| Abstract|| |
Opioids are one of the most problematic illegal substances globally. Opioid abuse is associated with complications in various spheres of the user's life, his/her family, and the society. Injecting drug use (IDU) is also linked to public health problems such as HIV infection and viral hepatitis. Medications form an important cornerstone in the treatment of opioid dependence. Treatment strategies such as “detoxification” alone or long-term treatment with opioid antagonist have limited acceptability and retention rates. Opioid substitution therapy (OST) has demonstrated better retention rates than other existing treatment strategies and helps improve the individual's functioning as well as his/her quality of life. The use of OST in India spans three decades, with initial use of low-dose buprenorphine followed by higher strength buprenorphine and buprenorphine-naloxone. Other medications such as slow-release oral morphine, and recently, methadone have also been introduced. Indian research also confirms the findings from Western literature on the effectiveness as well as acceptability of this treatment modality. OST received its biggest thrust when it became a part of the National AIDS Control Programme. In recent years, the number of OST centers in India has increased manifold. Practice guidelines, standard operating procedures, and capacity-building mechanisms have been put in place for effective OST implementation. Despite such widespread use, many challenges exist for OST implementation. The targets for ensuring adequate coverage of the population with this treatment are still far away. There is concern of OST being branded as a “harm reduction” intervention reserved only for injecting drug users. Despite three decades of advancements, certain sections of policymakers and practitioners still have reservations with this treatment modality. There is a need to overcome these barriers for OST to become easily accessible to those who need it.
Keywords: Agonist maintenance treatment, opioid dependence, opioid substitution therapy
|How to cite this article:|
Rao R. The journey of opioid substitution therapy in India: Achievements and challenges. Indian J Psychiatry 2017;59:39-45
| Introduction|| |
Thank you for giving me the opportunity to deliver the prestigious Tilak Venkoba Rao Oration started in the name of the son of late Prof. Venkoba Rao. Rightly called the father of the Indian Psychiatry, Prof. Venkoba Rao's body of work in his lifetime continues to inspire a host of psychiatrists to further the cause of mental health not only in India, but also the world over. This award serves as an aspiration to scores of young psychiatrists like me to focus on an area of psychiatry and work toward significant achievement in that area.
I remain indebted to my teachers and mentors who have infused interest in the area of addiction psychiatry, whom I must name here: Prof. Rajat Ray, Prof. Anju Dhawan, Prof. Atul Ambekar, and Dr. M Suresh Kumar. I also express my gratitude to Prof. Sudhir Khandelwal for placing his faith on me by nominating me for the award. My gratitude to my dear friends and colleagues not only in my department, but also at the National AIDS Control Organisation (NACO) and the United Nations Office on Drugs and Crime (UNODC), where I worked earlier. I would like to also thank the jury members of the award for selecting me for the award. Finally, I would like to thank my family for their support.
| Opioid Dependence and Its Management|| |
It is well known that opioids are one of the world's most problematic illegal substances. There were an estimated 33 million opioid users globally in 2014, much less than184 million cannabis users. However, among illegal substances, opioid dependence is the highest contributor to the number of disability-adjusted-life-years lost (9.2 million) and to drug-related deaths (43.5 deaths/million people aged 15–64 years)., Another concern is with the injecting route used to administer opioids. There are about 12 million injecting drug users (IDUs) globally, who face some of the most severe harms due to drug use, including blood-borne infections and deaths due to overdose. About one in seven IDUs is HIV-positive, and about half are hepatitis C positive.
India too has a sizeable problem of opioid use. The national survey published in 2004 estimates the prevalence of current opioid use to be 0.7% in general population. This corresponds to 2 million current opioid users and 0.5 million opioid-dependent people. These figures are likely to be much higher if the findings from recent surveys in some states are an indication. Similarly, the problem of Injecting Drug Use (IDU) in India seems insignificant if their numbers (177,000) alone is considered. IDUs, however, have the highest rates of HIV (9.9%) and hepatitis C compared to other population.,, IDUs also face other problems including abscesses (56%), blocked veins (53%), and overdose episodes (41%). In addition, almost all IDUs (98%) are dependent on opioids, because of which IDUs incur harms associated with opioid dependence as well. Opioid dependence itself affects the individual's physical, psychological, and occupational status, as well as his/her family.
While various strategies have been adopted to manage opioid dependence, not all of them are equally effective. Short-term withdrawal management (detoxification) alone or antagonist maintenance therapy with naltrexone results in high relapse rates and is less acceptable to patients., Agonist maintenance treatment with opioids (commonly referred to as opioid substitution therapy [OST] in India), on the other hand, has displayed better outcomes compared with other existing treatment strategies. OST helps in retaining the patient in treatment, reducing the use of illicit opioids and other substances, and in improving the individual's productivity and his/her quality of life. OST is, perhaps, the most researched treatment strategy. Various systematic reviews, including Cochrane review, meta-analysis, and review of reviews have found OST to work well in opioid dependence.,, Therefore, most treatment guidelines recommend that OST should be provided to all opioid-dependent individuals, unless there are specific contraindications to start OST in an individual.,,,
Clear pharmacological distinction between illicit opioids and the opioids used as medicines governs the practice of OST. The amount and the route of consumption of illicit opioids lead to their rapid onset of action and peak action lasting for short time. This compels the individual user to repeat the act of consumption several times a day. The repeated acts of consumption, experiencing the high at peak, and the withdrawals and craving at trough do not leave the individual with any time to focus on his/her work or family. Furthermore, the prohibitive cost of illicit opioids such as heroin leads the individual to spend his/her earnings on drugs, or worse, commit crimes to continue his/her drug use. The opioids used as OST medicine, on the other hand, have slower onset of action, longer duration of action, and are absorbed through safer routes. An adequate dose of OST gives much needed relief to the user for an entire day, and provides him/her with an opportunity to take charge of his/her life.
Globally, the journey of OST began more than 50 years back, when Dole and Nyswander used methadone to treat opioid dependence in New York and published their seminal work in the year 1965. Since then, OST has expanded to several countries. The 2016 report on the Global Status of Harm Reduction reports that OST is available in eighty countries. Methadone is most commonly used, followed by buprenorphine. Other agents such as slow-release oral morphine (SROM), codeine, and even heroin, are also used, but in a limited number of countries.
| Journey of Opioid Substitution Therapy in India|| |
Some argue that OST existed in India even before the USA began to use methadone as OST, and that the “opium registry” system was similar to the present-day OST. During British rule in India, regular opium users who required opium on a long-term basis were registered and provided with the option to purchase fixed quota of opium from a licensed shop. After India gained independence, new registrations were stopped in the year 1959 because of the principle of prohibition of nonmedical use of intoxicating substances enshrined in constitution. The number of cases has reduced from 200,000 in 1956 to few hundreds in the last decade. Whether registering users and regular supply of opium can be construed as OST is open to debate. I have divided the journey of OST in India into three broad phases. Since we are discussing addiction here, let us go with the analogy of the “stages of change model.” In keeping with the changing attitude of the country toward OST, let us call these phases of evolution of OST in India as “contemplation,” “preparation,” and “action” phases.
The phase of “contemplation” (1989–2004)
The modern journey of OST began with the use of buprenorphine for the treatment of opioid dependence in 1989 by the then Deaddiction Centre, AIIMS, New Delhi, which has continued till date. The lower strength of 0.2 mg tablet was used initially till the launch of higher strengths of 0.4 and 2 mg in 2000. A nongovernmental organization (NGO) in New Delhi also started OST in community settings in 1993. The cumulative dose of buprenorphine used then was low (around 2 mg a day per patient). Yet, the retention rates were excellent (81% at 24 weeks), with recorded improvement in opioid use and addiction severity. However, OST remained confined to a handful of medical college hospitals and NGOs in this phase. In a way, the country was contemplating this particular treatment option.
“Preparation” phase (2005–2007)
This phase witnessed two distinct projects on OST that helped the change in attitude toward OST in India though their purpose was different from each other. A project supported by the Department for International Development, the United Kingdom, supported OST in various centers across India with an aim to increase OST for the prevention of HIV among IDUs. It provided financial support as well as built capacities of more than thirty NGOs to provide OST for a limited time duration. Around the same time, UNODC, Regional Office for South Asia with the help of National Drug Dependence Treatment Centre (NDDTC), AIIMS, started a study across five centers in 2005–2006 to prove to the critics that OST works the same way in India as elsewhere. More than 250 opioid-dependent patients were provided OST and followed up for 9-month period. The study found high retention rates with OST (79% at 3 months and 64% at 9 months). There was a notable improvement in the addiction severity, opioid use, injecting episodes, and in the patients' quality of life by the end of 9 months.,
Similarly, there were developments in the pharmacological agents for OST in this phase. Since the plain buprenorphine formulation was susceptible to diversion and injecting, it had to be dispensed only as “directly observed treatment.” This meant that patients had to come to the center daily to receive their dose of buprenorphine, which was a major drawback when patients resumed their working. In 2006, the combination product of buprenorphine with naloxone was launched in India to prevent diverting buprenorphine to injecting and provide choices for “take-home” dispensing. This changed the practice of using OST in government and private settings. At NDDTC, we started dispensing buprenorphine-naloxone for up to one week to patients who had improved after stabilization on plain buprenorphine for three months. NDDTC also tried SROM for the treatment of opioid dependence in 2005. Literature published on SROM showed that it was equally effective to buprenorphine in the control of opioid withdrawal and craving and in maintaining improved quality of life at least in short term.,
However, a greater development was in the HIV/AIDS sector. By 2005, with the threat of an explosive HIV epidemic looming large, the country started systematic planning of the third phase of the National AIDS Control Programme (NACP III). The NACP III “Strategy and Implementation Plan” document outlined various “harm reduction” services to prevent HIV among IDUs, including needle syringe exchange, abscess management, condoms, and residential care services. However, for OST, the document stated that guidelines and best practices on OST are lacking in India and there was a need for national consensus on OST. This was true in some measure as India did not have experience of running a large-scale OST program. The noninclusion of OST was surprising as, by then, the United Nations agencies had bought out a position paper suggesting the definite role of OST in the prevention of HIV among IDUs.
Thus, by 2007, some medical college hospitals used buprenorphine for OST and gained clinical and research experience. Higher strength buprenorphine as well as buprenorphine-naloxone became available, and limited multicentric projects were implemented to build evidence base and to expand OST in India. By now, the country has been adequately prepared to move to the action phase.
“Action” phase (2007 – till date)
After completing my senior residency in 2007, I had an opportunity to work in NACO, which is the nodal government agency in the Ministry of Health and Family Welfare (MoHFW), for addressing HIV problem in India. The experience was unique not only for me, but also for the organization! For the first time, a psychiatrist was appointed to work on the IDU program at NACO. My brief as the Programme Officer (IDU) was to assist NACO in scaling up HIV prevention services for IDUs in India, with a major focus on OST.
One of my first tasks was to prepare and get a scheme of OST approved for implementation as the NACO Programme. Questions on OST were still raised both within the establishment and from outside. The comments ranged from scorn (government as an “official” drug dealer, money being “wasted” on undeserving people) to fear for OST (officials can be jailed if OST medicine is misused). Despite this, all government departments and ministries, including those from drug supply reduction and from drug demand reduction sectors, approved the scheme. The scheme proposed to use both buprenorphine and methadone as OST medicines, with a plan to provide 20,000 IDUs with OST by the end of the NACP III, i.e., 2012. Although methadone was cheaper to buprenorphine globally, NACO started its OST Programme with buprenorphine as India did not have methadone then.
The next step for NACO was to take-over the existing OST centers working for HIV prevention among IDUs, funded by other “donor” agencies. For this, an evaluation exercise was carried out in 2007–2008 with the support of NDDTC and UNODC to assess the status of OST centers and to identify any gap in their functioning. The evaluation revealed several interesting findings. All the 52 centers providing OST as part of HIV prevention were NGOs. Medical care made up a small part of OST, and many centers were “community based” run by people who use drugs. There were distinct advantages of this service delivery model: the clients could seek treatment without feeling stigma and discrimination, and the centers provided all possible help to the clients. A certain air of informality existed in the functioning of these OST centers. The informality also had its own downsides. The centers did not follow recordkeeping strictly, and on occasions, the nonmedical staff dispensed or changed the doses of buprenorphine! To address such issues, documents outlining the clinical practice guidelines for buprenorphine-based OST and the standards in a NACO-supported OST center were prepared., To lend further credibility to the NACO OST Programme, an external agency, the National Accreditation Board for Hospitals and Healthcare Providers, was tasked with accrediting the NACO OST centers. An elaborate supply chain mechanism for buprenorphine was put in place to prevent potential diversion or stock-out of OST medicines. Buprenorphine was procured centrally for all NACO OST centers, which resulted in notable drop in its price, and huge savings to the national program.
All these still did not lead to the expansion of OST Programme beyond 52 NGO centers catering about 5000 IDUs. One of the reasons was the extensive time utilized in setting up various systems, including accreditation, procurement, supply chain, and reporting. Another reason was concern about nonsustainability of and resulting lack of faith in the NGOs. Government hospitals, which are permanent systems of medical care, were perceived by NACO as better alternatives to provide a medical service such as OST. However, there were certain concerns in involving the government hospitals too. Most government hospitals did not have experience with OST, and one was not sure how comfortable would the IDUs feel in using OST services in government hospitals. To address these issues, a scheme was drafted which proposed a unique collaborative model. By 2010, there were more than 150 targeted interventions (TIs) providing other harm reduction services in India. NGOs used to handle these TIs and had a good connection with IDUs in the field. Therefore, the TI working near the government hospital was tasked with motivating the IDU client for OST in the field and helping him/her in initial access to the OST center located in the hospital. Field-based follow-up was also entrusted to the selected TI. The government hospital was entrusted with the medical part of the OST (assessment, diagnosis, daily dispensing of medication, and counseling as well as clinic-based follow-up). The psychiatrist or senior medical officer of the hospital was made in-charge of the OST center and was provided with a team of one doctor, nurse, and counselor hired on contract basis. The scheme was piloted in five government hospitals in the state of Punjab in 2010. Punjab was chosen due to documented evidence of large number of IDUs with a high prevalence of HIV among IDUs in the state.
The pilot scheme in Punjab was a huge success and allayed the initial concerns on the feasibility of scheme. The pilot scheme demonstrated that the collaborative model can harness the strengths of the two different types of institutions, with good retention rates on OST. The experience gained from the pilot scheme guided further expansion of the NACO OST Programme. Most of the expansion of NACO OST Programme is now through the collaborative model of OST, with two-thirds of the OST centers located in government hospitals. An interesting aspect of this expansion is that many psychiatrists and psychiatry departments in medical colleges are now experienced in providing OST. We conducted an assessment of NACO OST centers in 2012 and found that most centers adhered to the NACO OST guidelines and standards, and the clients were satisfied with the treatment. However, there were certain problems in the functioning of OST centers. The dose of buprenorphine used was on the lower side (average: 4.4 mg/day). Sizeable proportion of clients (35%–40%) reported withdrawal and craving and used illicit opioids (28%). There was an urgent need to improve the capacity of the staff working in OST centers to cater to the rapid scale-up of NACO OST Programme.
It is well known that training in addictive disorders in undergraduate medical, nursing, or paramedical courses is minimal. Most psychiatrists were also not familiar with the clinical practice of OST during the early scale-up of NACO OST Programme. The Punjab pilot project had set up the modality, duration, and module for training on OST. What was needed now was an institution mechanism for delivering training on OST. Thus, through a project supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria, OST training was integrated in psychiatry departments of certain medical institutes. Psychiatry departments in five (later expanded to eight) medical colleges provided training on medical part of HIV prevention among IDUs. NDDTC as the National Technical Training Centre took lead in the OST training and conducted 41 training programs on OST from 2012 to 2016 and trained around 900 staff members delivering OST services. Later, National Institute of Mental Health and Neurosciences and Regional Institute of Medical Sciences, Manipur, also undertook OST training with initial support from NDDTC. A study conducted to assess the effectiveness of induction training showed a significant improvement in the knowledge of all the staff cadres over the 5-day training. We have also developed an online OST training for NACO in collaboration with the Public Health Foundation of India to further standardize the training. In keeping with the knowledge and experience of OST in India, we also have updated the NACO clinical practice guidelines for buprenorphine-based OST.
After working for three years, I moved out of NACO in 2010 to join the South Asian Regional Office of the UNODC. At the UNODC, I was involved in efforts to set up methadone maintenance treatment (MMT) in India. The office of the Drug Controller General, India (DCGI), granted license for domestic sale of methadone in 2010, and the project took off in February 2012 after clearances from various government departments. NDDTC, AIIMS, was the technical lead agency for this initiative, and MMT was piloted in five centers, including in NDDTC. I continued working on the MMT project after joining as faculty in NDDTC, AIIMS, in June 2012. The project ended in 2014 after the release of the report documenting the experiences and results with MMT. The project showed that it is feasible to use methadone for the treatment of opioid dependence in India across different government hospital settings (medical college hospitals, district hospitals, and government hospital-run community clinic). The project also set up procedures related to procurement, supply, and dispensing of methadone, and training of staff on MMT. Although the retention rates were lower, the improvement noted in opioid use, other substance use, as well as quality of life was similar to that of buprenorphine-based OST. Thus, another pharmacological option for OST became available in India.
A major limitation of the OST programme as it exists today is that most OST centers are funded by NACO and restriction of OST only to IDUs. People who are opioid dependent but use opioids through noninjecting routes do not get access to OST from these centers. An opportunity to scale-up OST for all opioid-dependent patients presented when the Drug De-addiction Programme (DDAP), MoHFW, asked NDDTC to draft a scheme to strengthen the existing DDAP. Thus, NDDTC launched the scheme titled, “Strengthening DDAP: Establishing 'Drug Treatment Clinics' (DTC),” under which selected government hospitals would open outpatient-based clinic (DTCs) for the treatment of all substance use disorders. The issue of nonprovision of staff and medicines from the state in the de-addiction centers is addressed through central funding for contractual staff and medicine for DTC. As of January 2017, 14 DTCs are operational, and another 6 DTCs would be functional by 2017. The DTCs also provide OST (including methadone and buprenorphine) to opioid-dependent patients. The scheme won the prestigious British Medical Journal South Asia Award 2016 under the “Noncommunicable Disease Initiative of the year” category. Discussions with MoHFW are ongoing to scale-up this scheme in India in the coming years.
Thus, so far, the journey of OST has been quite turbulent and eventful in India though it is far from over. Let us now look at various achievements and challenges with regard to OST in India.
| Achievements and Challenges|| |
India has rich clinical experience in OST and expertise of carrying out large-scale OST Programme. Different OST models (stand-alone NGO centers, stand-alone government centers, and the NGO-government hospital collaborative model) have been tried and found to be feasible and useful. Most OST models in India have adopted a “low-threshold” approach, in keeping with the current scientific understanding, which provide OST on an outpatient basis, with no undue strict entry criteria. Patients using illicit opioids while on OST are not punished; rather their dose is optimized. Even those who want to restart OST after relapse are provided smooth re-entry. India has also been able to develop, test, and use various capacity-building materials such as training modules and clinical guidelines. Thus, we now have the necessary recipe for a successful scaled-up OST Programme. Most of these models and tools have been developed and fine-tuned using in-country expertise. The availability of OST services in some government medical college hospitals ensures that young psychiatry trainees receive clinical exposure to OST.
Although there has been significant expansion of OST in the past 10 years with roughly 25,000–30,000 recipients of OST, even if the old data from the only national survey conducted were considered, till date, only 5% opioid-dependent individuals receive this treatment which is recommended by most guidelines. Another issue is with the ambit of expansion of OST in India. While the NACO Programme helped in major scale-up of OST, it is feared that OST may become branded as an intervention reserved only for IDUs as harm reduction. The fact of OST as a long-term treatment of opioid-dependent people irrespective of their injecting status may take a backseat. Other countries where OST has started or scaled up mainly for HIV prevention among IDUs have also witnessed such concerns.
India has a thriving pharmaceutical industry which produces and supplies medicines at cheaper costs. This is also the case with OST medicines, and a major reason for cheaper availability of buprenorphine is because of its domestic production. The price of 2 mg buprenorphine is already down to INR 4–5 a tablet because of large-scale procurement, and the cost of therapy for a patient comes down to INR 20–25 a day. The cost of per-day treatment for methadone is already nearly equal to buprenorphine, even though currently, only one pharmaceutical company has license for domestic sale. If more companies enter the fray, the resulting competition can bring methadone prices down. Thus, cost of medicines cannot be cited as an excuse now for slowing down the scale-up of OST in India. However, at times, overzealous marketing by pharmaceutical companies can also lead to erroneous use of OST medicines and bring disrepute to the overall treatment.
Since its enactment, Narcotic Drugs and Psychotropic Substances (NDPS) Act allows the use of narcotic and psychotropic substances for medical and scientific purpose. NDPS Act lists methadone and buprenorphine under the category of narcotics and psychotropic substances, respectively. The laws for manufacture, transport, and sale of these two groups were different till recently. The licensing authority and licensing requirements for narcotics were different for different states as the power to frame laws for narcotics lied with the state governments. The MMT centers required licenses to transport and store methadone, which had to be renewed annually. After the amendment of NDPS act in 2014, certain narcotics, including methadone, are labeled as “Essential Narcotic Drugs.” The amendment has made it far easier to use methadone for opioid dependence treatment. The law on using buprenorphine was not strict; storage license or annual renewal was not required. However, the condition imposed by the DCGI for sale of higher strength buprenorphine to “deaddiction” centers only has led to confusion. As there is no standard definition of a “deaddiction center,” some states have drafted their own definition, and has made it difficult for psychiatrists, especially in private sector, to prescribe and dispense buprenorphine. Thus, we have a situation where it may become easier to use a full agonist such as methadone than a partial agonist such as buprenorphine, which is safer than full agonist. India seems to be moving away from practices followed in other countries, which regulate methadone strictly and allow buprenorphine for use as office-based practice. The issue of harassment of private psychiatrists for prescribing OST is a serious one. It is well known that out-of-pocket spending on health is higher than public health spending in India. In such a scenario, keeping private sector away from OST would mean continuing the wide gap between demand and supply for OST. Of course, training and following ethical practices and clinical guidelines in private sector are also important. The gap between demand and supply also increases the potential chances of diversion of OST medicines, which then brings disrepute to the entire treatment itself.
| Conclusion|| |
It has taken more than 25 years for OST to reach to the current status in India. There has been considerable progress on this front, especially in the last decade. Multiple factors have worked for OST in India. These include involvement of professionals right from the onset, working within and with the national programs, developing and implementing county's own models of delivery of OST, and an active collaboration between professionals and the affected community. However, OST is still viewed by some as a “substitute” rather than as a “treatment” of opioid dependence. Various stakeholders, including psychiatrists, still have fear using opioid medications resulting in denial of OST for most people who need it. The OST journey has begun well, but there are still miles to go before we can ensure that opioid dependence treatment with opioid agonists is placed on the same pedestal as treatment of other mental illnesses.
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Department of Psychiatry, National Drug Dependence Treatment Centre, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None