Selincro (Nalmafene): new medication for the alcohol dependent patient in primary care

In this guest post, Dylan Kerr Clinical Nurse Manager at HAGA explores Selincro, a new medication recently licensed in England and Scotland to aid treatment for alcohol for alcohol problems.

Selincro (Nalmefene) is a newly licensed medication aimed at treating mild “alcohol dependence”. It is produced by Lundbeck Pharmaceuticals who over recent years have been carrying out a range of alcohol activities including sponsorship of NHS and other organisations in the alcohol field.

Selincro has undergone three studies looking at its efficacy in drinking risk level (DRL). This term includes having a significant score on the Severity of Alcohol Dependence Questionnaire (SADQ) and drinking more than:

• 5 units in a drinking day if female
• 7.5 units in a drinking day if male

Doing so is considered a “Heavy Drinking Day” (HDD), a definition used throughout this research. Once a threshold of “HDDs” is reached then the participants were considered to have a sufficient “DRL” to be included in the study. Those patients with physical withdrawals, psychiatric co-morbidities, who were over 65 years old and those with significant liver or renal impairment were excluded.

The studies carried out an initial screen using SADQ and HDD’s. Patients were then re-screened 1-2 weeks later. If they retained a high enough DRL then they were started on Selincro whilst receiving a psychosocial intervention called “BRENDA”. BRENDA is an American acronym similar to FRAMES (common in IBA practice in the United Kingdom). Lundbeck indicate that this intervention lasts 5-10 minutes and was administered monthly throughout the study – for up to 6 months. All studies had control groups who received a placebo and the psychosocial intervention.

The three studies had several significant features:

There was a significant improvement in DRL between screening and re-screening 1-2 weeks later, which could be attributed to ‘brief intervention’ (‘IBA’) effects. This was present in all studies and meant that those who no longer had a significant DRL (average daily consumption dropped below the limits outlined above). This initial brief intervention effect was: 18% and 33% in two different studies respectively.

Another feature was the similarities of improvement between the control and the Selincro groups in the trials. All improved their DRL (by reducing it) in the studies. For example in Study 2 – at 6 months the DRL reduction was 30% for the Selincro group and 28% for the Control. In Study 3 – at 12 months the Drinking days total had dropped from 19 days to 7 days in a month with Selincro cohort, compared with 19 days to 10 days in a month with the Control cohort.

In this post there are four areas that I’d like to explore in relation to Selincro and implications for the treatment of alcohol problems.

Is Selincro’s “Alcohol Dependence” different to a clinicians definition of alcohol dependence?

Alcohol Dependence is indicated by several measures – ICD-10, DSM-V being the comprehensive diagnostic manuals for the condition. There are identification tests such as SADQ, which Lundbeck recommend for the GP or prescriber to identify potential patients. However the key exclusion criteria for Selincro is those experiencing physical withdrawal symptoms - often what many people associate with alcohol dependence. Indeed many treatment services have been focused on prescribing alcohol withdrawal medications such as benzodiazepines for physically dependent drinkers.

By excluding those with physical withdrawal symptoms, Lundbeck are targeting a large sub-section of the alcohol dependent population; those only with psychological dependency. In fact most increasing or higher-risk drinkers with some level of psychological dependency will not have physical dependency (people tend to develop physical dependency later). As a result many will be unaware they have some degree of psychological dependency and would be very often be surprised or even offended by the suggestion of being ‘alcohol dependent’.

In my role, we see those scoring between 15-25 on the AUDIT identification test who could also be assessed as having mild-moderate  or ‘psychological’ symptoms of alcohol dependence. The symptoms reported are usually: compulsion to drink, acquired tolerance to alcohol, narrow repertoire of drinking, and salience of their drinking over other responsibilities or duties.

Such mildly dependent drinkers can be helped by structured alcohol treatment, often anchored by motivational interviewing. ‘Keyworking’ or regular monitoring of progress with the patient over several weeks (maybe months) by a trained professional is also a key feature. 

Untill the arrival of Selincro mildly dependent drinkers have not been prescribed medication - unless they’ve abstained and wanted to prevent themselves from drinking again (in the cases of NICE-approved Acamprosate and Disulfiram). Selincro therefore targets a group of drinkers who are not typical of notions of alcohol dependence or prescribing.

IBA – the power of this alone to affect change in patient’s alcohol behavior

Identification and Brief Advice (IBA) has a long history of 56 studies showing its efficacy, low-cost and influence in a variety of settings. The Selincro medication has a re-assessment criteria following a patient screening positive for alcohol dependence. This is as the Selincro trials showed a significant proportion of patients (18% and 33% in two different studies respectively) reduced their drinking in the 1-2 weeks following screening without taking the medication.

This could be seen as IBA having its well-described effect on patients. Also, as highlighted already, the level type of alcohol dependent population we are looking at excludes those with physical withdrawals. I would arguably call it the higher risk drinking groups (as identified using AUDIT scores 16-19), and possibly some range either side of this.

Psychosocial interventions: the major driver of the drinking behavior change seen in Selincro’s studies?

In the studies the patients were started on Selincro whilst receiving a psychosocial intervention called “BRENDA”. BRENDA is an American acronym similar to FRAMES which underpins most IBA delivery in the UK. We’ve been told that this intervention lasted 5-10 minutes each session in the studies and was given monthly throughout the study – up to 6 months. All studies had control groups who received a placebo and the psychosocial intervention.

A striking feature of the studies was the similarities of improvement between the control and the Selincro groups in the trials. All groups improved their DRL (drinking risk level), by reducing consumption of alcohol in the studies. For example in Study 2 – at 6 months the DRL reduction was 30% for the Selincro group and 28% for the Control. In Study 3, at 12 months the Drinking days total had dropped from 19 days to 7 days in a month with Selincro cohort, compared with 19 days to 10 days in a month with the Control cohort.

Will all treatment services deliver the psychosocial support needed or will they prescribe the medication on it’s own?

Already guidance has been issued in Scotland, and is being explored in Haringey where I work in North London. The issue we are focusing on is ensuring that the structured psychosocial support is delivered as a fundamental part of the medication. Ongoing prescribing will be hard to justify beyond twelve months, as treatment for this sub-section of the alcohol dependent patient group shouldn’t normally last that long.

As a result, we’ll be working to a 3-month timeframe and then review of prescribing with any Selincro patient. If non-attendance of psychosocial sessions occurs, then communication with the prescriber (GPs usually) will take place immediately to prevent the medication being given alone. There is a risk that if such standards aren’t followed, prescribing continues where there is no evidence that Selincro alone is effective (without psychosocial interventions). At £3.03 a dose, this cost could be significant across the population.

Comments

[Peter]

I am profoundly disappointed but not particularly surprised to find that the hype surrounding Selincro seems to be based more on the skills of Lundbeck's PR department than on a substantial medical breakthrough.

As someone for whom psychosocial intervention has not been successful but who would otherwise fit the criteria for Selincro, the revelation that there was very little difference in outcome between the Selincro groups with intervention and the control groups with intervention was disheartening.

I instinctively see medication as a last resort and you and Niamh Fitzgerald (comment #2) have together persuaded me there is precious little evidence that Selincro is likely to be of any benefit for someone for whom psychosocial intervention has proved ineffective.

Disappointed, yes, but grateful to you for providing the evidence to allow me to see through the hype.

[James Morris]

Some really important issues raised here. Also a good SMMGP post with some similar points

http://www.smmgp.org.uk/blog/?p=106

[NiamhCreate]

My comments on this excellent piece were so extensive that I have posted a blog to accommodate them on www.alcoholiba.com