Table Of ContentHandbook of Methadone
Prescribing and
Buprenorphine Therapy
Ricardo A. Cruciani
Helena Knotkova
Editors
123
Handbook of Methadone Prescribing
and Buprenorphine Therapy
Ricardo A. Cruciani (cid:129) Helena Knotkova
Editors
Handbook of Methadone
Prescribing and
Buprenorphine Therapy
Editors
Ricardo A. Cruciani Helena Knotkova
Department of Pain Medicine Department of Pain Medicine
and Palliative Care and Palliative Care
Beth Israel Medical Center Beth Israel Medical Center
New York , NY , USA New York , NY , USA
ISBN 978-1-4614-6973-5 ISBN 978-1-4614-6974-2 (eBook)
DOI 10.1007/978-1-4614-6974-2
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2013936725
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Foreword
This volume describes the evolving role of methadone and buprenorphine—
pharmacologically distinct opioids that share clinical utility in the management of
both pain and addiction. It is a timely work given the attention now focused on the
effort to improve the safety of long-term opioid therapy for pain, in part by better
management of drug abuse outcomes. By highlighting the role of two drugs with
complex pharmacologies that have the potential for both liability and benefi t in two
types of challenging disorders, it explores larger issues that have profound impor-
tance for the broader use of opioids in practice.
Opioids have been used therapeutically for millennia and it is diffi cult to imagine
a class of substances that has had a more tumultuous history. During the past 50
years, the medical community has repeatedly revised standards and practices related
to opioid therapy in response to new information, experience, or risk-related con-
cerns. Practice guidelines have appeared repeatedly, but become outdated quickly.
Changes in the perception of opioid drugs and their clinical use in the treatment
of pain or addiction have diverse and complicated drivers. To some extent, changes
over time refl ect the emergence of a large basic science literature related to endor-
phin physiology, nociception and brain reward mechanisms, and opioid pharmacol-
ogy. Perhaps more important from the clinical vantage, however, is a large literature
comprising mainly short-term trials and epidemiologic studies that have supported
the effi cacy of opioid therapy in heterogeneous patient populations while delineat-
ing a complicated risk profi le that includes overt and occult side effects and toxici-
ties, and the potential for abuse, addiction, and overdose. Although the latter data
may be criticized for their questionable relevance to long-term opioid therapy in
populations of patients with pain or addictive disease, they demonstrate the types of
responses that must be assessed and managed if clinical use of these drugs is to be
safe and effective.
The complexity inherent in the clinical use of opioid drugs means that it is pos-
sible to frame a deeper discussion from any of a very broad array of directions. The
literature focused on pain, for example, can variably address the clinical pharma-
cology of the agents available or the challenges posed by specifi c populations.
v
vi Foreword
There are very stark differences in the information presented if the narrative
focuses on acute pain in inpatient settings, opioid management of pain related to
advanced illness, or the controversial use of long-term opioid therapy to treat
chronic pain. In the same way, the literature on opioid agonist therapy for addiction
reveals large differences in tone and content if the focus is on methadone therapy
or offi ce-based therapy using buprenorphine.
These issues, which are touched upon in this volume, are less pressing now than
the emerging literature on opioid risk assessment and management, which promotes
the need for risk-related knowledge and skills irrespective of the specifi c drugs,
indications, or populations receiving care. The essential nature of risk management
has become increasingly clear with evidence that drug abuse outcomes and uninten-
tional overdose have increased greatly with the rising prevalence of long-term opi-
oid treatment of chronic pain. With millions of patients exposed to these compounds
in an effort to provide analgesia and hundreds of thousands more receiving them in
an effort to suppress addiction, the skills necessary to minimize risk and manage
adverse outcomes are an obligation of every prescriber, in every context.
Methadone and buprenorphine each has characteristics unique among clinically
used opioids. They both deserve critical analysis from this perspective, particularly
as it relates to their expanding use for analgesia. Methadone has long been viewed
as a drug that offers a relatively inexpensive alternative to other pure mu agonists for
the treatment of pain, and one that can offer surprising effi cacy and potency when
initiated on rotation from another opioid. Increased prescribing for pain during the
past decade, however, has highlighted its challenges. It is now evident that metha-
done is more likely to yield serious adverse effects when prescribed for pain than
other mu agonists. This potential for adverse effects, which may be related to the
long and variable half-life, the unpredictable high potency when started after another
mu agonist has been on board, or the potential for QTc prolongation, must be under-
stood and managed to minimize adverse outcomes. Only clinicians familiar with
these issues should undertake prescribing for pain. The concern about toxicity
should not limit the use of this drug in the management of addiction, but should still
inform guidelines for initiating and monitoring therapy.
There is also extensive experience in the use of buprenorphine for pain, particu-
larly in transdermal formulations now available in Europe and the United States. In
the United States, the dose of this formulation is low and the use of oral transmuco-
sal formulations approved for addiction also could be considered for analgesic pur-
poses. Analgesic uses of this drug may be complicated, however, by the potential
for withdrawal when it is started during treatment with a pure mu agonist, and the
potential for a ceiling effect in practice. The management of withdrawal is appreci-
ated by those who are treating addiction, but guidelines for converting opioid-treated
pain patients to buprenorphine have yet to be tested. This challenge notwithstand-
ing, buprenorphine may be a drug with a broader potential as an analgesic given
favorable characteristics, such as a ceiling effect for respiratory depression and
lesser inhibition of the gonadal function.
Opioids are essential drugs and the problems they address are among the most
common and challenging in medicine. Risk assessment and management are critical
Foreword vii
elements in their use, irrespective of context. Methadone and buprenorphine are
accepted as effective treatments for addiction, and offer options for pain manage-
ment that may have advantages in selected patients. This volume describes the phar-
macology and clinical use of these agents and provides information that can assist
in ensuring safe use for addiction and effective integration of these drugs into pain
management.
New York, NY, USA Russell K. Portenoy, MD
Preface
I am a great believer in luck. The harder I work, the more of it
I seem to have.
Attributed to Thomas Jefferson and F.L Emerson. The Yale Book
of Quotations, ed.
Fred R. Shapiro (New Haven, CT: Yale University Press, 2006).
The opening quote on the relation between work and luck is clever but although
attributed to one of the Founding Fathers for many years it seems that Emerson
might have been who said it. Not surprisingly the “level of evidence” is intermediate
on this topic so we reference the Year Book of Quotations by Fred R. Shapiro that
is considered to be the most reliable source [1]. This situation, where the level of
evidence is not strong, is not uncommonly seen in the opioid fi eld where evidence
tends to be limited and recommendations often rely on expert opinions and best
practice guidelines [2]. Being aware of these limitations we invited to participate of
this book experts, world-renowned researchers, and clinicians that made the
commitment to present only information that is based on the highest level of
evidence or that what is considered to be the best practice.
Only two opioids, methadone and buprenorphine, are indicated for the manage-
ment of both pain and opioid-related drug addiction and, interestingly, both present
unique pharmacodynamic and pharmacokinetic challenges to the general practitio-
ner and pain specialist, justifying a separate analysis from the rest of the drugs in the
same family.
Methadone, fi rst synthesized as an analgesic in the period that preceded WWII,
in the 1960s became the drug of choice for maintenance therapy in patients with
opioid-related drug addiction. Due to the “stigma” associated to this drug its use
as an opioid analgesic became less popular, but about 20 years ago due to its very
good analgesic properties, long half life and low cost, became a viable option to the
newly commercialized long acting opioid formulations [3].
With the increase in methadone prescribing emergency room visit and deaths
attributed to methadone showed a sharp increase. Indeed, according to the Center
ix
