04/5/16

I Smell a RAT

© antonihalim | Stockfresh.com

© antonihalim | Stockfresh.com

Medication Assisted Treatment (MAT) for addiction comes in various forms that are often (unhelpfully) lumped together into one category. Replacement or substitution methods, like methadone or Suboxone maintenance are radically different from using naltrexone to treat alcohol or opioid use disorders. Yet they are combined into the single category of MAT. While naltrexone is not a cure for addiction, it has been shown to help minimize cravings for urges for both alcohol and opioids. And there is some evidence emerging that it could be useful to blunt cravings for methamphetamine.

In 2010 Karlia et al. did a literature review on pharmacological approaches to treat methamphetamine use disorders. They concluded there was no substantial evidence for effective treatment at the time. “Clinical trials using aripiprazole [Abilify], GABA agents (gabapentin [Neurontin], baclofen, vigabatrin), SSRIs, ondansetron and mirtazapine [Remeron] have failed to show efficacy.” They noted where there was some indication where “agonist replacement medications” like d-amphetamine and modafinil may hold some promise.

The unavoidable problem with “treating” methamphetamine addiction with d-amphetamine is you are using a similarly addictive substance to “treat” methamphetamine addiction. Again, it repeats the error of opioid substitution/replacement therapy. While methamphetamine and amphetamine are Schedule II controlled substances, Modafinil still has an addictive potential as a Schedule IV. It is used to treat narcolepsy and shift work disorder, and it is touted as a “life hack” on Wall Street or “smart pill”—until you decide to stop taking it.

They also pointed to the work of Swedish researcher, Nitya Jayaram-Lindström, who showed in a 2005 study where naltrexone significantly reduced the subjective effects of dexamphetamine and blocked cravings in dependent patients. Additionally, the frequency and amount of amphetamine use was significantly reduced. A double blind study by Jayaram-Lindström in 2008 again showed the efficacy of naltrexone in reducing cravings and self-reported use of amphetamine. A further double-blind, placebo-controlled study by Jayaram-Lindström again demonstrated a significant reduction in cravings and self-reported use of amphetamine. “Naltrexone therefore appears to be a highly promising medication for amphetamine dependence.”

Now there is a study by UCLA researchers on naltrexone as a treatment for methamphetamine addiction. Here is a link to a pre-publication manuscript of the study by Ray et al. Again it was found that naltrexone blunted cravings for methamphetamine and lowered self-reports of subjective effects. Lara Ray, a UCLA psychology professor said: “The results were about as good as you could hope for.” The UCLA press release on the study and an article on The Fix by Zachary Siegel noted where clinical trials into the efficacy of naltrexone to treat methamphetamine addiction have already begun.

One clinical trial with naltrexone was completed and last updated in May of 2013 but no results are posted yet; and another study is ongoing. Although results for the complete trail by California Pacific Medical Center Research Institute were not posted on Clinicaltrails.gov, it does seem to be reported in a 2015 study by Pal et al. reported in the Journal of Addictive Medicine. There was not an improved treatment response found in this study. The Pal et al. study was quite small and does not really argue against further clinical trials into the potential use of naltrexone to treat methamphetamine addiction. The replication of Jayaram-Lindström’s results by Ray et al. are sufficient to see further research into this potential treatment.

The side effects from naltrexone are minimal, making it a viable medication to assist addicts trying to establish and maintain abstinence from dependence upon alcohol, opioids, and now—apparently—methamphetamine. Substitution or replacement medications for addiction need to be distinguished from other medications such as naltrexone within the catchall category of MAT. Perhaps they would be better labeled as SAT—Substitute Addiction Treatment—or RAT—Replacement Addiction Treatment—instead of MAT, Medication Assisted Treatment. Personally, I’m partial to RAT.

11/30/15

The Seduction of Opioid Substitution

© Everett Collection Inc. | Dreamstime.con

© Everett Collection Inc. | Dreamstime.con

Heroin and prescription opioid abuse is a widely recognized public health crisis in the United States. In 2014, Attorney General Eric Holder referred to overdose deaths from heroin and other prescription pain-killers as an “urgent public health crisis.” The CDC reported that heroin use more than doubled among young adults between 18 and 25 over the past ten years. Forty-five percent of the people who use heroin are also addicted to prescription opioids.

A July 2015 “Morbidity and Mortality Weekly Report” report by the CDC recommended a comprehensive response to this public health crisis. The recommendations included: reducing inappropriate prescribing and use of opioids, stronger prescription drug monitoring programs, improved access to evidence-based substance abuse treatment—including medication-assisted treatment for opioid use disorders and greater access and training in the use of naloxone to treat overdoses. There have been several steps taken towards making these recommendations a reality. For example, on November 18, 2015, the FDA approved the first nasal spray version of naloxone hydrocloride: Narcan nasal spray. But not all of the proposals have the same potential to free the individuals caught up in the opioid health crisis.

And legislation has been introduced in the Senate to “combat the opioid crisis.” “The Opioid and Heroin Epidemic Emergency Supplemental Appropriations Act” would dedicate $600 million to this crisis. About $250 million would support programs related to prevention, treatment and recovery. Another $200 million would fund local and state law enforcement programs. Fifty million would go toward the CDC; and $35 million would go to NIDA to monitor prescription drug programs and do targeted research on drug addiction. “We are losing lives daily and our first responders, healthcare providers and criminal justice system are overwhelmed.”

I’m not a fan of increasing the use of opioid maintenance medications such as methadone and buprenorphine because they’re “treating” an opioid addiction with addictive opioids. And I’m concerned that in the midst of the existing health crisis, increased access to such treatment seems to be indiscriminately promoted as the most effective “treatment” approach. Sometimes the studies of medication-assisted treatment fail to consider the negative consequences to individuals when promoting opioid substitution treatment. And sometimes studies that suggest the “effectiveness” of opioid maintenance have a biased interpretation of their results. Often what emerges is a program for the social control of addicts rather than one that helps them establish and maintain a recovery-oriented lifestyle. Here is an example of one such study.

The National Institute on Drug Abuse (NIDA) turned a “Science Spotlight” on a new study that looked at intervention approaches for opioid dependent patients in emergency departments (ED). The idea is a good one—developing an intervention for ED medical personnel to help opioid-dependent patients get into treatment. But what it doesn’t make clear is that the “treatment” is primarily ongoing participation in opioid substitution treatment.

This study showed that patients who received buprenorphine, along with a brief intervention to discuss opioid use, and up to 12 weeks of buprenorphine maintenance, were more likely to get follow-up addiction treatment and had reduced self-reported illicit opioid use. In addition, they were also less likely to need inpatient addiction treatment services, saving treatment costs. This adds to the growing body of literature suggesting that opioid-dependent patients may benefit from immediate initiation of medication while awaiting more comprehensive substance use disorder treatment.

Let’s take a closer look at the study by D’Onofrio et al. to see if it truly lives up to the endorsement it received from NIDA.

The primary outcome was what the researchers called “engagement in treatment.” This was defined as being enrolled in and receiving formal addiction treatment on the 30th day following randomization. “Formal addiction treatment” could include a range of clinical settings such as an opioid treatment program, such as a methadone clinic, inpatient or residential treatment and outpatient services. The outpatient services could be intensive outpatient programs and “office-based physicians who prescribe buprenorphine or other forms of medication-assisted treatment.”

The patients in the buprenorphine group of the study received buprenorphine in the hospital and take-home doses of buprenorphine to last until a scheduled appointment in the hospital’s primary care center, which was within 72 hours of their placement in the group. The buprenorphine patients continued to receive office-based burprenorphine treatment for 10 weeks. At that time they were transferred to a maintenance treatment program or a clinician for ongoing treatment. If they preferred, they were offered a 2-week detoxification.

In the buprenorphine group, 78% of the patients were still engaged in treatment at the thirty-day follow-up. Only 37% of the referral only group and 45% of the brief intervention and referral group were engaged in treatment. But remember what the study considered as “treatment.” Any patient in the buprenorphine group who was still active in the free, office-based treatment after 30 days would have been counted as “still engaged in treatment.”  And they would have had another 40 days of free buprenorphine coming.

There was no information or data available on any of the groups beyond the thirty-day follow-up. So there was no clear indication if the patients in the buprenorphine group remained in treatment beyond the 10 weeks of the study’s subsidy of their substitution treatment. If the goal was to eventually engage individuals in more comprehensive treatment services, this “interim opioid agonist treatment,” should not have been lumped in with others as the outcome measure of “formal addiction treatment.” The failure of the researchers to distinguish this level of care from the others confounds the findings within the study’s primary outcome measure.

These patients had buprenorphine treatment initiated before they left the hospital. They also had an appointment scheduled within 3 days of their initial dose, with sufficient take-home medication to prevent any withdrawal until that appointment time. The other two groups did not receive any medication and so were on their own medically until they made an appointment and became engaged in treatment. They were sitting ducks for resuming the illicit opioid use that initially brought them to the ED. So the deck was staked in favor of the primary outcome measure.

Additionally, the buprenorphine care in the study was provided at no cost to the patients. The researchers dismissed this as a potential bias in their study, saying that 80% of the study’s patients had health insurance. However there are potential cost issues in health insurance despite the authors’ dismissal. Buprenorphine maintenance treatment is not always covered by insurance, as it is considered a “niche” medicine by insurance plans, as it is approved solely for the treatment of opioid dependence. Insurance companies predict that a limited number of their covered clients will need or use it. When there is coverage, there can be high co-pays. Insurance may pay for the prescription but not the office visits. Some Suboxone doctors don’t take insurance.

A secondary outcome measure for the study was self-reported use of illicit opioids. The buprenorphine group reported greater reductions in the mean number of days of illicit opioid use, from 5.4 days per week to .9 days per week. Patients in the referral group decreased from 5.4 days per week to 2.3 days; and the brief intervention group went from 5.6 days to 2.4 days. Remember that the buprenorphine group was treated with medication (buprenorphine) that forestalled withdrawal symptoms from the time they were placed in that treatment group while still in the hospital ED. Also, all three groups reduced their illicit opioid use over time. Comparing the buprenorphine treatment group to the others indicated that even with the medication, there were only 1.4 or 1.5 days less per week of illicit opioid use in the buprenorphine group.

Finally, the decreased use of inpatient treatment by the buprenorphine group was to be expected. The withdrawal symptoms that often precipitate detoxification or residential treatment were being addressed by the buprenorphine.

It has long seemed to me that the so-called harm reduction approach of opioid substitution treatment is more social control than actual treatment aimed at helping the individual addict to establish and then maintain sobriety. The positive outcomes and effects that are highlighted are typically things like lowered costs for residential treatment; lowered ED visits and costs; decreased drug-related crime.

There is proposed legislation, the Recovery Enhancement for Addiction Treatment Act, which would broaden the definition of a qualifying practitioner to include certain nurse practitioners or physician assistants and doctors with a board certification from the American Board of Addiction Medicine. The number of patients that a qualifying practitioner could dispense buprenorphine to within their first year would increase from 30 to 100. After one year, qualifying physicians could request approval to treat an unlimited number of patients under specified conditions. Writing about this proposed bill for the Huffington Post, James Charkis said:

The consensus among the medical establishment is that medically assisted treatments such as buprenorphine (and methadone), along with counseling, represent the best chance for addicts to gain a foothold on sobriety. Both medications can make withdrawal less painful and can significantly diminish further cravings for opioids — greatly reducing the chance of relapse.

One of the problems as I see it is that this “best chance” description is often mostly rhetoric. The “along with counseling” add-on becomes more window dressing than reality. Even where there is a tighter requirement for Suboxone patients to be active in some kind of counseling, individuals either fall through the cracks with counseling or just take up space because their presence in counseling is required for them to get what they really think will “treat” them—their Suboxone. Some individuals merely want Suboxone handy in case they can’t get any heroin or their opioid of choice to get high. Others want it to sell on the street to make some cash.

There is a place for opioid substitution treatment as we attempt to address the opioid health crisis. But the potential adverse consequences to the individual receiving the treatment need to be more clearly communicated. And studies of its “effectiveness” need to look beyond just the social benefits and the ability of opioid substitution treatment to seduce addicts into a more socially controlled form of opioid use.