Addiction Treatment Progress and Obstacles

Addiction Treatment Progress and Obstacles
Published on Psychiatric Times
(http://www.psychiatrictimes.com)
Addiction Treatment Progress and Obstacles
May 01, 2002 | Addiction [1], Forensic Psychiatry [2], Alcohol Abuse [3]
New medications for the treatment of various addictions are currently under investigation. However,
there are still substantial barriers, on the part of health and social policies and the patients
themselves, to patients receiving these new treatments. Many of these issues were explored at the
2001 American Society of Addiction Medicine's State of the Art in Addiction Medicine conference.
Progress in developing medications and strategies for treating addiction were juxtaposed with the
challenges of implementing accessible and effective treatment programs at The State of the Art in
Addiction Medicine conference conducted by the American Society of Addiction Medicine (ASAM)
Nov. 1-3, 2001, in Washington, D.C. The conference, themed "From Molecules to Managed Care,"
was co-sponsored by the Center for Substance Abuse Treatment (SAT), the National Institute on
Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Drug Abuse (NIDA). Evaluating
New Medications for Addiction Treatment
Ahmed el-Kashef, M.D., acting chief of the clinical/medical branch of the division of treatment
research and development in NIDA, described NIDA's efforts to develop and evaluate agents to treat
addiction. The program currently involves 55 medications in different phases of development,
ranging from products marketed for other indications to new molecular entities developed for
specific addictions. Among the agents being evaluated by NIDA for stimulant addiction are two
investigational monoamine uptake inhibitors (MAOIs); the MAOI selegiline (Zelapar, Eldepryl); the
antidepressants desipramine (Norpramin), sertraline (Zoloft) and venlafaxine (Effexor); dopamine
agonists cabergoline (Dostinex) and amantadine (Symmetrel); serotonin antagonist ondansetron
(Zofran); γ-aminobutyric acid agonists tiagabine (Gabitril) and gabapentin (Neurontin); and
catechol-O-methyltransferase inhibitor tolcapone (Tasmar). El-Kashef characterized the opioid
agonist-antagonist buprenorphine (Subutex) -- alone and in combination with antagonist naloxone
(Narcan) -- as well as the opioid antagonist naltrexone in depot formulation (Depotrex) as very
promising agents for treatment of opiate addiction.
Although naltrexone (ReVia) is principally being evaluated as a means to support abstinence from
opiate use, researchers outside the United States have employed it in protocols for rapid opiate
detoxification. In a July 2001 press release, researchers in Brisbane, Australia, discussed findings
from the first controlled trial of heroin-addiction treatment, contrasting rapid opiate detoxification
with naltrexone and general anesthesia to methadone maintenance. The researchers characterized
the naltrexone approach as less expensive and more effective at reducing heroin usage than
conventional treatments. One of the researchers in the Australian study, John Saunders, M.D.,
professor of alcohol and drug studies at University of Queensland in Brisbane, commented to the
press, "I am hoping that these trials and their results will provide considerable impetus to establish
rapid detoxification and naltrexone-supported abstinence treatment as a viable treatment option."
El-Kashef indicated that NIDA is also investigating neuroendocrine, electrophysiological and
neuroimage changes in response to addictive drugs and remedial measures. "New interest has
arisen in biological markers of addiction to identify subtypes of patients who may respond differently
to specific medications," he noted. "This approach may be promising in maximizing medication
effect, or predicting relapse."
Also at the 2001 conference, Raye Litten, Ph.D., chief of the treatment research branch in the
division of clinical and prevention research of NIAAA, described naltrexone and the glutamatergic
modulator acamprosate (Campral) as the most promising and successful medications developed to
date to treat alcoholism. "Although naltrexone is not a 'magic bullet,'" Litten explained, "it appears to
have a moderate effect in reducing drinking, particularly decreasing relapse to heavy drinking."
The success of naltrexone for alcoholism may depend in part upon patient characteristics. A recently
published trial (Krystal et al., 2001) in a mostly male Veterans Affairs population with chronic, severe
alcohol dependence did not evidence benefit from naltrexone. In the multicenter, double-blind trial,
627 patients were randomized to receive either 12 months of naltrexone, 50 mg daily; three months
of naltrexone followed by nine months of placebo; or 12 months of placebo. All patients were offered
counseling and were encouraged to comply with the study medication regimen and attend Alcoholics
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Addiction Treatment Progress and Obstacles
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Anonymous meetings.
At 13 weeks, the investigators found no significant differences between the groups in the number of
days to relapse. Also, after 52 weeks, no difference in the groups was found in the percentage of
days drinking or the number of drinks per drinking day. In an accompanying commentary supporting
the use of naltrexone and offering reasons why the results from the Krystal et al. study may not be
generalizable to all populations, Fuller and Gordis (2001) pointed out that recovering alcoholics who
are married and employed are more likely to remain abstinent and that only one-third of this
population had a spouse or live-in partner and, apparent from the disability pensions, only two-thirds
appeared to be employed, both which possibly affected their motivation to stop drinking. Fuller and
Gordis also questioned the adequacy of counseling in this study.
While naltrexone is only the second agent to be approved by the U.S. Food and Drug Administration
for treating alcoholism, some 50 years after approval of disulfiram (Antabuse), it is anticipated that
acamprosate will soon be the third. Acamprosate is now approved for this indication in 40 countries.
A New Drug Application is expected to be filed with the FDA in this year, according to Forest
Laboratories, which would market acamprosate in the United States.
Acamprosate would offer not only a third option of therapeutic agents for alcoholism, but also a
mechanism that differs from both the "reward circuit" blunting ascribed to naltrexone and the
aversive effects of disulfiram. Acamprosate is thought "to inhibit the stimuli that can make alcohol
'negatively reinforcing,'" as alcohol levels in the central nervous system recede (Littleton and Mayer,
1999). In animals, it appears highly effective in inhibiting alcohol consumption prompted either by
alcohol withdrawal or restriction.
In addition to affecting aspects of alcohol withdrawal, however, acamprosate exerts clinical effects
independent of the presence of alcohol. At the 1999 State of the Art Conference, John Littleton, M.D.,
Ph.D., professor of pharmacology at University of Kentucky, described clinical findings with
acamprosate. "Relapse actually seems to be prevented in many cases, rather than just ameliorated,"
he told attendees. "For this reason, it has been suggested that acamprosate may inhibit those
cue-induced signs and symptoms that are very similar to withdrawal and that may precipitate
relapse in abstinent alcohol dependent patients."
Litten has been enthusiastic about the clinical experience with acamprosate since that conference in
1999. "Alcoholic patients treated with acamprosate are more likely to complete treatment, have
longer times to their first drink, and have higher abstinence rates than placebo-treated patients," he
noted at the 2001 conference.
Litten also indicated that NIAAA is now investigating whether the combination of naltrexone and
acamprosate is synergistic in treating alcoholism. The multi-site protocol contains tracks with
acamprosate alone and in combination with naltrexone, and it also compares two types of
behavioral/psychosocial therapies. Other promising agents under NIAAA research, Litten disclosed,
include another opioid antagonist, nalmefene (Revex), and the serotonin (5-HT3) antagonist
ondansetron.
"Development of more effective medications has the potential to vastly improve treatment outcome
and reduce the suffering of millions of alcoholic patients and their families," Litten concluded.
Accessing and Succeeding in Treatment Programs
A recurrent issue at the conference was the gap between promising new treatments and the health
and social policies that fail to provide addicts access to effective treatment programs. Suggesting
one means of bridging the gap, Lee Dixon, director of the National Conference of State Legislatures'
Health Policy Tracking Service, discussed recent RAND center research, indicating that the addition
of full parity benefits for substance abuse and mental health care to private insurance plans can be
accomplished with only a 3% to 4% increase in premium. The addition of only substance abuse
benefits was estimated to result in a 0.3% increase.
The RAND study director, Roland Sturm, Ph.D., testified in July 2001, "Our results suggest that parity
in employer-sponsored health plans is not very costly under comprehensively managed care, which
is the standard arrangement in today's market place."
Substantial barriers to successful treatment outcome are also presented by the addicted patients
themselves, and several speakers at the ASAM conference described intervention modalities that
motivate or facilitate participation. Carlo DiClemente, Ph.D., chair of the department of psychology at
University of Maryland, Baltimore County, discussed Project MATCH (Matching Alcoholism
Treatments to Client Heterogeneity) and research with motivational enhancement therapy (MET) to
promote treatment participation and successful recovery from substance abuse.
DiClemente (1999) previously suggested that the readiness of drug dependent patients for
treatment and successful recovery occurs in stages: considering change (precontemplation stage);
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Addiction Treatment Progress and Obstacles
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intermediate decision-making (contemplation stage); planning (preparation stage); making the
change (action stage); and sustaining the change over time (maintenance stage). "Most treatment
programs are action-oriented," DiClemente pointed out to conference attendees, "but clients seeking
treatment at these programs are not always ready for action."
DiClemente (1999) distinguished between imposed and intentional change, noting that the former is
often short-lived. Although supportive of therapeutic interventions within the corrections-penal
system, he also noted that court-mandated attendance at treatment programs does not indicate that
individuals are necessarily motivated to change substance-abusing behavior. DiClemente also
contrasted readiness for change to readiness for treatment. He notes that many
substance-dependent patients will relapse after the first attempt at treatment and suggested that
treatment, as a time-limited event, should be considered as a part of the larger process of change.
One method to increase the level of participation intensity and the likelihood of treatment success is
to incorporate contingency management, according to a presentation at the ASAM conference by
Nancy Petry, Ph.D., associate professor at University of Connecticut Health Center. Petry and
colleagues (2001) recently argued, "A primary benefit of positive-incentive contingency
management approaches is that they increase the percent of patients who respond favorably to
treatment."
Often taking the form of contingency contracting with the patient, this treatment strategy involves
frequent monitoring of target behaviors, such as drug abstinence and obtaining employment;
tangible, positive reinforcers for the target behavior; and withdrawal of the reinforcer when the
target behavior does not occur. (For more information on contingency management, please see
related article "Contingency Management in Addiction Treatment" -- Ed.)
Petry has acknowledged criticism of contingency management approaches, however, on the basis of
cost and the question of their applicability in community-based treatment programs. Clinics without
research funding are unlikely to be able to offer voucher programs or other tangible reinforcers, and
less expensive approaches may be necessary for adaptation in community-based settings.
Still, as noted in their research, Petry and colleagues (2001) remain hopeful:
As more and more clinicians and researchers apply contingency management procedures to
treat substance-abusing patients, new developments and refinement in the techniques may
emerge. We may discover less expensive yet efficacious reinforcers, determine the best
behaviors to target, and evaluate the time course and optimal duration of interventions.
David Gastfriend, M.D., assistant professor of psychiatry at Massachusetts General Hospital
and co-chair of the 2001 ASAM conference, discussed treatment-placement considerations.
He distinguished between the matching of patients with an optimal theoretical treatment
modality, as evaluated in Project MATCH, and placement matching for the least restrictive
setting and resource intensity.
Criteria for placement match have been developed by ASAM, Gastfriend noted, and relate
patient requirements to such treatment factors as hours of supervision and presence of
medical and other specialties.
Despite progress in determining appropriate matches, Gastfriend et al. (2000) reported
difficulty in implementing the solutions in the market-driven system of services
reimbursement within the United States:
To solve many of these problems, it will be necessary in the future to move from a
model in which levels of care are predetermined and patient's needs are clustered to
fit these criteria, to a patient-based model in which patient assessment is the starting
point for determining the optimal service to provide.
References: References
1. DiClemente CC (1999), Motivation for change: implications for substance abuse treatment.
Psychological Science 10:209-213.
2. Fuller RK, Gordis E (2001), Naltrexone treatment for alcohol dependence. N Engl J Med
345(24):1770-1771 [letter].
3. Gastfriend DR, Lu SH, Sharon E (2000), Placement matching: challenges and technical progress.
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Addiction Treatment Progress and Obstacles
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Subst Use Misuse 35(12-14):2191-2213.
4. Krystal JH, Cramer JA, Krol WF et al. (2001), Naltrexone in the treatment of alcohol dependence.
N Engl J Med 345(24):1734-1739.
5. Littleton J, Mayer S (1999), Acamprosate and alcohol dependence: another glimmer of hope?
Presented at the ASAM State of the Art Conference. Washington, D.C., Nov. 5.
6. Petry NM, Petrakis I, Trevisan L et al. (2001), Contingency management interventions: from
research to practice. Am J Psychiatry; 158(5):694-702.
7. Sturm R (2001), The Costs of Covering Mental Health and Substance Abuse Care at the Same
Level As Medical Care in Private Insurance Plans. Testimony presented to the Health Insurance
Committee at the National Conference of Insurance Legislators. Chicago; July 13.
Source URL: http://www.psychiatrictimes.com/articles/addiction-treatment-progress-and-obstacles
Links:
[1] http://www.psychiatrictimes.com/addiction
[2] http://www.psychiatrictimes.com/forensic-psychiatry
[3] http://www.psychiatrictimes.com/alcohol-abuse
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