In this recent post on Science News, more information about a potential cocaine vaccine. You know my view: we need as many tools as possible to fight addiction. Use everything available.
MW
Vaccine against cocaine makes headway
Injections gin up antibodies that limit drug's effects, study in mice showsBy Nathan Seppa Web edition : Thursday, January 20th, 2011
Vaccine against cocaine makes headway
Injections gin up antibodies that limit drug's effects, study in mice showsBy Nathan Seppa Web edition : Thursday, January 20th, 2011 Mice vaccinated against cocaine show less agitated behavior when exposed to the drug than do unvaccinated mice on the drug, as shown by the average time the animals spend on various activities.Crystal et al/Molecular Therapy 2011Antibodies generated by a new vaccine can capture molecules of cocaine in the precious few seconds that lapse before the drug reaches the brain, a study in mice shows. Although the antibody brigade doesn’t snag all the cocaine, it seems to collar enough to greatly subdue the agitation that mice exhibit when given the drug.
Based on these findings, the researchers are moving on to studies in rats and monkeys in hopes of testing the vaccine in people. The new report will appear in the March Molecular Therapy.
“When someone takes cocaine — whether snorted, smoked or injected — you don’t have much time,” says study coauthor Ronald Crystal, a pulmonary physician at Weill Cornell Medical College in New York City. “It takes about six second to pass from the lungs to the blood to the brain.”
A vaccine would need to elicit a standing army poised to intercede. “You need avid antibodies, at high levels,” Crystal says.
In the new study, Crystal and his colleagues gave mice three injections over six weeks. Some of the animals received a placebo while the others got the experimental vaccine, which combines a cocainelike substance with noninfectious portions of an adenovirus that stimulate an immune response but don’t cause disease. Four weeks later, all the mice were exposed to cocaine by injection.
Antibodies elicited by the vaccine kept about three-fifths of the cocaine from reaching the brain in vaccinated animals, according to examinations of the mice, which were given the maximum dose of cocaine. This effect translated into behavioral changes: Cocaine makes mice hyperactive, Crystal says, and in this study the unvaccinated mice were running around much of the time. In contrast, vaccinated mice ran one-third as much and performed repetitive motions half as much, behavior similar to that of mice not given cocaine at all.
Crystal says the vaccine might be ready to test in people in a year or two. “The most obvious strategy is to use it in people who are addicted but who want to stop and have enrolled in a program. This would help them,” he says.
Cocaine dependence accounts for more than one-third of illicit-drug-related emergency room visits, according to the U.S. Drug Abuse Warning Network.
About 40 percent of cocaine users are in denial about their addiction, and another 40 percent are not yet willing to take on the challenge of quitting, says Stephen Ross, an addiction psychiatrist at New York University. “The other 20 percent are ready to make a change,” he says. Such people need behavioral therapy and all available support. “The more tools we have, the better,” Ross says. “A vaccine could be part of that arsenal.” Vaccination might also prevent cocaine addiction in young adults and adolescents who are at high risk, he says.
Any prospective anticocaine vaccine needs a lot of testing, in part because it isn’t clear whether just taking more of the drug might overwhelm a vaccine’s effect, says Frank Orson, a physician and immunologist at the Baylor College of Medicine in Houston. Also, the researchers in the new study used an additive called complete Freund’s adjuvant to boost the immune reponse in the mice. The adjuvant cannot be used in people because of side effects, he says.
Other researchers have sought to build vaccines using adenoviruses, which normally cause the common cold and other ailments, Orson says. These efforts include work on vaccines for HIV, influenza, malaria and other ailments. Adenovirus particles are good at triggering an immune response, he says, which is important for vaccines against addictive drugs because the drugs otherwise go largely unnoticed by immune forces, which are geared up to catch infectious microbes, he says.
Nevertheless, Orson says, “I think there is a good chance we will have vaccines against some of these agents — cocaine being pretty high on the list because of its properties of being fairly short-lived.” Since cocaine is naturally degraded in the blood stream more rapidly than some other illicit drugs, such as methamphetamine, cocaine might make a better target, he says. Orson and his colleagues are currently working on vaccines against cocaine, heroin and methamphetamines.
Monday, January 24, 2011
Two recent presentations available on the web
Colleagues and friends,
After a prolonged absence from the blog due to holidays and the press of other business, I'll be now keeping up with the blog again. I now have a site for posting my presentations, and I recently uploaded two of my most recent slide sets. I'll be posting additional ones as they are developed. The URL is https://show.zoho.com/public/mwillenbring.
Much has happened in the past 3 months. I have incorporated a new company, ALLTYR, Inc. ALLTYR is dedicated to transforming treatment for addictions through multiple activities. My goal is to open a clinic, the ASSET Clinic, in the Twin Cities in the fall of 2011. The ASSET Clinic will be a model for providing scientifically informed specialty treatment for addictions and will serve as a prototype, laboratory and clinical teaching site. The Clinic will provide the full array of services for all degrees of substance involvement and for as long as needed. It is not a "program," but will function like any other professional specialty clinic. A key focus will be on customer service. ALLTYR will also provide consultation to existing healthcare systems to help them integrate attention to substance use throughout their organization, especially in primary care, mental health care, the ed, and inpatient services. ALLTYR will provide materials, training, technical support, and will also offer the opportunity to either operate or develop an ASSET Specialty Clinic within existing health care organizations (HCOs). Much more on this later as it develops.
MW
After a prolonged absence from the blog due to holidays and the press of other business, I'll be now keeping up with the blog again. I now have a site for posting my presentations, and I recently uploaded two of my most recent slide sets. I'll be posting additional ones as they are developed. The URL is https://show.zoho.com/public/mwillenbring.
Much has happened in the past 3 months. I have incorporated a new company, ALLTYR, Inc. ALLTYR is dedicated to transforming treatment for addictions through multiple activities. My goal is to open a clinic, the ASSET Clinic, in the Twin Cities in the fall of 2011. The ASSET Clinic will be a model for providing scientifically informed specialty treatment for addictions and will serve as a prototype, laboratory and clinical teaching site. The Clinic will provide the full array of services for all degrees of substance involvement and for as long as needed. It is not a "program," but will function like any other professional specialty clinic. A key focus will be on customer service. ALLTYR will also provide consultation to existing healthcare systems to help them integrate attention to substance use throughout their organization, especially in primary care, mental health care, the ed, and inpatient services. ALLTYR will provide materials, training, technical support, and will also offer the opportunity to either operate or develop an ASSET Specialty Clinic within existing health care organizations (HCOs). Much more on this later as it develops.
MW
Tuesday, November 9, 2010
Abstinence based treatment for opioid addiction kills people
So how can abstinence based programs not inform patients about these studies and the alternatives to abstinence? In any other branch of medicine this is called negligence and the Supreme Court has clearly ruled that to not inform a patient of alternative therapies and relative rates of recovery is unethical and negligent practice. Why do state licensing agencies allow this to happen? As noted below, although this new study adds to the literature, many other studies have shown reduced mortality from maintenance as opposed to either detox, stabilize and taper or simply abstinence-based treatments. In my view, programs that are based on an ideological belief in abstinence but who do not inform patients of the relative risks, benefits and likelihood of recovery are risking a lawsuit because they are not providing basic informed consent for patients and families.
MW
From Medscape Medical News
Opiate Replacement Treatment Reduces Mortality in Addicted Patients
Deborah Brauser
October 29, 2010 — Year-long treatment with either buprenorphine or methadone can substantially decrease the number of drug-related deaths in opiate misusers, suggests new findings from British researchers.
In fact, results from this large cohort study showed that patients given "opiate substitution treatment" for 12 months or more had a greater than 85% reduced overall mortality risk.
"This treatment reduces the risk of death — but treatment duration matters," investigative team member Matt Hickman, professor in public health and epidemiology at the School of Social and Community Medicine at the University of Bristol in the United Kingdom, told Medscape Medical News.
In addition, the investigators write that "closer supervision is needed" because significant mortality risks were found for these patients during both the first 28 days after beginning and the first month after ending treatment compared with other times.
"We found that the risk of death in the first month leaving...was about 4 times higher than rest of time off treatment, which is very similar to difference in risk of death after leaving prison," said Professor Hickman.
The investigators write that although "the difference in mortality between opiate users in and out of treatment is stark and well known," few studies have looked at this risk at specific time points.
"We hypothesize that the raised risk of death in the first month of treatment and especially in the month after the end of treatment may negate any protective effect of opiate substitution treatment, unless treatment is prolonged," they add.
The study was published online October 27 in the British Medical Journal.
Opiate Use Continues to Increase
For opiate users, "systematic reviews estimate annual death rates of about 1%, which is more than 10 times that of the general population and contributes more than 10% of adult mortality," write the study authors. Most of these deaths are due to overdose.
"Estimates of the prevalence of opiate use in the UK suggest 30-fold increases between 1970 and 2000, but more recent estimates are stable at around 250,000 opiate users," they add, noting that opiate substitution therapy in their country is given mainly within primary care.
For this study, the investigators pulled information from the United Kingdom's General Practice Research Database. They then evaluated data on 5577 primary care patients between the ages of 16 and 59 years (58% younger than 30 at start of treatment, 69% male) diagnosed as having "substance misuse" and prescribed noninjectible methadone or buprenorphine between 1990 and 2005.
A total of 267,003 prescriptions were written for these patients. A total of 57% of the patients were prescribed methadone only; 19% were prescribed methadone and dihydrocodeine; 9% were prescribed methadone and buprenorphine; 8% were prescribed buprenorphine only; 4% were prescribed buprenorphine and dihydrocodeine; and 4% were prescribed methadone, buprenorphine, and dihydrocodeine.
All patients were followed up "until 1 year after the expiry of their last prescription, the date of death before this time had elapsed, or the date of transfer away from the practice," report the investigators. The median length of follow-up was 2 years.
The main outcome measure was all-cause mortality. Secondary measures included risk for death at different periods during and after treatment.
They also estimated "the probability that opiate substitution treatment reduces average mortality for patients exposed to different durations of treatment compared with if they had been unexposed."
Mortality Doubled When Not Receiving Treatment
Results of the analysis showed that 178 of the patients died (62 while undergoing treatment, 116 within 1 year of their last prescription).
The overall crude mortality rates were 0.7 per 100 person-years while receiving opiate replacement treatment and 1.3 while not receiving treatment.
"The crude mortality rate off treatment was almost double that on treatment, and after adjustment (for age, sex, calendar period, and comorbidity) the mortality rate ratio was more than twice as high" (2.3; 95% confidence interval [CI], 1.7 – 3.1), write the investigators.
Standardized mortality ratios, "comparing death rates among study patients with the population of England and Wales," were 5.3 (95% CI, 4.0 – 6.8) while undergoing treatment and 10.9 (95% CI, 9.0 –13.1) while not undergoing treatment.
In addition, men using opiates almost doubled the risk for death of women users (mortality rate ratio, 1.97; 95% CI, 1.4 – 2.9). However, the standardized mortality ratios were similar between men and women when both receiving and not receiving treatment.
Also, "mortality increased with age and was positively associated with comorbidity score," report the researchers.
When looking at treatment duration, the crude mortality rate was highest during the first 2 weeks at 1.7 per 100 person-years. After adjustment, this was 3.1 (95% CI, 1.5 – 6.6) times higher than the rate during the remainder of time receiving treatment.
The crude mortality rate during weeks 3 and 4 of treatment was 1.3, and the adjusted mortality rate ratio was 2.4 (95% CI, 0.95 – 6.0).
The mortality rates and ratios during the first month after stopping treatment were even higher:
Table. Mortality Rates and Ratios
Time Not Receiving Treatment Crude MR Adjusted MR Ratio (95% CI)
1-2 weeks 4.8 9.0 (5.4 – 14.9)
3-4 weeks 4.3 8.0 (4.7 – 13.7)
Remainder of time 0.95 1.9 (1.3 – 2.8)
CI = confidence interval; MR = mortality rate
"We found no evidence of any difference in the risk of death between buprenorphine and methadone when we compared the whole period on and off treatment," the study authors write.
Finally, short treatment durations of between 20 to 30 weeks reduced the overall risk for death by less than 25%. However, that rate increased to 65% at 40 weeks' duration and to more than 85% at durations "approaching or exceeding a year.
"The overall risk of death, standardized mortality ratios, and overall difference in mortality between time on and off treatment for opiate users in UK primary care in this study are consistent with international literature," report the investigators.
"Further research is needed to investigate the effect of average duration of opiate substitution treatment on drug related mortality," they write.
"We hope that others also will examine further what interventions might reduce risk of relapse following treatment," added Professor Hickman.
Twice as Likely to Live If in Treatment
"This study is based on the British concepts of treatment, which are different from the US," Mary Jeanne Kreek, MD, professor and head of the Laboratory of the Biology of Addictive Diseases at Rockefeller University in New York City, told Medscape Medical News.
"They simply took all comers over a protracted period of 15 years who were labeled as receiving prescriptions for opiate substitution treatment. So their data will not look like US, Swedish, Norwegian data. Any place where they carefully follow up their people with more oversight," said Dr. Kreek.
She said that the British do not have tight control regarding this treatment "because individual doctors can do the prescribing."
Also, she noted that the word "substitution" is not used in the United States. "That's not allowed. Instead, we call it 'replacement treatment' or simply 'maintenance treatment.'"
Dr. Kreek, who was not involved with this study, has served on the National Institute on Drug Abuse National Advisory Council and is a past president of the College on Problems of Drug Dependence.
She said that "the most important result" from this study is the substantial crude mortality rate difference between people receiving and not receiving treatment. "That's the critical thing."
However, this finding isn't new. Dr. Kreek noted that Dr. Lars Gunne wrote that heroin addicts untreated had a death rate that was "multifold higher, based on a randomized study of methadone treatment in Sweden in the late 70s" (Drug Alcohol Depend. 1981;7:249-256).
She also noted that "there isn't really an end-of-treatment phase" for these types of patients in the United States.
"There is only about 5% to 10% who've been successfully treated and request to have their medication dose reduced and eliminated," said Dr. Kreek. "To take people off treatment is, to us, unethical unless they really ask and will work with you as a care provider to be followed up in a medication-free state.
"So why are these people [in this study] coming off treatment? The [investigators] don't really get into that, but in Britain there is more of a casual entry to and exit from treatment."
Another big difference is that "we've never seen a death in this country at the induction of this treatment," reported Dr. Kreek. "With buprenorphine, we don't watch people, but we have a very tight induction schedule that's well regulated, starting low and going on up."
Overall, Dr. Kreek said that this study is interesting to look at but "isn't really relevant to US practice" — except for the crude mortality rate difference.
"It doesn't matter what kind of program you have, people are twice as apt to live if they're in treatment than if they're not in treatment. That's what's important. Methadone and buprenorphine both can be very effective if properly used," she summarized.
This study was funded in part by a grant from the National Institute of Health Research (NIHR) for the Center for Research on Drugs and Health Behavior, a career scientist fellowship award from the NIHR, and an Medical Research Council new investigator award. The study authors and Dr. Kreek have disclosed no relevant financial relationships.
BMJ. Published online October 27, 2010.
MW
From Medscape Medical News
Opiate Replacement Treatment Reduces Mortality in Addicted Patients
Deborah Brauser
October 29, 2010 — Year-long treatment with either buprenorphine or methadone can substantially decrease the number of drug-related deaths in opiate misusers, suggests new findings from British researchers.
In fact, results from this large cohort study showed that patients given "opiate substitution treatment" for 12 months or more had a greater than 85% reduced overall mortality risk.
"This treatment reduces the risk of death — but treatment duration matters," investigative team member Matt Hickman, professor in public health and epidemiology at the School of Social and Community Medicine at the University of Bristol in the United Kingdom, told Medscape Medical News.
In addition, the investigators write that "closer supervision is needed" because significant mortality risks were found for these patients during both the first 28 days after beginning and the first month after ending treatment compared with other times.
"We found that the risk of death in the first month leaving...was about 4 times higher than rest of time off treatment, which is very similar to difference in risk of death after leaving prison," said Professor Hickman.
The investigators write that although "the difference in mortality between opiate users in and out of treatment is stark and well known," few studies have looked at this risk at specific time points.
"We hypothesize that the raised risk of death in the first month of treatment and especially in the month after the end of treatment may negate any protective effect of opiate substitution treatment, unless treatment is prolonged," they add.
The study was published online October 27 in the British Medical Journal.
Opiate Use Continues to Increase
For opiate users, "systematic reviews estimate annual death rates of about 1%, which is more than 10 times that of the general population and contributes more than 10% of adult mortality," write the study authors. Most of these deaths are due to overdose.
"Estimates of the prevalence of opiate use in the UK suggest 30-fold increases between 1970 and 2000, but more recent estimates are stable at around 250,000 opiate users," they add, noting that opiate substitution therapy in their country is given mainly within primary care.
For this study, the investigators pulled information from the United Kingdom's General Practice Research Database. They then evaluated data on 5577 primary care patients between the ages of 16 and 59 years (58% younger than 30 at start of treatment, 69% male) diagnosed as having "substance misuse" and prescribed noninjectible methadone or buprenorphine between 1990 and 2005.
A total of 267,003 prescriptions were written for these patients. A total of 57% of the patients were prescribed methadone only; 19% were prescribed methadone and dihydrocodeine; 9% were prescribed methadone and buprenorphine; 8% were prescribed buprenorphine only; 4% were prescribed buprenorphine and dihydrocodeine; and 4% were prescribed methadone, buprenorphine, and dihydrocodeine.
All patients were followed up "until 1 year after the expiry of their last prescription, the date of death before this time had elapsed, or the date of transfer away from the practice," report the investigators. The median length of follow-up was 2 years.
The main outcome measure was all-cause mortality. Secondary measures included risk for death at different periods during and after treatment.
They also estimated "the probability that opiate substitution treatment reduces average mortality for patients exposed to different durations of treatment compared with if they had been unexposed."
Mortality Doubled When Not Receiving Treatment
Results of the analysis showed that 178 of the patients died (62 while undergoing treatment, 116 within 1 year of their last prescription).
The overall crude mortality rates were 0.7 per 100 person-years while receiving opiate replacement treatment and 1.3 while not receiving treatment.
"The crude mortality rate off treatment was almost double that on treatment, and after adjustment (for age, sex, calendar period, and comorbidity) the mortality rate ratio was more than twice as high" (2.3; 95% confidence interval [CI], 1.7 – 3.1), write the investigators.
Standardized mortality ratios, "comparing death rates among study patients with the population of England and Wales," were 5.3 (95% CI, 4.0 – 6.8) while undergoing treatment and 10.9 (95% CI, 9.0 –13.1) while not undergoing treatment.
In addition, men using opiates almost doubled the risk for death of women users (mortality rate ratio, 1.97; 95% CI, 1.4 – 2.9). However, the standardized mortality ratios were similar between men and women when both receiving and not receiving treatment.
Also, "mortality increased with age and was positively associated with comorbidity score," report the researchers.
When looking at treatment duration, the crude mortality rate was highest during the first 2 weeks at 1.7 per 100 person-years. After adjustment, this was 3.1 (95% CI, 1.5 – 6.6) times higher than the rate during the remainder of time receiving treatment.
The crude mortality rate during weeks 3 and 4 of treatment was 1.3, and the adjusted mortality rate ratio was 2.4 (95% CI, 0.95 – 6.0).
The mortality rates and ratios during the first month after stopping treatment were even higher:
Table. Mortality Rates and Ratios
Time Not Receiving Treatment Crude MR Adjusted MR Ratio (95% CI)
1-2 weeks 4.8 9.0 (5.4 – 14.9)
3-4 weeks 4.3 8.0 (4.7 – 13.7)
Remainder of time 0.95 1.9 (1.3 – 2.8)
CI = confidence interval; MR = mortality rate
"We found no evidence of any difference in the risk of death between buprenorphine and methadone when we compared the whole period on and off treatment," the study authors write.
Finally, short treatment durations of between 20 to 30 weeks reduced the overall risk for death by less than 25%. However, that rate increased to 65% at 40 weeks' duration and to more than 85% at durations "approaching or exceeding a year.
"The overall risk of death, standardized mortality ratios, and overall difference in mortality between time on and off treatment for opiate users in UK primary care in this study are consistent with international literature," report the investigators.
"Further research is needed to investigate the effect of average duration of opiate substitution treatment on drug related mortality," they write.
"We hope that others also will examine further what interventions might reduce risk of relapse following treatment," added Professor Hickman.
Twice as Likely to Live If in Treatment
"This study is based on the British concepts of treatment, which are different from the US," Mary Jeanne Kreek, MD, professor and head of the Laboratory of the Biology of Addictive Diseases at Rockefeller University in New York City, told Medscape Medical News.
"They simply took all comers over a protracted period of 15 years who were labeled as receiving prescriptions for opiate substitution treatment. So their data will not look like US, Swedish, Norwegian data. Any place where they carefully follow up their people with more oversight," said Dr. Kreek.
She said that the British do not have tight control regarding this treatment "because individual doctors can do the prescribing."
Also, she noted that the word "substitution" is not used in the United States. "That's not allowed. Instead, we call it 'replacement treatment' or simply 'maintenance treatment.'"
Dr. Kreek, who was not involved with this study, has served on the National Institute on Drug Abuse National Advisory Council and is a past president of the College on Problems of Drug Dependence.
She said that "the most important result" from this study is the substantial crude mortality rate difference between people receiving and not receiving treatment. "That's the critical thing."
However, this finding isn't new. Dr. Kreek noted that Dr. Lars Gunne wrote that heroin addicts untreated had a death rate that was "multifold higher, based on a randomized study of methadone treatment in Sweden in the late 70s" (Drug Alcohol Depend. 1981;7:249-256).
She also noted that "there isn't really an end-of-treatment phase" for these types of patients in the United States.
"There is only about 5% to 10% who've been successfully treated and request to have their medication dose reduced and eliminated," said Dr. Kreek. "To take people off treatment is, to us, unethical unless they really ask and will work with you as a care provider to be followed up in a medication-free state.
"So why are these people [in this study] coming off treatment? The [investigators] don't really get into that, but in Britain there is more of a casual entry to and exit from treatment."
Another big difference is that "we've never seen a death in this country at the induction of this treatment," reported Dr. Kreek. "With buprenorphine, we don't watch people, but we have a very tight induction schedule that's well regulated, starting low and going on up."
Overall, Dr. Kreek said that this study is interesting to look at but "isn't really relevant to US practice" — except for the crude mortality rate difference.
"It doesn't matter what kind of program you have, people are twice as apt to live if they're in treatment than if they're not in treatment. That's what's important. Methadone and buprenorphine both can be very effective if properly used," she summarized.
This study was funded in part by a grant from the National Institute of Health Research (NIHR) for the Center for Research on Drugs and Health Behavior, a career scientist fellowship award from the NIHR, and an Medical Research Council new investigator award. The study authors and Dr. Kreek have disclosed no relevant financial relationships.
BMJ. Published online October 27, 2010.
Monday, October 18, 2010
Do AA and Medications Mix?
Any addiction professional who has worked with program directors of 12 step-based treatment centers, sponsors in Alcoholics Anonymous (AA), and long-term members of AA has experienced the anti-medication bias harbored by some.
However, there is nothing inherent in the 12-step approach that contradicts the use of medication for craving reduction, abstinence enhancement, or for that matter any psychiatric condition or disorder (Brigham 2003). An interesting side note to history occurred during the 1960s and involved a conversation between Dr. Vincent Dole, co-originator of methadone maintenance for heroin addiction, and Bill Wilson, co-founder of AA. Dr. Dole served as a trustee of AA, became friends with Bill Wilson, and recalled a conversation they had (Dole, 1991) where Wilson expressed his concern over alcoholics who could not achieve sobriety despite repeated attempts through AA:
“At the last trustee meeting (of AA) that we (Vincent Dole and Bill Wilson) both attended, he (Bill Wilson) spoke to me of his deep concern for the alcoholics who are not reached by AA, and for those who enter and drop out and never return. Always the good shepherd, he was thinking about the many lost sheep who are lost in the dark world of alcoholism. He suggested that in my future research I should look for an analogue of methadone, a medication that would relieve the alcoholic’s sometimes irresistible craving and enable him to progress in AA toward social and emotional recovery, following the Twelve Steps.”
This highly revealing anecdote reflects the open-mindedness and recognition by the co-founder of AA that some alcoholics require a pharmacotherapeutic intervention to bridge the gap from initial abstinence to stable abstinence and integration in AA. How unfortunate it is that many ardent believers in the 12-step approach have adopted an attitude of rigidity and dogmatism regarding addiction medicine.
Brigham GS. 12-step participation as a pathway to recovery: The Maryhaven experience and implications for treatment and research. Clinical Perspectives-12 Steps and Treatment. 2003;46:43-52.
Dole V. Addiction as a Public Health Problem. Alcoholism: Clinical and Experimental Research. 1991;15:749-752.
Mark Rose
However, there is nothing inherent in the 12-step approach that contradicts the use of medication for craving reduction, abstinence enhancement, or for that matter any psychiatric condition or disorder (Brigham 2003). An interesting side note to history occurred during the 1960s and involved a conversation between Dr. Vincent Dole, co-originator of methadone maintenance for heroin addiction, and Bill Wilson, co-founder of AA. Dr. Dole served as a trustee of AA, became friends with Bill Wilson, and recalled a conversation they had (Dole, 1991) where Wilson expressed his concern over alcoholics who could not achieve sobriety despite repeated attempts through AA:
“At the last trustee meeting (of AA) that we (Vincent Dole and Bill Wilson) both attended, he (Bill Wilson) spoke to me of his deep concern for the alcoholics who are not reached by AA, and for those who enter and drop out and never return. Always the good shepherd, he was thinking about the many lost sheep who are lost in the dark world of alcoholism. He suggested that in my future research I should look for an analogue of methadone, a medication that would relieve the alcoholic’s sometimes irresistible craving and enable him to progress in AA toward social and emotional recovery, following the Twelve Steps.”
This highly revealing anecdote reflects the open-mindedness and recognition by the co-founder of AA that some alcoholics require a pharmacotherapeutic intervention to bridge the gap from initial abstinence to stable abstinence and integration in AA. How unfortunate it is that many ardent believers in the 12-step approach have adopted an attitude of rigidity and dogmatism regarding addiction medicine.
Brigham GS. 12-step participation as a pathway to recovery: The Maryhaven experience and implications for treatment and research. Clinical Perspectives-12 Steps and Treatment. 2003;46:43-52.
Dole V. Addiction as a Public Health Problem. Alcoholism: Clinical and Experimental Research. 1991;15:749-752.
Mark Rose
Sunday, October 17, 2010
Agonist Therapy for Stimulant Addiction
Agonist therapy is the use of a (usually) long-acting medication that stimulates the same brain receptors as the drug of addiction. The most obvious example is opioid agonist therapy for opioid addiction using methadone or buprenorphine. Several medications potentially useful for alcohol addiction stimulate GABA receptors as does alcohol. One reason agonist therapy works is that it relieves drug hunger without inducing intoxication. Antagonist therapy, such as using naltrexone to treat opioid addiction can work, but it usually does not relieve drug hunger, so people stop them to seek intoxication. In this new study in Neuropsychopharmacology, a controlled-release form of amphetamine was studied as a treatment for cocaine addiction, with some intriguing results.
MW
Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball’-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers
Mark K Greenwald1, Leslie H Lundahl1 and Caren L Steinmiller1,2
1. 1Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA
2. 2Department of Pharmacology and Toxicology, University of Toledo, Toledo, OH, USA
Correspondence: Dr M Greenwald, Department of Psychiatry and Behavioral Neurosciences, Substance Abuse Research Division, 2761 East Jefferson Ave., Detroit, MI 48207, USA. Tel: +1 313 993 3965; Fax: +1 313 993 1372; E-mail: mgreen@med.wayne.edu
Received 18 May 2010; Revised 27 August 2010; Accepted 28 August 2010; Published online 29 September 2010.
Top of page
Abstract
The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball’-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); ‘speedball’ (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy.
MW
Sustained Release d-Amphetamine Reduces Cocaine but not ‘Speedball’-Seeking in Buprenorphine-Maintained Volunteers: A Test of Dual-Agonist Pharmacotherapy for Cocaine/Heroin Polydrug Abusers
Mark K Greenwald1, Leslie H Lundahl1 and Caren L Steinmiller1,2
1. 1Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA
2. 2Department of Pharmacology and Toxicology, University of Toledo, Toledo, OH, USA
Correspondence: Dr M Greenwald, Department of Psychiatry and Behavioral Neurosciences, Substance Abuse Research Division, 2761 East Jefferson Ave., Detroit, MI 48207, USA. Tel: +1 313 993 3965; Fax: +1 313 993 1372; E-mail: mgreen@med.wayne.edu
Received 18 May 2010; Revised 27 August 2010; Accepted 28 August 2010; Published online 29 September 2010.
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Abstract
The aim of this study was to determine whether oral sustained release d-amphetamine (SR-AMP) reduces cocaine and opioid/cocaine combination (‘speedball’-like) seeking in volunteers with current opioid dependence and cocaine dependence. Following outpatient buprenorphine (BUP) 8 mg/day stabilization without SR-AMP, eight participants completed a 3-week in-patient study with continued BUP 8 mg/day maintenance and double-blind ascending SR-AMP weekly doses of 0, 30, and 60 mg/day, respectively. After 3 days (Saturday–Monday) stabilization at each SR-AMP weekly dose (0, 15, or 30 mg administered at 0700 and 1225 each day), on Tuesday–Friday mornings (0900–1200 hours), participants sampled four drug combinations in randomized, counterbalanced order under double-blind, double-dummy (intranasal cocaine and intramuscular hydromorphone) conditions: cocaine (COC 100 mg+saline); hydromorphone (COC 4 mg+HYD 24 mg); ‘speedball’ (COC 100 mg+HYD 24 mg); and placebo (COC 4 mg+saline). Subjective and physiological effects of these drug combinations were measured. From 1230 to 1530 hours, participants could respond on a choice, 12-trial progressive ratio schedule to earn drug units (1/12th of total morning dose) or money units (US$2). SR-AMP significantly reduced COC, but not HYD or speedball, choices and breakpoints. SR-AMP also significantly reduced COC subjective (eg, abuse-related) effects and did not potentiate COC-induced cardiovascular responses. This study shows the ability of SR-AMP to attenuate COC self-administration, as well as its selectivity, in cocaine/heroin polydrug abusers. Further research is warranted to ascertain whether SR-AMP combined with BUP could be a useful dual-agonist pharmacotherapy.
Monday, October 4, 2010
Navy Offers On-Line Help for Addictions
Now, if only they'd offer CBT and medications as well... (sigh)
MW
October 3, 2010
Navy Offers Sailors Online Help to Quit Addictions
By THE ASSOCIATED PRESS
Filed at 1:13 p.m. ET
RICHMOND, Va. (AP) — The Navy is teaming up with a highly regarded addiction treatment center to provide Web-based support for thousands of sailors, their families and retired personnel struggling with alcohol and drug abuse.
The $3.25 million program is intended to keep sailors with addiction problems on the road to recovery and links them to support programs anywhere in the world, at anytime, even when they're deployed. It is tailored primarily to younger sailors, who are at greater risk and are comfortable navigating the Internet and social programs.
It was developed in collaboration with Hazelden, a nonprofit alcohol and drug addiction treatment center based in Minnesota, and aimed at the 10,000 patients who receive primary treatment annually under the Navy's Substance Abuse and Rehabilitation Services program. While families and retired Navy also receive treatment, the majority of patients are on active duty.
The online program launched in August is called Navy MORE, an acronym for My Ongoing Recovery Experience. An estimated 1,000 patients are expected to use the program in its first year.
"It's patient-centered care," said Master Chief Michael P. Brown, a Navy recovery coach for the Pacific Northwest, the Great Lakes and Hawaii. "We just assist them along the way.
Capt. Richard D. Bergthold, a clinical psychologist with the Navy, said the program is tailored to military use but also provides the continuing, immediately accessible support and resources that anyone overcoming addiction needs.
"We know it's the investment in the continuing care that makes or breaks a successful treatment," said Bergthold, chief of staff for the Navy's Wounded, Ill and Injured directorate. "We recognize more and more the importance of maintaining continuous engagement with an individual's recovery plan."
A 2005 Department of Defense study found that all military personnel between the ages of 18-25 were more likely to drink heavily than their civilian counterparts. Seventeen percent of Navy personnel described themselves as heavy drinkers, defined as someone who consumes five or more alcoholic drinks at one sitting at least once a week. Illicit drug use has trended down over the past few decades, according to the Pentagon.
Hazelden, which has worked with the Navy for 10 years and already trains Navy counselors, developed MORE over several years to help sailors who have struggled with addiction problems to stay clean and sober once they have gone through the Navy's treatment program.
"One of the main reasons for relapse is the loss of that connectivity during early recovery," said Nick Motu, a Hazelden vice president who worked with the Navy on the program. "We believe that if you can maintain a real solid recovery platform for the first 18 months, the chances of your success and long-term recovery are much higher."
Navy MORE extends this connectivity by putting Navy-specific programs online, including 12-step recovery approaches and a suicide hotline as well as treatment programs tailored to sailors or retirees who are suffering from post traumatic stress disorder.
Sailors, their families and retirees also will have access to a virtual "recovery coach" to manage their post-treatment progress; an online library of recovery topics; and online support groups, including real-time connections with counselors.
"They don't have access to the traditional recovery communities that someone on the outside world would have," Motu said of sailors who are deployed around the world.
While a sailor assigned to an aircraft carrier would have access to program counselors, other military personnel including Marines in a carrier group might not have the same access to services, Bergthold said.
The Web program's key benefits are immediacy and the ability to access resources with the click of a mouse.
"It's when they go back to their homes, when they go back to their ships, when they go into the increasingly stressful environments in which they work that they require these continuing care services," he said.
Brown, who is based at Naval Hospital Bremerton in Washington, said it's in the Navy's interest to return "productive sailors to the fleet."
"Everyone in life has their bumps. We're here to assist them and we're here to help them on their path," he said.
The program is free to its users and the Navy has signed a five-year contract. Motu said Hazelden is in discussions with other branches of the military to develop similar programs.
___
Online:
Navy MORE: http://www.navymore.org/home.html
MW
October 3, 2010
Navy Offers Sailors Online Help to Quit Addictions
By THE ASSOCIATED PRESS
Filed at 1:13 p.m. ET
RICHMOND, Va. (AP) — The Navy is teaming up with a highly regarded addiction treatment center to provide Web-based support for thousands of sailors, their families and retired personnel struggling with alcohol and drug abuse.
The $3.25 million program is intended to keep sailors with addiction problems on the road to recovery and links them to support programs anywhere in the world, at anytime, even when they're deployed. It is tailored primarily to younger sailors, who are at greater risk and are comfortable navigating the Internet and social programs.
It was developed in collaboration with Hazelden, a nonprofit alcohol and drug addiction treatment center based in Minnesota, and aimed at the 10,000 patients who receive primary treatment annually under the Navy's Substance Abuse and Rehabilitation Services program. While families and retired Navy also receive treatment, the majority of patients are on active duty.
The online program launched in August is called Navy MORE, an acronym for My Ongoing Recovery Experience. An estimated 1,000 patients are expected to use the program in its first year.
"It's patient-centered care," said Master Chief Michael P. Brown, a Navy recovery coach for the Pacific Northwest, the Great Lakes and Hawaii. "We just assist them along the way.
Capt. Richard D. Bergthold, a clinical psychologist with the Navy, said the program is tailored to military use but also provides the continuing, immediately accessible support and resources that anyone overcoming addiction needs.
"We know it's the investment in the continuing care that makes or breaks a successful treatment," said Bergthold, chief of staff for the Navy's Wounded, Ill and Injured directorate. "We recognize more and more the importance of maintaining continuous engagement with an individual's recovery plan."
A 2005 Department of Defense study found that all military personnel between the ages of 18-25 were more likely to drink heavily than their civilian counterparts. Seventeen percent of Navy personnel described themselves as heavy drinkers, defined as someone who consumes five or more alcoholic drinks at one sitting at least once a week. Illicit drug use has trended down over the past few decades, according to the Pentagon.
Hazelden, which has worked with the Navy for 10 years and already trains Navy counselors, developed MORE over several years to help sailors who have struggled with addiction problems to stay clean and sober once they have gone through the Navy's treatment program.
"One of the main reasons for relapse is the loss of that connectivity during early recovery," said Nick Motu, a Hazelden vice president who worked with the Navy on the program. "We believe that if you can maintain a real solid recovery platform for the first 18 months, the chances of your success and long-term recovery are much higher."
Navy MORE extends this connectivity by putting Navy-specific programs online, including 12-step recovery approaches and a suicide hotline as well as treatment programs tailored to sailors or retirees who are suffering from post traumatic stress disorder.
Sailors, their families and retirees also will have access to a virtual "recovery coach" to manage their post-treatment progress; an online library of recovery topics; and online support groups, including real-time connections with counselors.
"They don't have access to the traditional recovery communities that someone on the outside world would have," Motu said of sailors who are deployed around the world.
While a sailor assigned to an aircraft carrier would have access to program counselors, other military personnel including Marines in a carrier group might not have the same access to services, Bergthold said.
The Web program's key benefits are immediacy and the ability to access resources with the click of a mouse.
"It's when they go back to their homes, when they go back to their ships, when they go into the increasingly stressful environments in which they work that they require these continuing care services," he said.
Brown, who is based at Naval Hospital Bremerton in Washington, said it's in the Navy's interest to return "productive sailors to the fleet."
"Everyone in life has their bumps. We're here to assist them and we're here to help them on their path," he said.
The program is free to its users and the Navy has signed a five-year contract. Motu said Hazelden is in discussions with other branches of the military to develop similar programs.
___
Online:
Navy MORE: http://www.navymore.org/home.html
Monday, September 13, 2010
Acamprosate Review Concludes It's Effective
The most recent meta-analysis regard acamprosate concluded that it was safe and effective for treating alcohol dependence, with a number needed to treat (NNT) of 9 (9 patients have to be treated to prevent one relapse.) This NNT is quite acceptable. I remain skeptical, however. I'm going to look the paper over in more detail and weigh in with my own take.
MW
Medscape Medical News
Acamprosate May Be Helpful to Treat Alcohol Dependence
Laurie Barclay, MD
September 13, 2010 — Acamprosate appears to be effective and safe for supporting continuous abstinence after detoxification in alcohol-dependent patients, according to the results of a systematic review reported September 8 in the Cochrane Database of Systematic Reviews.
"Alcohol dependence is among the main leading health risk factors in most developed and developing countries," write Susanne Rösner, from the University of Munich in Munich, Germany, and colleagues. "Therapeutic success of psychosocial programs for relapse prevention is moderate, but could potentially be increased by an adjuvant treatment with the glutamate antagonist acamprosate."
To compare the efficacy and tolerability of acamprosate vs placebo or active control, the reviewers searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE, and CINAHL in January 2009. They also asked manufacturers and investigators for data from unpublished studies.
Inclusion criteria were double-blind, randomized controlled trials (RCTs) comparing drinking-related outcomes obtained with acamprosate vs those obtained with placebo or with other pharmacotherapy. Two authors independently extracted data; one author evaluated trial quality, and a second author verified this assessment. Primary efficacy outcomes were confirmed with use of meta-analyses of individual patient data.
There were 24 RCTs meeting selection criteria, enrolling a total of 6915 alcohol-dependent participants. Risk of any drinking was significantly lower with acamprosate vs placebo (relative risk [RR], 0.86; 95% confidence interval [CI], 0.81 - 0.91). The number needed to treat [NNT] to benefit was 9.09 (95% CI, 6.66 - 14.28), and cumulative abstinence duration MD was significantly higher (10.94; 95% CI, 5.08 - 16.81). However, gamma-glutamyltransferase (GGT) levels, heavy drinking, and other secondary outcomes did not reach statistical significance.
"Acamprosate is certainly no magic bullet, but it is a safe and effective treatment for patients who are trying to stop drinking," Dr. Rösner said in a news release. "The benefits we have seen in these trials are small. However, we must remember that these are additional benefits on top of those from other non-drug therapies."
The only adverse effect reported more frequently with acamprosate vs placebo was diarrhea (RD, 0.11; 95% CI, 0.09 - 0.13). The NNT to harm was 9.09 (95% CI, 7.69 - 11.11). Compared with nonprofit-funded trials, findings from industry-sponsored trials were not significantly different, and the linear regression test did not demonstrate any significant risk for publication bias (P = .861).
"Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol dependent patients," the study authors write. "Even though the sizes of treatment effects appear to be rather moderate in their magnitude, they should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment."
Limitations of this study include those inherent in the included trials, such as poor compliance with assigned study drug, as well as some heterogeneity between studies.
Three of the reviewed trials compared acamprosate vs naltrexone. These trials showed comparable effects of the 2 drugs on return to any drinking, return to heavy drinking, and cumulative abstinence duration.
"Patients' doubts and reservations against a strategy that uses one substance to treat dependency on another should be taken seriously, while interventions that have been shown to work should not kept back from patients," Dr. Rösner said.
The Federal Ministry of Education and Research supported this study.
MW
Medscape Medical News
Acamprosate May Be Helpful to Treat Alcohol Dependence
Laurie Barclay, MD
September 13, 2010 — Acamprosate appears to be effective and safe for supporting continuous abstinence after detoxification in alcohol-dependent patients, according to the results of a systematic review reported September 8 in the Cochrane Database of Systematic Reviews.
"Alcohol dependence is among the main leading health risk factors in most developed and developing countries," write Susanne Rösner, from the University of Munich in Munich, Germany, and colleagues. "Therapeutic success of psychosocial programs for relapse prevention is moderate, but could potentially be increased by an adjuvant treatment with the glutamate antagonist acamprosate."
To compare the efficacy and tolerability of acamprosate vs placebo or active control, the reviewers searched the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, PubMed, EMBASE, and CINAHL in January 2009. They also asked manufacturers and investigators for data from unpublished studies.
Inclusion criteria were double-blind, randomized controlled trials (RCTs) comparing drinking-related outcomes obtained with acamprosate vs those obtained with placebo or with other pharmacotherapy. Two authors independently extracted data; one author evaluated trial quality, and a second author verified this assessment. Primary efficacy outcomes were confirmed with use of meta-analyses of individual patient data.
There were 24 RCTs meeting selection criteria, enrolling a total of 6915 alcohol-dependent participants. Risk of any drinking was significantly lower with acamprosate vs placebo (relative risk [RR], 0.86; 95% confidence interval [CI], 0.81 - 0.91). The number needed to treat [NNT] to benefit was 9.09 (95% CI, 6.66 - 14.28), and cumulative abstinence duration MD was significantly higher (10.94; 95% CI, 5.08 - 16.81). However, gamma-glutamyltransferase (GGT) levels, heavy drinking, and other secondary outcomes did not reach statistical significance.
"Acamprosate is certainly no magic bullet, but it is a safe and effective treatment for patients who are trying to stop drinking," Dr. Rösner said in a news release. "The benefits we have seen in these trials are small. However, we must remember that these are additional benefits on top of those from other non-drug therapies."
The only adverse effect reported more frequently with acamprosate vs placebo was diarrhea (RD, 0.11; 95% CI, 0.09 - 0.13). The NNT to harm was 9.09 (95% CI, 7.69 - 11.11). Compared with nonprofit-funded trials, findings from industry-sponsored trials were not significantly different, and the linear regression test did not demonstrate any significant risk for publication bias (P = .861).
"Acamprosate appears to be an effective and safe treatment strategy for supporting continuous abstinence after detoxification in alcohol dependent patients," the study authors write. "Even though the sizes of treatment effects appear to be rather moderate in their magnitude, they should be valued against the background of the relapsing nature of alcoholism and the limited therapeutic options currently available for its treatment."
Limitations of this study include those inherent in the included trials, such as poor compliance with assigned study drug, as well as some heterogeneity between studies.
Three of the reviewed trials compared acamprosate vs naltrexone. These trials showed comparable effects of the 2 drugs on return to any drinking, return to heavy drinking, and cumulative abstinence duration.
"Patients' doubts and reservations against a strategy that uses one substance to treat dependency on another should be taken seriously, while interventions that have been shown to work should not kept back from patients," Dr. Rösner said.
The Federal Ministry of Education and Research supported this study.
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