October 2013 Newsletter

It's almost the end of the year. In our setting, because we are moving into summer and festivities, this usually sees a drop in those seeking help for their substance use issues, but often their is a brief spike shortly after new year as resolutions are made and the after-effects of the partying are felt! I recently attended the Dan Siegel Interpersonal Neurobiology workshop that was held in Cape Town, hence the photo. In this month's edition of Addiction Information we hope to spark some thought around some controversial topics, but one topic that should become less controversial is that of opioid substitution therapy, for which their seems to be mounting evidence as a stand-alone treatment modality.

We look at: An opioid addiction switch, Behavioural Interventions and Buprenorphine Maintenance, Chronic Care, Remission Rates, Choice and Will Power, Dr Dan Siegel and the Mind & Life Conference.

Opiate Addiction Switch?
Recent research by Dr Steven Laviolette has identified a molecular switch in the amygdala of rats with chronic exposure to heroin. This switch is linked to environmental triggers. The paper,Opiate Exposure and Withdrawal Induces a Molecular Memory Switch in the Basolateral Amygdala between ERK1/2 and CaMKII╬▒-Dependent Signaling Substrates was recently published in the Journal of Neuroscience. The perpetuation of heroin addiction is often caused by environmental cues having an abnormally strong link to pleasurable memories related to heroin use. What Laviolette and his team discovered was that the move from use to addiction was linked to a change in the way memories were formed in the amygdala.

In a non-dependent state they found that extracellular signal-related kinase (ERK) was recruited in the creation of drug-related memories. Once the addiction had developed a functional switch to a seperate molecular memory pathway occurred. This pathway was controlled by CaMKII. What is also interesting is that the initial memory process involving ERK requires intra-basolateral amygdala D1 transmission, whereas the addiction phase involves a D2 mediated mechanism.

This is indeed really fascinating when we consider the roles of D1 and D2 receptors and memory in addiction, and I look forward to further research in this area.

Behavioural Interventions and Buprenorphine Maintenance
It seems that every month there is another research piece that says there is little benefit when adding behavioural therapies to maintenance therapies. Last month it was methadone and counselling, and this month it is Buprenorphine and CBT and Contingency Management. Ling and others conclude "There remains no clear evidence that cognitive behavioural therapy and contingency management reduce opiate use when added to buprenorphine and medical management in opiate users seeking treatment." The paper, Comparison of behavioral treatment conditions in buprenorphine maintenance, adds to the body of evidence that shows effective pharmacology is often all that is needed in the case of heroin addiction where there is no co-occuring psychiatric disorders (personally, I may add severe environmental/social challenges - more research in this area is needed).

What stands out to me is the manner in which the treatment was administered: There was a significant incentive to engage in the treatment - gift cards to a potential value of US$410 could be earned if all assessments were completed over the 52 weeks. Then there were also twice weekly urine tests for 18 weeks, and there was a discussion around the results, and perhaps most importantly, dosages were adjusted until an optimal therapeutic dose was established. The outcome showed at least a 50% suppression in illicit opioid use, even at the most conservative measures.

I would like to see more studies with a more representative treatment setting - indeed we may find that application does not match the research findings, in which case we would need to improve the treatment application. I would also like to see research done in more vulnerable populations with significant social problems, such as homelessness, and using more intensive outpatient services (the study by Ling used a single CBT session per week). A recent review of OST studies in low and middle income countries as shown that quality of life does improve, although I have not looked into this in any depth.

Certainly I have shifted my position regarding maintenance therapies from "showing promise" to "essential option" when it comes to treating opioid dependency.

More evidence for Opioid Substitution Therapy
Predicting biopsychosocial outcomes for heroin users in primary care is a fascinating longitudinal prospective cohort study conducted in at a Primary Care Addiction Service in Shefield, England over 11 years. Over the period 53% of the patients achieved a drug free discharge (22%) or retention in medically assisted recovery. 21% dropped out, including those in prison or who died, which is significantly lower than the usual 40% cited in most literature.

One of the key findings was that retention in a continuous treatment process produced significantly better results as opposed to having revolving door patients - this, as the authors point out, has significant implications regarding public policy. Overall, there was a 98% reduction in heroin  and opiate use.

Is there benefit from chronic care management?
Possibly the most controversial study in this period was published in the JAMA: Chronic care management for dependence on alcohol and other drugs: The AHEAD randomized trial. The conclusion of this paper reads: "Among persons with alcohol and other drug dependence, CCM compared with a primary care appointment but no CCM did not increase self-reported abstinence over 12 months. Whether more intensive or longer-duration CCM is effective requires further investigation." 

The authors describe chronic care management as "multidisciplinary patient-centered proactive care, a way to organize services that provides coordination and expertise, and has been effective for depression, medical illnesses, and tobacco dependence (a substance use disorder)". What this meant in the application of this study was that the individuals randomized to the CCM group received not only an appointment with the primary care physician, but also motivational enhancement therapy, relapse prevention and onsite treatment, as well as referrals and social work assistance. That may sound like a lot of services, but in fact service the average number of appointments was only 6.This would certainly not constitute "treatment". What was shown was that a greater number of visits to the AHEAD clinic (>3 vs. <3) had a significant effect on abstinence levels.

The study only looked at 1-year outcomes. I would have been interested to look at specific sub-populations within the study, such as those who had decided to engage in in-patient services or self-help groups, but this data was not reported. Interestingly the alcohol group did show a statistically significant improvement. Perhaps the primary care environment is suitable for the delivery of some services, but not for others.

One of the authors, Dr Samet, who was interviewed, had this to say:
"If you feel sometimes that treating patients with addiction is even harder than treating asthma or depression, there may be some basis for that feeling in reality. As shown in these results, a care system that worked for other chronic diseases didn’t work for these patients.
Moving forward, we need to be creative with our patients who have these problems. In terms of improving quality of care, we need both randomized control trials and observational studies. I wouldn’t steer the ship away from primary care treatment; the reality is that most patients with depression and addiction get their care in primary care. Do we need specialist help? Yes, but we need a primary care system that will do its bit as well."
We do remit
Most definitions of the term "addiction" will use the words "chronic" and "progressive". But what do the remission rates of those who can be diagnosed with substance use disorders say? While looking into the paper cited in the previous section, I came across Gene Heyman's very well written paper Quitting Drugs: quantitative and qualitative features.

Heyman has relied on four major epidemiological studies to examine remission rates. The main findings of his analysis may surprise many of us: Firstly, addictive disorders are generally not chronic, with approximately 80% showing remission for a period of a year or more. In fact, the chances of an individual giving up cocaine, given enough time, are in the region of 98%.

The second even more suprising finding is that remission rates remained constant. That means that no matter how long an individual had been using, the likelihood of remission in any particular year remained unchanged. If addiction was a progressive disease, this would not be true. Heyman states that addiction "involves a steady but fragile state that can abruptly shift to a new state".

Heyman usefully examines a number of other issues around the data, such as racial/ethnic differences and the legal status of drugs in relation to remission. Many of the main findings have also been supported and discussed in another study: Probability and predictors of remission of life-time nicotine, alcohol, cannabis or cocaine dependence: Results from the National Epidemiological Survey on Alcohol and Related Conditions.

For a more complete analysis of both papers, I would highly recommend the Drug and Alcohol Findings site.

In a separate paper, Heyman draws some conclusions that would be considered very controversial by many in the addiction field. In the paper Addiction and choice: theory and new data, he disputes the brain disease model, and proposes that the data supports his conclusion that addiction is more clearly "choice" based than "compulsion" based. This is not a comfortable conclusion, but when we look at research that shows that motivational interviewing and other motivational interventions have a strong evidence base, we must at least consider that there may be truth in Heyman's conclusions. Having said this, I think it is quite safe to conclude that there are degrees of choice, and in life there are very few opportunities to exercise "free" choice.

Choice and Will Power 
Marc Slors discusses the issue of free choice in his paper Conscious Intending as Self-programming (Thank you Marc Lewis for pointing this paper out to me and your discussion around it). He starts by pointing out that much of the discussion these days revolves around the idea that we actually have very little conscious control over our behaviour. In other words, "free choice" is not as free as we may suspect, but is rather the result of a number of underlying unconscious processes. When it comes to our conscious actions "there is merely temporal succession and no causation." Slors argues that while this may be true of proximal (short-term) conscious intentions, distal intentions may result from earlier conscious intention, allowing us a greater degree of control over our behaviour. He argues that when we make distal decisions, we may well be evaluating various scenarios, which requires consciousness. Slors theorizes that if we create clear distal intentions, we undertake "self-programming", and this can inform proximal actions in a way that facilitates distal choices, ensuring the chosen outcome.

The relevance for addiction is quite profound. Indeed we know that a trigger can result in a cascade of events that happen so quickly that there is no chance for rational thinking. Or rather, immediate intentions are not congruent with actions or behaviours. This would seem to indicate that planning ahead may be the best way to prevent relapse.

This idea is supported in another recent paper Restricting Temptations: Neural Mechanisms of Precommitment. Will power is something that is in short supply when it comes to addictive disorders, and delay discounting and ego depletion tend to over power will power in the presence of the drug of choice, or even a trigger. It seems that a much more effective strategy is precommittment. Precommitment is when the individual makes advance decisions about their actions when they are aware of possible future failures in will power. For example, putting money on a 30-day call. In the case of addiction, it may be choosing a different route home so as not to pass the dealer, even though it will take much longer. Dirk Hanson provides a brief summary of this paper here. The bottom line is that precommitment seems to be a viable means of avoiding future failure, or to frame it from Slors perspective, it may be a form of self-programming that will improve our ability to make conscious choices. 

It is also interesting to note that different brain regions are involved in these processes, with the DLPFC, PPC and inferior frontal gyrus being activated when exerting will power, while LFPC became active during precommitment and showed increased functional connectivity with the DLPFC and PPC and the relationship between impulsivity and LFPC connectivity was mediated by value-related activation in ventromedial PFC.

So much for "just for today"!

Dr Dan Siegel 
As mentioned earlier, I attended the Dan Siegel training workshop entitled Mindsight & Interpersonal Neurobiology. Siegel is currently the clinical professor of psychiatry at UCLA and he is the Co-Director of the mindful Awareness Research Center . Dr Siegel also coined the term "mindsight" -  "to describe our human capacity to perceive the mind of the self and others. It is a powerful lens through which we can understand our inner lives with more clarity, integrate the brain, and enhance our relationships with others. Mindsight is a kind of focused attention that allows us to see the internal workings of our own minds. It helps us get ourselves off of the autopilot of ingrained behaviors and habitual responses. It lets us “name and tame” the emotions we are experiencing, rather than being overwhelmed by them."

Although Dr Siegel's work is not specifically related to addiction, I found much of it very helpful and relevant to the field. His desire to seek similar patterns in diverse approaches is something that I think is essential when trying to develop an understanding of addictive disorders.

I have also used his wheel of awareness mindfulness practice to good effect in contemplation groups. I would strongly advise those who would like to get a better understanding of issues such as attachment and mindful awareness in addiction to have a look at Dan Siegel's work.

Mind & Life XVII
Speaking of mindfulness, the Dalai Lama has been hosting the Mind & Life conference which this year focuses on craving, desire and addiction. This has brought a number of leading thinkers into the same room to discuss their insights and debate the various views that their various backgrounds bring to our understanding. Delegates and their topics are:

Marc Lewis: The Role of Craving in the Cycle of Addictive Behaviour
Kent Berridge: Brain Generators of Intense Wanting and Liking
Thupten Jinpa: Psychology of Desire, Craving and Action
Nora Volkow: The Role of Dopamine in the Human Addicted Brain
Vibeke Asmussen Frank: Beyond the Individual: The Role of Society and Culture in Addiction
Mitthieu Ricard: From Craving to Flourishing: Buddhist Perspectives on Desire
Wendy Farley: Contemplative Christianity, Desire, and Addiction
Sarah Bowen: Application of Contemplative Practices in Treatment of Addiction

The discussions have been webcast, and have been extremely interesting. The videos can be found on YouTube.

Thought of the Month
In the words of Victor Frankl: "between stimulus and response there is a space. In that space is our power to choose our own personal response and in that response lies our growth and freedom."

Unfortunately narrowed focus, implicit memory and learned response all shorten the gap between stimulus and reaction. By becoming more mindful and aware, we can exploit that space, expand it and explore that opportunity for growth and become free of our perceived constraints.

Until next time.