Clinical & Policy Updates:
SMMGP Clinical Update August-September 2012
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Persistent cannabis users show neuropsychological decline from childhood to midlife
Meier MH, Caspi A, Ambler A, et al. Proc Natl Acad Sci USA Published online: 27 August 2012
This study set out to investigate the association between persistent cannabis use and neuropsychological functioning. They used a birth cohort of 1,037 individuals from Dunedin, New Zealand, who were born in 1972/3. Intelligence was assessed at ages 7, 9, 11 and 13 years before the onset of cannabis use. They were then reassessed at age 38 years. They measured past-year cannabis dependence using the Diagnostic Interview Schedule at ages 18, 21, 26, 32 and 38 years. The study members were then grouped according to the number of times they had been diagnosed as dependent in each "study wave". These ranged from "never" to "three or more study waves".
Some of the key study questions and results were:
Do study members with more persistent cannabis use show greater IQ decline?
The authors looked at IQ change from childhood to age 38 years. The study members with more persistent cannabis dependence showed greater IQ decline. Those who were cannabis dependent in "three or more study waves" typically lost an average of six IQ points.
Is impairment specific to certain neuropsychological domains or is global?
The study did a battery of various tests to assess executive functions, memory, processing speed, perceptual reasons and verbal comprehension. The greatest impairments for those with more persistent cannabis dependence were generally in the areas of executive functioning and processing speed.
Is impairment apparent even after controlling for years of education?
The change in IQ remained highly significant (p=0.0007) even after controlling for years of education.
Does cannabis-associated neuropsychological impairment translate into functional problems in daily life?
The study also had an informants element - they asked "people who knew them well" to complete a questionnaire on issues such as memory and attention. Informants reported more problems in those with persistent cannabis dependence.
Are adolescent cannabis users particularly vulnerable?
Yes, they showed greater IQ decline than cannabis users who started in adulthood.
What is the effect of cessation of cannabis use?
The results showed that amongst adolescent cannabis users the cessation of cannabis use did not fully restore neuropsychological functioning.
Commentary: This really is an impressive piece of work. It's a long cohort study and it has controlled for many of the factors that were previously suspected of confounding results. Lower IQ is associated with increasing cannabis dependence but as the authors rightly point out, in theory, this remains an association and it could all be due to some hitherto unrecognised further variable. However, in practice, it is very challenging to see what this mystery agent could be - this study has controlled for education, tobacco and alcohol dependence, other substance misuse, and schizophrenia. It's very robust. It's also worth remembering that although the issues in adolescents were widely picked up by the media, this study showed an association with cannabis and neuropsychological impairment, in a dose-dependent way, across all adults.
Prevalence of common chronic respiratory diseases in drug misusers: a cohort study
Palmer F, Jaffray M, Moffat MA, et al. Primary Care Respiratory Journal. Published online: 8 August 2012
This study took a historical cohort study of "drug misusers" matched them to controls and compared routinely collected primary care data. It was retrospective in nature and the anonymous data were collected from general practices in Scotland. They looked for a "drug misuse group" (aged 16-59 years) who had ever had a drug misuse Read clinical classification code (READ) documented and/or a record of having been prescribed an opiate substitute medication in the past. They looked at the prevalence of common respiratory problems as well as the type of medications used, such as short acting beta-agonists, long-acting beta agonists (LABA), combination LABA and inhaled corticosteroid medications.
In total there were 18,570 patients (9,285 in each group). The types of drug misuse picked up by the drug misuse READ code were (some had more than one READ code): drug misuse non-specified 71.6%, opioid misuse 41.3%, hypnotic or anxiolytic misuse 19.5%, cannabis misuse 9.0%, cocaine misuse 2.6%, glue sniffing misuse 2.5%, amphetamine or other psychostimulant misuse 2.1%, ecstasy misuse 0.6%, hallucinogen 0.3%. They adjusted for age, gender, deprivation and smoking status. The results showed that more drug users than controls had a diagnosis of asthma or COPD (17.1% vs 10.9%). The drug misuse cohort was also prescribed more medications (2.4% vs 0.8%). In the drug misuse group 85.9% were either current or ex-smokers compared with 46.6% of the control group.
Commentary: This paper is highly recommended and is a good example of data that already exist being put to good use. Clinically, it's an obvious problem amongst users - but it is one with a lamentable lack of research. This study demonstrates increased respiratory disease in drug users but we would make the point that the structure of this study could under-report the respiratory issues in a specialised substance misuse or shared care clinic. The population captured is very wide - encompassing all forms of substance misuse. In research terms it is perfectly sensible to adjust for smoking and there remained a significant difference when this was done. However, without the adjustment the risk of COPD was ten times greater.
This study is only applicable to those who have received a diagnosis. It can say nothing about the potential for undiagnosed and untreated respiratory illness in both the drug misusing group and the control group. However, given the known issues with poor attendance at GP practices it seems probable that this study will have underestimated the burden of respiratory disease in some substance using groups.
In many substance misuse clinics smoking is near ubiquitous with rates of 74-98% being quoted in the literature. There is an increasing appreciation of the need to blend harm reduction with promotion of abstinence when it comes to smoking. Intermediate smoking goals - such as reduced consumption are valid and have been shown to be associated with an increased probability of future abstinence. There may be a role for smokeless tobacco and long-term nicotine maintenance. Increased attempts to improve a wide range of lifestyle behaviours can also help someone to stop smoking and there is a role for physical exercise to encourage abstinence and offset the detrimental effects of tobacco.
Substance misuse of gabapentin
Smith BH, Higgins C, Baldacchino A, et al. Br J Gen Pract 2012;62:406-7
This short report in the BJGP highlights some concerns about the abuse potential of gabapentin recently noted in Scotland. They point out the important role of gabapentin as an evidence-based treatment for neuropathic pain - and that 8% of the population is affected by neuropathic pain. It highlights the steady rise in the number of patients being prescribed gabapentin. In Scotland, the total number of prescriptions has risen exponentially in the past few years.
The substance misuse services in Tayside found that, of those who had been attending for at least 4 years, 5.2% were currently receiving gabapentin on prescription with a mean dose of 1343mg. They also noted they were >3 times more likely to admit to non-medical use of analgesics (p=0.006). They also comment on a recent police report in Scotland which highlighted that gabapentin is being used as a cutting agent in heroin.
Commentary: The issue of gabapentin misuse is unlikely to come as a huge surprise to many readers and there has been a thread on this topic on the SMMGP Forum going back to 2009. It has also been raised in relation to other topics - particularly when there have been discussions of the abuse potential for pregabalin and tramadol. There seems little doubt that it is a drug that can be abused - however, it is also a medication that has a legitimate use for the unpleasant problem of neuropathic pain. Initially, the fact that 5% of the individuals in Tayside are on gabapentin seems high - but, as the authors point out, neuropathic pain has a prevalence of 8% and it might be worth considering that the population seen in substance misuse clinics carry a high burden of physical trauma. There is always going to be a tension, most acutely seen in prisons, when good treatments have the potential for abuse. It's important for clinicians to be aware of these problems but it's important that individuals in a population known to be under-treated don't miss out on good pain management.
To contribute to the discussion visit the SMMGP Forum thread.
Retrospective accounts of injection initiation in intimate partnerships
Simmons J, Rajan S, McMahon JM. Int J Drug Policy 2012;23:303-11
This paper uses narrative data collected from semi-structured ethnographic interviews with 25 relatively stable drug-using couples from two New York City areas. The analyses, and this paper, concentrate on the retrospective accounts of the initiation to injection in current or former intimate partnerships.
The results showed that transition to injection in intimate partnerships was common - particularly among women. Notably, the results also suggested that, even when all the dangers were known, emotional and pragmatic concerns tended to override these. In all but two cases men initiated women after injecting themselves. In the majority of cases the women insisted that they be initiated after witnessing partners injecting - and while this was usually met with resistance from the partner it ended up with both partners injecting. Many of the couples came together in the hope of overcoming their dependencies or to have someone with whom they could "trust and confide in whilst living life on the margins". Injecting was seen as part of the relationship and injection initiation was "motivated by a desire to increase intimacy, satisfaction and commitment in the relationship".
Commentary: It is common for people attending substance misuse services to strike up relationships. Keyworkers are often familiar with the relationships, both past and present, of individuals in treatment. This paper points out that while some injection initiations were abusive (and it describes a couple of serious examples) the majority were about people who viewed injection in the context of a deeper and more intimate relationship. This study explores some of these issues further and strengthens the case for services to formally consider these relationships when planning services. This could take the form of couples-based interventions - though, as the authors highlight, there is little or no evidence on these at present. The paper reports that some evidence is now emerging for a couples-based approach to HCV/HIV prevention measures and reducing sexual risk.
A couples-based approach may fly in the face of any assumptions that couples need to separate in order to "get clean and recover". The paper reports that in the US some services are positively hostile to partners - this is perhaps not the case in the UK. However, like a good qualitative paper can do, this study challenges our views and preconceptions on how we interact with those in treatment and their relationships with others in the same service.
Brief case finding tools for anxiety disorders: Validation of GAD-7 and GAD-2 in addictions treatment
Delgadillo J, Payne S, Gilbody S, et al. Drug Alcohol Depend 2012;125:37-42
The setting for this study was a community drugs treatment service in Leeds. The aim was to test the validity and reliability of the generalised anxiety disorder (GAD-7) questionnaire which comprises seven items. They also tested the very brief version of the same tool which has just two questions (GAD-2).
They took a sample of 103 patients who first completed brief screening questionnaires. They then went on to take part in structured diagnostic assessments using CIS-R (revised clinical interview schedule) which, as well as being regarded as a gold standard, can be administered by trained lay interviewers with the help of a computer. A subgroup of 60 patients was retested at 4 weeks. A GAD-7 score of ≥9 had a sensitivity of 80% and specificity of 86% for any anxiety disorder. A GAD-2 score ≥2 had 94% sensitivity and 53% specificity.
Commentary: Overall, the results of this study support the use of GAD-7 as a measure with decent internal consistency and diagnostic accuracy for picking up anxiety disorders. It's an important point that we don't simply assume that a substance misusing population has the same characteristics when using these types of questionnaires. GAD-7 is simple to do and is recommended as a routine screening tool under the national Improving Access to Psychological Therapies (IAPT) programme in the UK.
The paper also highlights the importance of managing anxiety disorders in the substance misuse setting. The acute symptoms of withdrawal can mimic anxiety disorders and, similarly, chronic anxiety issues can lead to concerns about withdrawal from opiate substitution therapy. Not all clinicians will feel comfortable using measures such as GAD-7 and it is worth remembering the warning of the authors of this paper: there is very limited evidence to suggest that there are improved outcomes or treatment as a consequence of this screening. They have their limitations but this study points out that they do also have their use in a community drug treatment setting in England.
Involvement of general practitioners in managing alcohol problems: a randomized controlled trial of a tailored improvement programme
van Beurden I, Anderson P, Akkermans RP, et al. Addiction 2012;107:1601-11
The aim of this cluster randomised controlled trial was to assess the effect of a multi-faceted improvement programme on GPs' behaviour towards prevention of hazardous and harmful alcohol consumption. It was conducted in general practices in the Netherlands. They managed to get 77 practices to participate with a total of 119 GPs. All the GPs in a practice had to agree to participate and the practices were then randomised to the intervention group and the control group. The intervention group received the improvement programme which consisted of educational training sessions and support visits by a trained facilitator.
They did not get the desired 32 practices to complete the programme - only 28 practices did (there were 29 practices in the control group at the analysis stage). They reviewed data from 6318 patients and 765 (12.1%) of these were at risk. The primary outcomes were the number of eligible patients who received screening and advice. The results showed that there was no significant difference between the groups in terms of screening offered or advice given - the two main outcomes assessed from the medical notes.
Commentary: We have raised in the past, through presentation of various surveys into alcohol management in general practice in the UK, that GPs often feel under-skilled and lacking in the necessary knowledge to manage alcohol problems. On that basis, this study makes sense - a randomised trial of an educational programme that planned to use hard clinical endpoints as the outcomes. Difficulty with recruitment and poor participation (only 20 of the 77 practices met the minimal demands agreed to on enrolment) made it an uphill struggle for the researchers. Perhaps one of the biggest flaws in the study design was the requirement that all GPs in a practice had to participate - there was no scope for just a few to receive training who could then return to practice to cascade skills and act as practice expert.
In addition, it is difficult to see how there wouldn't be some kind of Hawthorne effect here - the well-documented finding that people behave differently when they are being watched. The results did suggest that there was some initial improvement that wasn't sustained but by the end the differences weren't significant. Again, this fits with findings about behaviour change that it can take months or years of reinforcement to achieve persistent alterations in behaviour. There remains little doubt that screening and brief interventions are effective - however, for anyone who has an interest in improving the implementation of these in general practice there are a number of salutary lessons in this paper on the deep challenges that exist to get GPs to deliver improved care around alcohol.
Buprenorphine/naloxone and dental caries: a case report
Suzuki J, Park EM. Am J Addict 2012;21:494-5
This short report discusses the case of a 35-year old female who presented for treatment in 2008. She had a one-year history of prescription opioid misuse culminating in her using up to 160mg oxycodone daily. She had no other history of opiate misuse. She was started on buprenorphine-naloxone and stabilised on 16mg daily. After 18 months of treatment she was discovered to have extensive dental caries. Despite a history of excellent dental hygiene and no change in diet she had experienced a significant increase in decay coinciding with the start of her opiate substitution therapy. She didn't experience any dry mouth or other symptoms of xerostomia at any point.
There are a couple of potential mechanisms for why opiates may cause such problems with dental health. The first is the dry mouth resulting from the reduction in salivary flow. This means the normal role of saliva to alter plaque pH and wash away plaque and debris is compromised. The second is the immunosuppressive effect that opioids are reported to have - there may be a direct role for naloxone to affect this too but it is all rather theoretical and lacking in hard data. There may, and again this is speculative, be an issue with the increased duration of contact with the teeth a sublingual preparation like buprenorphine-naloxone will have.
Commentary: This is only a single case report, so it features low on the evidence hierarchy, but it serves to highlight an important and neglected area - dental health and substance misuse. This case involved prescription opioid misuse so was distinctive in that it was someone who had otherwise good dental health. Community drug teams dealing with homeless, injecting drug users will be more used to seeing people with shattered teeth and oral health in ruination. Dental health remains a Cinderella issue in people with substance misuse. It always seems to be too far down the list of priorities - yet it causes issues with pain, self-esteem and is associated with wider health problems too.
See also the paper on our website on Factors influencing the use of dental health services by substance users: a study paper.