Should we be prescribing medication to help people with alcohol use disorders?

This post was originally written by Andrew Jones for the Mental Elf. You can see the original here.

Alcohol Use Disorders (AUDs) are common, chronic conditions which cause substantial harm to the individual and society. They are associated with substantial morbidity (Schuckit, 2009) and responsible for approximately 4% of all deaths annually. The approximate cost of AUDs to the National HEALTH Service is upwards of £3 billion per year.

Less than one-third of patients with AUDs will receive any treatment and an even smaller number (<10%) will be prescribed medications to assist in reducing their alcohol use. There are a number of FDA approved medications for AUDs such as acamprosate, disulfiram and naltrexone. However, various barriers exist for health-care professionals prescribing these medications including a lack of familiarity and a lack of confidence in their effectiveness.

A recent systematic review and meta-analysis published in the Journal of the American Medical Association, set out to examine the benefits and harms of pharmacotherapy for adults with AUDs (Jones et al, 2014).

Methods

The authors searched databases (including the Cochrane Library, Pubmed etc) for relevant studies from January 1^st 1970 to October 11, 2013. They also searched for unpublished studies using various trial registration platforms and requested data from medication manufacturers.

In order to be included in the analyses studies had to include adults with AUDs who were treated with an FDA approved or off-label medication for at least 12 weeks in an outpatient setting. The studies were required to assess either:

1. Alcohol consumption,
2. HEALTH outcomes (i.e. accidents, mortality etc), or
3. Adverse effects of the medication.

Results

One hundred and twenty three studies were included in the meta-analysis, with a total of 22,803 PARTICIPANTS. All the studies except one were randomised controlled trials. The majority of the studies assessed acamprosate or naltrexone alone or in combination with repeated behavioural interventions.

Both acamprosate and naltrexone were associated with complete abstinence from alcohol

Consumption measures

• Acamprosate was associated with:
  • An increase in total abstinence from drinking (Number needed to treat (NNT) = 12, 95% Confidence Interval (CI) 8 to 26; Risk difference (RD) -0.09; 95%CI, -0.14 to -0.04)
  • But not in abstinence from heavy drinking
• Oral naltrexone was also associated with:
  • An improvement in total abstinence from drinking (NNT = 20, 95% CI, 11 to 500; RD, -0.05; 95%CI -0.10 to -0.002)
  • Abstinence from heavy drinking (NNT = 12, 95% CI, 8 to 26; RD -0.09; 95%CI, -0.13 to -0.04)
• Injectable naltrexone was only associated with a reduction in heavy drinking days (Weighted Mean Difference = -4.6%, 95% CI, -8.5% to -0.56%)
• A comparison between acamprosate and naltrexone found no statistically significant differences between the two medications on alcohol consumption measures
• Disulfiram demonstrated no significant improvements in alcohol consumption measures
• There was some evidence that off-label drugs such as nalmefene and topiramate were associated with reductions in alcohol consumption measures (fewer heavy drinking days)

Health outcomes

There was insufficient evidence to examine whether treatments lead to an improvement in HEALTH outcomes.

Adverse effects

Again, there was insufficient evidence to examine potential adverse effects. However, the authors noted that for most of the specific adverse effects in head-to-head studies, estimates favoured placebo.

Do these results give clinicians and patients the evidence they need to make prescribing decisions?

Conclusions

The use of pharmacotherapy as a TREATMENT FOR AUDs is underutilized (Harris et al, 2010) but may lead to clinically beneficial results. Both acamprosate and naltrexone were associated with complete abstinence from alcohol, and naltrexone was also associated with a reduction in heavy drinking days. There was also some limited evidence for off-label prescriptions of topiramate and nalmefene.

A recent commentary (Bradley et al, 2014) suggests that ‘no single treatment is superior to all others’ and many health-care professionals do not fully explore the treatment options for AUDs. These findings demonstrate that patients should be offered individual treatment options, including medications shown to be effective through evidence.

There are some limitations to the current research. Only trials with at least 12 weeks of treatment were eligible. However, such short treatment periods may yield misleading conclusions about benefits in the long term. Furthermore, the authors suggest that most studies included were at a moderate risk of bias, i.e. selective or incomplete reporting of important variables within studies.

In conclusion, the authors suggest their findings have the potential to inform clinicians and health-care providers who are reluctant to prescribe medication for AUDs. Future research should focus on establishing the efficacy of pharmacotherapy for AUDs in patients for which controlled-drinking, rather than complete abstinence, is a realistic goal.

Links

Jones, D.E., Amick, H.R., Feltner, C., et al (2014). Pharmacotherapy for adults with alcohol use disorders in outpatient settings: a systematic review and meta-analysis. The Journal of the American Medical Association, 311(18), 1889-900.

Bradley, K.A., Kivlahan, D.R. (2014). Bringing patient-centered care to patients with alcohol use disorders. The Journal of the American Medical Association, 311(18), 1861-2

Harris, A.H., Kivlahan, D.R., Bowe, T., Humphreys, K.N. (2010). Pharmacotherapy of alcohol use disorders in the Veterans Health Administration. Psychiatric Services, 61(4), 392-8.

Schuckit, M. Alcohol-use disorders. Lancet, 2009 Feb 7, 373 (9662), 492-501.

Research Roundup Spring 2014

Welcome to the latest research roundup from the Addiction Research Group based in the Department of Psychological Sciences, University of Liverpool. As ever, we have been working hard over the past few months on many different research topics, and in this blog post we have condensed some of our recent publications and activities into bite-size portions for your enjoyment. 

The first two publications reported investigations of how our drinking behaviour is influenced by that of other people.

A study conducted in our bar lab was published in Alcoholism: Clinical and Experimental Research. We examined how social acquaintances influence each other’s alcohol consumption using a confederate design. A pair of social drinkers was invited to the laboratory, and one of them (the confederate) was secretly informed to choose either alcoholic or soft drinks when offered them by the experimenter. Both individuals were subsequently offered drinks to consume while they played a game together (the popular ‘4 pics 1 word’ game). The key variable of interest was the amount of alcohol that the naïve participant chose to consume. We found that naïve participants were strongly influenced by their acquaintance’s choice: if the confederate chose alcoholic drinks, the naïve participant was much more likely to choose them as well. Furthermore, the majority of participants believed that their drinking was not influenced by their partner’s choices. This study was the first to use the confederate design in individuals who knew each other before the study, and it has important implications for the psychological mechanisms that underlie effects of imitation on drinking behaviour. The study was conducted by Rebecca Dallas, an undergraduate psychology student who is first author on the paper. The paper was the topic of a press release and it was covered by several print and online media outlets, including the Metro and science website RedOrbit.  The research was also covered by some other unexpected news sources, including ‘RealBollywood’, which surprised and excited us (mostly the former).  

The second paper, by Eric Robinson and colleagues, was published in Substance Use and Misuse. This Internet study investigated if there is an association between perceived drinking norms and usual drinking behaviour in UK students.  We also included interventions to correct misperceptions about the drinking behaviour of others, and increase intentions to drink responsibly. We found that peer drinking was associated with individual differences in drinking: individuals who believed other students drank responsibly also drank responsibly. However, interventions based on accurate norm messages did not influence intentions to drink responsibly, possibly because they were not seen as credible. This study adds to a growing literature suggesting that social norm interventions may have limited efficacy in reducing hazardous drinking in UK students.  

Speaking of bite-size portions, we have diversified from only studying alcohol. We recently published two papers that examined the motivation to obtain and consume chocolate and pizza. 

The first paper by Charlotte Hardman and colleagues was published in Appetite. This research continued previous work by our group (see here and here) examining whether the anticipation of receiving a reward, in this case delicious cheese and tomato pizza, would influence physiological (salivation) and attentional responses in hungry participants. Whilst there was no evidence for any effects of anticipation on salivation, we demonstrated that anticipation influenced initial attentional processing of pizza pictures. While this result wasn’t quite as clear cut as our previous studies with beer and chocolate, it does suggest that anticipation of reward plays a role in attentional bias for rewarding cues.  

Our second snack-themed paper was published by Jessica Werthmann, Matt Field and colleagues in Journal of Behavior Therapy and Experimental Psychiatry. In this study we examined whether manipulating attention towards or away from chocolate using a modified anti-saccade task could influence craving and consumption of chocolate. We found that participants who shifted attention towards chocolate cues subsequently ate more chocolate during an ad-libitum taste test compared to those shifted their attention away from chocolate.  These findings suggest that training attentional bias away from food-cues can reduce consumption of that food, although in other papers we have been sceptical about the clinical applications of ‘attentional bias modification’, particularly in addiction.

Last but no means least, Jasna Martinovic and colleagues published a paper in PLoS One (we support open access!). In this study we examined electrophysiological correlates of Pavlovian-to-Instrumental transfer (PIT) in individuals who regularly drink beer and eat chocolate. PIT is the phenomenon whereby drug-cues evoke an anticipation of drug reward and thereby increase instrumental responding for drug reward. The brain mechanisms that underlie PIT effects are poorly understood and this was the focus of this study. We examined whether electrophysiological indices of the motivational salience of beer and chocolate pictures (the P300 and Slow Potential) would be associated with behavioural PIT responses for beer and chocolate rewards. We found clear behavioural PIT effects and some indication of increased Slow Potentials in response to the beer and chocolate pictures, but unfortunately these were not related to each other. Possibly, behavioural PIT effects are generated by subcortical structures that cannot be detected using EEG, or maybe we just didn’t use the right method. 

As well as writing papers we also like to get out and see the world, all in the name of science of course...

Inge Kersbergen, Jay Duckworth and Natasha Clarke attended Alcohol Research UK’s first postgraduate and early career symposium in London in March. Natasha and Inge both gave oral presentations. Inge presented her own study, ‘Visual attention to health information on alcoholic drinks containers’ which was an eye-tracking study examining responses to warning labels on alcohol drinks containers, and Natasha presented the paper, ‘Alcohol-induced risk taking on the BART mediates alcohol priming’ which we discussed in a previous roundup. 

Matt Field discussed the role of attentional bias in addiction at the ‘Maastricht symposium on the role of attentional bias in psychopathology’, in March. After the conference, our former (temporary) colleague Jessica Werthmann successfully defended her PhD thesis, for which we offer our congratulations!!

That is all for this research roundup. Thank you for reading! As always, if you would like to get in touch about anything featured here please contact Prof. Matt Field, and if you are interested in taking part in our research please contact Andy Jones

Illicit drug use: personality and poverty

 This post was originally written by Paul Christiansen for the Mental Elf. You can see the original here.

A considerable amount of research has attempted to shed light on the key antecedents of drug use. The role of personality traits, in particular, has been explored in great detail; indeed the idea of “the addictive personality” has often been discussed.

Although we elves feel that the addictive personality is a simplification of a much more complicated problem (Kerr, 1996), there is no doubt that certain personality traits are associated with drug use, for example personality traits such as impulsivity reliably predict substance misuse (Verdejo-Garcia, 2008).

Lower socioeconomic status is a risk factor for drug use

Of course drug use does not occur in isolation purely driven by an individual’s traits; complex social and economic factors also influence the expression behaviour. For example, living in relative poverty is associated with increased drug use (Degenhardt, 2012).

The current study (Sutin, 2013) investigates which of the big five personality traits (Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness) predict opiate and cocaine use. The authors also investigate whether poverty mitigates or increases the impact of these personality traits on drug use in an urban population.

Methods

Participants were taken from the Healthy Aging in Neighbourhoods of Diversity across the Life Span (HANDLS) study (Evans et al., 2010). This is a larger study that aims to investigate the affects of race and socioeconomic status on major health issues in the US.

The 412 individuals described in the current study were from the Baltimore area, 66% were female, 55% African-American, and 50% were living below the federal poverty line.

Participants were included in the current analysis if they had given information on use of opiates, cocaine, and completed the Revised NEO Personality Inventory (NEO-PI-R). This questionnaire assesses the big 5 personality domains (Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness) as well as 30 sub factors.

Results

• Drug use prevalence was high; 98 participants were classified as current users of cocaine and/or opiates (opiates only = 27, cocaine only = 40, both = 31)

Heroin and cocaine use was associated with low Agreeableness and high Neuroticism

• As expected, lower scores on Agreeableness (OR 0.54, 95% CI = 0.40 to 0.74) and Conscientiousness (OR 0.66, 95% CI = 0.53 to 0.83) were associated with increased likelihood of drug use
• Higher levels of Neuroticism were also associated with an increased likelihood of drug use, (OR 1.24, 95% CI = 1.05 to 1.46), indeed drug use was associated with all neuroticism subscales (anxiety, hostility, depression, impulsivity and vulnerability to stress) except for Self-Conscientiousness
• Interestingly, poverty was a significant moderator of the impact of Conscientiousness on drug use (OR 1.05: 95% CI = 1.01 to 1.10). Specifically, decreases in Conscientiousness were associated with increased likelihood of drug use only in those above the federal poverty line
• Openness was associated with drug use in females only
• Race and age did not moderate the impact of personality on drug use

Conclusions

Drug use was found to be associated with personality traits, particularly Agreeableness, Conscientiousness and Neuroticism. Low Conscientiousness (the tendency to lack discipline and act without thinking) was only associated with drug use in more affluent individuals. The authors suggest that the impact of poverty on drug use is so great it overwhelms the contribution of the Conscientiousness trait to drug use.

Low Conscientiousness was also associated with drug use in more affluent individuals

Of course this study does not shed light on whether individual differences in personality traits are a cause or consequence of drug use. Indeed, the authors acknowledge this as a limitation and argue for the importance of longitudinal research in this area, with continued assessment of personality along with changes in socio-economic status.

This certainly makes interesting reading and really highlights the role of society, rather than just the individual, in the aetiology of drug abuse.  It is, however, disappointing that the authors did not look at the direct association between poverty and drug use.

Links

Sutin AR, Evans MK, Zonderman AB. Personality traits and illicit substances: the moderating role of poverty. Drug Alcohol Depend. 2013 Aug 1;131(3):247-51. doi: 10.1016/j.drugalcdep.2012.10.020. Epub 2012 Dec 21. [PubMed abstract]

Degenhardt L, Hall W (2012) Extent of illicit drug use and dependence, and their contribution to the global burden of disease. The Lancet 379: 55-70. [Abstract]

Kerr JS (1996) Two myths of addiction: The addictive personality and the issue of free choice. Human Psychopharmacology 11: S9-S13. [ResearchGate]

Verdejo-Garcia A, Lawrence AJ, Clark L (2008) Impulsivity as a vulnerability marker for substance-use disorders: Review of findings from high-risk research, problem gamblers and genetic association studies. Neuroscience and Biobehavioral Reviews 32: 777-810. [PubMed abstract]

Evans MK, Lepkowski JM, Powe NR, LaVeist T, Kuczmarski MF, Zonderman AB. Healthy aging in neighborhoods of diversity across the life span (HANDLS): overcoming barriers to implementing a longitudinal, epidemiologic, urban study of health, race, and socioeconomic status. Ethn Dis. 2010 Summer;20(3):267-75.

Research Roundup Winter 2014

Welcome to the latest research round up from the Addiction Research Group based in the Department of Psychological Sciences, University of Liverpool. We have been working very hard over the winter months (because typing keeps hands warm in badly heated offices), and this is what we have produced…

We have published three review papers covering a broad range of topics in addiction. 

The first by Pawel Jedras and colleagues, published in Neuroscience and Neuroeconomics (open access) examined the role of drug anticipation in addiction and reward. They examined the available evidence, discussing the necessary role of drug expectancy in conditioned responses to drug-related cues, the role of impulsivity and the underlying neural circuitry of anticipation. Finally, they provided a discussion of how perceived drug availability can lead to poor treatment responses and what might be done to mitigate this. 

Our second review was by Margot Peeters (who visited us from the Netherlands) with Matt Field. They conducted a narrative review, published in Alcohol and Alcoholism, summarising the evidence base for cognitive impairments in heavy drinking adolescents, with an emphasis on elucidating any causal relationship(s). They examined both cognitive impairments and impulsivity as risk factors for alcohol use in youth, but also the possibility that heavy drinking may cause further cognitive impairments and impulsiveness due to neurotoxic effects on the brain. 

Our final review paper was by Andy Jones and colleagues, published in Frontiers in Psychiatry (open access). The aim of this review was to identify the psychological and environmental variables that may cause state changes in (dis)inhibition leading to increases in drinking and drug use. Some of these variables include stress, self-control depletion and exposure to cues. They concluded that identifying these variables and targeting them for treatments may help reduce the risk of heavy drinking, drug use and relapse. 

We have also published some interesting original research:

Paul Christiansen published a paper in Drug and Alcohol Dependence demonstrating that individualised stimuli may increase the predictive validity of attentional bias tasks. Using a Stroop task containing words related to the individual’s favourite drink, they found performance predicted variance in drinking above and beyond performance on a Stroop using general alcohol words. This paper was a direct follow up to a commentary Paul and Matt published in 2012. 

Abi Rose and colleagues published a paper in Psychopharmacology, investigating the relationship between alcohol-induced risk taking using the Balloon Analogue Risk Task (BART) and urge to drink. They found that alcohol increased risk taking and urge to drink. Furthermore, it was found that risk taking after alcohol consumption mediated alcohol priming, suggesting that those susceptible to alcohol-induced risk taking may be more likely to drink excessively, due to an increased urge to drink.

In other news, we have been travelling around the country to disseminate our research. 

The addiction group is a core member of the UK Centre for Tobacco and Alcohol Studies (UKCTAS), a leading centre of tobacco and alcohol research and policy excellence. The inaugural meeting of UKCTAS in York in September was attended by Matt Field, Abi Rose, Eric Robinson, Jay Duckworth, Lisa Di Lemma and Inge Kersbergen.

Matt Field attended the Society for the Study of Addiction conference in York in November and gave an invited talk on the contributions of basic science to our understanding of addiction.

Andy Jones, Eric Robinson and Matt Field also attended the UK Society for Behavioural Medicine (UKSBM) in Oxford in December.  Andy gave a poster and short oral presentation discussing ‘Response Inhibition in everyday life. Validating a mobile version of the Stop-Signal Task’. Eric gave an oral presentation entitled ‘GPs don't know what obesity looks like and this reduces their likelihood of initiating treatment’. Congratulations to Eric, who was awarded a prestigious early career award at UKSBM.

We also attended the North West Alcohol Conference, at the Hilton hotel in Liverpool in November. Jay, Inge and Natasha did an excellent job of summarising the conference highlights here

Finally, Matt is working as an advisor for Alcohol Concern’s Dry January campaign. If you are taking the challenge yourself and finding it a bit of a struggle, you can log on to the Facebook page or follow the Twitter feed for advice, details here

That is a wrap for this research roundup. Thank you for reading! As always, if you would like to get in touch about anything featured here please contact Prof. Matt Field, and if you are interested in taking part in our research please contact Andy Jones.

It's Christmas!

This post was originally written by Natasha Clarke and taken from her personal blog, which you can find here.

So Christmas is over once more. It’s been a month of overindulgence and excessiveness particularly with alcohol, made acceptable simply by using the phrase “It’s Christmas”. I’ll give you some examples:

1. My Grandma replacing her morning tea with sherry
2. My orange juice (alright 3 orange juices) containing more bubbly than fruity goodness.
3. My friend drinking a whole bottle of wine on the train before arriving on New Year’s Eve. On his own.

These are things that are not normal in everyday life; if I started every day with a bucks fizz I’d have a serious problem. Yet, over Christmas, it is almost weird not to do these things. Thankfully it’s not just me; as a nation we drink 41% more in December than the monthly average. Furthermore, a recent survey of over 2000 adults by the British heart foundation (BHF) found that 58% of Britons think it is standard behaviour to drink by 1pm on Christmas day, and 16% want to have a tipple earlier, at 11am. I’m also guessing many of these first drinks will be top-ups from the night before, after a Christmas Eve spent drinking at the pub.

There are many explanations as to why we consume more alcohol: tradition, sociability and relaxation are an obvious handful. However, reasons may not always be so celebratory. For example the survey mentioned previously found that 9% of people drank so they did not feel left out of family celebrations, and this rises in the older generation, with 12% consuming alcohol on Christmas Day to fit in. I can emphasise this using a conversation my Grandma had with a teetotal family member- “You don’t drink?” – “I don’t like people who don’t drink, they’re boring”. Thankfully this didn’t lead to him reaching for the whiskey bottle, but pressure by others can be a core reason for non-drinkers changing their behaviour on this special day. Another reason for increased drinking is pressure and stress, with one in five of those surveyed by the BHF consuming more than they would usually to help them de-stress.

What does this overconsumption mean? Starting with the bleak death statistics, figures in 2010 and 2011 where the underlying cause was alcohol and drugs were 13% above the daily average between December the 21^st and January 19^th. Some of these deaths are due to drink driving; in 2012 the Association of Chief Police Officers (ACPO) Christmas anti-drink and drug driving campaign showed 7123 drivers tested positive, failed or refused their breathalyser. Being over the limit significantly increases reaction times and therefore your risk of crashing. There is also the “holiday heart phenomenon”, this is the incidence of cardiac arrhythmias following excessive alcohol consumption, which most often occur on Mondays (e.g. after a particularly heavy weekend) or between Christmas and New Year’s Day. These are grave facts which may only affect a minority of us, but are extremely important to keep in mind.

Of course there are aspects of increased consumption likely to relate to all of us. Firstly there are the things we do when drunk that we wouldn’t usually, when the excitement of the festive period lead to illness, injuries or a night spent in a cell for being drunk and disorderly. To highlight this on Mad Friday Manchester Police used the hashtag #MadMancFriday on Twitter to expose some of the humiliating and regrettable things we get up to on the biggest night out before Christmas. Then there are long term effects on our body, a month of overindulgence leads to noticeable effects on our appearance. In particular I’m referring to the extra weight that slowly creeps up on us. We eat more, we don’t exercise, and we are too hung over to exercise. Although many of these calories are more attributable to the box of quality streets and the dozen mince pies, a lot of them can be due to alcohol’s empty calories. For example: three glasses of Buck’s fizz, one bottle of red wine, three beers, one baileys and one port equates to just under 2000 calories, nearly a woman’s daily allowance. It’s also around 25 units, more than the recommended allowance in a week for both males and females.

Obviously overindulgence is something of a normality when it comes to Christmas and New Year celebrations, and it definitely wouldn’t be as joyous if we spent our time calculating our units and calories, replacing our champagne with Schloer and our roasties with a salad. But, it’s fascinating just how much our behaviour can change depending on the time of year. All I can say is thank the lord for Dry Jan and post-Christmas diets.