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.


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

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.


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

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)


October 3, 2010

Navy Offers Sailors Online Help to Quit Addictions


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.



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.


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.

Tuesday, September 7, 2010

The Only Effective Treatment for Opioid Dependence is Maintenance (again)

Here is a report on Medscape about a large study comparing short and long-term tapering strategies using Suboxone to treat prescription opioid dependence. As with virtually every other study comparing taper and discontinuation with maintenance, virtually all participants relapsed following discontinuation. It didn't matter whether they tapered over one month or nine. It didn't matter whether they received only medical management or enhanced addiction counseling. Drug free treatment for established (> 1 years) opioid dependence does not work! (Except in highly unusual situations such as airline pilots or physicians who are required to get a shot of extended release naltrexone once a month.)In spite of this and dozens of other high quality studies, treatment programs continue to promote "drug free" treatment for opioid dependence, thus condemning their unwitting customers to relapse. And why? Because they don't believe in it. How would you feel if your doctor knew of an antibiotic that would treat your chronic infection but who didn't tell you about it because she didn't believe in using drugs to treat infections? Or who knew of a surgery that would cure your disability but didn't offer it and discouraged you from having it because he didn't believe in surgery? How long are we going to let this happen before treatment programs are held accountable to offer scientifically sound treatment and advice?



Authors and Disclosures
Caroline Helwick
From Medscape Medical News
For Prescription Opioid Dependence, Relapses Associated With Shorter Treatment Course
Caroline Helwick
May 24, 2010 (New Orleans, Louisiana) — In persons dependent on prescription opioids, tapering with buprenorphine during a 9-month period, whether initially or after a period of substantial improvement, led to nearly universal relapse in the National Drug Abuse Treatment Clinical Trials Network Prescription Opioid Addiction Treatment Study, presented here at the American Psychiatric Association 2010 Annual Meeting.
"There has been virtually no research on the treatment of persons dependent on prescription opioids, in spite of the major increase in prescription opioid abuse and in the numbers of persons entering treatment for addiction to prescription opioids," said Roger D. Weiss, MD, professor of psychiatry at Harvard Medical School, Boston, and chief of the Division of Alcohol and Drug Abuse, McLean Hospital, Belmont, Massachusetts.
The study, which is the largest treatment study ever conducted for prescription opioid dependence (POD), sought to answer several questions regarding the optimal length of pharmacotherapy, the value of intense counseling, and the role of chronic pain.
Specifically, the study asked whether adding individual drug counseling to buprenorphine-naloxone (a semisynthetic opioid and a partial agonist) plus standard medical management improves outcomes, what duration of buprenorphine is best for these patients, and whether presence or absence of current chronic pain influences outcomes.
"The trial was designed to help the physician manage patients who are dependent on opioids and want off the drugs but refuse treatment in a drug abuse treatment program," Dr. Weiss said.
The study enrolled 653 persons with POD and offered them standard medical management, which included buprenorphine (usually 12 - 16 mg maximum, adjusted for addiction, not pain), an initial 1-hour visit, and weekly 20-minute sessions with a physician who counseled the patients and monitored for drug adverse effects. Half the group remained in this standard medical management (SMM) group and half received enhanced medical management (EMM), which included twice-weekly 60-minute individualized drug counseling focusing on interpersonal issues, coping with triggers and high-risk situations, homework, and so forth.
Under a somewhat complicated schema, patients were evaluated after periods of individualized buprenorphine tapering and maintenance and were assessed for abstinence from opioids at various times.
Study Population
All patients had a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, diagnosis of opioid dependence and had used opioids for at least 20 of the last 30 days. Other substance abuse disorders were allowed, with the exception of active heroin use or history of injecting heroin. All patients expressed an interest in stopping opioids.
The population was made up of 60% men, was 91% white, had a mean age of 33 years, was likely to be cigarette smokers (71%), and had been using opioids for an average of 4.5 years. Most patients had received some college education and were employed full-time. There were no significant differences at baseline between the SMM and EMM groups.
A number of patients reported current chronic pain (42%), and some were taking opioids for this condition. Although current polypharmacy was uncommon, many patients reported a lifetime history of heroin use (23%), alcohol abuse (60%) or dependence (27%), cannabis abuse (47%) or dependence (15%), and cocaine abuse (32%) or dependence (18%). Stimulant and sedative use were less common.
Opioids used within 30 days included sustained-release oxycodone (35%), hydrocodone (32%), immediate-release oxycodone (19%), methadone (6%), and others (8%).
Thirty percent of subjects had received some previous treatment for opioid dependency, primarily "self help" (59%), inpatient/residential treatment (42%), outpatient counseling (40%), and methadone maintenance (31%).
"For most subjects, this was the first treatment for opioid dependence," said Dr. Weiss.
Treatment and Maintenance
Treatment success was defined as 4 or fewer days of opioid use per month, no positive urine screens for opioids for 2 consecutive weeks, no other formal substance abuse treatment, and no injection of opioids.
Phase 1 included 1 month of tapering and 2 months of stabilization. At the end of this time, few patients were successfully treated, and enhanced management did not influence the results, Dr. Weiss reported.
In the SMM group, only 7% met the criteria for success, as did just 6% of the EMM group (P = .45). "Nearly all patients relapsed after a 4-week taper," Dr. Weiss said.
Patients who relapsed were asked to enter phase 2, at which time 360 patients were again randomly assigned to SMM or EMM and received 3 months of buprenorphine stabilization, then had treatment tapered for 1 month, with a 2-month follow-up.
At the end of the stabilization (at week 12), substantial improvement was noted for 52% of the EMM group and 47% of the SMM group, though again there was no additional benefit to enhanced management (P = .3). Substantial improvement was defined as abstinence for 3 or more of the final 4 weeks of buprenorphine stabilization (urine-confirmed self-report).
However, by the end of the stabilization period, many patients had relapsed again, Dr. Weiss reported.
"We went from an average success rate of 49% to 26% at week 16,"he said. At week 24 (8 weeks posttaper), only 9% of patients remained successfully treated.
"At the end of the study, we were back into phase 1 territory," he said. "Seven of 8 patients doing well on buprenorphine maintenance had relapsed."
Predictors of Outcome
The only predictor outcome was ever-use of heroin. At week 12, improvement was noted for 37% of those reporting lifetime heroin use compared with 54% of those without such a history (P = .003); at week 24, this was 5% and 10%, respectively (P = .13). "Having dabbled in heroin was a bad prognostic sign," Dr. Weiss observed.
The presence of chronic pain did not influence outcomes. Patients with chronic pain were equally likely to enter phase 2 (indicating early treatment failure) and were equally likely to be substantially improved at week 12 of phase 2 (53% vs 47% for those without chronic pain).
Chronic pain tended to be lumbar/sacral (65%) and classified as only moderate (median 4.4 on 10-point scale) but was of long duration, as more than half the patients had suffered from it for at least 4 years, he said.
"Interestingly, we found that in many cases the patient's pain got better," he added. More than half the subjects reported at least a moderate reduction of pain from baseline (≥30%), and one third had a substantial improvement (≥50%).
Nevertheless, Dr. Weiss said one cannot assume that buprenorphine itself improved the pain, as there was no control group, "but it is an intriguing possibility," he commented.
Sean Mackey, MD, PhD, associate professor of anesthesia and chief of the Division of Pain Management at Stanford University, Palo Alto, California, who delivered an overview of the treatment of pain in patients with addiction at the session, commented on the current study for Medscape Psychiatry.
He was particularly interested in the finding that persons with a history of heroin use had worse outcomes. "Could it be that prior exposure to heroin fundamentally alters the neurobiology in this group such that they need higher doses of buprenorphine to prevent relapse?" he asked.
Dr. Mackey maintained that the study is important because it asked a clinically relevant question: "Does putting people on a short period of buprenorphine maintenance combined with counseling lead to reductions in relapse? It's a great idea, and a wonderful hypothesis, because if it does work then this would be a huge win. We would not have to use extended maintenance. Unfortunately, it did not work, but the study needed to be done."
He further noted that the standard management group was likely getting better care in this study than is delivered in usual practice, which may have diluted potential differences.
Dr. Weiss has reported receiving research support from Eli Lilly. Dr. Mackey has disclosed no relevant financial relationships.
American Psychiatric Association 2010 Annual Meeting: Symposium 36, presentation 4. Presented May 23, 2010.
Medscape Medical News © 2010 Medscape, LLC
Send press releases and comments to news@medscape.net.

Monday, August 16, 2010

And another response to Dr. Johnson

From The Huffington Post

Deni Carise

Chief Clinical Officer, Phoenix House
Posted: August 16, 2010 12:00 PM

Examining the Viability of Substance Abuse Treatment Today

Earlier this week, I was more than a little put off by Bankole Johnson's Washington Post editorial, "We're Addicted to Rehab. It Doesn't Even Work." It's interesting to note that this piece comes just six months before the release of his new book on medications that "conquer alcoholism," which will join countless other tomes that also claim to have the cure.

In his searing op-ed, Johnson, chair of psychiatry and neurobehavioral sciences at the University of Virginia, argues that there is little empirical evidence to suggest that substance abuse treatment programs are effective. Making sweeping generalizations, he points a finger at our country's treatment centers, including nonprofit providers, calling them both "ruinously expensive" and "divorced from state-of-the-art medical knowledge."

I take issue with these charges first and foremost as a scientist who has dedicated her career to studying the effectiveness of substance abuse treatment. In equal measure, I disagree with Johnson's allegations as a person in long-term recovery who might not be here were it not for the treatment I received.

Johnson calls substance abuse a devastating disease, yet he fails to acknowledge the limitations of treating a condition that is chronic by nature, like diabetes and hypertension. When evaluating the effectiveness of a particular medication for diabetes, treatment providers don't expect their diabetic patients to be "cured" after one treatment, nor do they define success as never having another sugar crisis. Similarly, defining successful substance abuse treatment as one that produces 100 percent abstinence for the rest of a person's life is a naïve and useless benchmark. However, if we define success as learning to manage your condition and gaining the support needed to do so, there are literally hundreds of controlled studies documenting the effectiveness of various forms of treatment. And they meet FDA levels of effectiveness.

As for Johnson's claim that substance abuse treatment is "too costly for most people," this is simply not the case. The two programs he mentions, Promises and Hazeldon, are geared toward individuals of higher socioeconomic status. However, there are many programs in our country that serve those with more modest means. When I entered substance abuse outpatient treatment in 1984, I paid just five dollars for each counseling session I attended. I later found out that the remainder of my treatment costs had been covered by the federal block grant. At Phoenix House, where our programs receive both state and federal funding, some clients stay with us even when they have no funds to cover their care. Many other non-profits do the same. Listing two expensive programs as if they are representative examples does not convey the wide range of treatment options available to people from all walks of life.

Johnson primarily aims his criticism at AA and it's true that not every substance abuser who enters AA will achieve long-term recovery. Likewise, not every diabetic who tries a particular medication will achieve long-term recovery from diabetes. As with other chronic conditions, there are many evidence-based treatment methods for substance abuse--not just the 12-step model. To discredit an entire spectrum of care that has worked for hundreds of thousands of people--and has been backed by scientific research--is to ignore the facts. It says to those of us who work with substance abusers each day that our efforts to help them are futile. And it says to those who need treatment that there is no real help available. That's inaccurate and irresponsible.

I'm certainly not dismissing the benefits of incorporating medication into substance abuse treatment. That would be irresponsible as well. But research has shown that meds alone will not produce a cure and traditional "rehab" components such as group counseling are equally important. Dr. Johnson himself runs a treatment program that includes cognitive behavioral therapy in addition to pharmacology. So why can't he acknowledge that any and all empirically-proven methods of helping people with this disease need to be included in their treatment options?

Maybe it's simply the fact that presenting a more balanced op-ed piece wouldn't sell as many books.

More on Dr. Johnson's Critique of 12-step Programs

Letters to the editor in response:

The pros and cons of 12-step rehab

Thursday, August 12, 2010

I take issue with Bankole A. Johnson's Aug. 8 Outlook commentary, "12 steps to nowhere," which essentially devalued alcohol rehabilitation in order to sell "effective medicine" to treat alcoholism.

I have been treating alcoholism in the Defense Department and the Navy for 33 years. Alcoholics Anonymous works for us. Both the Defense Department and the Navy have used AA and Twelve Step Facilitation Treatment for 40 years and have a recovery rate five years after treatment of about 75 percent. The Navy has some experience with drinking -- and it knows how to treat alcoholism. Our lives depend on it. Marines like to go to war sober.

Dr. Johnson is paid to develop drugs as the primary treatment for alcoholism. However, he knows so little about how AA works and takes quotes from the Big Book completely out of context.

Two million sober members of AA, most not on medication, will see his article and know how wrong he is for them.

Ronald Earl Smith, Bethesda

The writer is a captain in the Navy's medical corps and a senior psychiatrist and psychoanalyst at the National Naval Medical Center.


I attended 150 12-step meetings in 90 days (versus the prescribed 90 meetings in 90 days) and have not been to a meeting since, in about 12 years. I also have had no alcohol in that time. The pros and cons of 12-step rehab

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I agree with everything Bankole Johnson said about the problems with 12-step rehabilitation. However, he failed to appreciate that if AA works for only a minority of people who try it, for that group "it works if you work it." Let others try something else.

If Dr. Johnson and his colleagues find a better cure, more power to them. Only do not let them or anyone say that AA does not work. It does for countless thousands, and at virtually no cost but time and effort.

Philip Saunders, Dunn Loring


In his commentary, Bankole Johnson stated that "no experimental studies have unequivocally demonstrated the effectiveness" of the 12-step approach to addiction.

In an experimental study in 2006 conducted at the Veterans Affairs Palo Alto Health Care System, randomly selected addicted patients who received a structured introduction to Alcoholics Anonymous and Narcotics Anonymous had a more than 60 percent greater reduction in the severity of their substance abuse problems six months later than did patients not receiving such an introduction. In a different experimental study, also in 2006, of a 12-step-oriented sober-living home, addicted individuals were, relative to those receiving other forms of care, twice as likely to be abstaining from substance use and three times as likely to not be incarcerated.

Both of these widely cited studies were funded by major, peer-reviewed federal research grants and were published in high-profile peer-reviewed journals.

Dr. Johnson's failure to mention them resulted in a mischaracterization of what research has established about the effectiveness of the 12-step approach.

Keith Humphreys, Palo Alto, Calif.

Tuesday, August 10, 2010

Controversial editorial in Washington Post

In case you missed it, Bankole Johnson wrote an op-ed for the Washington Post that appeared 2 days ago. Here's a link: http://www.washingtonpost.com/wp-dyn/content/article/2010/08/06/AR2010080602660.html

You may need to register with the Post to see this link, but it's free and they don't hassle you in any way, such as spam or solicitations.

What do you think about his piece? I'm really interested in hearing.

Sunday, August 8, 2010

The Need for Medical Treatment for Addiction

It's been some time since I've blogged. For those of you who are followers or check in on the blog I'm sorry for the lack of activity. The transition to Minnesota has taken a lot of energy, but I have a lot of progress to report.

My practice here in Minnesota has really taken off. Once the other physicians in the hospital and indeed throughout the entire community have become aware of an alternative to another run through rehab the referrals have become consistent. I was just away from the hospital for a week, and I suspect that the hospitalists who take care of most hospitalized patients have missed me. Once they got a taste of getting help with complex pain patients, difficult withdrawal problems, and a physician who was willing to take their referrals for patients with addiction in conjunction with medical and psychiatric disorders, they have gotten very enthusiastic. This is similar to my experience when I first started a clinic for medically ill alcoholics at the Minneapolis VA hospital years ago. The attitude towards alcohol dependent patients admitted with liver disease, pancreatitis, withdrawal, and other problems up to then had been hopeless, nihilistic. What was the use when a consultation resulted in a nurse or counselor suggesting another run through rehab even if the patient had already had that treatment multiple times? But when there was a clinic where these patients could receive ongoing care that incorporated medical, psychiatric and addiction treatment, you could almost feel the change throughout the medical center. Staff became enthusiastic about identifying and referring patients like this to the clinic. It took about 3 years to develop the clinic and figure out how to provide this type of treatment. After that, I received a grant from the the VA to study whether this treatment was effective. In order to do that, we had to assign study participants to either this new clinic or to usual care which consisted of referral to primary care clinic. At that point, it became difficult, because staff were so enthusiastic about this new approach they were reluctant to have patients assigned to usual care. That's the hardest thing about test new treatments; although you might believe strongly in the new treatment you have to be willing to randomized and let the chips fall where they may. It turned out that the new approach was significantly more effective: mortality was reduce by 30% after two years, and more patients were able to achieve abstinence. So I'm finding that the same thing is happening where I currently work at United Hospital in St. Paul. Only it's even better: I'm providing a much broader range of services. One thing that has become apparent: there is a tremendous need for innovation in treating complex chronic pain. Chronic pain and how to appropriately use opioid (narcotic) medication is one of the most difficult and under-appreciated areas in medicine right now.

Tuesday, May 25, 2010

Vodka Eyeballing: The latest stupid drinking trend

or, "kids do the darnedest things"...

KTLA News (Los Angeles)
Dangerous 'Vodka Eyeballing' Popular with College Students
Eyeballing can cause damage to the optic nerve, leading to blindness.
9:11 AM PDT, May 20, 2010

LOS ANGELES -- A dangerous drinking fad known as "Vodka eyeballing" is growing in popularity on college campuses in the UK and the United States, and experts say it could leave students blind.

So-called "eyeballers" claim it's an instant high with a splash of alcohol giving them a buzz, literally, in the blink of an eye.

But, doctors say, it's a dangerous trend that could cause permanent vision damage.

Dr. Elise Brisco of the Hollywood Vision Center told KTLA that the practice creates an almost instant buzz "because it's going into the central nervous system into the brain."

The alcohol can damage the optic nerve, creating spotty vision and even complete blindness.

"If it's severe enough and there's a lot of optic nerve damage, your vision may not return," Brisco said.

Some eyeballers have posted videos of themselves online, and there are even "fan" pages for the practice on Facebook.

It's believed the dangerous trend started in the United States, but it is quickly gaining popularity at British universities, according to the UK Daily Mail.

Wednesday, May 19, 2010

Why do you think they call it DOPamine?

More on that infamous substance we all seem to be trying to maximize day to day:

U.S. Department of Health and Human Services
National Institutes of Health
NIH News
National Institute on Alcohol Abuse and Alcoholism (NIAAA) http://www.niaaa.nih.gov

EMBARGOED FOR RELEASE: Tuesday, May 18, 2010 @ 9:00 AM EDT
Contact: NIAAA Press Office, 301-443-3860, NIAAAPressOffice@mail.nih.gov<mailto:NIAAAPressOffice@mail.nih.gov>

Receptor Variant Influences Dopamine Response to Alcohol

A genetic variant of a receptor in the brain’s reward circuitry plays an important role in determining whether the neurotransmitter dopamine is released in the brain following alcohol intake, according to a study led by researchers at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health.  Dopamine is involved in transmitting the euphoria and other positive subjective effects produced by alcohol.

A report of the findings, which help explain the diverse genetic susceptibility for alcohol use disorders, will appear online in Molecular Psychiatry on May 18, 2010.

“By advancing our understanding of the neurobiology that underlies the addictive properties of alcohol, this finding helps us understand why alcohol affects people in very different ways,” says NIAAA Acting Director Kenneth R. Warren, Ph.D. “This kind of information also aids the development of personalized medications for alcohol problems.”

Receptors for brain molecules known as opioid peptides help initiate the neurochemical reactions that underlie the positive effects produced by alcohol.  Activation of the mu-subtype of opioid receptor following alcohol consumption triggers the release of dopamine from the forebrain.

“But there is much variation in alcohol-induced responses that are thought to be related to dopamine,” explains Markus Heilig, M.D., Ph.D., NIAAA clinical director and the study’s senior author.  “Previous studies by our group and others suggest that variants of opioid genes may contribute to the observed variation, possibly through effects on alcohol-induced dopamine release.”

He notes, for example, that people who carry the mu-opioid receptor variant designated as 118G report increased euphoria following alcohol consumption.  Dr. Heilig’s group has reported that a similar mu-opioid receptor variant in monkeys heightened the stimulating effects of alcohol and increased their alcohol consumption.

In the current study, first author Vijay A. Ramchandani, Ph.D., an investigator in NIAAA’s Laboratory of Clinical and Translational Studies, Dr. Heilig, and their colleagues explored whether the 118G mu-opioid receptor variant influences dopamine release from a forebrain region called the ventral striatum in response to alcohol.

Using human positron emission tomography (PET), an imaging technique that allowed the researchers to analyze dopamine activity in the brain, they compared dopamine release in two groups of people that had been given a dose of alcohol. The groups consisted of those who carried a copy of the gene for the 118G mu-opioid receptor variant, and those who carried only genes for the more common 118A variant. They found that only people with the 118G variant had a dopamine response to alcohol – no such response happened in subjects with the 118A receptor variant.

In a separate experiment, they inserted genes for the human 118G or 118A mu-opioid receptor variants into mice and then directly measured the animals’ dopamine response to a dose of alcohol.  Mice with the 118G variant showed a fourfold higher peak dopamine response to the alcohol challenge compared to mice with the 118A variant.

“Taken together, our data strongly support a causal role of the 118G variant of the mu-opioid receptor to confer a more vigorous dopamine response to alcohol in the ventral striatum,” says Dr. Ramchandani. “The findings add further support to the notion that individuals who possess this receptor variant may experience enhanced pleasurable effects from alcohol that could increase their risk for developing alcohol abuse and dependence. It may also explain why these individuals, once addicted, benefit more from treatment with blockers of endogenous opioids.”

Additional Information

Why Meds Work for Some People, but Not for Others<http://nihrecord.od.nih.gov/newsletters/2010/05_14_2010/story2.htm>
NIH Record, 5/14/2010

Alcohol’s effects on endogenous opioids in the brain<http://www.niaaa.nih.gov/Resources/GraphicsGallery/Neuroscience/31_4_endogenous.htm>

The National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems. NIAAA also disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at www.niaaa.nih.gov<http://www.niaaa.nih.gov>.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

Wednesday, May 12, 2010

More on "process addictions"

This new study found that the same brain mechanisms that are dysregulated in drug addiction are also dysregulated in binge eating. This is not surprising, of course, since behavior is dysregulated in similar ways in both disorders. That is, the behavior already tells us that the same underlying brain regulatory systems are not working properly, so these studies help confirm what we already suspected. However, these findings are not profound or startling unless one starts with the assumption that behavior can become consistently dysregulated without the corresponding systems in the brain also becoming dysregulated. To put it simply: dysregulated behavior<=>dysregulated brain. In addition, social interactions also have a correlary dysfunction, and there are additional corresonding changes at other levels of analysis, such as gene function, metabolism, and so forth. In other words the system changes at all levels at once. The other thing to keep in mind is that a study such as this does not mean that compulsive behaviors are just and only "brain diseases," since there are correlary changes up and down the system chain of events. It also does not mean the the only appropriate place to intervene is by directly manipulating neurotransmitters, e.g. medication therapy. Although that might be a useful tool, because all of these subsystems are interconnected, it is also possible to change the brain by changing the environment, or to focus on changing behavior and so forth. In addition, the study does not demonstrate that "obese people really cannot help it," or at least it is not news that this is true. We already knew that, with hundreds of studies showing that 95% of weight loss is regained after 5 years. Finally, remember that, as technically impressive as this study is, it is still a short-term study of rodents, and humans are not rodents. Rodent models give us clues, but findings in rodents do not directly translate to humans.


Compulsive Eating Shares Addictive Biochemical Mechanism With Cocaine, Heroin Abuse, Study Shows

ScienceDaily (Mar. 29, 2010) — In a newly published study, scientists from The Scripps Research Institute have shown for the first time that the same molecular mechanisms that drive people into drug addiction are behind the compulsion to overeat, pushing people into obesity.
The new study, conducted by Scripps Research Associate Professor Paul J. Kenny and graduate student Paul M. Johnson, was published March 28, 2010 in an advance online edition of the journal Nature Neuroscience.
The study's startling findings received widespread publicity after a preliminary abstract was presented at a Society for Neuroscience meeting in Chicago last October. Articles heralding the new discovery appeared in news publications around the world, focusing on the point obese patients have been making for years -- that, like addiction to other substances, junk food binging is extremely difficult to stop.
The study goes significantly further than the abstract, however, demonstrating clearly that in rat models the development of obesity coincides with a progressively deteriorating chemical balance in reward brain circuitries. As these pleasure centers in the brain become less and less responsive, rats quickly develop compulsive overeating habits, consuming larger quantities of high-calorie, high-fat foods until they become obese. The very same changes occur in the brains of rats that overconsume cocaine or heroin, and are thought to play an important role in the development of compulsive drug use.
Kenny, a scientist at Scripps Research's Florida campus, said that the study, which took nearly three years to complete, confirms the "addictive" properties of junk food.
"The new study, unlike our preliminary abstract, explains what happens in the brain of these animals when they have easy access to high-calorie, high-fat food," said Kenny. "It presents the most thorough and compelling evidence that drug addiction and obesity are based on the same underlying neurobiological mechanisms. In the study, the animals completely lost control over their eating behavior, the primary hallmark of addiction. They continued to overeat even when they anticipated receiving electric shocks, highlighting just how motivated they were to consume the palatable food."
The scientists fed the rats a diet modeled after the type that contributes to human obesity -- easy-to-obtain high-calorie, high-fat foods like sausage, bacon, and cheesecake. Soon after the experiments began, the animals began to bulk up dramatically.
"They always went for the worst types of food," Kenny said, "and as a result, they took in twice the calories as the control rats. When we removed the junk food and tried to put them on a nutritious diet -- what we called the 'salad bar option' -- they simply refused to eat. The change in their diet preference was so great that they basically starved themselves for two weeks after they were cut off from junk food. It was the animals that showed the "crash" in brain reward circuitries that had the most profound shift in food preference to the palatable, unhealthy diet. These same rats were also those that kept on eating even when they anticipated being shocked."
Lethally Simple
What happens in addiction is lethally simple, Kenny explained. The reward pathways in the brain have been so overstimulated that the system basically turns on itself, adapting to the new reality of addiction, whether its cocaine or cupcakes.
"The body adapts remarkably well to change -- and that's the problem," said Kenny. "When the animal overstimulates its brain pleasure centers with highly palatable food, the systems adapt by decreasing their activity. However, now the animal requires constant stimulation from palatable food to avoid entering a persistent state of negative reward."
After showing that obese rats had clear addiction-like food seeking behaviors, Johnson and Kenny next investigated the underlying molecular mechanisms that may explain these changes. They focused on a particular receptor in the brain known to play an important role in vulnerability to drug addiction and obesity -- the dopamine D2 receptor. The D2 receptor responds to dopamine, a neurotransmitter that is released in the brain by pleasurable experiences like food or sex or drugs like cocaine. In cocaine abuse, for example, the drug alter the flow of dopamine by blocking its retrieval, flooding the brain and overstimulating the receptors, something that eventually leads to physical changes in the way the brain responds to the drug.
The new study shows that the same thing happens in junk food addiction.
"These findings confirm what we and many others have suspected," Kenny said, "that overconsumption of highly pleasurable food triggers addiction-like neuroadaptive responses in brain reward circuitries, driving the development of compulsive eating. Common mechanisms may therefore underlie obesity and drug addiction."
Consistent with common mechanisms explaining addiction and obesity, levels of the D2 dopamine receptors were significantly reduced in the brains of the obese animals, similar to previous reports of what happens in human drug addicts, Kenny noted. Remarkably, when the scientists knocked down the receptor using a specialized virus, the development of addiction-like eating was dramatically accelerated.
"This addiction-like behavior happened almost from the moment we knocked down the dopamine receptors," Kenny noted. "The very next day after we provided access to the palatable food, their brains changed into a state that was consistent with an animal that had been overeating for several weeks. The animals also became compulsive in their eating behaviors almost immediately. These data are, as far as we know, the strongest support for the idea that overeating of palatable food can become habitual in the same manner and through the same mechanisms as consumption of drugs of abuse."
The study was supported by a Bank of America Fellowship, The Margaret Q. Landenberger Research Foundation and the National Institutes of Health.

Tuesday, May 11, 2010

Parkinson's Medications and Impulsive Behavior

There have now been several studies documenting an increase in impulse control disorders such as compulsive gambling, sexuality, shopping and other similar behaviors in people taking medications for Parkinson's Disease. These studies demonstrate that the brain, which regulates thinking, feeling and behaving, can become disordered in certain ways. In this case it is from a medication to treat Parkinson's Disease. These medications increase dopamine release, thus they add evidence to the dopamine hypothesis of impulse control disorders, including addiction to drugs. What I find interesting about them is that these were not previous drug or sex addicts or compulsive gamblers. But once their dopamine balance became dysregulated, their behavior became dysregulated. Thus, if our brain is dysregulated in certain ways, it constrains our ability to exercise choice or will. This complicates questions about responsibility, moral blameworthiness, and criminal liability. But what is becoming ever more clear as I work with many patients again is that there is a dysregulation of the ability to control behavior. The ethical and political arenas will simply have to deal with that. Here is a recent study:

Impulse Control Disorders in Parkinson Disease
A Cross-Sectional Study of 3090 Patients
Daniel Weintraub, MDJuergen Koester, PhDMarc N. Potenza, MD, PhDAndrew D. Siderowf, MD, MSCEMark Stacy, MDValerie Voon, MD;Jacqueline Whetteckey, MDGlen R. Wunderlich, PhDAnthony E. Lang, MD, FRCPC 
Arch Neurol. 2010;67(5):589-595.
Context  An association between dopamine-replacement therapies and impulse control disorders (ICDs) in Parkinson disease (PD) has been suggested in preliminary studies.
Objectives  To ascertain point prevalence estimates of 4 ICDs in PD and examine their associations with dopamine-replacement therapies and other clinical characteristics.
Design  Cross-sectional study using an a priori established sampling procedure for subject recruitment and raters blinded to PD medication status.
Patients  Three thousand ninety patients with treated idiopathic PD receiving routine clinical care at 46 movement disorder centers in the United States and Canada.
Main Outcome Measures  The Massachusetts Gambling Screen score for current problem/pathological gambling, the Minnesota Impulsive Disorders Interview score for compulsive sexual behavior and buying, and Diagnostic and Statistical Manual of Mental Disorders research criteria for binge-eating disorder.
Results  An ICD was identified in 13.6% of patients (gambling in 5.0%, compulsive sexual behavior in 3.5%, compulsive buying in 5.7%, and binge-eating disorder in 4.3%), and 3.9% had 2 or more ICDs. Impulse control disorders were more common in patients treated with a dopamine agonist than in patients not taking a dopamine agonist (17.1% vs 6.9%; odds ratio [OR], 2.72; 95% confidence interval [CI], 2.08-3.54; P < .001). Impulse control disorder frequency was similar for pramipexole and ropinirole (17.7% vs 15.5%; OR, 1.22; 95% CI, 0.94-1.57; P = .14). Additional variables independently associated with ICDs were levodopa use, living in the United States, younger age, being unmarried, current cigarette smoking, and a family history of gambling problems.
Conclusions  Dopamine agonist treatment in PD is associated with 2- to 3.5-fold increased odds of having an ICD. This association represents a drug class relationship across ICDs. The association of other demographic and clinical variables with ICDs suggests a complex relationship that requires additional investigation to optimize prevention and treatment strategies.

Monday, May 10, 2010

Useful information about opioid misuse in chronic pain

With all the concern recently about misuse of prescription opioids in pain patients, this study offers additional information about risk factor evaluation when considering one's approach. The study also adds further to the large body of knowledge concerning different patterns and reasons for using intoxicants between men and women. There's an old adage about this: Men go to the bar, women go to the doctor. 


From Medscape Medical News

Risk Factors for Opioid Misuse Among Pain Patients Differ by Sex

Barbara Boughton
Physician Rating: 3.5 stars  ( 11 Votes )           
Rate This Article:
Therapeutic Goals in Major Depressive Disorder (MDD)
In a survey published in JAMA, <22% of respondents received adequate treatment for 12-month MDD. Explore pharmacotherapy for patients in therapy for depression.
Click here
May 4, 2010 — A new study published in the April issue of theJournal of Pain reveals men and women with chronic pain who misuse opioid medications — including taking these medications at a dose frequency unsanctioned by treating physicians — do so for different reasons.
Women with chronic pain are more likely to misuse opioids because of emotional issues and psychological distress, whereas men who do the same are more likely to report social and behavioral problems, such as associating with friends who use drugs or alcohol, having a bad temper, or having legal difficulties.
"We found from our analysis that women tend to misuse pain medications for mood problems — when they are anxious or depressed — while men misuse them for euphoric or behavioral reasons that are less associated with mood," lead researcher Robert Jamison, PhD, associate professor in the Department of Anesthesia and Psychiatry at Brigham and Women's Hospital, Boston, Massachusetts, told Medscape Psychiatry.
"So these may be important markers for clinicians that can help identify patients who might have trouble with opioid misuse — and it's important to provide these patients with interventions that might be helpful. For women, the characteristics to look for are whether they are depressed or anxious, and for men, past history would be a marker," Dr. Jamison added.
Pain Severity Similar Between Sexes
In the study, 662 patients with chronic noncancer pain who take opioid medications were recruited from medical centers in 5 states and surveyed with pain assessment questionnaires to examine rates and characteristics of problematic opioid use.
The investigators also examined predictive associations between risk factors for abuse and misuse by patients of their prescription medications. At baseline, patients completed a series of questionnaires, including the revised Screener and Opioid Assessment for Pain Patients and the Brief Pain Inventory, a multidimensional pain questionnaire.
After 5 months, they underwent a structured prescription drug use interview with a clinician, the Prescription Drug Use Questionnaire (PDUQ), and their clinicians completed the Physician Opioid Therapy Questionnaire (POTQ) — an 11-item scale used to assess misuse of opioids.
Patients were asked to undergo a urine toxicology screen and were classified by the Aberrant Drug Behavior Index (ADBI) concerning their opioid medication abuse based on a combination of self-report in the PDUQ, the physician-reported POTQ, and urine toxicology results. Because some patients had missing data on 2 or more variables, they were excluded from the final analyses — leaving a total of 455 patients or 74.2% of those who began the study.
Results indicated that there was little difference between men and women in the severity of their pain or their rate of opioid misuse — the ADBI indicated prescription opioid misuse in 31% of males and 36.7% of females in the final analysis, a difference that was not statistically significant.
Yet results from both patient self-reports and clinician evaluations indicated that women who misused their opioid medications were more likely to report a history of physical and sexual abuse, psychiatric diagnoses, or a history of psychiatric illness and family concerns. Counting pain pills was also predictive of opioid misuse among women.
High Rate of Misuse
By contrast, men who misused opioids were more likely to have close friends who used alcohol or drugs, to have a bad temper, to have legal problems, and to have a history of drug and/or alcohol abuse.
Other research by Dr. Jamison and colleagues, based on satisfaction questionnaires of chronic pain patients who misuse prescription medications, have suggested that women may benefit most from clinical interventions such as antidepressant and individual and group cognitive or behavioral therapy that addresses the psychological risk factors for misuse. Education about avoiding the use of opioids as a way of dealing with anxiety or sleep disturbances due to stress may also be helpful, he said.
Yet, men may benefit more from monthly urine screens, pill counts, and compliance monitoring to reduce opioid misuse, as well as behavioral consequences of misuse such as more frequent dosing and clinic visits, he added.
Certainly, the study calls attention to the problem of opioid misuse among chronic pain patients. And although only a small percentage of these patients actually develop dependence or addiction, clinicians at the pain management center of Brigham and Women's Hospital have found through urine screens that up to 42% of pain patients misuse their medications, he said.
"These folks have terrible pain as well as clinical history issues that make them very difficult to manage. It really is very challenging to treat these patients, and the idea of the study was to help piece together the puzzle of how to best help them," he said.
"Opioid misuse is a growing concern for chronic pain patients," commented Larissa Mooney, MD, assistant professor of psychiatry at the University of California–Los Angeles. "The vast majority of patients with chronic pain don't develop a problem, but there are vulnerable subgroups," she said.
"This study adds to an emerging literature on gender differences in addiction — how men and women are different in terms of etiology, consequences, and the mechanisms of drug misuse," she said.
Dr. Mooney cautioned that the study's conclusions may not be applicable to all patients with chronic pain. Many of the patients in the study were older (older than 50 years), had long-standing chronic pain, and were often disabled by their pain conditions. "It would be interesting to see if these findings apply to younger patients with less chronic pain history," she said.
She noted that counseling, as well as careful monitoring, for pain patients who misuse prescription opioids or have risk factors for prescription abuse may be helpful for both men and women, she said.
"I don't think that these treatment recommendations are applicable only to men or women," she added.
The study was supported by grants from the National Institute on Drug Abuse and the Arthritis Foundation. Dr. Jamison reported research support from Inflexxion Inc. Dr. Mooney has disclosed no relevant financial relationships.
J Pain. 2010;11:312-320

Sunday, May 9, 2010

Study: Viagabatrin not effective for cocaine addiction

Here is the latest in a long series of studies that have failed to demonstrate a single medication with efficacy in treating cocaine dependence. In some ways this is surprising because cocaine is a single receptor focused drug, so it simplifies the search for medications that have activity at that receptor. Alcohol, on the other hand, is highly complex and affects many areas of the brain at once. It is not receptor focused. Yet, there are proven effective treatments for alcohol dependence. 

From Medscape Medical News

Vigabatrin Fails to Achieve Efficacy for Cocaine Dependence in Phase 2 US Trial

Barbara Boughton
Physician Rating: 4.5 stars  ( 2 Votes )           
Rate This Article:
April 23, 2010 (San Francisco, California) — A double-blind, placebo-controlled phase 2 clinical trial of the anticonvulsant agent vigabatrin for cocaine dependence in the United States failed to show that the drug was effective for achieving abstinence, according to research presented here at the American Society of Addiction Medicine 41st Annual Medical-Scientific Conference.
The trial's results contradict those of a similar phase 2 Mexican trial, published in the American Journal of Psychiatry in 2009, which showed a significant difference between subjects given vigabatrin vs placebo for cocaine addiction.
Yet researchers who conducted the US trial said the negative results may have been the result of problems with study design, rather than failure of vigabatrin to achieve efficacy in treating cocaine dependence.
"The take-home message from our trial is that it didn't work," said Eugene Somoza, MD, PhD, from the University of Cincinnati College of Medicine and the Veteran's Administration Medical Center in Cincinnati, Ohio. "But it's not that vigabatrin doesn't work — the study didn't work."
High Drop-Out Rate
In the US trial, 186 participants from 11 medical centers were randomly assigned either to 3 g/day vigabatrin daily by mouth in 2 divided doses or to placebo for 12 weeks. All patients received computerized behavioral therapy and counseling once a week, and urine specimens were collected 3 times a week to test for cocaine use.
There was a high drop-out rate — 61 patients dropped out of the study and only 125 completed at least 12 weeks of treatment. Abstinence was defined as not having used cocaine for the last 2 weeks of the study treatment period, validated by self-report and levels of benzoylecgonine in urine samples. Treatment adherence was evaluated through pill counts and self-reports.
The study failed to meet its primary endpoint — a significantly greater rate of drug abstinence in the vigabatrin group. However, the researchers found that patients receiving vigabatrin used consistently less cocaine than placebo during the 12-week treatment phase (P = .006), as measured by benzoylecgonine levels.
In a secondary analysis, the researchers also examined patient compliance with their medication regimens by reviewing urine vigabatrin concentrations in the treatment group. They found that 47.6% of the 61 patients who had completed the study in the vigabatrin group were not compliant with their medication regimens. Compliers were considered to be those with vigabatrin concentration of 630 μg/mL or more, and partial compliers were defined as those with levels of 158 μg/mL or more in urine samples. Secondary analysis indicated that those in the complier vigabatrin group used cocaine for fewer days than those in the noncomplier group (P = .084).
Although concerns have been raised about visual field defects with long-term use of vigabatrin, the researchers did not observe this adverse effect in either the treatment or placebo group. Adverse events included headache, nasopharyngitis, diarrhea, nausea, and back pain.
Lack of Adherence
So why did the US study fail while the Mexican trial showed that vigabatrin was effective for achieving abstinence? "The 2 main reasons are that patients didn't take their medications in the American study, and those in the Mexican study may have been a lot more motivated to abstain from cocaine," Dr. Somoza said in an interview with Medscape Psychiatry.
He noted that in the Mexican study, patients were observed taking their medication for 2 of 7 days. The subjects in the Mexican study were also parolees from prison, and showing up at least once per week at the vigabatrin study treatment center satisfied requirements for parole. In contrast, the American study consisted of patients who had been recruited by academic medical centers through radio and TV ads and who were paid for their participation. Dr. Somoza said.
The 9-week phase 2 Mexican trial of 103 patients randomly assigned to either vigabatrin or placebo used a treatment dosage similar to that administered in the US trial, and cocaine use was also determined with twice-weekly urine toxicology tests. In that trial, 28% of vigabatrin-treated patients vs 7.5% of participants in the placebo group achieved abstinence, defined as 3 weeks without using cocaine.
In an accompanying editorial to the publication of the Mexican trial in the American Journal of Psychiatry in November 2009, Kathleen Brady, MD, PhD, from the Medical University of South Carolina, Charleston, noted that the results were "not tremendously robust." She also cautioned that vigabatrin can cause visual field defects in 30% to 50% of patients who take it for more than 12 months. The question of whether this adverse effect could affect those with cocaine dependence who use the drug for a shorter time remains open, she said.
"We've been looking for a medication for cocaine addiction for 35 years, and to date we have no [US Food and Drug Administration]-approved medications. We haven't found anything that works," commented Timothy Fong, MD, assistant professor of psychiatry and codirector of the addiction medicine clinic at the University of California–Los Angeles.
Whether or not the differences in the Mexican and US trial results could be the result of dissimilarity in the 2 studies' population characteristics is difficult to assess, Dr. Fong noted. "But when we have used advertisements to recruit people for cocaine trials in Los Angeles, we find that their motivations are pretty high to quit — even though it's sometimes difficult to get them to stay and finish the experiment," he said.
New Trial Planned
One problem with studies on cocaine dependence is that cocaine addiction is a complicated disease, and cocaine addicts are not all the same, Dr. Fong said. "The differences between those who use crack vs powder and those who inject vs snorting need to be teased out a little more," he added. "There may be people with cocaine addiction who may respond to vigabatrin, but I don't think we've figured out who that would be yet," he said.
Although Dr. Fong noted that, in his clinical experience, vigabatrin is not that effective for treating cocaine addiction, the investigators working on the US trial plan to continue studying the drug.
A new trial funded by the National Institute on Drug Abuse is planned, Dr. Somoza said. The investigators hope to address some of the problems in the US trial by using more observed doses, by adding a marker substance to vigabatrin and placebo formulations to better assess adherence, and by enrolling patients who might be more motivated to quit cocaine, such as those in substance abuse treatment centers, Dr. Somoza added.
The study was supported by Catalyst Pharmaceutical Partners. Dr. Fong disclosed being on speakers' bureaus for Reckitt-Benckiser, Pfizer Pharmaceuticals, and Lilly Pharmaceuticals. Dr. Somoza has disclosed no relevant financial relationships.
American Society of Addiction Medicine 41st Annual Medical-Scientific Conference: Abstract 4. Presented April 16, 2010.