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.

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?

Can Alcohol Dependent Patients Adhere to an ‘As-Needed' Medication Regimen? Yes: Study

According to researchers, AUD patients can benefit from as-needed medication regimens:

Abstract:

A pooled analysis of ‘as-needed medication use' data from 1,276 patients in two randomised, double-blind, placebo-controlled, parallel-group trials of nalmefene in the treatment of alcohol dependence was performed to explore whether an ‘as-needed' regimen is an acceptable and feasible strategy in patients seeking help for alcohol dependence. Adherence was defined as alcohol consumption and medication intake, or no alcohol consumption (with or without medication intake). Nalmefene was taken on approximately half of the study days; placebo was taken more often than nalmefene (52.8 vs. 64.5% of days, respectively). In each treatment group medication intake appeared to vary according to patients' needs in that intake correlated with the baseline drinking pattern. Sixty-eight percent of the nalmefene-treated patients (78% of the study completers) adhered to the as-needed treatment regimen on at least 80% of the study days. In conclusion, as-needed use is a feasible, patient-centred approach that engages patients with alcohol dependence in the active management of their illness. © 2014 S. Karger AG, Basel

Source: http://www.karger.com/Article/FullText/357865