Researchers: Supervised Methadone and Buprenorphine Dosing Adds Little Therapeutic Benefit

Methadone, the full agonist synthetic opioid, is one of the most tightly regulated medications on the planet - at least, that is, when it's being used to treat opioid addiction.  Here in Minnesota, no fewer than 5 regulatory bodies oversee the clinics that provide methadone maintenance treatment (MMT).  One of the core federal requirements of "opiate treatment programs" is daily supervised dosing, requiring patients to come daily to the clinic to receive their dose, observed by trained nursing staff for at least the first 3 months.  After that, patients earn one additional day of "take-home" doses at a time until they've earned 1 week (after the 8th month of treatment), then 2 weeks (after the first year in treatment), and finally 4 weeks of take-home doses (after 2 years of sustained participation in the program).  The rationale for these highly restrictive federal rules, ostensibly, has been that it will protect patient safety, decrease diversion, and will improve outcomes among MMT patients.

A recent review of the literature throws these assumptions into question.  The review, analyzed and shared by the folks at Drug and Alcohol Findings, found "no evidence that supervising consumption meant patients were better safeguarded or that the treatment more effectively reduced illegal drug use."  Instead, these policies tend to be quite costly to programs and burdensome to patients.  They reinforce negative stereotypes about MMT patients and have prevented people from seeking potentially lifesaving treatment. 

Here at Alltyr Clinic, we routinely hear from patients that the ability to receive a monthly prescription of Suboxone has meant they could keep their job or maintain their role within the family.  With all the national attention being given to the recent spike in overdose statistics, maybe it's time the feds re-visit these burdensome regulations and increase access to the highly effective treatments. 

From the Findings UK article:

Supervised dosing with a long-acting opioid medication in the management of opioid dependence
http://findings.org.uk/PHP/dl.php?file=Saulle_R_1.txt&s=eb&sf=sfnos

Key points
From summary and commentary

Guidelines recommend making opioid-dependent patients take their methadone or other opioid substitutes at the clinic or pharmacy to safeguard the patient and prevent medication being ‘diverted’ to other people.

Randomised trials and studies study which monitored patients in routine treatment afforded no evidence that supervising consumption meant patients were better safeguarded or that the treatment more effectively reduced illegal drug use.

However, introduction of supervision to UK treatment services was associated with fewer methadone-related overdose deaths.

Findings and expert opinion support initial supervised consumption and its relaxation on an individual basis, depending on assessment of the patient.

The Myth of "Cross-Addiction" Debunked

For decades, the conventional wisdom and clinical lore in rehab facilities and recovery communities has warned against the risks of so-called "cross-addiction". "Be careful," they say, "you're at-risk of picking up a new addiction now that you've kicked one habit." Heroin addicts are warned against developing an addiction to alcohol, and cocaine addicts are warned against developing an addiction to opiates, Cross-addiction can even occur to things like exercise or sugar, according to pamphlets and even therapists who have worked in the field for years and years.

But is it even true? Is the notion of cross-addiction supported by empirical evidence - or does it fall on its face under scientific scrutiny?

According to a new report, published September 10 in JAMA Psychiatry, the answer is a resounding, "No."

The study, "Testing the Drug Substitution Switching-Addictions Hypothesis," analyzed data from the National Epidemiological Study on Alcohol and Related Conditions (NESARC) to investigate whether participants developed new-onset substance use disorders (SUD) after remission from a previous SUD. These data were then compared against people with a SUD who did not achieve remission but also developed a new-onset SUD.

The authors discovered that, "As compared with those who do not remit from an SUD, remitters have less than half the risk of developing a new SUD. Contrary to clinical lore, achieving remission does not typically lead to drug substitution but rather is associated with a lower risk of new SUD onsets."

This is probably the best evidence to-date that addresses the concept of cross-addiction. Will counselors and agencies begin to pull back from this concept - or will clients still be subjected to homework assignments and lectures warning against it?

Here's the abstract from JAMA Psychiatry (found here: http://archpsyc.jamanetwork.com/article.aspx?articleid=1901525):

Importance  Adults who remit from a substance use disorder (SUD) are often thought to be at increased risk for developing another SUD. A greater understanding of the prevalence and risk factors for drug substitution would inform clinical monitoring and management.

Objective  To determine whether remission from an SUD increases the risk of onset of a new SUD after a 3-year follow-up compared with lack of remission from an SUD and whether sociodemographic characteristics and psychiatric disorders, including personality disorders, independently predict a new-onset SUD.

Design, Setting, and Participants  A prospective cohort study where data were drawn from a nationally representative sample of 34 653 adults from the National Epidemiologic Survey on Alcohol and Related Conditions. Participants were interviewed twice, 3 years apart (wave 1, 2001–2002; wave 2, 2004–2005).

Main Outcomes and Measures  We compared new-onset SUDs among individuals with at least 1 current SUD at wave 1 who did not remit from any SUDs at wave 2 (n = 3275) and among individuals with at least 1 current SUD at wave 1 who remitted at wave 2 (n = 2741).

Results  Approximately one-fifth (n = 2741) of the total sample had developed a new-onset SUD at the wave 2 assessment. Individuals who remitted from 1 SUD during this period were significantly less likely than those who did not remit to develop a new SUD (13.1% vs 27.2%, P < .001). Results were robust to sample specification. An exception was that remission from a drug use disorder increased the odds of a new SUD (odds ratio [OR] = 1.46; 95% CI, 1.11-1.92). However, after adjusting for the number of SUDs at baseline, remission from drug use disorders decreased the odds of a new-onset SUD (OR = 0.66; 95% CI, 0.46-0.95) whereas the number of baseline SUDs increased those odds (OR=1.68; 95% CI, 1.43-1.98). Being male, younger in age, never married, having an earlier age at substance use onset, and psychiatric comorbidity significantly increased the odds of a new-onset SUD during the follow-up period.

Conclusions and Relevance  As compared with those who do not remit from an SUD, remitters have less than half the risk of developing a new SUD. Contrary to clinical lore, achieving remission does not typically lead to drug substitution but rather is associated with a lower risk of new SUD onsets.

A Sad State of Affairs: Psychostimulant Addiction Treatment Leaves Much to be Desired

The authors of a new paper, published ahead of a special issue of Neuropharmacology, give the reader a good look at the current state of psychostimulant substance use disorder treatment - and the results are disappointing. Starting with behavioral treatments and ending with a review of medications, the clear fact remains that there is no single treatment that outperforms most others.

Meta-analyses of behavioral interventions for the treatment of cocaine use disorder have shown modest benefits; while one review found, "there is currently no evidence for a differential treatment effect of any psychosocial treatment in the management of" cocaine or amphetamine use disorders. CBT and Contingency Management (CM) remain the mainstay of psychostimulant treatment, and the authors cite data suggesting a combination of CM plus Community Reinforcement Approach might produce the best outcomes.

In terms of pharmacological treatments, researched medications include antagonist therapy, agonist therapy, medications to treat withdrawal symptoms and medications to treat co-occurring psychiatric symptoms or disorders; and the authors of the present paper devote the bulk of their attention to weighing the evidence of such options.

Naltrexone, they note, has shown some promise in laboratory studies, as it has been shown to weaken amphetamine- and cocaine-related effects in some subjects in both human and animal trials. Because it also seems to weaken the subjective euphoric effects of methylphenidate (Ritalin), one area of promise could be in the combination of naltrexone and methylphenidate to limit the abuse potential of an agonist-like treatment.

Disulfiram (aka Antabuse) has also shown some promise in the lab, but mainly in the treatment of cocaine-use disorders. It was shown to increase the brain ratio of dopamine to norepinephrine and to prevent stress-induced cocaine reinstatement. In pilot studies, disulfiram was shown to be effective in reducing cocaine use in patients with cocaine use disorders (CUD), and among buprenorphine-maintained polydrug users. However, in a more recent study, disulfiram showed less promise reducing cocaine use among methadone-maintained patients. The authors of the review point to evidence that disulfiram may only be effective among CUD patients with specific genotypes - and may be more effective among men than women.

Agonist-like treatments are also reviewed by the authors, and appear to offer some of the more exciting, and possibly effective, interventions for psychostimulant addiction. D-amphetamine has been shown to improve treatment retention and reduce illicit cocaine use in early trials; while a later study showed a reduction in withdrawal and craving, but a failure to reduce methamphetamine use. Not mentioned in the review, but a small study we wrote about in 2012 appeared to show promising results in the combination of mixed amphetamine salts (Adderall) and topiramate (Topamax)

For its part, sustained-release methamphetamine has been tested as a maintenance agent for CUD, and appeared to significantly reduce cocaine-positive urine samples and cocaine craving. The familiar medication, methylphenidate, has been shown to be non-superior to placebo in some studies for meth/amphetamine use and cocaine use, but appears to warrant further research at improved dosages. The other agonist-like medication discussed, modafanil, seems to be an interesting candidate for maintenance treatment. Known to be a cognitive enhancer, modafanil may be useful in addressing the impairments in a range of cognitive functions that can result from psychostimulant addiction; but studies have thus far produced more "equivocal" results in most trials as treatments for cocaine or for methamphetamine - even when combined with D-amphetamine. Post-hoc analysis of the available data does, however, suggest efficacy in the less severe cases of addiction.

Additionally, researchers in Latin America have argued in favor oral coca for the treatment of cocaine use disorder. Their "Handbook on Oral Cocaine as Agonist Therapy for Cocaine Dependence" is an intriguing read, and the authors of the review posit that political, cultural and commercial barriers - not scientific ones - are likely to blame for the "lack of follow-up on this line of research".

A host of other medications have been tried and tested for psychostimulant use disorders, with little success. Vaccines, on the other hand, are now gaining momentum in the field and are being used in multiple studies at various phases. A vaccine that that produces antibodies to prevent cocaine from crossing the blood-brain barrier has performed well in Phase I and Phase II trials. A methamphetamine vaccine is still in preclinical development, but initial results have shown good levels of antibodies in animal models and a Phase I  trial is scheduled to begin in 2015.

Considering the vast global toll which is the result of psychostimulant addiction, treatment for these disorders is as desperately needed as ever. If there is one thing that this review makes clear, it's the fact that we still have a long way to go before we can say that we have effective treatment options for the consumer. A question for readers of this blog: what are the techniques and interventions that you have found to be helpful stimulant use disorders? Is there a particular line of research that you feel would be important to investigate further? Do you see the utility of agonist-like medications? Your thoughts are always appreciated.

Many Patients with Alcohol Use Disorders Not Offered Medications

An exhaustive and brand new meta-analysis and systematic review, published today in the Journal of the American Medical Association, paints a disappointing picture of medication access for those with alcohol use disorders (AUD) in the US. The authors included 123 studies, involving nearly 23,000 participants, and determined that while acamprosate and naltrexone have been shown to be effective treatments, fewer than 10% of those who might benefit are ever prescribed an AUD medication.

Here's the Abstract, via JAMA:

IMPORTANCE Alcohol use disorders cause substantial morbidity and early mortality yet

remain greatly undertreated. Medications are considerably underused.

OBJECTIVE To conduct a systematic review and meta-analysis of the benefits and harms of

medications (US FDA-approved and others) for adults with alcohol use disorders.

DATA SOURCES PubMed, Cochrane Library, PsycINFO, CINAHL, EMBASE, FDA website, and

clinical trials registries (January 1, 1970, to March 1, 2014).

STUDY SELECTION Two reviewers selected randomized clinical trials (RCTs) with at least 12

weeks’ duration that reported eligible outcomes and head-to-head prospective cohort

studies reporting health outcomes or harms.

DATA EXTRACTION AND SYNTHESIS We conducted meta-analyses using random-effects

models and calculated numbers needed to treat for benefit (NNTs) or harm (NNHs).

MAIN OUTCOMES AND MEASURES Alcohol consumption, motor vehicle crashes, injuries,

quality of life, function, mortality, and harms.

RESULTS We included 122 RCTs and 1 cohort study (total 22 803 participants). Most assessed

acamprosate (27 studies, n = 7519), naltrexone (53 studies, n = 9140), or both. The NNT to

prevent return to any drinking for acamprosate was 12 (95% CI, 8 to 26; risk difference [RD],

−0.09; 95% CI, −0.14 to −0.04) and was 20 (95% CI, 11 to 500; RD, −0.05; 95% CI, −0.10 to

−0.002) for oral naltrexone (50 mg/d). The NNT to prevent return to heavy drinking was 12

(95% CI, 8 to 26; RD −0.09; 95% CI, −0.13 to −0.04) for oral naltrexone (50 mg/d).

Meta-analyses of trials comparing acamprosate to naltrexone found no statistically significant

difference between them for return to any drinking (RD, 0.02; 95% CI, −0.03 to 0.08) or

heavy drinking (RD, 0.01; 95% CI, −0.05 to 0.06). For injectable naltrexone, meta-analyses

found no association with return to any drinking (RD, −0.04; 95% CI, −0.10 to 0.03) or heavy

drinking (RD, −0.01; 95% CI, −0.14 to 0.13) but found an association with reduction in heavy

drinking days (weighted mean difference [WMD], −4.6%; 95% CI, −8.5% to −0.56%). Among

medications used off-label, moderate evidence supports an association with improvement in

some consumption outcomes for nalmefene (heavy drinking days per month: WMD, −2.0;

95% CI, −3.0 to −1.0; drinks per drinking day: WMD, −1.02; 95% CI, −1.77 to −0.28) and

topiramate (% heavy drinking days: WMD, −9.0%; 95% CI, −15.3% to −2.7%; drinks per

drinking day: WMD, −1.0; 95% CI, −1.6 to −0.48). For naltrexone and nalmefene, NNHs for

withdrawal from trials due to adverse events were 48 (95% CI, 30 to 112) and 12 (95% CI, 7 to

50), respectively; risk was not significantly increased for acamprosate or topiramate.

CONCLUSIONS AND RELEVANCE Both acamprosate and oral naltrexone were associated with

reduction in return to drinking. When directly compared with one another, no significant

differences were found between acamprosate and naltrexone for controlling alcohol

consumption. Factors such as dosing frequency, potential adverse events, and availability of

treatments may guide medication choice.

Would love to know what readers think about the results of this large study. What are the main drivers of this gap, and why aren't more patients requesting these medications? What needs to be done to improve access?

Who Benefits from Additional Drug Counseling among Prescription Opioid Dependent Patients on Suboxone?

In a secondary analysis of the Prescription Opioid Addiction Treatment Study (POATS), the original study's author, Roger Weiss, and colleagues parse the data to determine if there are common characteristics among those who benefited from additional opioid dependence counseling (ODC) - above and beyond the standard medical management (SMM) and buprenorphine-naloxone medication. It is a very good question, considering the host of recent studies which found no additional benefit to counseling in terms of measured outcomes, including the large and highly-regarded POATS.

In searching for an answer, the authors looked at two sources of variability - patient characteristics, and adherence to treatment. Specifically, the authors sought to answer three questions: 1) Did participants with more severe problems have better outcomes with SMM + ODC than with SMM alone (N=360)? 2) Among participants with adequate adherence to treatment, were those assigned to SMM + ODC more likely to have successful outcomes than those receiving SMM alone, regardless of severity (n = 266)? And 3), among participants with adequate adherence to treatment, were those with more severe problems more likely to succeed with additional counseling than with standard medical management only (n = 266)?

In response to question 1, the analysis found that "the association between severity and outcome did not vary by treatment condition for any of the three severity measures." Those without past use of heroin had more favorable outcomes across the entire study. Regarding question 2, "adequate adherence" was defined as attending at least 60% of scheduled scheduled sessions in both treatment conditions, and most participants (73.9%) attended at least 60% of sessions. Subjects in the SMM-only condition were more likely meet this criterion but, once again, outcomes did not differ by treatment condition. Finally, in answering question 3, the authors found that, "Among participants who had ever used heroin, those assigned to SMM + ODC were more likely to succeed than those in SMM only (66.7% vs. 35.0%, n = 70, χ2(1) = 6.88, p=.016)."

 Table 1

Likelihood of successful opioid use outcomes at Phase 2, weeks 9–12. ^a

	OR	95% CI      p Value
(a) All participants ( n= 360)
Main effects
Heroin	2.0	1.3–3.3      .004
Chronic pain	1.3	0.8–2.0      .240
Drug severity	2.9	0.2–58.2    .484
Interaction with Phase 2 treatment
Heroin	1.6	0.6–4.2      .342
Chronic pain	0.6	0.2–1.4      .218
Drug severity	0.2	0.0–76.8    .585	.
(b) Participants with adequate adherence to treatment ( n= 266)
Main effect of Phase 2 treatment	0.7	0.4–1.1     .107
Interaction with Phase 2 treatment
Heroin	3.7	1.1–11.8     .03
Chronic pain	0.5	0.2–1.5      .213
Drug severity	1.5	0.001–4023.5   .915

^a All models were adjusted for Phase 1 treatment condition.

Treatment outcomes did not appear to differ among those who had never used heroin, suggesting that prescription opioid-addicted patients with a history of heroin use may be the participants who are most likely to benefit from additional counseling in suboxone treatment. Importantly, those patients had to also attend enough sessions (and receive an adequate "dose" of counseling) in order to see their outcomes improve to rates similar to those without a history of heroin use.

So, do these results line up with the experience of the readers of this blog? Are there populations with whom you believe counseling is especially important? Or, do the results simply reinforce the lessons of past studies? Let us know

Study: Are Drug Screens Sufficient for Adolescent Treatment?

Could it be that we are missing something when it comes to treating adolescents with a substance use disorder? According to a study in the most recent edition of the Journal of Studies on Alcohol Drugs, if you aren't using drug screens when treating this population, the answer is likely "Yes".
In the article, Schuler, et al. looked at data from SAMHSA's CSAT 2007 adolescent treatment database, which tracks outcomes for CSAT-sponsored providers. The total sample consisted of 5,186 adolescents who received either Motivational Enhancement Therapy/Cognitive Behavioral Therapy5 (MET/CBT5) - with or without biological drug screen (BDS) - or were part of the BDS-only or No-Treatment groups within another study. Below is a breakdown of the subjects:

All participants responded to the GAIN structured clinical interview, so scores on the Substance Use Frequency Scale and Substance Problem Scale were the primary outcomes measured. Propensity score methods were used to adjust for baseline differences among youth in the four groups, given the non-randomized nature of the data. The results are striking:

The BDS-only condition seemed to outperform all groups at baseline, 3-, 6- and 12-months on Substance Problem Scale scores and at 6- and 12-months on Substance Frequency Scale scores.
What could account for the significant differences? The authors point out that many adolescents who are involved in treatment and/or the criminal justice system may earn rewards for negative drug screens - or face significant consequences for positive screens. Therefore, the self-report nature of the data could skew the results. That would not necessarily explain the consistent differences across groups, however.

What do you think about these results? If you work with adolescents, does this surprise you? Could evidence like this impact the interventions you use?

What Aren't More Docs Prescribing Buprenorphine?

On the heels of recent coverage over the "dangers" of the medication buprenorphine, researchers are seeking to better understand what keeps doctors from using one of the two the most effective tools for opioid use disorders at their disposal. The most recent study, "Barriers to Primary Care Physicians Prescribing Buprenorphine", was published in the Annals of Family Medicine and is available in-full online - for free. The study came out of the Rural Opioid Addiction Management in Washington state, during which 120 physicians were trained in opioid addiction and buprenorphine prescribing. Disappointingly, of the 78 respondents who were analyzed for the study, 50 went on to obtain a DATA waiver, yet a mere 22 doctors ever went on to prescribe the medication to anyone. It begs the question: why aren't more docs prescribing buprenorphine?

Here's the breakdown from the piece of perceived barriers to prescribing:

Among the barriers cited by the doctors in the study, "Lack of psychosocial support" was cited as the number one barrier by both prescribers and non-prescribers, despite the lack of evidence that behavioral adjuncts or additional counseling improve outcomes. (Granted, the authors point out that in order to get reimbursed by a number of payers, additional counseling must be offered to patients.)

A quick scan across the literature leads us to another important and common driver of physician attitudes toward this medication: institutional support. It appears that study after study cite the impact of the hospital/clinic/practice culture on the subsequent interest. training and prescription of buprenorphine by its docs. In the present study, "resistance from practice partners" and "lack of institutional support" were commonly cited as barriers. A recent article from the March issue of the Journal of Substance Abuse Treatment described how important "A strong leader championing the new treatment" was to the implementation of buprenorphine prescribing across a large system. 

What do you think? How can we be more effective at impacting change at the prescriber level? If culture plays an important role, how do we improve the culture around this proven tool?

Is Addiction Always Permanent?

Recently, a colleague challenged what he perceived to be my "insistence that addiction is permanent." Here is my reply:

Dear John (not his real name):

As you know, I'm well aware of the studies regarding the life course of people who at some point in their lives meet dxic criteria for a SUD. And also, as you are aware, I've been talking about that, and therefore the need to have a wider continuum of care and to individualize approaches to SUDs for at least 10 years. In my presentation, Alcoholism Isn't What It Used to Be, which you frequently reference, I point out that 20 years after onset of DSM IV Alcohol Dependence, the most common outcome is low-risk drinking (40%), followed by abstinence (roughly 1/3), partial remission (about 20%) and then finally currently dependent (8%). So I'm not sure what the basis is for concluding that I have made blanket statements about ALL addicts in ALL circumstances.

 

What I do believe, and here I think the science and epidemiology are equally persuasive, is that in the case of severe addiction, there are brain neuroadaptations that are irreversible. For example, the likelihood of achieving non-abstinent recovery is inversely related to the severity of alcohol dependence. Conversely, abstinent outcomes become more likely as severity increases. This is as true in rodents as in humans. Since rehab and AA are populated almost exclusively by people at the very severe end of the spectrum, the likelihood of sustained non-abstinent recovery for current treatment seekers or AA members is relatively low. Thus, the AA stance is accurate for most AA members. Severity of dependence is the strongest predictor of AA affiliation, especially long-term affiliation, as opposed to a few weeks or months after a spell in rehab. Established heroin or other opioid addiction is another example; thus buprenorphine and methadone maintenance and the virtually complete failure of abstinence (or moderation) for treatment seekers. Those who could stop on the their own do so and therefore do not present for tx. That, of course, is a function of the awfulness, expense, stigmatization and disruption most current treatment includes.

 

At Alltyr Clinic, for example, I have seen many pts who come with a mild AUD who achieve non-abstinent recovery.

 

Just as abstinence is not a requirement for everyone who develops a SUD, neither is moderation possible for a sizeable proportion of them. The size varies by drug: Probably close to 100% of dependent smokers will require lifelong abstinence, whereas, most cannabis users will not, etc. Heroin, meth and cocaine addiction also probably have high to relatively high proportions where abstinence (which includes people taking opioid agonist therapy) is the only positive outcome option. In alcohol, I think it's probably somewhere in the middle, a large minority achieve non-abstinent recovery.

 

So the newer data simply seem to affirm the NESARC data, that conclusions have been based on clinical samples, and that if you look at community samples, the picture is very different. That's true for almost all common complex diseases, such as asthma or arthritis or even hypertension, the difference being that with SUDs there is a very high full remission rate, something that happens in very few other common complex diseases. Depression is very likely to be a pretty good analogue as well.

 

Finally, noting that many people have milder, self-limiting forms of SUDs doesn't mean they aren't brain disesases. How can you have a behavioral illness that doesn't include failures in brain regulation of behavior? It's just that in too many instances, people misinterpret "brain disease" to mean "permanent". Also, it hasn't helped that NIDA and SAMHSA keep stressing the chronicity of addiction, something I constantly fought against when i was at NIH. It's often not chronic. Neither is asthma, but I suspect you wouldn't have trouble thinking of mild, self-limited childhood asthma as a lung disease, or immune disease.

Researchers Take a Novel Approach to Vivitrol Induction

Researchers and clinicians at Duke University performed a small, open label study to test a new induction protocol for opioid detoxification in an outpatient setting. Much has been written about the pros and cons of antagonist medication for opioid dependence, with most evidence supporting agonist medications like buprenorphine or methadone. One of the most difficult aspects of maintenance antagonist treatment is the detoxification and induction phases of treatment, considering the intolerability of the experience to most patients - especially those in outpatient settings. So, the authors of a new study, published recently in Drug and Alcohol Dependence, sought to make this experience a little more tolerable. The administered increasing doses of naltrexone and decreasing doses of buprenorphine to treatment-seeking opioid addicts until their first dose of extended-release injectable naltrexone (Vivitrol). The results were encouraging:

Abstract

BACKGROUND

The approval of extended release injectable naltrexone (XR-NTX; Vivitrol®) has introduced a new option for treating opioid addiction, but studies are needed to identify its place within the spectrum of available therapies. The absence of physiological opioid dependence is a necessary and challenging first step for starting XR-NTX. Outpatient detoxification gives poor results and inpatient detoxification is either unavailable or too brief for the physiological effects of opioids to resolve. Here we present findings from an open label study that tested whether the transition from opioid addiction to XR-NTX can be safely and effectively performed in an outpatient setting using very low dose naltrexone and buprenorphine.

METHODS

Twenty treatment seeking opioid addicted individuals were given increasing doses of naltrexone starting at 0.25 mg with decreasing doses of buprenorphine starting at 4 mg during a 7-day outpatient XR-NTX induction procedure. Withdrawal discomfort, craving, drug use, and adverse events were assessed daily until the XR-NTX injection, then weekly over the next month.

RESULTS

Fourteen of the 20 participants received XR-NTX and 13 completed weekly assessments. Withdrawal, craving, and opioid or other drug use were significantly lower during induction and after XR-NTX administration compared with baseline, and no serious adverse events were recorded.

CONCLUSIONS

Outpatient transition to XR-NTX combining upward titration of very low dose naltrexone with downward titration of low dose buprenorphine was safe, well tolerated, and completed by most participants. Further studies with larger numbers of subjects are needed to see if this approach is useful for naltrexone induction.

Mean opioid withdrawal and craving scores during induction and after naltrexone extended release administration (Days 1-9), using SOWS (Subjective Opioid Withdrawal Scale), COWS (Clinical Opioid Withdrawal Scale) and VAS (Visual Analog Scale) for craving. Time point scores are the results of the mean score of each day of treatment, error bars represent + -1 SEM. Number of participants is reported on the X-axis.

In-treatment proportion of opioid positive urine samples (Day1-9, N = 20).

Source:

http://www.sciencedirect.com/science/article/pii/S0376871614000568

Computerized Vs In-Person Brief Intervention for Drug Misuse: RCT

We have written much about the challenges of widespread implementation of SBIRT in the US. Well, authors of a new study, published online this month in the journal, Addiction, have suggested a novel tool which they believe could help ensure that scores of additional patients are being screened: computerized brief intervention. And according to their study, it works as well and the in-person version:

Abstract

Background and aims

Several studies have found that brief interventions (BIs) for drug misuse have superior effectiveness to no-treatment controls. However, many health centers do not provide BIs for drug use consistently due to insufficient behavioral health staff capacity. Computerized BIs for drug use are a promising approach, but their effectiveness compared with in-person BIs has not been established. This study compared the effectiveness of a computerized brief intervention (CBI) to an in-person brief intervention (IBI) delivered by a behavioral health counselor.

Methods

Two-arm randomized clinical trial, conducted in two health centers in New Mexico, USA. Participants were 360 adult primary care patients with moderate-risk drug scores on the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) who were randomly assigned on a 1:1 basis to a computerized brief intervention (CBI) or to an in-person brief intervention (IBI) delivered by a behavioral health counselor. Assessments were conducted at baseline and 3-month follow-up, and included the ASSIST and drug testing on hair samples.

Results

The IBI and CBI conditions did not differ at 3 months on global ASSIST drug scores (b=-1.79; 95% CI=-4.37,-0.80) or drug-positive hair tests (OR=.97; 95% CI= 0.47,1.94). There was a statistically significant advantage of CBI over IBI in substance-specific ASSIST scores for marijuana (b=-1.73; 95% CI= -2.91,-0.55; Cohen's d=.26; p=.004) and cocaine (b= -4.48; 95% CI= -8.26,-0.71; Cohen's d=.50; p=.037) at 3 months.

Conclusions

Computerized brief intervention can be an effective alternative to in-person brief intervention for addressing moderate drug use in primary care.

What do you think - could computerized brief interventions be the key to widespread SBIRT implementation?

Source: http://onlinelibrary.wiley.com/doi/10.1111/add.12502/abstract 

Gaps in Clinical Prevention and Treatment for Alcohol Use Disorders

Dr W's article, "Gaps in Clinical Prevention and Treatment for Alcohol Use Disorders" was published this month online in the journal Alcohol Research: Current Reviews. Here's the abstract:

Abstract

Heavy drinking causes significant morbidity, premature mortality, and other social and economic burdens on society, prompting numerous prevention and treatment efforts to avoid or ameliorate the prevalence of heavy drinking and its consequences. However, the impact on public health of current selective (i.e., clinical) prevention and treatment strategies is unclear. Screening and brief counseling for at-risk drinkers in ambulatory primary care has the strongest evidence for efficacy, and some evidence indicates this approach is cost-effective and reduces excess morbidity and dysfunction. Widespread implementation of screening and brief counseling of nondependent heavy drinkers outside of the medical context has the potential to have a large public health impact. For people with functional dependence, no appropriate treatment and prevention approaches currently exist, although such strategies might be able to prevent or reduce the morbidity and other harmful consequences associated with the condition before its eventual natural resolution. For people with alcohol use disorders, particularly severe and recurrent dependence, treatment studies have shown improvement in the short term. However, there is no compelling evidence that treatment of alcohol use disorders has resulted in reductions in overall disease burden. More research is needed on ways to address functional alcohol dependence as well as severe and recurrent alcohol dependence.

And check out the full piece here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3908715/

Study: Healthcare Utilization Rates After Treatment Are Equivalent Among Abstinent and Low-Risk Drinkers

A fascinating new study will add to the small, but growing, treatment literature suggesting that low-risk drinking is a viable option for people receiving treatment for alcohol-use disorders. The paper, published this month in Alcoholism: Clinical and Experimental Research, measured healthcare utilization rates and associated costs over a 5-year period among clients receiving treatment in a large Northern California healthcare system. The results show that outcomes for abstainers and lower-risk drinkers were equivalent (and far better than the high-risk drinkers), despite the fact that the abstinence-based treatment received by all groups was the same.

According to the authors, "The finding that lower-risk drinkers did not differ from those of abstinent individuals, in inpatient use in particular, even when controlling for patient characteristics, suggests that a health policy perspective may consider benefits of lower-risk drinking."

Here's the abstract via Wiley:

Background

Lower-risk drinking is increasingly being examined as a treatment outcome for some patients following addiction treatment. However, few studies have examined the relationship between drinking status (lower-risk drinking in particular) and healthcare utilization and cost, which has important policy implications.

Methods

Participants were adults with alcohol dependence and/or abuse diagnoses who received outpatient alcohol and other drug treatment in a private, nonprofit integrated healthcare delivery system and had a follow-up interview 6 months after treatment entry (N = 995). Associations between past 30-day drinking status at 6 months (abstinence, lower-risk drinking defined as nonabstinence and no days of 5+ drinking, and heavy drinking defined as 1 or more days of 5+ drinking) and repeated measures of at least 1 emergency department (ED), inpatient or primary care visit, and their costs over 5 years were examined using mixed-effects models. We modeled an interaction between time and drinking status to examine trends in utilization and costs over time by drinking group.

Results

Heavy drinkers and lower-risk drinkers were not significantly different from the abstainers in their cost or utilization at time 0 (i.e., 6 months postintake). Heavy drinkers had increasing odds of inpatient (p < 0.01) and ED (p < 0.05) utilization over 5 years compared with abstainers. Lower-risk drinkers and abstainers did not significantly differ in their service use in any category over time. No differences were found in changes in primary care use among the 3 groups over time. The cost analyses paralleled the utilization results. Heavy drinkers had increasing ED (p < 0.05) and inpatient (p < 0.001) costs compared with the abstainers; primary care costs did not significantly differ. Lower-risk drinkers did not have significantly different medical costs compared with those who were abstinent over 5 years. However, post hoc analyses found lower-risk drinkers and heavy drinkers to not significantly differ in their ED use or costs over time.

Conclusions

Performance measures for treatment settings that consider treatment outcomes may need to take into account both abstinence and reduction to nonheavy drinking. Future research should examine whether results are replicated in harm reduction treatment, or whether such outcomes are found only in abstinence-based treatment.

Figure 1 shows Adjusted odds ratios of utilization by 6-month drinking group over time:

Figure 2 shows Adjusted average costs per member month by 6-month drinking group over time:

                                               






As mentioned above, these are the results from patients who attended abstinence-based treatment. It will be
interesting to see if these results are replicated among patients who are instructed on low-risk drinking. What experience do readers have with this issue? Do results like these make those directing abstinence-based programs think twice about the policy? It would be great to hear from you.

Hat tip: Thanks, Dr Reid Hester, for bringing this study to our attention.

Source: Kline‐Simon, A. H., Weisner, C. M., Parthasarathy, S., Falk, D. E., Litten, R. Z., & Mertens, J. R. (2013). Five‐Year Healthcare Utilization and Costs Among Lower‐Risk Drinkers Following Alcohol Treatment. Alcoholism: Clinical and Experimental Research.
http://onlinelibrary.wiley.com/doi/10.1111/acer.12273/abstract

Do Adverse Childhood Experiences Make Amphetamine More Pleasurable?

In a fascinating new study, researchers from the University of Maryland and Johns Hopkins University observed the way amphetamine affects the brain, comparing subjects who reported adverse childhood experiences (ACE) with those who did not. They found significant differences between groups in the way the drug impacted the dopamine (DA) neurotransmitter in the ventral striatal (VS) region of the brain, finding a significant positive correlation between early childhood trauma and VS DA release.

The results, published online in the journal, Psychopharmacology, suggest that adverse childhood experiences may enhance vulnerability to amphetamine-use disorders later in life by changing the way the brain transmits dopamine. Interestingly, a positive association between childhood trauma and amphetamine-induced pleasure was suggested for men, but vice versa for women.

Here's the abstract via SpringerLink, and an interesting image from the article:

Abstract

Rationale

Childhood exposure to severe or chronic trauma is an important risk factor for the later development of adult mental health problems, such as substance abuse. Even in nonclinical samples of healthy adults, persons with a history of significant childhood adversity seem to experience greater psychological distress than those without this history. Evidence from rodent studies suggests that early life stress may impair dopamine function in ways that increase risks for drug abuse. However, the degree to which these findings translate to other species remains unclear.

Objectives

This study was conducted to examine associations between childhood adversity and dopamine and subjective responses to amphetamine in humans.

Methods

Following intake assessment, 28 healthy male and female adults, aged 18–29 years, underwent two consecutive 90-min positron emission tomography studies with high specific activity [11C]raclopride. The first scan was preceded by intravenous saline; the second by amphetamine (AMPH 0.3 mg/kg).

Results

Consistent with prior literature, findings showed positive associations between childhood trauma and current levels of perceived stress. Moreover, greater number of traumatic events and higher levels of perceived stress were each associated with higher ventral striatal dopamine responses to AMPH. Findings of mediation analyses further showed that a portion of the relationship between childhood trauma and dopamine release may be mediated by perceived stress.

Conclusions

Overall, results are consistent with preclinical findings suggesting that early trauma may lead to enhanced sensitivity to psychostimulants and that this mechanism may underlie increased vulnerability for drug abuse.

http://link.springer.com/article/10.1007%2Fs00213-013-3407-z

Study: Burden of Disease Associated with Alcohol-use Disorders Higher Than Previously Thought

In a paper published online last week in the journal, Alcoholism: Clinical and Experimental Research, a group of international researchers have brought fresh eyes to a familiar data set: the NIAAA's NESARC. Whereas past studies have estimated the alcohol-attributable global burden of disease, or rates of alcohol-attributable deaths and years of life lost, no study has focused specifically on the burden of disease in the United States associated with alcohol-use disorders (AUD). This is important, the authors note, because alcohol-use disorders (including "abuse" and "dependence" from DSM or "the harmful use of alcohol" from ICD) "were identified as the largest disease category contributing to the alcohol-attributable global burden of disease for the year 2004, making up approximately one-third of this burden." By using US-specific data, including population and death statistics as well as Waves 1 and 2 of the NESARC, the authors were able to estimate the burden of disease from AUD in the US in 2005.


Results

"In the United States in 2005, 65,000 deaths, 1,152,000 years of life lost due to premature mortality (YLL), 2,443,000 years of life lost due to disability (YLD), and 3,595,000 disability-adjusted life years (DALYs) lost were associated with AUD. For individuals 18 years of age and older, AUD were associated with 3% of all deaths (5% for men and 1% for women), and 5% of all YLL (7% for men and 2% for women). The majority of the burden of disease associated with AUD stemmed from YLD, which accounted for 68% of DALYs associated with AUD (66% for men and 74% for women). The youngest age group had the largest proportion of DALYs associated with AUD stemming from YLD."

Some figures from the article:

Prevalence of alcohol use disorders by category, sex, and age in 2005. 

And:

Proportion of all deaths associated with alcohol use disorders in 2005, by sex and age


You can read the abstract of the paper by Rehm, et al. here:

http://onlinelibrary.wiley.com/doi/10.1111/acer.12331/abstract

Would love to hear readers reactions to these numbers. 

Study: Sex-Dependent Differences in Subjective Cannabis Effects (Do Women Enjoy Pot More Than Men?)

A new article by researchers at the New York State Psychiatric Institute and Department of Psychiatry at Columbia University explores the differences in the way men and women report their subjective experiences of the effects of cannabis. The authors reviewed data from four separate outpatient studies evaluating a range of cannabis-induced effects. In the final analysis, the subjects (35 men and 35 women) were all daily or near-daily cannabis users and their responses to standardized measures of mood, physical symptoms, and cannabis-related drug effects were recorded over time, beginning immediately after consumption.

It turns out, women were significantly more likely to report more feelings associated with enjoyment (and abuse liability) than men were:

According to the authors: "The results from this study demonstrate that when cannabis smokers are matched for use, ratings of cannabis’ subjective effects that are associated with abuse liability are higher in women compared to men. Although men and women significantly differed in body weight, sex differences were not observed for all subjective effects, including ratings of cannabis intoxication. "

In addition, cannabis use is more prevalent among men than women in the US (51.4% vs 37.4%, resp.). "Yet among cannabis smokers, women have a faster trajectory to cannabis-use disorders, which the current findings might in part explain." The authors call for more research to further explain the clinical significance of sex differences in the effects of cannabis and cannabis-use disorders.

The article by Cooper & Haney can be viewed here:

http://www.drugandalcoholdependence.com/article/S0376-8716%2813%2900529-2/abstract

Study: Hallucinogen Use Predicts Reduced Criminal Justice Recidivism

In a potentially fascinating article, published in this month's Journal of Psychopharmacology, researchers identified a correlation between naturalistic hallucinogen use and reduced recidivism among substance-involved offenders under community corrections supervision. The sample is very large (n=25,622) and it appears the relationship remains after controlling for "an array of potential confounding factors." Given the report last year that lifetime psychedelic use was not associated with current mental health problems in an adult population, this study's implications could be especially interesting.

Unfortunately, my institution doesn't allow me access to this journal - if there are any readers who can access the full article, please let me know.

(Comment after the fact: Keep in mind that this shows a correlation and that correlation does not establish directionality. That it, it's at least equally plausible that people with a diagnosis of psychedelic use disorder (a tiny fraction of the population) are different in ways that statistical controls cannot compensate for, and are therefore less like to reoffend. This makes sense in that psychedelic drug use is minimally addictive, if at all, and craving and urges are not typical in this group. It seems highly implausible to me that hallucinogen use had a beneficial effect. The authors should never have been allowed to make that claim, a fault of the editor. In addition, use of LSD or psilocybin has never been associate with increased incidence of mental disorders, in contrast to MDMA or synthetic cannabinoids.)

Here's the abstract via SagePub:

Abstract

Hallucinogen-based interventions may benefit substance use populations, but contemporary data informing the impact of hallucinogens on addictive behavior are scarce. Given that many individuals in the criminal justice system engage in problematic patterns of substance use, hallucinogen treatments also may benefit criminal justice populations. However, the relationship between hallucinogen use and criminal recidivism is unknown. In this longitudinal study, we examined the relationship between naturalistic hallucinogen use and recidivism among individuals under community corrections supervision with a history of substance involvement (n=25,622). We found that hallucinogen use predicted a reduced likelihood of supervision failure (e.g. noncompliance with legal requirements including alcohol and other drug use) while controlling for an array of potential confounding factors (odds ratio (OR)=0.60 (0.46, 0.79)). Our results suggest that hallucinogens may promote alcohol and other drug abstinence and prosocial behavior in a population with high rates of recidivism.

Sources:
http://jop.sagepub.com/content/28/1/62.abstract
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063972

Update:
Thanks to Paul and Jason for sending the full piece. 
Treatment Accountability for Safer Communities (TASC)provided the authors access to de-identified records on 25,622 felony-charged individuals on community corrections supervision from  between 2002-2007. "Any hallucinogen use" was not a descriptor in the data, so they were confined to hallucinogen-use disorder, abuse or dependence, assuming that case workers would likely interpret any use as disordered. Interestingly, 73.6% of folks with a hallucinogen-use disorder in the sample were white/Caucasian. And, according to the researchers, hallucinogen-use disorder was the third strongest predictor of recidivism rates, behind cocaine- and cannabis-use disorder, respectively, which most strongly (but positively) predicted recidivism.The authors call for RCTs to explore hallucinogen-based therapies in the criminal justice population.