kathmandu Valley was the first centre for MMT programme in Nepal. The study started in the year 1994 and continued till 1998. These clients were followed up till 2002. Detailed demographic data, history of drug abuse, history of criminality, the daily amount of money spent on drugs, previous efforts for detoxification was recorded for all the clients recruited in the programme. Their family members were also interviewed as far as possible to correlate with the history. Detailed physical cum psychiatric evaluation was done for every client enrolled for the programme. Serological Status for HIV, HBV and HCV was done for many clients before initiating on methadone, since it was not mandatory. HIV sero-positive and Intravenous drug users were given the preference for methadone. The dose of methadone was adjusted on clinical judgment made by the principal investigator on the dose of Heroin or Buprenorphine the drug user was using before being put on Methadone. Initially in most cases 30-40 mg/day was provided in the first 24 hours, but if the dose was reported to be inadequate in the following day, depending on the symptoms of withdrawal, the dose was increased by 10 mg to make it more user friendly. It was further increased on later days, if necessary. Urine test for other opiates was not carried out and it was not mandatory. Also, it was not available at that time. There was take-home service facility also for a few selected clients, e.g., clients during hospital admission for treatment of other illness, clients' inability to come to clinic during mourning period for death in the family, accidents, during childbirth and patients in maternity hospital, having to travel for a few days in the course of the client's job as trekker's guide and other genuine reasons. All possible precautionary measures were observed to stop possible diversion of Methadone. At times the family members were encouraged to pick up the take home methadone for the methadone users. In few cases the drug distributing nurse would visit the client in other hospital to confirm their admission. For foreign nationals visiting Nepal and needing methadone in Kathmandu, they had to provide the latest valid documents of them being on methadone from the clinics of their countries of origin, their daily dose of Methadone, their intended length of stay in Nepal, their duration of travel outside of Kathmandu for sightseeing and trekking for supply of take-home doses. Fortunately, we did not receive any bad news of overdose accidents or deaths from them. An identity card of Methadone users was issued to each client to prevent police harassment and facilitate their movements easy, especially, during curfews during the public agitation. To find out the impact of methadone, a behaviour inventory was prepared. It focussed on six domains of behaviour. These were (i) demand of money from family to procure drugs, (ii) Social responsibility toward family members, (iii) Positive changes in behaviour, (iv) general health condition, (v) retention in occupation or job and (vi) attitude of family members toward methadone.
As it was the first clinic in this region, it had a very simple and humble beginning. Methadone was provided in a very rudimentary form. It was procured in tablet form as there was a problem for storing liquid in the hospital setting. Each tablet was in 40 mg circular white form dissolving in water. To make the dose adjustment different from 40 mg tablet, tablet had to be broken, then divided into different dosage form, grounded finely in mortar and pestle or over a piece of paper and dissolved in a small amount of water in a beaker, in front of the client, before given to drink by the dispensing nurse. It was a cumbersome job, yet carried out by the nurse with dedication and patience. Methadone users were recruited for the study from 1994 till 1998, for a period of 5 years. They were followed up till 2002, when the programme got discontinued due to some administrative and other reasons. Data thus obtained was tabulated in a simple frequency and percentage table. Data obtained from this study is compared with that of other studies, that has been published in Nepal in subsequent years, over a period of next two decades.  Amongst married clients (129), one hundredtwelve clients (86%) had 1 to 4 children and rest 17 (14%) of them were childless. Alcohol Dependence in father was found to be in 11 (5.4%) patients. Fifteen spouses, 25 brothers and one son admitted to be abusing opiates, at the time of the study period. Amount of heroin use was varying between 1-5 gm in 24 hrs. Buprenorphine abuse was between 1-6 ampoules (2 ml per ampoule) per day. Eighty-one (40%) of them were sharing the injecting equipment. About 38% of them had been in police custody in the past, for various reasons like theft, cheating, possessing, trafficking, violence and antisocial behaviour. Duration in the police custody ranged from a few days to couple of years. The frequency in police custody ranged from 1-6 times. It was observed that foreign nationals needed higher Methadone doses than local clients. In some foreigners the dose exceeded more than 80 mgs, whereas for Nepalese clients 40 mg was the average optimum dose. This may be due to high dose and better purity of heroin used in other countries than in Nepal.

RESULT
Ninety-two (45%) clients were retained at the end of 5 Years. Rest one-hundred-and-twelve (55%) clients dropped out for different reasons. Out of 70 Methadone clients registered in year 1998, thirty-six (51%) of them were found to be HIV Positive. Sixty-nine family members (spouses, mothers, brothers) from these 92 regular methadone clients were interviewed to find out the changes in the behaviour of methadone users. Eighty-six percent of the interviewed family members reported significant improvement in clients' health. Thirty-eight percent of the clients had been in the custody before being included in MMT programme; but, only 3% were in custody while being on methadone. Eighty-one percent of the family members reported significant improvement among the methadone users' family and financial responsibilities and interest in work. Eighty-eight percent of the family members reported that methadone users were not using any other additional drugs but 12% of them were using substances like alcohol and nitrazepam. Fifty methadone clients who tested negative for HIV prior to start of MMT regiment, were re-tested after one year. Only 2 clients turned HIV positive during this period. Sixty-nine family members (spouses, mothers, brothers) from our 92 regular methadone clients were interviewed to find out the changes in behaviour of methadone users. Few significant changes in our clients' behaviour were observed by the family members, while they were on Methadone treatment. The areas of improvement noticed mainly were holding on to occupation and Job, reduced demand of money from the family members, reduction in criminal behaviour, improvement in their general health condition and an increased sense of family responsibilities. First MMT programme was discontinued in the year 2002. In various articles, during subsequent years, it has been mentioned that this programme was stopped due to technical problems. Those problems were never discussed with the first author (DMS) by anyone in the past. Being the sole first MMT programme runner, first author (DMS) would like to narrate following reasons behind stoppage of this programme. 1. The programme was doing well even though it was an one man show. However, it could not be institutionalized properly. Very minimal staff was involved so as to reduce the possibility of diversion and misdistribution of methadone. 2. Impact evaluation of methadone could not be done in time and thus the report could not be presented to concerned Ministry for getting approval for extension of the programme. There was a delay and confusion in forming the body to evaluate the programme so as to make it bias free but at the end, the principal author (DMS) himself had to complete the evaluation. 3. Oral Buprenorphine was being promoted at that time as the alternative opioid substitution therapy (OST); hence Methadone was not being brought into limelight. Even NGOs having Syringe and Needle Exchange programme were not in favour of MMTP.

4.
Ex-drug users running so-called Rehabilitation Centres (Custodial Therapeutic Community Centres or Recovery Centres) were opposed to MMT as it was becoming popular and it was posing a threat to their source of income. Those rehabilitation centres were charging exorbitant amounts of money from the drug addicts and their families. Moreover, there were very high rate of relapses, even after a long stay in the residential rehab centres. There was no system of monitoring those centres. They were mushrooming in Kathmandu valley and slowly opening outside the valley also. 5. Drug Users who could not be registered for Methadone, tried to spread false rumours like methadone to be more harmful and being a poisonous drug. Some drug users even brought out fake tablets looking like methadone and sold them it in market, thus, in essence, tried to make the programme a failure. 6. Group of users who were terminated from the programme because of their anti-social activities like selling of drugs inside the methadone premises, irregularly irregular methadone users and frequent drop-outs, picking up fights, etc., were found spreading false anti-MMT messages. 7. Thus, overall attempts were made to create bad image about it and discourage clients to go for methadone. Some NGOs even came out in local magazines against methadone. 8. The other cause was the different perception and attitude towards methadone among the believers in complete abstinence theory and the harm reduction philosophy. A cumulative effect of all those issues lead to closure of first MMTP in Nepal in the year 2002. Nurse DB served the methadone clinic continuously for 7 years, not taking even a single day off. She was the solo person involved in methadone distribution. She used to live close-by outside the hospital and hence she was able to come every-day. She used to carry methadone tablet containing bottles in her uniform apron pocket (she became popular as the 'methadone nurse').

Opioid Dependence and Methadone Maintenance Treatment Programme (MMTP) in 2001-2010:
During first decade of the new millennium we have seen the discontinuation of existing MMT programme by 2002. Few studies on opioid abusers were reported during this period 18,19 . In a socio-psychological study among 393 male injectable drug users in Kathmandu valley, it was found that most frequently used psychoactive substance was injection Buprenorphine, followed by mixture of various substances (opiates, benzodiazepines, antihistamines) and Diacetyl morphine (Brown sugar) 18 . In another study on opioid abusers from the border town Bhairahawa, most characteristic opioid abuse pattern was found to be abuse of brown sugar through inhalation 19 . Seventy-six opioid abusers, who were admitted over a period of one year, were included in the study. A total of 32 (42.1%) among them had a history of injectable drug abuse (IDU). Their lifetime diagnosis revealed a polysubstance abuse pattern. There were high instances of injectionrelated side effects in the form of the presence of thrombophlebitis, HIV positivity, and clinical AIDS 19,20 . In 2006, United Nations office on Drugs and Crime (UNODC) in cooperation with Nepal Government restarted MMTP in 3 sites at Kathmandu, Lalitpur and Pokhara 10,14 . Pressure from drug user groups had also helped its reintroduction. Interestingly, these developments have taken place during a period of political instability in Nepal, with the help of strong advocacy from multiple stakeholders. As we mentioned above this time also MMT programme had to face resistance from those people running drug treatment centres. Coverage of MMT was low among high-risk injecting and sexual behaviour patients. The finance for MMT was largely from the external donors and these donations became scarce with the advent of global economic problems 14  83.5%, inhalants 12.7%, hallucinogens 8.7%, stimulant 5.2% and other drugs 1.2% 12 . The highest number of the drug users were found in Kathmandu valley (36,998) followed by Sunsari (7,407) and Kaski (6917). Especially growing number of youth and children were found to be getting involved in drug addiction 12,14 . About 70,390 drug users were below the age of 30. Among the total drug users, 57% (52,174) were IDUs and among them 13% shared needles with someone else 12 . The use of intravenous opioid is gradually increasing and so is the risk of transmitting blood borne illnesses like HIV, Hepatitis B and C as well as their participation in criminal activities 12  clients participated in each session and all the FGDs were conducted by an experienced epidemiologist. Thus, a total of 60-70 clients took part in the study. This study revealed that despite many lacunae, the participants found the programme useful in terms of developing good relation with family members, decreasing the necessity of money, being able to attend social functions, health and economic benefits, time saving, easily getting job 11 . Sharma et al., (2016) conducted a survey to determine the rate of adherence to and factors associated with compliance with a methadone maintenance treatment program (MMTP) among injecting drug users in Nepal. They conducted face-to-face structured interviews with 165 methadone treatment patients aged 20-54 years during April 2015 21 . Respondents without a previous history of relapse were 2.7 times more likely to adhere to the MMTP than those with a history of relapse. Clients with a good knowledge of the MMTP are 9.4 times more likely to adhere to the MMTP 21  Currently there are 14 MMTP sites in total across the country with an estimated 2500 PUDs enrolled on the program. All MMTP sites have SSU managed by drug users themselves. SSUs have a canteen within their premises which are run by MMTP patients themselves thereby supporting their livelihoods. SSU provides mechanical and mobile maintenance trainings to patients thus many patients have started their own auto-mobile workshops. Whenever MMTP patients are arrested by police because of their past drug use history, SSUs tried to rescue these users and even provide methadone to patients while in custody 30 . A detailed report of MMTP from these sites is awaited.

CONCLUSION:
Principal author (DMS) has lived through nineteen-sixties (Hippie era), when the whole scenario started in Kathmandu, Nepal, probably along with Varanasi in India, till date. First MMT programme in Nepal was carried out by him (DMS) at the Mental Hospital, Lalitpur, Kathmandu in the year 1994 with great risk, supported only by the then WHO Director of Mental Health at SEARO, New Delhi and Ministry of Home affairs, Government of Nepal with ambivalent attitude. This paper presents the findings of the study of 204 patients, who were put on Methadone Maintenance Treatment (MMT)programme over a period from 1994 to 1998. These patients were followed up for the next five years till the year 2002, when the programme got discontinued. Principal author (DMS) presented the findings of this study at 'Asian Workshop on Rapid Assessment and Response on psychoactive substance use and sexual risk behaviour (SEX-RAR)' conducted by the Sahai Trust, Chennai, India in the year 2002 16 . Out of a total of 204 clients,122 (60%) of them were abusing buprenorphine. Key findings of the present study were the following: (i)severity of buprenorphine abuse was between 1-6 ampules (2 ml per ampule) per day; (ii)approximately 40% (81) of them were sharing the injecting equipment; (iii)about 38% of them had been in police custody in the past, for various reasons like theft, cheating, possessing, trafficking, violence and antisocial behaviour; (iv) foreign nationals needed higher Methadone doses than local clients; (v) forty-five percent (92) of the clients were retained at the end of 5 Years and the rest one-hundred-and-twelve (55%) clients dropped out due to various reasons. Spouses of our regular methadone clients reported significant changes in the behaviour of these methadone users. Eighty-six percent of the interviewed family members reported significant improvement in clients' health. Eighty-one percent of the family members reported significant improvement among the methadone users' family and financial responsibilities and interest in work. Though the data of the present study may appear to be of historical value at present, we thought of presenting these data, in the light of findings of the newer studies published of late from Nepal. Our study till date remained the largest MMT Programme in Nepal, in terms of number of patients studied, number of years of study and number of years of follow up of these patients. Finally, our study found that most of the Methadone clients who had some kind of good family support and were already on some kind of income generating activities had shown significant improvement in their social and drug use behaviour. MMTP was found to have reduced the amount of illicit drug abuse significantly in these patients.