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Supervised injectable heroin for refractory heroin addiction

by Eleanor Kennedy @Nelllor_

This blog originally appeared on the Mental Elf site on 28th August 2015.

Opioid use is the number one reason for seeking substance misuse treatment across 30 European countries. Opioids are drugs derived from the opium poppy and these include the drug heroin (EMCDDA, 2015).

Heroin dependence has negative consequences for both the individual and society as persistent use of the drug is associated with poor health, criminal offences and damaged personal relationships (Ferri et al, 2011). Drug-free treatments and substitution treatments are the two interventions used to overcome heroin dependence.

Methadone is the most common substitution treatment in the EU, however, heroin prescribing is well established in Denmark, Germany and The Netherlands, an option in the UK and Spain, and currently under investigation in Belgium and Luxembourg (EMCDDA, 2015).

A recent systematic review and meta-analysis aims to compare supervised injectable heroin (SIH) as a treatment for heroin users who have not responded to more standard treatments such as methadone maintenance treatment (MMT) or residential rehabilitation (Strang et al, 2015).

NICE guidance recommends the use of methadone or buprenorphine as the first-line treatment in opioid detoxification.

Methods

Electronic databases (PubMed, Web of Science and Scopus) were searched for studies that reported on the effects of SIH treatment in participants with heroin-dependence unresponsive to standard treatments.

The studies had to have opiate use, retention in treatment, mortality and side-effects as outcome variables.

Studies were excluded if they were methodological papers, assessed unsupervised heroin treatment provision, focused on policy aspects, cost effectiveness, community perspectives or patient satisfaction.

The meta-analysis focussed on Mantel-Haenszel random effects pooled risk ratios for SIH treatment compared to the comparison groups.

Results

There were a total of six papers included in the main review and meta-analysis. These studies were based in Switzerland, The Netherlands, Spain, Germany, Canada and England.

All studies explored SIH compared to MMT (oral methadone) in chronic heroin-dependent individuals who have repeatedly failed in orthodox treatment.

The results of rate of retention and the use of illicit heroin following treatment are shown in Table 1. The rates of retention varied across studies, with only one study reporting a lower rate of retention for the SIH group (Van den Brink et al, 2003). The statistical evidence indicated a lower rate of illicit heroin use in individuals receiving SIH treatment in all six studies.

Table 1: Retention in treatment and use of illicit heroin results

Study Retention in treatment Use of illicit heroin
Perneger et al, 1998 SIH 93% vs MMT 92% p = 0.002
Van den Brink et al, 2003 SIH 72% vs MMT 85% P = 0.002
March et al, 2006 SIH 74% vs MMT 68% P = 0.02
Haasen et al, 2007 SIH 67% vs MMT 40% P < 0.001
Oviedo-Joekes et al, 2009 SIH 88% vs MMT 54% P = 0.004
Strang et al, 2010 SIH 88% vs MMT 69% P < 0.0001

Meta-analysis

A meta-analysis was conducted to explore retention in treatment, mortality outcome and side-effects.

  • Retention in treatment was significantly better for the SIH than for the MMT treatment groups as demonstrated by four studies; RR = 1.37, 95% CI = 1.03 to 1.83
  • Mortality was lower in the SIH than in the MMT treatment groups but this was not significant; RR=0.65, 95% CI = 0.25 to 1.69
  • There was a higher risk of side effects in the SIH compared to the MMT treatment groups based on analysis of five studies; RR = 4.99, 95% CI = 1.66 to 14.99

This review provides good evidence that heroin-assisted treatment works for a small group of patients with refractory heroin dependence.

Strengths and limitations

All of the included studies were randomised controlled trials comparing traditional oral MMT to SIH in participants with chronic heroin-dependence who have not been successfully treated. The review followed PRISMA guidelines and was inclusive of all languages and publication dates, so the likelihood of important papers being excluded is minimal.

In this review the authors focussed on supervised administration of heroin only, which contrasts with a 2011 Cochrane Review that also included studies where heroin was prescribed for take-home administration (Ferri et al, 2011). By restricting the inclusion criteria, stronger conclusions can be made about the efficacy of this type of treatment which may guide the introduction of new interventions. Additionally the authors’ address several key misgivings about SIH, which further supports the argument that SIH is an effective treatment for treatment-resistant heroin dependence. For example, the concern that SIH may undermine other existing treatments is countered by the difficulty in recruitment experienced by many of the six trials under review.

There are some limitations, e.g. the safety of injectable diamorphine requires further research as the instances of sudden-onset respiratory depression is at a rate of about 1 in 6,000 injections.

The supervision and administration of SIH makes it more expensive than oral forms of opioid maintenance treatment.

Conclusions

The authors concluded that:

Based on the evidence that has been accumulated through these clinical trials, heroin-prescribing, as a part of highly regulated regimen, is a feasible and effective treatment for a particularly difficult-to-treat group of heroin dependent patients.

The importance of supervision during administration is emphasised throughout the review. As mentioned above, all of the participants engaged in SIH had previously repeatedly failed in orthodox treatment, however, the evidence supports SIH as a treatment option for these individuals.

Will this systematic review and meta-analysis be sufficient for policy makers to start recommending supervised injectable heroin for heroin users who have not responded to other standard treatments?

Links

Primary paper

Strang J, Groshkova T, Uchtenhagen A. et al. (2015) Heroin on trial: systematic review and meta-analysis of randomised trials of diamorphine-prescribing as treatment for refractory heroin addictionBr. J. Psychiatry 2015;207:5-14. doi:10.1192/bjp.bp.114.149195.

Other references

EMCDDA (2015) European Monitoring Centre for Drugs and Drug Addiction. emcdda.europa.eu. 2015. Available at: http://www.emcdda.europa.eu

Ferri M, Davoli M, Perucci CA. Heroin Maintenance for chronic heroin-dependent Individuals. Cochrane Database of Systematic Reviews 2011, Issue 12. Art. No .: CD003410. DOI: 10.1002 / 14651858.CD003410.pub4.

Van den Brink W, Hendriks VM, Blanken P, Koeter MWJ, van Zwieten BJ, van Ree JM. (2003) Medical prescription of heroin to treatment resistant heroin addicts: two randomised controlled trialsBMJ 2003;327(August):310. doi:10.1136/bmj.327.7410.310.

Perneger T V, Giner F, del Rio M, Mino A. (1998) Randomised trial of heroin maintenance programme for addicts who fail in conventional drug treatmentsBMJ 1998;317(July):13-18. doi:10.1136/bmj.317.7150.13.

March JC, Oviedo-Joekes E, Perea-Milla E, Carrasco F. (2006) Controlled trial of prescribed heroin in the treatment of opioid addiction. J. Subst. Abuse Treat. 2006;31:203-211. doi:10.1016/j.jsat.2006.04.007. [PubMed abstract]

Haasen C, Verthein U, Degkwitz P, Berger J, Krausz M, Naber D. (2007) Heroin-assisted treatment for opioid dependence: Randomised controlled  trialBr. J. Psychiatry 2007;191:55-62. doi:10.1192/bjp.bp.106.026112.

Oviedo-Joekes E, Brissette S, Marsh DC, et al. (2009) Diacetylmorphine versus methadone for the treatment of opioid addiction. N. Engl. J. Med. 2009;361:777-786. doi:10.1056/NEJMoa0810635. [Abstract]

Strang J, Metrebian N, Lintzeris N, et al. (2010) Supervised injectable heroin or injectable methadone versus optimised oral methadone as treatment for chronic heroin addicts in England after persistent failure in orthodox treatment (RIOTT): a randomised trial. Lancet 2010;375(9729):1885-1895. doi:10.1016/S0140-6736(10)60349-2. [Abstract] [Watch Prof John Strang talk about the RIOTT trial]

– See more at: http://www.nationalelfservice.net/mental-health/substance-misuse/supervised-injectable-heroin-for-refractory-heroin-addiction/#sthash.hvYELhgt.dpuf

Are changes in routine health behaviours the missing link between bereavement and poor physical and mental health?

by Olivia Maynard @OliviaMaynard17 

This blog originally appeared on the Mental Elf site on 6th July 2015.

While bereavement can occur at any point during the lifespan, it is much more common later in life and is a risk factor for both poor physical and mental health.

While the Mental Elf has blogged previously about the impact of childhood bereavement on mental health, the impact of bereavement on the health of older people can be even more severe, given the ongoing declines in health as a result of their age.

Due to the high prevalence of bereavement in this age group, understanding how bereavement leads to declines in health among older adults is important. Behavioural changes may partially account for these negative health outcomes.

To examine this, Stahl and Schulz (2014) conducted the first systematic review to examine the relationship between bereavement and five routine health behaviours:

  1. Physical activity
  2. Nutrition
  3. Sleep
  4. Alcohol use
  5. Tobacco use

As well as one modifiable risk factor associated with health:

  1. Body weight

This review

Methods

The authors searched databases to find 34 studies which met the following criteria:

  • Quantitative and qualitative studies with either observational or intervention-based designs;
  • Older adults (aged over 50 years) who had experienced the death of a spouse;
  • Health behaviours were assessed.

Results

Physical activity

18 studies: 4 cross-sectional, 8 prospective longitudinal, 5 post-bereavement longitudinal

  • Physical activity was assessed using self-report in all studies and physical activity ranged from social activities such as visiting friends to sports activities.
  • As a result, the evidence was mixed, with bereavement increasing the prevalence of social activities, but decreasing the prevalence of sports. Furthermore, while this pattern applied to bereaved women, bereavement decreased all forms of physical activity among men.

Nutrition

12 studies: 5 cross-sectional, 5 prospective longitudinal, 3 post bereavement longitudinal

  • Nutrition was assessed using a range of self-report questionnaires.
  • There was consistent evidence for a strong relationship between bereavement and increased nutritional risk, including worse nutrient intake and poor dietary behaviours, particularly within the first year of bereavement.

Sleep quality

9 studies: 1 cross-sectional, 0 prospective longitudinal, 8 post-bereavement longitudinal

  • Sleep quality was assessed using both self-report and objective measures such as electroencephalography and actigraphy (measurement of movement using small body sensors).
  • While the self-report studies consistently showed strong support for a link between bereavement and poorer sleep quality, no relationship was observed when sleep disturbance was measured objectively.

Alcohol consumption

7 studies: 2 cross-sectional, 3 prospective longitudinal, 2 post-bereavement longitudinal

  • There was moderate evidence (from longitudinal studies only) that bereavement was associated with increased self-reported alcohol consumption, for both men and women.

Tobacco use

7 studies: 2 cross-sectional, 4 prospective longitudinal, 1 post-bereavement longitudinal

  • Smoking status and frequency of tobacco use was assessed using self-report.
  • There was inconsistent evidence for the impact of bereavement on smoking behaviour, with bereavement reducing smoking frequency among current smokers (particularly men) but increasing the likelihood of smoking initiation among female non-smokers.

Weight status

6 studies: 1 cross-sectional, 5 prospective longitudinal, 0 post-bereavement longitudinal

  • There was consistent evidence across the studies that bereavement led to unintentional weight loss among both men and women.

nutrition, sleep quality and weight status

Limitations and directions for future research

  • The studies were heterogeneous and many did not report effect sizes, meaning that quantitatively assessing them (i.e. using meta-analysis) was not possible.
  • The majority of studies used self-report which may be affected by recall bias. For studies exploring sleep quality, only those which used self-report, rather than objective measures observed a negative effect of bereavement.
  • Few of the longitudinal studies reported the length of the bereavement period or when assessments were taken. Precise information on measurement intervals is important in determining when behavioural changes are most likely to occur and would be important for treatment.

More

Discussion

This systematic review observed:

  • Strong support for changes in nutrition, sleep quality and weight status after bereavement
  • Moderate evidence for an impact on alcohol consumption
  • Mixed evidence for effects on physical activity and tobacco use

Although this review did not explore why bereavement led to these changes in health behaviours, the authors provide a number of explanations, which should be examined in future studies:

  • Loss of social support and the onset of depression and grief. This may reduce motivation to engage in health-promoting behaviours such as physical activity and also exacerbate or trigger physical symptoms such as poor sleep and headaches.
  • Changes in daily routines. Previously shared activities, such as exercise, food preparation or sleeping, may be difficult to maintain following spousal loss.

Crucially, however, this review is only one part of the puzzle. While it shows us that bereavement is associated with changes in health behaviours, we don’t know whether these changes mediate the relationship between bereavement and physical and mental health, the key outcome we’re interested in.

Given the known health burden associated with bereavement, it is critical that we further investigate this link and if this link were observed, interventions could target health behaviours to reduce the impact of bereavement on physical and mental health.

Future studies should explore whether specific health behaviours can reduce the negative impact that bereavement has on our physical and mental health.

Links

Primary paper

Stahl ST, Schulz R. (2014) Changes in routine health behaviors following late-life bereavement: A systematic reviewJournal of Behavioral Medicine, 37, 736-755.

– See more at: http://www.nationalelfservice.net/mental-health/are-changes-in-routine-health-behaviours-the-missing-link-between-bereavement-and-poor-physical-and-mental-health/#sthash.QRsZgV2E.dpuf

Financial incentives for smoking cessation in pregnancy

By Meg Fluharty @MegEliz_

This blog originally appeared on the Mental Elf site on 11th March 2015.

shutterstock_90615607

Smoking during pregnancy is thought to cause approximately 25,000 miscarriages per year in the United Kingdom (Health and Social Care Information Centre, 2010).

Additionally, smoking while pregnant is attributable to 4-7% of stillbirths (Flenady et al., 2011), and 3-5% of infant deaths (Gray et al., 2009) with these rates even higher in deprived areas, where remaining a smoker during pregnancy is more common (Gray et al., 2009).

In 2009, 24% of women attending antenatal appointments in Scotland were smokers (NHS, 2009). However only 1 in 10 reported using cessation services, and 3% were abstaining by four weeks (Tappin et al., 2010).

A recent Cochrane systematic review suggested financial incentives may be beneficial in helping pregnant women stop smoking, although it concluded that further evidence was needed (Chamberlain et al., 2013). Tappin et al (2015) investigated the effectiveness of shopping vouchers in addition to NHS Stop Smoking Services to aid quit attempts in pregnant women.

Nearly 1 in 4 women attending antenatal appointments in Scotland were smokers (NHS, 2009).

Methods 

The authors conducted a randomised controlled trial of 609 pregnant smokers recruited from NHS Greater Glasgow and Clyde. Women were randomly allocated to routine smoking cessation care (control group) or to routine care and up to £400 in shopping vouchers if they engaged with services and successfully quit smoking (incentives group).

Routine care

Routine specialist pregnancy care involved an initial meeting to discuss quitting smoking and set a quit date. This was followed by 4 weekly telephone calls, and free nicotine replacement therapy for 10 weeks.

Incentives group

The incentives group received £50 in shopping vouchers for attending the initial meeting to set a quit date. If participants were smoke-free 4 weeks later, they would receive another £50 voucher, and if smoke-free at 12 weeks, participants received £100 in gift vouchers. Between 34-38 weeks gestation, women were once again asked smoking status, and those who had quit received a final £200 voucher. In all instances, smoking status was verified by a carbon monoxide breath test. 

Women who successfully quit smoking in this study received up to £400 in shopping vouchers.

Results 

  • More women successfully quit smoking in the incentives group (22.5%) than the routine care group (8.6%).
  • There was a higher quit rate at 4 weeks in the incentives group compared to the routine care group.
  • 12 months after quit date, there was still large difference in self-reported quit rates (15% incentives, 4% control).
  • Women lost to follow-up were assumed to be smokers, which was validated by analysing residual routine blood samples for cotinine.

shutterstock_56322052

Summary

This study demonstrated that financial incentives with routine care could be beneficial in motivating quit attempts in pregnant smokers, as well as aiding them in continuing to abstain up to 12 months after their quit date. Furthermore, the quit rates reported in this trial were larger than many pharmaceutical (Coleman et al., 2012) or behavioural (Chamberlain et al., 2013) intervention trials in pregnant women. Although, it should be noted that women in the control group had higher nicotine addiction scores than those in the incentives group.

While the evidence from this study suggests using financial incentives may be beneficial in helping pregnant smokers to stop, there may be practical and ethical issues in implementing this as an intervention.

Additionally, other studies are needed to determine the generalizability and possible cost effectiveness of this intervention, as well as what cessation services are best suited to pair with financial incentives. However, it will be interesting to see how this study may be used to inform future policy.

Links

Tappin D, Bauld L, Purves D, Boyd K, Sinclair L, MacAskill S et al. Financial incentives for smoking cessation in pregnancy: randomised controlled trial (pdf). BMJ 2015; 350:h134

Health and Social Care Information Centre, Infant feeding survey 2010 (pdf). HSCIC, 2012. www.hscic.gov.uk/pubs/ifs2005.

Flenady V, Koopmans L, Middleton P, Frøen JF, Smith GC, Gibbons K, et al. Major risk factors for stillbirth in high-income countries: a systematic review and meta-analysis. Lancet 2011;377:1331-40. [Abstract]

Gray R, Bonellie SR, Chalmers J, Greer I, Jarvis S, Kurinczuk J, et al. Contribution of smoking during pregnancy to inequalities in stillbirth and infant death in Scotland 1994-2003: retrospective population based study using hospital maternity records. BMJ 2009;339:b3754.

Information Services Division, NHS National Services Scotland. Births and babies: smoking and pregnancy, 2009. www.isdscotland.org/isd/2911.html.

Tappin DM, MacAskill S, Bauld L, Eadie D, Shipton D, Galbraith L. Smoking prevalence and smoking cessation services for pregnant women in Scotland. Subst Abuse Treat Prev Policy 2010;5:1.

Coleman T, Chamberlain C, Davey MA, Cooper SE, Leonardi-Bee J. Pharmacological interventions for promoting smoking cessation during pregnancy. Cochrane Database Syst Rev 2012;9:CD010078. [Abstract]

Chamberlain C, O’Mara-Eves A, Oliver S, Caird JR, Perlen SM, Eades SJ, et al. Psychosocial interventions for supporting women to stop smoking in pregnancy. Cochrane Database Syst Rev 2013;10:CD001055

– See more at: http://www.thementalelf.net/mental-health-conditions/substance-misuse/financial-incentives-for-smoking-cessation-in-pregnancy/#sthash.upeNCXSE.dpuf

Welcome to the TARG blog

Hi there everyone!

I’m Suzi Gage, a PhD student in TARG, and an avid blogger. I have a science blog called Sifting the Evidence, which is on the Guardian website. I love writing about science, for a variety of reasons. I believe that since most research conducted in Universities is carried out using money which has ultimately come from the public, we as researchers have a duty to share any results we find. This can be hard due to journals sometimes having paywalls, meaning research isn’t freely available. Also, academic papers are often written in dry technical language which can be confusing or boring to read.

Blogging is a great way of sharing our findings with those people who are interested in what we get up to. We intend to use this TARG blog to do just this, as well as writing posts more generally about the type of research we do, or background summaries of areas of research we are interested in.

If there’s anything you’d like us to cover, do let us know.

A first post will be up soon. Enjoy!

sgbap