Clinical Concepts
- Taming Drug Interactions Serious Concerns
Each year in the U.S. there are more than 2 million adverse drug
reactions, broadly defined as any unexpected, unintended, undesired,
or excessive response to a medicine. Such reactions may require discontinuing
or changing medication therapy, or can more seriously result in hospitalization
and/or permanent disability. Annually, there are more than 100,000
deaths attributed to reactions involving prescribed medications (Cohen
1999).
Three-fourths of those adverse reactions relate to drug interactions,
which occur when two or more drugs react with each other. Avoiding
these can be difficult, since the number of potential interactions
among diverse drugs used in clinical practice can be overwhelming.
More than 2,000 have been described in the literature and new cases
appear monthly (Levy et al. 2000). There are at least 100 substances – medications,
illicit drugs, OTC products, etc. – that can interact in some
fashion to affect patient response to methadone.
There also is the problem of polypharmacy. While multiple drugs are
often necessary for treating complex or resistant conditions, side
effects of the drugs themselves may induce disease symptoms, rather
than any pathological processes (Farrell et al. 2003).
This is of vital importance for patients in methadone maintenance treatment
(MMT) programs. These individuals often have co-occurring physical
and mental disorders requiring multiple medications.
However, it is estimated that 34% of prescriptions written in the US
are unnecessary. This trend is fueled by patients’ demands for
quick and effective medications for even minor ills, although they
seldom consider the potential negative consequences (Farrell et al.
2003).
In light of these considerations, MMT practitioners, as well as patients,
need strategies for avoiding or managing often unexpected and potentially
hazardous drug interactions.
Clinical Action Steps
The potential for certain drugs and drug combinations to interact with
methadone requires careful consideration when prescribing comedications.
Furthermore, polysubstance abuse may place patients at risk for hazardous
interactions of methadone with other opioids and drugs such as alcohol,
cocaine, barbiturates, and benzodiazepines.
Clinical experience, intuition, and common sense can be valuable tools
for MMT practitioners in taming drug interactions. Following are some
suggestions: (Chung 2002; Cohen, 1999; Levy et al., 2000; Piscattelli
and Rodvold, 2001)
Develop a working knowledge of methadone-drug
interactions. Methadone is metabolized by the P450 enzyme system,
primarily CYP3A4. The metabolic requirements of other medications
can be checked in manufacturers’ literature or standard references.
Maintain an accurate, updated profile for
each patient that includes all prescribed and illicit drugs, and
OTC products (including herbal remedies and dietary supplements).
Use alternative, non-interacting, drugs whenever
possible. Usually, there are differences in the interactive properties
of at least some members of any drug class. For example, the macrolide
antibiotic erythromycin is a strong CYP3A4 inhibitor, likely to
interact with methadone, whereas the macrolide azithromycin does
not appear to have this effect. Similarly, divalproex might be
substituted for carbamazepine, which is a potent CYP3A4 inducer.
If a potentially interacting drug absolutely
must be used with methadone, it is better to adjust the methadone
dose based on patient response rather than in advance based on
an expected interaction. The magnitude of drug interactions varies
dramatically from patient to patient, and it is unlikely that the
selected methadone dosage adjustment would exactly offset the effect
of the second drug.
Signs/symptoms of either abstinence syndrome
(withdrawal) or overmedication (sedation) can help gauge serum
methadone level (SML) adequacy in the presence of an interacting
drug. Adjustments of methadone or concomitant drug(s) may be appropriate
to overcome such adverse reactions.
If there are concerns about adverse effects
of increased methadone concentrations, patients should be advised
in advance of physical signs/symptoms of overmedication that might
occur and what to do. It may be desirable to monitor SMLs.
Whenever possible, avoid concurrent administration
of drugs with overlapping adverse-effect profiles. Otherwise, signs/symptoms
of major variations in methadone concentration may be confused
with side effects of concomitantly administered drugs, and vice
versa.
Consider preexisting disease states. For example,
conditions associated with impaired renal or hepatic function may
significantly alter drug metabolism and excretion. Patients with
preexisting cardiovascular conditions – particularly those
with congestive heart failure or left ventricular systolic dysfunction – may
be more sensitive to arrhythmogenic effects of certain drugs (including
methadone).
In some cases, adverse drug reactions can
be resolved by prescribing a medication with or without food, by
altering dosing schedules, or by splitting doses into smaller increments.
Unreported or seemingly inconsequential factors
may play a role in drug interactions. For example, grapefruit juice
can hinder metabolism and increase methadone serum levels, while
large amounts of vitamin C may boost excretion and decrease methadone
effects.
Patients may not adhere to prescribed medication
regimens, which could affect adverse reactions, and the more complicated
the regimen the less likely that the patient will adhere to it.
This can be important in MMT patients prescribed multiple medications.
The traditional advice when adding drugs to a therapeutic regimen is
to start low, go slow, and monitor closely. This may be
especially prudent during MMT, since many commonly prescribed drugs
are associated with dose- and concentration-dependent toxicities,
and individual response may vary by several orders of magnitude.
Potential adverse reactions also can be minimized by using the smallest
effective doses for drugs added to methadone therapy. In many cases,
doses of adjunctive medications lower than those recommended by the
manufacturer may be sufficient for desired therapeutic effect (Cohen,
1999).
Patient Education is Essential
It has long been recognized that patient education is essential for
successful MMT outcomes and this should be initiated early in treatment.
Several important points need to be emphasized with patients regarding
potential interactions of methadone with other substances and to help
them avoid all drug interaction. These are noted in the Table.
Better informed patients can partner more effectively with clinic staff
regarding their pharmacotherapy. However, as with all other aspects
of MMT, this relies on mutual trust and effective communication.
References:
Chung EP. A review of clinically significant drug interactions.
California Pharmacist. 2002 (Summer):56-65.
Farrell VM, Hill VL, Hawkins JB, Newman LM, Learned RE. Clinic for
identifying and addressing polypharmacy. Am J Health-Syst Pharm. 2003;60(18):1830-1835.
FDA/CDER (Center for Drug Evaluation and Research). Drug Interactions:
What You Should Know. Available at: http://www.fda.gov/cder/.
Levy RH, Thummel KE, Trager WF, Hansten PD, Eichelbaum M, eds. Metabolic
Drug Interactions. Philadelphia, PA: Lippincott Williams & Wilkins;
2000.
NCPIE (National Council on Patient Information and Education). Be MedWise®.
2003. Available at: http://www.bemedwise.org/
Piscitelli SC, Rodvold KA (eds). Drug Interactions in Infectious Diseases.
Totowa, NJ: Humana Press; 2001.
Beyond
Methadone - Drug Relapse: A Detour, Not An End of Recovery
An important goal of methadone maintenance treatment
(MMT) is sustained abstinence from illicit opioids and, ideally,
all other substances of abuse. However, one of the greatest impediments
to treatment success may be viewing drug relapse as an end of the
road to recovery, rather than as a temporary detour.
Lapse vs Relapse
Recovery commonly refers to a process of initiating abstinence from
illicit drug and/or alcohol use, along with necessary life changes
to help maintain sobriety over time. The process can be long and
arduous – a lifelong progression – with many obstacles
and setbacks along the way, including lapses or relapses.
The term lapse – often called a "slip" – denotes
an initial episode of drug or alcohol use after a period of abstinence.
It can end quickly or it may precipitate a more extensive relapse
of varying proportions.
Relapse is viewed as a breakdown in the recovery
process; a major digression in the individual’s attempt
to escape the bonds of addiction. Relapse involves both
a period during which there are usually observable signs
that the person is headed toward trouble as well as the
act of resuming extensive substance use, usually at a level
equal to or greater than previously. A repeated tendency
to relapse is often called "recidivism."
Patients, and sometimes treatment staff, often negatively view relapse
as a devastating personal failure indicating that the individual
may be incapable of achieving total abstinence. The reality is that
drug addiction is now accepted by most medical authorities as a chronic
relapsing disease, so periodic setbacks should be anticipated
and plans established for dealing with them.
Drug addiction frequently has been compared with chronic illness,
such as diabetes, hypertension, and asthma. Persons in treatment
for any of these may have difficulty adhering to the treatment regimen,
may sometimes drop out prematurely, and/or may experience setbacks
requiring more intensive care for their conditions.
Staying the Course
Some research studies have reported relapse rates of more than 70%
among persons in alcohol- or drug-abuse treatment. Most of those
occurred during the first year of treatment, with two-thirds of relapses
occurring within the first 90 days. As might be expected, patients
remaining in treatment the longest, staying the course, ultimately
have the best outcomes.
A belief that one drink or one drug-taking episode inevitably leads
to another and a return to total loss of control can be an obstacle
to recovery. Clear distinctions must be made between a "lapse" and "relapse";
otherwise, patients may assume that a little bit is just as bad as
a lot and turn every sobriety lapse into a relapse, possibly dropping
out of treatment entirely.
This has been called the "abstinence violation effect." A
person with a strict abstinence goal may view the slightest lapse
as a major failure rather than a learning experience, and with a "what
the heck, I blew it" attitude proceed to all-out relapse.
Since relapse is a process, slips leading up to it are not purely
accidental. Participants in 12-step programs say that SLIP stands
for "Something Lousy I Planned." Many small, seemingly
irrelevant, decisions may bring about a sampling of drug often leading
to relapse, and relapse prevention hinges on learning to recognize
those decisions earlier in the chain of thought.
It should be noted that 12-step programs make little distinction
between lapse (slip) and relapse; any use of an illicit drug
or alcohol is forbidden, no matter how fleeting. While this is sound
in principle, the practical side is that substance-addicted persons
are likely at some point to sample their drug of choice, especially
early in recovery, and this need not turn into a catastrophic event.
Readiness to Change
Relapse prevention is essentially about change, as is recovery itself.
However, for a person with addiction, change can be a fearful and
painful process, and relapse might be viewed as a lost struggle between
a person’s readiness to change and internal or external factors
that fight against it. Some patients prefer to dictate the rules
of recovery on their own terms, essentially maintaining the status
quo, and they repeatedly relapse.
Psychologists have wrestled with concepts of relapse to better understand
the process and develop models for its prevention. An important relapse
prevention model was developed by Marlatt and colleagues to extend
and enhance therapeutic gains during addiction treatment and to reduce
the possibility of recidivism.
A foundation of Marlatt’s approach is that it is easier to correct
the relapse process early rather than later. If the patient is provided
a set of recovery tools, a slip does not necessarily lead to a relapse,
and a relapse is not the end of recovery. Some of those "tools" are
listed in Table 1.
This notion of developing a set of recovery tools is common to 12-step
programs and most addiction therapies. Many of them are directed
at overcoming the pain and shame of lapses in sobriety; but foremost
is staying with the program no matter what happens.
Relapse triggers or cues, whether known or unknown, can be everywhere
and intimately woven into the fabric of a person’s life. Twelve-step
programs, always striving for practical approaches, emphasize that
following old habits and patterns of behavior associated with drug
use can rekindle cravings leading to slips. They also use the acronym
HALT – Hungry, Angry, Lonely, or Tired – to generally represent
critical situations and emotions to avoid.
Clinical Interventions
Marlatt classified precipitants of relapse into two broad categories:
intrapersonal and interpersonal. Intrapersonal factors include emotional
and physical states, a sense of personal control, and urges or temptations.
Interpersonal influences include relationship conflicts and social
pressures to use substances.
For example, Marlatt found that 19% of heroin addicts who relapsed
did so in response to negative emotional states (intrapersonal).
On the interpersonal side, some researchers have found that social
pressure was identified by 36% of heroin addicts as contributing
to their relapses; conversely, more positive social and spousal support
predicted a lower risk of relapse. In many cases, addicted persons
lacked coping skills for dealing in more positive ways with both
the intra- and interpersonal torment in their lives.
Many models of relapse intervention and prevention have been developed
and tested over the years. Most of these incorporate strategies from
Marlatt’s conceptualizations of relapse factors and, in one
way or another, focus on the patient’s need to develop personal
and interpersonal skills along with a broad repertoire of coping
strategies for dealing with previously baffling, upsetting, or high-risk
situations. Some practical clinical strategies for helping patients
are outlined in Table 2.
MMT Road to Recovery
MMT is a well-established, thoroughly studied, and successful model
of addiction treatment, combining pharmacotherapy (methadone)
with relapse prevention strategies. Yet, there is relatively
little scientific literature recommending how clinics can best
respond to lapses and relapses among patients.
MMT programs emphasize abstinence from opioids and, usually, all
other non-prescribed psychotropic substances. However, methadone
is a medication primarily proven useful for treating opioid addiction,
even though some research has found that, at adequate doses, methadone
curtails cocaine, alcohol, and other substance abuse in certain patients.
A critical factor is providing adequate methadone doses. If
patients are undermedicated they may be tempted to use other psychoactive
substances to overcome uncomfortable symptoms of withdrawal. This
then poses the dilemma of how to safely stabilize a patient on methadone
who is abusing other substances, some of which may interfere with
methadone metabolism or be harmful in themselves.
Relapse prevention strategies during MMT have varied. Some clinics
have successfully used reward incentives for continued illicit-drug
abstinence, but these can be expensive. Others have tried punishments
for even minor lapses, such as loss of take-home dose privileges
or reductions in methadone dose, which can be counterproductive.
More intensive counseling/therapy has been applied in some cases,
which seems like an appropriate strategy but also requires extra
time and patient motivation to change.
MMT programs may have an advantage over other addiction treatment
modalities in that regular clinic attendance to receive medication
is mandatory for an extended period of time – if those patients
are retained in treatment. There can be frequent opportunities for
patient interactions with staff, even apart from scheduled counseling
or group therapy sessions, during which principles expressed in the Tables above
can be reinforced.
As with all other addiction treatment modalities, there are no guaranteed
solutions for MMT practitioners to apply when it comes to preventing
lapses and relapses. The road to addiction recovery is never ending.
Whereas, sobriety lapses or slips might be best viewed as bumps along
the way, relapses always pose more difficult challenges.
If patients stumble and fall, it is important that they get back
up and move onward, rather than dwell too long on what tripped them
up. For some persons, stumbling, but falling in a forward direction,
is still a meaningful form of progress.
For further information see:
Daley DC, Marlatt GA, Spotts CE. Relapse prevention:
clinical models and intervention strategies. In: Graham AW, et al.
(eds). Principles of Addiction Medicine. 3rd Ed. Chevy Chase, Maryland:
American Society of Addiction Medicine; 2003:467-485.
Marlatt GA, Barrett K, Daley DC. Relapse prevention. In: Glanter
M, Kleber HD (eds). Textbook of Substance Abuse. 2nd ed. Washington,
DC: American Psychiatric Press;1999: 353-365.
Volpicelli J, Szalavitz M. Recovery Options. New York: John Wiley & Sons;
2000
American Group Psychotherapy Association Annual Meeting
February 26-28, 2004
New York, New York Contact: 877-668-2372
National Council for Community Behavioral Healthcare Annual
Conference
February 28 - March 2, 2004
New Orleans, Louisiana Contact: 301-984-6200; neworleans@nccbh.org
MARCH 2004 Anxiety Disorders Association of America 24th National
Conference
March 11-14, 2004
Miami, Florida Contact: 240-485-1001
Society of Behavioral Medicine Annual Meeting
March 24-27, 2004
Baltimore, Maryland Contact: 608-827-7267
UPCOMING 2004 35th Annual ASAM Medical-Scientific Conference
April 22-25, 2004
Washington, DC Contact: 301-656-3920; www.asam.org
American Psychiatric Association Annual Meeting
May 1-6, 2004
New York, New York Contact: 703-907-7300; apa@psych.org; http://www.psych.org
CPDD (College on Problems of Drug Dependence) 65th Annual Meeting
June 12-17, 2004
San Juan, Puerto Rico Contact: 1-800-759-5800
[To post your announcement in AT Forum and/or our Web site, fax
the information to: 847-392-3937 or submit it via e-mail from www.atforum.com]
From the Editor:
Will Physicians Get The Addiction Message?
The September issue of the Journal of the American
Medical Association (2003;290[10]:1299-1303) featured a disquieting
article titled "Addiction Poorly Understood by Clinicians."
"For all the lip service paid to the concept of addiction as a medical disease,
the idea has yet to gain traction with a large proportion of physicians," wrote
Brian Vastag.
Prejudice Permeates Medicine
This is rather astonishing, considering that in 1782 Benjamin Rush,
the first U. S. Surgeon General, described substance abuse (alcoholism,
in this case) as "a progressive and odious disease." Yet,
despite all the advances in other areas of medicine, an understanding
of addiction seems rooted in antiquated folklore.
Why? The JAMA article notes that merely 1% of the typical medical
school curriculum is devoted to drug addiction. Consequently, many
physicians still believe that medical interventions for addiction are
inappropriate and ineffective. Furthermore, a prejudice that addiction
is mainly a consequence of personal willfulness – that is, primarily
a moral or behavioral problem – still silently dominates medical
thinking.
Addiction Specialists Accountable
Part of the blame for such misunderstandings rests with the addiction
treatment community. Nora Volkow, MD, head of NIDA and quoted in the JAMA article,
suggests that addiction experts must emphasize the disease concept
of addiction. They also need to stress that addiction leads to other
medical problems. Each year, $133 billion is spent in the US treating
the short- and long-term medical complication of addiction.
"We can prevent a lot of other problems by addressing addiction, but somehow
we have failed to communicate that," she said.
It is time that the message of addiction – its origins and treatments – reaches
the rest of the medical community, and the burden of doing that rests
with addiction specialists. One resource, particularly for explaining
the treatment of opioid addiction, is Addiction Treatment Forum.
Share your copy with healthcare colleagues or direct them to http://www.atforum.com.
Respond to Reader Survey
Drug lapses (slips) and relapses are a discouraging facet of addiction
treatment, as noted in the feature article in this edition. To help
us further explore the extent of these difficulties during methadone
maintenance treatment (MMT), please respond to the following
questions:
What percentage of patients at your MMT clinic
experience drug lapses (slips) ____% or full-blown relapses ____%?
When are lapses (slips) most likely to
occur after starting MMT? (check one)
__ 1 month; __ 3 months; __ 6 months; __ 1 year; or, __ later.
When are relapses most likely to occur?
(check one) __ 1 month; __ 3 months; __ 6 months; __ 1 year; or,
__ later.
Which drugs are most commonly involved
in lapses or relapses? (check all that apply)
cannabis;
heroin;
other opioids;
cocaine;
benzodiazepines;
alcohol;
other _____________ (please specify).
Are you responding as a
patient, or
clinic staff member?
There are several ways to respond: A.
provide your answers on the postage-free feedback card in this issue; B.
write, fax, or e-mail [info below]; or, C. visit our web site
to respond online. As always,
your written comments also are important for helping
us discuss the results.
Practice
Pointers: Understanding Methadone Split Dosing
"I nod off at work in the
morning but by evening I feel like I’m in withdrawal."
Complaints such as this – of a methadone dose not properly "holding" – frequently
occur during methadone maintenance treatment (MMT). Although most
MMT patients do well on a once-daily dose of methadone, some do not.
The "not holding" problem typically stems from a sharp
rise and then rapid decline in serum methadone level (SML, measured
in nanograms per milliliter or ng/mL) during the dosing interval.
The patient experiences both over- and under-medication during the
course of a day. In other cases, patients may feel comfortable most
of the day, but the methadone seems to wear off long before the next
daily dose.
A solution is to shorten the dosing interval, while maintaining or
slightly increasing the total daily amount of methadone.
Staying Within the "Comfort Zone"
Typically, within 4 to 5 days of starting a dose or after a dose
increase, methadone reaches a steady-state condition during which
the low (trough) and high (peak) SMLs remain about the same from
one dosing interval to the next (see Figure 1). During
successful MMT, the methadone concentration should eventually reach
and stay within a comfort zone, which varies among individuals
but generally has a trough SML ranging from about 200 to 700 ng/ml
The peak SML should ideally be no more than twice the trough level;
that is, a P:T ratio £ 2.
If the SML is within the therapeutic comfort range, the patient will
experience no signs or symptoms of methadone overmedication or withdrawal
(undermedication). And, at an adequate methadone dose, drug
craving and illicit opioid use can be abolished.
However, due to individual differences in metabolism or methadone
interactions with other substances (e.g., drugs, medications, herbal
products, etc.), what is often expected to be a sufficient methadone
dose could be inadequate. Figure 2 illustrates methadone
being rapidly metabolized, leading to withdrawal prior to the next
dose (dotted line). However, simply increasing the dose amount results
in overmedication early in the cycle and withdrawal still persists
later on (dashed line).
The solution is to adjust the methadone dose interval, rather than
the amount. Splitting the dose keeps peak and trough values within
the comfort zone (solid red line). The size of the original methadone
dose is irrelevant; whether they are taking 60 or 600 mg/day,
certain patients may benefit from splitting their dose.
Concomitant medications influencing more rapid methadone metabolism
also are a common problem. Figure 3 illustrates an
interaction effect of the antiseizure medication phenytoin (Dilantin®),
which speeds methadone metabolism and greatly lowers the trough SML
(P:T = 14.8, dotted line).
By splitting the methadone dose, a more consistent methadone concentration
within the particular patient’s comfort zone is achieved throughout
the 24-hour period (P:T = 1.6, red line). Note: the extent of individual
reactions to medications may differ; also, if the interacting drug
is abruptly discontinued or reduced there could be a steep, possibly
unsafe, rise in methadone levels. (Also see the article in this issue
on drug interactions.)
Split Dosing Protocol
Measuring peak and trough SMLs can be helpful to verify the extent
of fluctuations (with peak occurring on average 2-4 hours after dosing).
However, of equal or greater importance, it is necessary to assess
clinical signs and patient-reported symptoms of methadone over- or
undermedication.
The recommended approach for beginning split dosing is to start with
an observed full dose of methadone and then administer half of
that dose 12 hours later (usually given to the patient as a take-home
dose). For example: 100 mg in the morning and 50 mg that evening.
This means the patient is administered 1.5 doses on day one, but
it should not be problematic in an opioid-tolerant patient who is
rapidly metabolizing the usual methadone dose. Note: starting the
regimen with only a half dose in a patient who is already likely
to be in withdrawal is not advised.
On the second day the patient assumes a regular schedule of half
doses 12 hours apart. After monitoring the patient’s clinical
response to the split dose – noting physical signs and patient-reported
symptoms of methadone adequacy – the amount can be adjusted
if it seems necessary. Doses may be further split into more than
two components, but this requires added monitoring and patient compliance
becomes more difficult.
Overcoming Limitations
Patient education and cooperation are critical for success. Split
dosing regimens are only suitable for otherwise stable and responsible
patients; those who have demonstrated an ability to properly handle
take-home doses, who are compliant with taking medications properly,
and in whom there would not be safety concerns regarding illicit
drug or alcohol use.
It is impractical to expect that patients will come to an MMT clinic
more than once daily for dosing. Yet, under current federal regulations,
it can take a year in continuous treatment before a full week’s
supply of take-home doses are allowed.
Usually, the need for split dosing becomes apparent after the patient
has been in treatment for some time and already qualifies for limited
take-homes. Many regulatory authorities will then grant exemptions
for patients who need additional take-home privileges for split dosing
purposes; however, clinic staff must be prepared to present a medical
justification for this, which may include trough and peak SML measurements
to support documented clinical signs/symptoms of abnormal methadone
metabolism.
AT Forum thanks J. Thomas Payte,
MD (Corporate Medical Director, Colonial Management
Group; Orlando, Fla.) for permission to adapt his educational
materials for this article, and for his helpful suggestions.
For more information on adequate methadone dosing see:Leavitt
SB. Methadone dosing and safety in the treatment of opioid addiction.
Addiction Treatment Forum. Special Report. 2003. Available at: http://www.atforum.com/SiteRoot/pages/addiction_resources/DosingandSafetyWP.pdf.
Adequate
Methadone During Pregnancy Not Harmful in Neonate
Since the 1970s, methadone maintenance
treatment (MMT) has been recognized as beneficial for pregnant opioid-addicted
women. However, the recommended daily methadone dose in these patients
has been controversial and is often based on attempts to avoid or
reduce abstinence syndrome in the neonate, rather than on achieving
optimally effective methadone dose in the mother.
Some researchers in the past have recommended that the dose during
pregnancy should not exceed 20 mg/day, even though adults usually require
at least 80 to 120 mg/d for maintenance therapy, often more. Other
research has demonstrated that dose increases may be required during
later stages of pregnancy to maintain methadone blood levels and prevent
withdrawal in the mother.
Recently, a team of researchers led by Vincenzo Berghella at Jefferson
Medical College, Philadelphia, conducted a retrospective review of
neonatal records to determine whether maternal methadone dosage correlates
with neonatal withdrawal. They identified 100 mother/neonate pairs
in whom the women received from 20 to 200 mg/d during their pregnancies.
An objective measure, the neonatal abstinence score (NAS), was used
to assess opioid withdrawal in the newborns. Clinical signs and symptoms
necessitating treatment for neonatal withdrawal were usually associated
with an NAS Z 8.0.
As the Graph illustrates, average highest NAS measures were
actually greater at methadone doses less than 40 mg/d; however, differences
between the NAS at any dose were not statistically significant. Also
of interest, mean duration of neonatal treatment for withdrawal was
longest in the low-dose group (19.6 days) compared with either <80
or 80+ mg/d (13.3 and 13.6 days, respectively). Again, these data were
statistically equivalent.
According to Berghella and colleagues, the data offer strong support
for the premise that daily methadone dose, at whatever amount is most
adequate for the mother, does not affect the incidence and severity
of neonatal withdrawal. A possible explanation for this is the highly
individual and variable metabolism of methadone.
For example, women receiving markedly different doses of methadone
may have the same serum levels of the medication in their systems,
so fetal exposure to methadone would be equivalent. Earlier research
did not take this into account.
Furthermore, other research did not fully consider that subtherapeutic
maternal methadone doses may promote illicit drug use, increasing the
risk to both mother and fetus. Berghella et al. found that neonates
born to mothers who abused benzodiazepines – possibly to quell
withdrawal symptoms – required significantly longer withdrawal
therapy.
Finally, earlier studies did not use objective scales to rate severity
of neonatal withdrawal, such as the NAS. Thus, they failed to discover
that the intensity and duration of neonatal withdrawal was not necessarily
dependent on methadone.
Berghella and his team conclude that methadone should be given to pregnant
opioid addicts during MMT at the most effective dose, which must be
individually determined and adequate to prevent withdrawal symptoms
in the mother. This, plus a program that includes prenatal care, can
reduce the incidence of obstetric and fetal complications, as well
as neonatal morbidity and mortality.
Reader
Response : "Graying of Methadone"
Last winter, AT Forum (2003,
Vol. 12, No. 1) had a feature article discussing the apparent growth
of an older "graying" population in methadone maintenance
treatment (MMT) programs. To further examine that trend, all readers
were invited to respond to a survey soliciting information about
the percentage of patients at their particular clinics within specific
age brackets, the total number of patients at each clinic, and years
of operation.
Significant Percentage Age 50+
There were a total of 78 valid responses submitted via survey cards
or at www.atforum.com, representing
different clinics in 25 states. The Graph shows the average
distribution across the 6 age brackets surveyed.
Nearly a quarter (24.5%) of patients in the responding clinics on average
were age 50 or greater; so, overall, this group clearly represents
a significant proportion of the treatment population. Yet, there was
a high degree of variation with percentages of patients in this age
group ranging from 0% to 90% across individual clinics.
Broad Clinic Diversity
It was expected that clinics with more years in operation would have
the largest percentages of older patients. On average, responding clinics
had been in operation for 18.4 years (range 1 to 40 years). There was
only a modest, but statistically significant, positive correlation
of years in operation with percentage of age 50+ patients (r =
+.29; p < 0.01).
Yet, there was a great deal of variation in this association. In one
clinic operating for only a year, 23% of patients were age 50 or older;
whereas, only 5% of patients were in that age bracket in another clinic
operating for 30 years.
The 78 responding clinics represented a total of about 30,500 patients
(average 401 per clinic), and clinic sizes ranged from 14 to 4,400
patients. There was very little correlation of clinic size with percentage
of age 50+ patients (r = +.07).
Of the 25 states represented in survey responses, those with the most
age 50+ patients were: California, Maryland, New Mexico, New York,
Ohio, Pennsylvania, Texas, Washington, and Washington DC. At the same
time, there was one clinic in Pennsylvania responding with 0% in the
50+ age bracket and one clinic in Maine without any patients older
than age 50.
Trend Worth Further Study
This survey was quite limited, representing less than 8% of MMT clinics
and only about 15% of patients in the U.S. However, the trend was similar
to that reported in the AT Forum article last winter for Beth
Israel Healthcare System in New York City. In 2002, this MMT program – one
of the largest and oldest in the country – found that 28.9% of
patients were age 50-59 and 6.4% were age 60 or greater (total age
50+ = 35.3%). Similarly, 18 respondents in this A.T. Forum survey
(23%) indicated at least a third of their population was age 50 or
older.
Clearly, there is a need for a more comprehensive survey of this nature;
perhaps, sponsored by the federal government or a national organization
of treatment providers. However, judging by the limited results of
this present survey, there already appears to be reasonable grounds
for organizing seminars, conferences, or other efforts focusing on
the very special needs of a "graying" MMT population.
