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Managing the risk of methadone toxicity during initial dose titration

Dr William flannery's article Harm reduction the key to managing problem drug users in the May issue (Practitioner 2007;251[1694]:99-106) makes many good points but I feel some of the statements are misleading.

I am a GP with a lot of experience in looking after drug misusing patients in a shared care framework. I also work as a GPwSI for drug misuse for my local PCT/DAT and help supervise a local enhanced service across 25 practices.

The pharmacokinetics of methadone are complex and its half-life varies considerably. This is a bugbear in initial dose titration and can lead to potential tissue saturation and toxic levels during the first week of therapy if the initial dosing frame is set too high.

Drug Misuse and Dependence – Guidelines on Clinical Management1 gives a sensible frame, recommending: "In general, the initial daily dose will be in the range of 10–40 mg. If neuroadaptation (ie tolerance to opiates) is present then the usual daily dose is 25–40mg. If tolerance is low, or uncertain, then 10–20mg is more appropriate. Care is needed in starting a dose greater than 30mg because of the risk of overdose."

Dr Flannery gives no suggested dose frame for initial titration, but goes straight on to talk about methadone maintenance doses, stating that "an effective dose is usually 60-120mg a day". This risks perpetuating one of the biggest misunderstandings I have to correct in my GP colleagues' prescribing – the fact that the initial dose required bears little resemblance to the ultimate maintenance dose needed. If GPs misread this as a sanction to start patients on 60mg or more of methadone, they run a significant risk of fatal overdose.

The Maudsley Addiction Profile is validated for use in secondary care and as such transfers poorly to primary care. It is unwieldy to deliver in general practice and I feel that GPs should be encouraged to use a simpler framework, such as a 5-day recall with targeted questions looking at longer periods for drugs of first and second choice, and alcohol. One criticism of NTORS is its reliance on 90-day recalls, as the memory of intoxicated individuals may lapse fairly quickly. A year is certainly expecting too much.

Dr Flannery states: "Blood testing is mandatory before commencing a patient on opiate substitution". This is not regarded as practical, particularly in primary care.

The drug misuse and dependence guidelines recommend that "urine analysis should be regarded as an adjunct to the history and examination in confirming drug use, and should be obtained at the outset of prescribing and randomly throughout treatment. Results should always be interpreted in the light of clinical findings, as false negatives and positives can occur."

Urinalysis, with a sound history and examination, is generally accepted as suitable and is both sensitive and specific as an indicator of heroin dependence.

Dr Flannery comments on motivational interviewing, referring to the essence of the technique as being to acknowledge "the positive aspects of drug use, which then encourages the patient to look at the negative aspects". This counterattitudinal stance is indeed an element of motivational enhancement therapy. The main drive is to enhance self-efficacy and the wherewithal to change. However, emphasising positives about addiction is a technique that, if used ill-advisedly and in isolation, may encourage continued use.

Dr David Davies, Regional training lead for London, RCGP Substance Misuse Unit

Dr William Flannery replies:

I would like to thank Dr Davies for making these useful comments. The article was not intended to be interpreted as guidelines, but as a guide to progress in the treatment of problem drug misusers. Since the article was published, in May, there have been further developments.

Many of the points on methadone prescribing raised by Dr Davies are explored by the National Treatment Agency for Substance Misuse (NTA) in their consultation document to update the current guidelines, which was released in June 2007.2

The NTA wants to update the guidance for a number of reasons, which includes bringing it into line with the NICE guidance and the consensus statement on doctors' competencies in substance misuse treatment issued by the RCPsych and RCGP in 2005.3

The document states that managing the risk of methadone toxicity during initial dose titration requires a balance between giving an effective dose, reducing the risk of toxicity and rapidly responding to the patient's need for appropriate treatment to ensure retention.

The NTA has developed a treatment outcomes monitoring instrument (TOP, see opposite page). The outcomes are based on four domains; drug and alcohol use, physical and psychological health, social functioning and criminal offences and involvement. The NTA believes that this instrument is simple and effective.

The TOP tool has been available since June 2007 and the NTA expects that all services will use it. From October 2007, the National Drug Treatment Monitoring System (NDTMS) will be requesting TOP scores from services.

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