Detox Opioid
-
Upload
kbsreeganesh -
Category
Documents
-
view
22 -
download
3
description
Transcript of Detox Opioid
1
OPIOID AGONISTS FOR TREATMENT OF OPIOID DEPENDENCE (OATOD):
GUIDELINES FOR IMPLEMENTATION IN THE STATE OF PUNJAB
A. Background
B. Rationale and Scope of this document
C. Objectives
D. Basic facts about opioid agonist treatment of opioid dependence (OATOD)
E. Essential pre-requisites for starting OATOD
F. Guidelines on OATOD for opioid withdrawal (vis-à-vis clonidine)
G. Guidelines on OATOD for opioid maintenance (Opioid Substitution Therapy, OST)
(vis-à-vis naltrexone)
H. Regulatory aspects
Prepared by: Dr. Debasish Basu and Dr. Ajit Avasthi, Professors, Department of Psychiatry,
PGIMER, Chandigarh
Date Submitted to the Govt. of Punjab: 9th October 2014
Date Accepted for implementation by the Govt. of Punjab:
Date of Revision of these Guidelines: Two Years from the date of acceptance/ implementation
2
ABBREVIATIONS USED IN THIS DOCUMENT
BN: Buprenorphine sublingual preparations
BNX: Buprenorphine-naloxone fixed dose combination sublingual preparations
DCGI: Drug Controller General of India
DHS: Directorate of Health Services
DOT: Directly Observed Treatment
IDU: Injecting Drug Use, or Injecting Drug User
IRCA: Integrated Rehabilitation Centre for Addicts
NACO: National AIDS Control Organization
NCB: Narcotics Control Bureau
NDPS Act: Narcotic Drugs and Psychotropic Substances Act, 1985
NGO: Non-Governmental Organizations
OATOD: Opioid Agonist Treatment of Opioid Dependence, or Opioid Agonists for Treatment of
Opioid Dependence
OST: Opioid Substitution Treatment
PGIMER: Postgraduate Institute of Medical Education & Research, Chandigarh
3
A. BACKGROUND
Opioids are chemical substances (“drugs” in common parlance) that are psychoactive (i.e., they
alter mood, thinking, judgment, perception or other mental functions) and are highly addictive
(i.e., with their regular intake, the user becomes dependent on them psychologically and
physically, as manifest from any three of the following):
• having repeated strong craving for the substances,
• loss of control in regulating their use of these substances,
• needing progressively higher doses of the substances to achieve the same effect
[tolerance],
• experiencing very unpleasant psychophysiological reactions upon abruptly stopping their
use [withdrawal syndrome],
• neglecting alternative pleasures, interests and responsibilities of life in favour of spending
time on seeking, using or recovering from the effect of these substances [salience], and
• persistence with the use of these substances despite psychological or physical harm
because of their use [e.g., depression, venous ulcers, HIV and other infections, etc.]
Common examples of opioids include crude opium (afeem), poppy husk (bhukki), poppy seeds
(khuskhus), heroin (impure street version of brownish colored powder known locally as “smack”,
and relatively pure white powder often used by injecting, locally known as “chitta”, “white” or
simply “heroin”), and a list of “pharmaceutical” or “prescription” opioids (often locally called
“medical nasha”) including morphine, pentazocine (Fortwin), pethidine, buprenorphine, codeine
(in cough syrups such as Corex, earlier Phensedyl and Rexcoff), tramadol and
dextropropoxyphene (Proxyvon, Spasmoproxyvon or “Neela”, Dexovon, etc).
Opioid dependence causes severe harm to the:
• Individual (addiction, overdose, health problems including several infections,
academic/work loss, financial loss, and higher mortality due to a combination of factors
including overdose toxicity, accidents, infections and other medical reasons, crime and
other antisocial consequences, etc.),
• Family (family burden, disruption, marital discord, financial drain, social stigma)
4
• Society (higher crime rates, loss of productivity, social disruption), and
• State/nation (blocked progress, economic backwardness, instability, and general
disrepute).
The state of Punjab has been grappling with the problem of drug addiction for quite some time
now, of which alcohol and opioids are the major substances of use. Although no exact state-wide
direct estimate is available, the magnitude of the problem is apparent to people living in Punjab
and can be gauged by indirect estimators such as drug-related crime rates, bookings under the
NDPS Act, and drug seizure records. The reasons for this state of affairs are complex and
multifaceted, and these are beyond the scope of this document, but the magnitude of the problem
is undeniable. It is a “clear and present danger” to the very rubric of the society.
In view of this, the present Government of Punjab has taken several interlinked multi-level
systematic state-wide proactive steps to curb the menace, including measures of supply
reduction, demand reduction and harm reduction. Again, the details of these measures are
beyond the scope of this document, but one particular facet of this battery of steps is of direct
relevance to serve as the background of this document. This concerns the supply and use of
buprenorphine (BN), buprenorphine-naloxone combination (BNX) and tramadol as opioid
agonist treatment of opioid dependence (OATOD).
OATOD is a recognized, effective, evidence-based, and generally safe option for treating opioid
dependence worldwide. OATOD essentially involves the medically assessed and supervised
administration of safer and longer-acting opioid drugs for either short-term use in opioid
detoxification, or, in selected cases, for longer-term use as opioid substitution treatment (OST)
for preventing relapse of use of illicit opioids and for helping the users to re-build their lives
while on the cover of OST. It is especially useful in the context of injecting drug use (IDU) to
prevent HIV and other infections, and also in non-IDU of severe, chronic, multiple-relapsing
nature associated with crimes and other major complications.
So far, there is no problem. But we have to remember that opioid agonists like BN, BNX and
tramadol are themselves opioids, with all the psychoactive and addictive properties of
opioids outlined above. Thus, use of OATOD is a double-edged sword. When used properly,
5
it can save and re-build lives. When used improperly, it can cause damage just like any other
opioids. Hence the whole issue rests upon a “proper”, “balanced” or “rational” use of OATOD.
In this regard, of late, serious concerns have been raised regarding the ways in which OATOD is
being used in Punjab. Several issues have been brought to the notice of the authorities, which, if
unchecked, can bring the entire philosophy and practice of OATOD to disrepute, and can cause
more harm than OATOD purports to reduce. These issues are mentioned in the following section
(Rationale and Scope of this document). Given this background, the present document provides
guidelines for the rational use of OATOD so that it reaches the needy, while minimizing the
improper and irrational use of opioids in the name of so-called OATOD.
It has to be emphasized that Guidelines are not made in vacuum or in absolute terms. They have
to be sensitive to the social context so as to strike a right balance between the “benefits” versus
the “risks” of any given approach. Further, the risk-benefit ratio is not a stable parameter. It is
fluid, and often reflects the current practice. Guidelines have to recognize this shift of balance
between risks and benefits of a particular approach, and have to be modulated accordingly; lest
the “use” of an otherwise excellent treatment can rapidly swing into its “misuse” or even
“abuse”, eventually harming the very excellence of the approach, unless proper cautions,
regulations and monitoring standards are set in place by Guidelines. Medical history is replete
with such instances, starting from thalidomide and digitalis, to lithium, to clozapine, and others.
These Guidelines, thus, are NOT meant for disparaging OATOD by any means but rather to
encourage its rational use and discourage otherwise.
B. RATIONALE AND SCOPE OF THIS DOCUMENT
While a clearly evidence-based effective approved therapy for opioid dependence, OATOD, if
misused, has the potential of causing similar harm that it is supposed to reduce.
Some of these harms include:
• Creating – and maintaining – an iatrogenic (= caused by the treatment itself) dependence
(which may precipitate withdrawal when the supply of the drug is suddenly withdrawn),
6
• Fostering addiction by overuse of the opioid agonist drugs (post-marketing surveillance
survey of buprenorphine showed that 44.5%, or nearly half, of those maintained on
therapeutic buprenorphine, reported “a sense of high (nasha)”, which means that if used
in a higher dose, these drugs can cause opioid induced addictive effects),
• Endangering the lives of people with combined overdose of buprenorphine and other
nervous system depressants such as alcohol or benzodiazepines (as abundantly evidenced
in several countries where high-dose buprenorphine has been used for years, e.g., France,
Australia, New Zealand)
• Most worryingly, generating a parallel market of these potentially addictive drugs by
diversion of legally obtained buprenorphine (through prescription of doctors) for abuse
by self or others. This can be done in a number of ways, e.g.,
o Asking for a much higher dose of buprenorphine than actually needed or for a
much longer period – often for 30-day refills - and thus siphoning off extra
medication;
o Getting prescriptions written from multiple doctors (same patient registered at
multiple places);
o ‘Faking’ opioid addiction (falsely claiming that one takes heroin and hence needs
buprenorphine);
o Even ‘proxy’ patients (‘uncle’ getting prescriptions for his ‘opioid addict
nephew’), etc.
o The system has become such that the prescribing doctor sells the medicine at a
higher price (2-3 times higher) and then these are further sold off in the “market”
at a further much higher price.
Unfortunately, there is evidence – both from practising doctors and from many patients – that
these practices are in existence. The exact extent of such practices is difficult to ascertain, but
from anecdotal evidence converging from multiple sources, it appears to be substantial.
7
More importantly, there does not appear to be any proper ‘check’ or regulatory measures to
monitor the situation. Hence there is apprehension that the actual extent of these harms could be
much higher than anticipated, and may create a situation of uncontrollable chaos if the tide is not
stemmed right now.
The other major harms of the ‘misused’ OATOD system is that:
• Patients who are in genuine need of long-term opioid maintenance treatment may be left
out because of the huge siphoning off of buprenorphine in the parallel market, and,
• Finally, bringing the whole philosophy and practice of OST into disrepute; this will be
very unfortunate indeed.
As mentioned in the earlier section of this document, there is no absolute ‘right’ or ‘wrong’
about any Guidelines. They have to be sensitive to the social context so as to strike a right
balance between the “benefits” versus the “risks” of any given approach. The risk-benefit ratio is
not a stable parameter. It is fluid, and often reflects the current practice. Guidelines have to
recognize this shift of balance between risks and benefits of a particular approach, and have to be
modulated accordingly. The rationale of this document is guided by the current grave concerns
raised because of the unregulated and often irrational way OATOD and particularly OST (or
whatever goes in the name of OST) is being used in Punjab and its vicinity.
The ‘target population’ of these guidelines in this document is comprised of:
• The Government of Punjab (particularly its Drug Control Section, Govt. Drug
warehouses and Mental Health/De-addiction Cell of DHS)
• The manufacturers and suppliers of sublingual buprenorphine (BN) and sublingual
buprenorphine-naloxone combination (BNX)
• The doctors working in both government and private sectors who prescribe sublingual
BN and BNX and also tramadol for opioid dependence
This document does NOT target the NGOs and government hospitals which run NACO-
accredited and NACO-funded OST Centres for IDU patients (because there are already existing
8
detailed Practice Guidelines and Standard Operating Procedures produced by NACO which are
mandatory for these OST Centres).
• However, the Government might consider writing to NACO flagging up its concerns and
requesting NACO or its State Wing (Punjab State AIDS Control Society – PSACS) to
ensure that those guidelines and procedural safeguards are actually in place, or even
asking for data regarding the same).
The jurisdiction of these guidelines will be limited to the State of Punjab, though other States
and Union Territories of India may consider using or adopting these guidelines for their own
implementation as well. Eventually, the Government of India might consider formulating its own
policy.
It is worthwhile to mention here that currently there are no existing guidelines at the national
level on OATOD in general and OST in particular. The National Policy on NDPS Act (2012)
does have a small section called “Harm Reduction”, which takes a rather narrow and disparaging
view that has been called into question and are under revision. It makes some general overview
statements, which are summarized in the Clause 73 of the National Policy (quoted below).
“73. In view of the above, the approach towards harm reduction will be as follows:
a) Drug addicts including injecting drug users (IDUs) will be identified and treated and their
drug-using habit will not be supported or incentivised.
b) However, in cases where it is not possible to convince an IDU to undergo de-addiction, as a
first step, clean needles and syringes or oral substitution may be provided to him.
c) Harm reduction techniques as indicated in (b) above may be practiced only by hospitals or
centres set up or supported by or recognized by the Central Government or any State
Government.
d) If anyone or any organisation other than those indicated in (c) above distributes needles and
syringes or drugs for oral consumption to addicts, it shall be treated as abetting consumption of
drugs and such person or organisation will be treated accordingly under the NDPS Act, 1985.
9
e) The centres indicated in (c) above promoting ‘harm reduction’ shall maintain records of each
of the addicts and shall switch them to de-addiction as soon as possible preferably within one
year but in no case later than two years.”
These statements have been criticized as focusing only on IDUs, and taking a rather strict and
narrow view of the complex issue. However, because this is still the National Policy in force, we
have taken note of them and have tried to accommodate them as much as possible without
eroding the scientific evidence base.
Levels of Recommendation used in these Guidelines
Based on the extensive scientific literature, existing guidelines and position papers of national
and international bodies, policies in other countries where OST is practiced, experience of using
OATOD in our country and relevant publications, an iterative consultation from multiple
stakeholders, and – last but not the least – emerging issues and concerns about the real-world
practice of OATOD in the State of Punjab and its vicinity as evidenced in recent times – these
Guidelines are formulated so as to provide THREE levels of recommendations in order of their
strength. Three verbs are used for statements of recommendation, in decreasing order of strength
of recommendation, as follows:
I. “MUST / MUST NOT” – it refers to recommendations that are felt to be mandatory. It
implies that, if not followed, penal or other administrative sanctions may be imposed by
the relevant authorities.
II. “SHOULD / SHOULD NOT” – it refers to recommendations that, although not
mandatory, are felt to be desirable. These should be followed to the extent possible, as a
matter of good practice.
III. “MAY / MAY NOT” – it refers to recommendations that, though generally advisable,
are felt to be optional. It will depend upon the individual or the agency concerned to act
upon these recommendations based upon their evaluation of other options.
10
C. OBJECTIVES
1. To ensure proper and rational use of OATOD and especially OST for opioid dependence
in Punjab.
2. To discourage and minimize improper and irrational use of the same.
3. To evolve a state-wide mechanism for achieving the above two objectives.
D. BASIC FACTS ABOUT OPIOID AGONIST TREATMENT OF OPIOID
DEPENDENCE (OATOD)
The basic premises of using an opioid agonist agent for treating opioid dependence are:
• The licit (medically given) opioid would block the withdrawal and craving for illicit
opioids (i.e., reduce ‘drug hunger’).
• The licit (medically given) opioid would block the intoxicating and rewarding effects of
illicit opioids (i.e., reduce ‘drug reinforcement’).
• The licit (medically given) opioid, being long-acting and relatively safe (because of
proper dose and lack of toxic adulterants, lack of injection and sharing related adverse
consequences), would reduce the harms associated with use of illicit opioids.
• Because of the above factors, the person on OATOD does not have to spend time, money
and efforts to procure or use of illicit opioids, including indulging in petty crimes, drug
smuggling, harming others, etc. The person can now focus on re-building one’s life, lead
a stable life, move towards rehabilitation, and eventually come out of the drug habit,
including the temporary dependence on the medically given opioid.
As of now, the only opioid agonist approved for the treatment of opioid dependence is
buprenorphine via sublingual route, either alone (BN) or in a fixed-dose combination with
naloxone (BNX). Oral tramadol is the other opioid commonly used for this purpose.
Dextropropoxyphene is now banned in India, and other opioids including methadone and slow-
release morphine are still not available other than research settings.
11
Of the two preparations of buprenorphine available in India, BNX is safer from the angle of
abuse than plain BN, because BN can be abused by injection but BNX causes unpleasant
withdrawal reaction if injected. Plain BN can only be advised if administered in front of one’s
own eyes and ensured that the patient has completely dissolved the entire tablet in saliva (known
as Directly Observed Treatment or DOT). DOT is administered in NACO-accredited OST
centres for IDUs. For all other purposes and in other settings especially take-home doses in
outpatient settings, BNX is a safer bet (though this too can be abused if taken in a higher dose
than required).
It is to be further noted that oral substitution treatments are approved for treatment of opioid
dependence only “by hospitals or centres set up or supported by or recognized by the
Central Government or any State Government” (National Policy on NDPS Act). The Drug
Controller General of India (DCGI) has further stipulated that BN and BNX can be supplied by
the manufacturers only to “designated de-addiction centres set up by the Govt. of India
funded by the Ministry of Health and Ministry of Social Justice & Empowerment and
hospitals with De-addiction facilities”, and further that “a list of the centres to whom supply
of the drug is made should be submitted to this Directorate periodically indicating the
quantity supplied to each centre.” (DCGI)
Tramadol, though outside the purview of these directions, and though available with retail
chemists against valid prescriptions, is used widely for opioid dependence. Although effective in
treating opioid withdrawal, tramadol has certain disadvantages, such as a short duration of action
and propensity to cause seizures when used in higher doses.
It is important to emphasize that OATOD is used for two very different indications and different
scenarios:
• Short-term Treatment of opioid withdrawal during detoxification phase
• Long-term treatment of opioid dependence during maintenance phase
The short term treatment is for acute opioid withdrawal during detoxification phase. This is
usually given for 7-14 days, where the dose of BN / BNX is built up to 6-8 mg/day (occasionally
up to 10-12 mg/day) and is tapered off without prolonging its use beyond this period after the
12
acute withdrawal is over. This is the current standard of treatment for opioid withdrawal during
detoxification phase. It is unlikely to cause major concerns regarding abuse and diversion.
The long term treatment is for opioid dependence during maintenance phase, also known as
opioid substitution treatment (OST). Most often this phase of treatment may be directly
continued from the initial (detoxification) phase. OST is long-term maintenance of the illicit
opioid user in a illicit-opioid-free but licit-opioid dependent state, for as long as the patient is
stabilized, crime-free, finds a job, gets into a stable relationship, has no longer craving and
preoccupation with drug seeking as an issue, can find enjoyment in an illicit-drug-free lifestyle,
has generated alternative interests and responsibilities, and has generally re-built his life and re-
integrated into mainstream society. OST typically employs lower opioid doses in Indian settings
(2-8 mg/day) but is continued for a longer period, typically 6 months to 2 years and occasionally
longer. The final aim is to gradually taper off OST after this period, with or without alternative
(non-opioid) medications.
In sum, the objectives of OST are:
• to reduce illegal and other harmful drug use, including repeated relapses,
• improve the patient’s health and well-being,
• reduce the risk of transmission of blood-borne infectious diseases,
• reduce death and other medical morbidities associated with drug use,
• reduce crime committed by patients,
• facilitate an improvement in the patient’s occupational and social functioning,
• improve the economic status of patients and their families, and, finally,
• to achieve abstinence from drug use, including cessation of the substitution treatment.
It is the OST phase of treatment that generates lots of controversies and is often misunderstood,
by the policy-makers, and often by doctors as well as by the patients. Perusal of the objectives of
OST stated above will clarify some of these misunderstandings. OST is NOT simply substituting
one addiction with another. It is about giving a chance to the patient to organize and lead a stable
illicit-drug-free lifestyle.
13
Neither doctors nor patients should take OST as a “Short-cut” or “Easy-way-out” to
obtaining illicit drugs in a licit manner and living indefinitely in this manner. To give an
analogy, when a leg bone is fractured, one has to use a plaster casing and a crutch to
support the leg as long as it takes for the internal stabilization and recovery takes place till
such time the bone heals and the leg again becomes functional. Then the plaster casing and
the crutch is taken off. The crutch is for providing support to enable the recovery taking
place, though it performs the work of the leg as long as it is used. The crutch is not the leg!
This brings us to the next section: Essential pre-requisites for starting OATOD.
E. ESSENTIAL PRE-REQUISITES FOR STARTING OATOD
1. The first essential pre-requisite of starting any OATOD (whether for short-term or long-
term use) is ESTABLISHING OPIOID DEPENDENCE. This may sound like stating
the obvious, but often is neglected, perhaps because it is too obvious!
2. The second essential pre-requisite is CHARACTERIZING OPIOID DEPENDENCE.
This includes the exact type(s) of opioid, route of use, quantity typically consumed, the
severity of dependence, and the adverse consequences of opioid dependence.
3. The third essential pre-requisite is CONSIDERING CAUTIONS AND
CONTRAINDICATIONS FOR OATOD. This includes exploring concomitant use of
other substances (especially other CNS depressants), and medical conditions that require
caution before starting OATOD (e.g., bronchial asthma, severe respiratory or hepatic
impairment, phaeochromocytoma, inflammatory bowel disease, and hypothyroidism).
4. The fourth essential pre-requisite is DOCUMENTING PREVIOUS ATTEMPTS AT
QUITTING (spontaneous and medically aided, including outdoor- and indoor-based de-
addiction treatments, with opioid or non-opioid medications).
14
5. The fifth essential pre-requisite is to have a PSYCHOSOCIAL MANAGEMENT
MODALITY, which is mandatory along with OATOD. This may be, at the minimum,
provision of a Counselor, and at best, a multidisciplinary team of psychiatric social
worker, psychologist, vocational instructor and psychiatric nurse. The point is that
OATOD is not complete without concurrent psychosocial management.
6. The sixth essential pre-requisite is to have a QUALIFIED PSYCHIATRIST to start,
monitor and terminate OATOD. Only psychiatrists must start OATOD (after proper
assessment and documentation and after meeting the other essential pre-requisites). Other
professionals (medical, nursing, counselors and others) should, however, be involved in
monitoring various aspects of OATOD as part of a multidisciplinary team.
7. The final essential pre-requisite is to have a VALID AND ACCOUNTABLE SET-UP
within which OATOD can be carried out. This includes (a) a designated de-addiction
centre or other valid treatment facilities, (b) a valid and documented supply of the opioid
agonist drug from the manufacturers, and (c) a valid and documented system of
dispensing of the opioid agonist drug to the opioid dependent patients.
ALL THESE PRE-REQUISITES MUST BE FULFILLED.
F. GUIDELINES ON OATOD FOR OPIOID WITHDRAWAL (VIS-À-VIS
CLONIDINE)
I. Role of buprenorphine (BN)/ buprenorphine-naloxone combination (BNX).
(a) Inpatient.
1. Inpatient treatment of opioid withdrawal is indicated in the following circumstances:
• Individuals with drug overdoses
• Individuals at risk for a severe or complicated withdrawal syndrome
• Individuals with acute or chronic general medical conditions
15
• Individuals with a documented history of not engaging in or benefiting from treatment in a less
intensive setting
• Individuals with marked psychiatric comorbidity who are an acute danger to themselves or
others
• Individuals manifesting opioid use or other behaviors who are an acute danger to themselves or
others
• Individuals who have not responded to less intensive treatment efforts and whose opioid use
disorder poses an ongoing threat to their physical and mental health
• Patients on OST who want to discontinue their sublingual opioid but cannot do so in outpatient
setting
2. Plain sublingual buprenorphine (BN) may be used in INPATIENT SETTINGS ONLY, TO
BE ADMINISTERED UNDER DIRECT SUPERVISION OF NURSING STAFF. However,
fixed-dose combination of buprenorphine-naloxone (BNX) should be PREFERRED
because of lower potential for diversion and injectable abuse. Plain BN must not be used in any
other settings (other than NACO-accredited OST Clinics for IDUs under DOT scheme, which is
beyond the mandate of these Guidelines).
3. BN treatment should start after mild opioid withdrawal has started (usually 6-12 hours after
last intake of illicit opioids).
4. The usual starting dose is 2-4 mg sublingual. It may be increased by another 2 mg increment
after 3-4 hours if needed. Once-daily morning dose is sufficient in most cases.
5. In the Indian setting, the usual daily dose of BN is 4-10 mg.
6. The dose of BN can often be tapered off in 10-14 days in the inpatient setting. However, in
certain circumstances (high-dose high-potency opioid dependence) it may be extended up to 3-4
weeks. It must not be extended beyond 4 weeks for detoxification purpose in any case.
7. Psychosocial management must be continued.
16
8. Towards the end of detoxification (once the acute withdrawal symptoms have settled down),
various options for long-term management should be discussed with the patient and family.
These include: only psychosocial management (no medicines), long-term management with oral
naltrexone (plus psychosocial management), and long-term management with sublingual BNX or
oral methadone if available (plus psychosocial management). The final choice depends upon
various factors including medical condition, social and occupational stability, financial aspects,
patient preference and family preference. It is NOT NECESSARY to prescribe OST to each and
every patient (see next section).
(b) Outpatient.
1. A large number of opioid dependent patients can be detoxified on outpatient basis.
2. ONLY THE FIXED-DOSE COMBINATION OF BUPRENORPHINE-
NALOXONE (BNX) MUST BE USED FOR OUTPATIENT DETOXIFICATION
BECAUSE OF ITS LOWER POTENTIAL FOR DIVERSION AND INJECTABLE
ABUSE.
3. The dosage and duration remain largely the same as above (for inpatients), except that the
total duration of detoxification may be slightly longer (14-21 days) in the outpatient
setting. It must not be extended beyond 4 weeks for detoxification purpose in any case.
4. Other notes and recommendations remain the same as above.
II. Role of Tramadol.
1. BN/BNX is not available in many centres/clinics as of now. Tramadol, a relatively weak
opioid agonist with adjunct monoaminergic action, may be used in such circumstances as
a second-level option where the severity of opioid dependence and withdrawal merits an
opioid agonist.
2. The major advantage of tramadol is that it is available on prescription from retail
pharmacists, unlike buprenorphine which has to be supplied by (or purchased from) bona
fide de-addiction centres or hospitals with de-addiction facilities.
3. The major disadvantages of tramadol are: (a) its short duration of action, necessitating
three to four times dosing per day (even long-acting preparations are administered twice a
17
day), and (b) its epileptogenic potential, especially at higher doses. Further it has
addictive liability of its own, being an opioid.
4. HENCE, TRAMADOL MUST NOT BE USED FOR LONG-TERM THERAPY. IT
CAN ONLY BE USED FOR SHORT-TERM TREATMENT OF OPIOID
WITHDRAWAL AS A SECOND-LEVEL OPTION.
5. The dose of tramadol should be tapered as follows: 50 mg tablets 2 tabs 4 times daily (8
tablets daily) for the first 3 days, then 2 tabs 3 times daily (6 tablets daily) for the next 4
days, then 1-1-2 (4 tablets daily) for the next 4 days, then 1-0-1 (2 tablets daily) for the
next 3 days, to be stopped after 14 days. Thus, in a typical case, 70 tablets of tramadol 50
mg would be sufficient for one person’s detoxification. Of course, in individual severe
cases the requirement may go up to a maximum of 100 tabs for a 3-week course. The
central purchases have to be toned up accordingly. This state is likely to persist for the
next few months at least, till the current spate of thousands of patients with their supply
line of opioids suddenly cut down are taken care of.
6. Tramadol should be prescribed to patients with INJECTABLE OPIOIDS USE or
NON-INJECTED BUT PURE HEROIN (“Chitta”) OR PURE OPIUM USE ONLY.
IT SHOULD NOT BE USED FOR ANY AND ALL CASES OF OPIOID USE, like
bhukki, doda, low-quality opium, codeine cough syrups (Rexcoff etc.), propoxyphene
capsules (Proxyvon, Spasmoproxyvon, “Neela”, etc.). In such cases clonidine 0.1 mg
tablets should be used instead, along with symptomatic treatment. [Note: Tramadol must
not be used for patients with epilepsy or seizures due to any cause. Clonidine should be
used instead. On the other hand, BNX or tramadol may be preferred for detoxification if
clonidine is judged to be medically risky for use, e.g., in an elderly person with long-
standing poppy husk use where use of clonidine might lead to hypotension and
bradycardia. In the end, it is a clinician’s medical judgment considering the benefits vs.
risk of use a particular medication for detoxification.]
7. In case a patient fails detoxification with the above, he should be referred to district or
other designated drug de-addiction centres, where he can be prescribed buprenorphine-
naloxone combination for further treatment.
18
III. Role of clonidine.
1. Clonidine is a non-opioid medicine used for withdrawal management.
2. It is better than no active medicines, and somewhat less effective than buprenorphine or
methadone.
3. Its major advantage is lack of abuse liability. Another advantage is smooth induction on
naltrexone immediately after detoxification.
4. Its major disadvantage is risk of hypotension and bradycardia at higher doses, though at
the usual dose range (0.3 to 0.6 mg per day in three divided doses) the risk is minimal.
5. It can definitely be used in inpatient setting, with monitoring of blood pressure and pulse
rate.
6. In the outpatient setting, though some guidelines discourage the use of clonidine in the
outpatient setting, there is a large clinical experience from many centres in India on the
safe use of clonidine over more than last three decades.
7. Based on this, it is recommended that both BNX and clonidine are viable options for
treatment of opioid withdrawal. Clonidine is preferred in: (a) inpatient setting,
especially when there is no plan for long-term opioid maintenance, and (b)
outpatient setting in selected cases where the severity of opioid dependence is low or
where OATOD is risky or contraindicated (see E.3 above). BNX is indicated in
circumstances other than above.
8. It is re-emphasized that only BNX sublingual preparation and no other preparation of
buprenorphine (e.g., plain sublingual BN, injectable BN, BN transdermal patch) must
be used for this purpose, except in inpatient setting where sublingual BN may be
administered under direct supervision and ensuring that the tablets are fully dissolved in
the mouth.
This brings us to the next and the most important section, on long-term opioid maintenance.
19
G. GUIDELINES ON OATOD FOR OPIOID MAINTENANCE (OPIOID
SUBSTITUTION THERAPY, OST) (VIS-À-VIS NALTREXONE)
I. OPIOID SUBSTITUTION THERAPY (OST)
1. ONLY THE FIXED-DOSE COMBINATION OF SUBLINGUAL
BUPRENORPHINE-NALOXONE (BNX) MUST BE USED BECAUSE OF
LOWER POTENTIAL FOR DIVERSION AND INJECTABLE ABUSE. No other
preparation of buprenorphine (e.g., plain sublingual BN, injectable BN, BN
transdermal patch) must be used for this purpose. Similarly, no other opioids (e.g.,
tramadol, tapentadol, dextropropoxyphene, codeine, etc.) must be used for this
purpose, with the exception of methadone in selected centres on pilot basis under
direct observation only (i.e., no take-home dose).
2. Before starting OST, ALL the essential pre-requisites as mentioned in Section E above
MUST be fulfilled. OST may be started in the inpatient or outpatient setting but is always
continued in the outpatient setting only.
3. The indications for OST: Candidates for OST MUST meet criteria (a) or (b), AND all
the other criteria (c) through (i):
a. Injecting opioid use (i.e., opioid use through parenteral routes by injection like
IM, IV, SC, etc.) as the predominant route of use.
b. In case of non-injecting opioid use, the predominant opioid should be either
relatively pure white heroin (“Chitta”), other varieties of heroin like impure street-
variety brownish heroin (“smack”), pure opium, or other potent opioids. OST
SHOULD NOT BE USED FOR ANY AND ALL CASES OF OPIOID USE,
especially low-potency opioids like poppy husk (bhukki, doda), low-quality
opium, codeine cough syrups (Rexcoff etc.), propoxyphene capsules (Proxyvon,
Spasmoproxyvon, “Neela”, etc.).
c. An established diagnosis of opioid dependence, as confirmed by direct history
taking from the patient himself and corroborated independently from family
20
members, physical and mental examination of the patient, and, if possible, urine
analysis for presence of opioids. Diagnosis by “proxy” (e.g., diagnosis made
only from history given by people claiming to be family members or friends)
is not acceptable.
d. Duration of opioid dependence for at least two years or more.
e. At least two failed de-addiction attempts with other medications.
f. Serious medico-legal or psychosocial consequences due to opioid use/seeking
behavior.
g. Lack of social support.
h. Craving being significant reason for multiple past relapses.
i. Patient providing informed consent and undertaking for OST (see APPENDIX).
4. OST must NOT be started:
a. Without confirming and documenting opioid dependence
b. For any other substance dependence
c. With concomitant use of high doses of sedative-hypnotics or alcohol
d. In those below 18 years of age
e. With known hypersensitivity to buprenorphine or naloxone
f. In the presence of severe respiratory or hepatic impairment, or in any
circumstances where the CNS depressant effect of opioids may be accentuated
g. Without obtaining informed consent and undertaking for OST (see APPENDIX).
[Note: OST should be avoided, or may be started with caution and close medical
monitoring in the presence of pregnancy, during breastfeeding, and select medical
conditions such as bronchial asthma, pheochromocytoma, inflammatory bowel
disease, and hypothyroidism.]
5. The patient should be started on 2-4 mg of BNX (1-2 tablets), at a time when he is in
mild withdrawal, in the presence of the doctor/nurse and ensured that he uses the
medication properly and completely.
21
6. The correct dose of BNX is that which adequately suppresses withdrawal and craving,
blocks the effect of illicit opioids, but does not induce a sense of euphoria or ‘high’ or
‘kick’.
7. If withdrawal is not suppressed within 2 hours of intake, another 2 mg may be given.
8. The usual sufficient dose in Indian population is 4 mg – 8 mg (i.e., 2-4 tablets of BNX)
daily. Dose requirements in excess of 10-12 mg (5-6 tablets) per day should necessitate
careful medical re-evaluation or alert the clinician to a possibility of diversion.
9. BNX combination can be given as a “Take-Home” dose, with the following
ESSENTIAL CLAUSES:
a. The patient must be registered in an OST Clinic with some unique identification
number by which he can be linked with a computerized database.
b. The exact total number of BNX tablets dispensed to the patient must be
documented in (a) patient’s treatment card, (b) patient’s case file), and (c)
dispensing register maintained by the nursing staff.
c. The BNX tablets should be dispensed by pharmacist or nursing staff in the same
place where the prescription is made, ideally in the same or adjacent room, or as
close to it as possible.
d. The usual take-home dose should be for one week (7 days) only.
e. In case the patient asks for a take-home dose longer than 7 days, the doctor must
be convinced about the genuineness and unavoidability of the situation. This can
be done by detailed questioning of the patient, inspection of supporting
documents if any, and confirmation from family members. The reason must be
documented in the patient’s case file, with corroborating facts.
f. Even with this exception as above, the maximum duration for which take-home
dose of BNX can be supplied is for two weeks (14 days).
g. Under such extraordinary circumstances where even this 14-day period has to
be breached (e.g., patient developing a fracture or needing an emergency surgery
when his BNX consumption may go higher, or he cannot attend the OST Clinic
22
because of physical restrictions of movement), the doctor must personally satisfy
such need, with documentary evidence in the case file, and be held accountable,
for dispensing beyond the 14-day period.
10. Psychosocial management must be continued during the entire duration of OST.
Depending upon the resources available, this will include (a) relapse prevention
counseling, (b) motivation building, (c) coping skills improvement, (d) assertiveness
training, (e) vocational guidance, counseling and liaison, (f) facilitating alternative
interests and hobbies, family involvement, lifestyle modification, etc. and finally (g)
constantly reminding the patient that OST is only a “Crutch” or a “Stepping Stone” for
enabling full recovery to take place, when OST may be terminated. This last bit is
especially vital, so that the ultimate goal of OST is not lost. The management may be
provided in an individual, group or even family setting.
11. The typical duration of OST is a contentious issue. The decision regarding duration of
treatment and treatment-completion (i.e., tapering of agonist maintenance medication to
make patient opioid free) should only be arrived at in consultation with the patient and
involves evidences that patient is stabilized, is leading an illicit opioid-free life and is
socially and occupationally rehabilitated. Till such criteria are evident, the OST should
continue, if required, for very long duration (running into years). However, there is
evidence that unless a clear “goal for termination of OST” is maintained, there is a risk
that OST may become interminable, especially in government settings with free supply of
the opioid medication. Many doctors feel helpless in the situation where they feel they
have simply been reduced to “legal drug peddlers” prescribing buprenorphine but the
patients not showing any progress in their socio-occupational rehabilitation. Thus it is
better to keep a “goalpost” in view, which may be flexible to an extent.
12. With this background, and also keeping in view the National Policy on NDPS Act
recommendation, it is recommended that OST should be terminated “preferably
within one year but in no case later than two years.” However, in exceptional cases,
23
select patients may need it for longer periods, perhaps for another year or so. In
such cases, the exceptional need must be clearly documented in the case file.
13. Weaning off from buprenorphine can be difficult. Many patients find it difficult to
completely discontinue buprenorphine, especially after prolonged use. In such cases,
inpatient admission may be necessary for a short period (7-10 days) when detoxification
is done using clonidine followed by induction on oral naltrexone for 6-12 months.
14. A system of monitoring the OST is pivotal for ensuring its success as well as
minimizing its abuse. This is dealt with in the next section (Regulatory Aspects).
II. Role of Naltrexone.
1. Naltrexone is an opioid antagonist that (a) blocks the effect of illicit opioids, and (b) has
purported ‘anti-craving’ effects. It is available as 50 mg oral tablets. The standard dose is
1 tablet/day, though occasionally 2 tablets/day can also be given. Periodic liver function
monitoring is important.
2. The major advantage of naltrexone is that it is non-addictive, and has a long duration of
action.
3. The major disadvantage of naltrexone is that patients do not like it (unlike OATOD,
which is liked by the patients for obvious reason). Hence treatment retention is often low,
resulting in relapse.
4. However, it has been found to be reasonably acceptable (though much less than OATOD)
in Indian patients, many of whom have relatively milder opioid dependence (compared to
western patients).
5. It has been suggested that the following may be good indicators of attempting naltrexone
therapy rather than OST:
a. Shorter duration (less than two years) lesser severity of opioid dependence
b. Lesser severity of opioid dependence (as suggested by less withdrawal, tolerance
and craving; less adverse medico-legal and/or psychosocial adverse effects; no
evidence of injecting drug use; use of lower potency opioids such as poppy husk,
codeine, dextropropoxyphene or tramadol)
24
c. Coming to treatment for the first or second time
d. High motivation
e. Better social and occupational support
f. Higher levels of education; professionals; white-collared occupation
g. Patients on parole or probation from prison
h. Patients with co-morbid alcohol use disorders for whom treatment with anti-
craving agents may be indicated
i. Patients who express a desire for remaining free of any kind of opioids including
OST
j. Where the regulatory aspects of OATOD are absent.
This brings us to the final part of the OATOD, i.e., Regulatory Aspects.
H. REGULATORY ASPECTS
In order to strike the right balance between the correct use of OATOD and to minimize its
improper use, certain regulatory aspects are a must. These involve the role of central and state
governments, suppliers of opioid medications, and individual treatment centres and prescribers.
I. Central Govt.
1. The Drug Controller General of India (DCGI) must keep surveillance on the
manufacture, supply and utilization of opioid agonist drugs (especially BN, BNX,
and methadone).
2. Similarly, the Narcotics Control Bureau (NCB) should maintain similar
surveillance.
II. State Govt.
1. The State Govt. must endeavor to establish OST CLINIC IN EACH
DISTRICT/SUBDIVISIONAL HOSPITAL AS A PART OF THE DE-
ADDICTION CENTRES. This is absolutely vital to ensure that the genuine
25
patients with genuine needs receive their OST in a proper way from a bona fide
source. This is a pivotal step to weed out dishonest practices, black marketing,
illicit diversion and abuse of buprenorphine.
2. The State Govt. should ensure adequate supply of BNX in its drug warehouses all
the time.
3. The State Govt. may provide BNX free-of-cost to the patients of the Govt.-run
OST Clinics.
4. The State Govt. (Drugs Control) should keep surveillance on the manufacture,
supply and utilization of opioid agonist drugs (especially BN, BNX, and
methadone). This may be done by evolving a system of monthly tally of such
drugs purchased by the Govt., drug warehouse ‘mother’ stocks, quantity of drugs
supplied to individual de-addiction centres or OST Clinics, and utilization of these
drugs at these centres/clinics.
5. The State Govt. (Drugs Control) should keep surveillance on the manufacture,
box labeling, licensing, and sale of various strengths of sublingual buprenorphine
tablets (and its combinations with naloxone) in accordance with DCGI approval.
6. The State Govt. (Directorate of Health Services, DHS) should keep similar
surveillance on the functioning of the de-addiction centres (both in the Govt.
Sector AND in the private sector) and the opioid prescription bulk and patterns of
individual prescribers.
III. Manufacturers and Suppliers of opioid medications
1. They must comply with DCGI directions in this regard, and provide the details of
supply of drugs to various treatment centres and doctors to DCGI and DHS on a
monthly basis.
IV. Individual de-addiction centres
1. The de-addiction centres, or hospitals with de-addiction facilities, must be:
a. Set up/funded/approved/recognized by the Government, under the Ministry of
Health & Family Welfare (Drug De-addiction Centres, or NACO funded OST
Clinics attached with Govt. Hospitals), or the Ministry of Social Justice &
26
Empowerment (Integrated Rehabilitation Centre for Addicts (IRCA), or
NACO-funded NGOs running OST Clinics); or
b. In case of privately run Hospitals and Nursing Homes or any other Health
Establishments, these must be monitored and approved by the State
formulated Guidelines for “Minimum Standards of Care” as mentioned in the
Punjab Govt. Gazette Notification in December 2010.
2. These de-addiction facilities must maintain immaculate and detailed records of
opioid medications purchase from the manufacturers and supply or sale to the
patients. They must maintain at least three registers:
a. Entry of each purchase of the opioid drugs in the Central Consumable Stock
Register;
b. Disbursement of stock to the OST Clinic Drug Register; and
c. Supply/sale of these medicines (with exact quantity disbursed at each visit) to
individual patients in the Patient Register maintained at the OST Clinic. These
three Registers must tally regarding the total quantity.
3. They must also maintain a registry of OST patients, with their identifying numbers.
There should be some mechanism to ensure that these numbers can be matched with
those of other Centres, in order to ensure that the same patient does not get opioid
medication from multiple sources.
4. Each patient registered in the OST Clinic must have an individual case file which
would document their diagnosis (and how it was established), indications and
cautions for OST, details of dosing, dispensing, and status of the patient; and
psychosocial management. Termination plan from OST should also be mentioned.
5. They must issue specific quantity of BNX tablets to individual patients, which must
be mentioned on their OPD/OST Clinic Cards.
6. They must be vigilant for any suspicious activity alerting to the possibility of
diversion or abuse of BNX, such as:
a. Repeated requests for increased quantity of BNX in the absence of withdrawal
b. “Losing” OPD cards and asking for refill prescriptions
c. Proxy family members turning up instead of the patient for refills
27
d. Asking for prescriptions for long periods (beyond 7 days) without convincing
circumstances or corroboration
e. Appearing drowsy or under influence of opioids at follow-up visits, etc.
______________________________________________________________________________
APPENDIX: INFORMED CONSENT FORM FOR OST
(Given on the following pages: English, Hindi, and Punjabi versions)
[NOTE: The English is the generic version, and the Hindi and Punjabi versions are being used in Drug De-addiction and Treatment Centre, Department of Psychiatry, PGIMER, Chandigarh, hence bearing its name. These serve as models which may be adopted by replacing the name of the Centre suitably.]
28
29
30