SPECIALIST PHARMACOLOGICAL & BIOCHEMICAL INTERVENTIONS

The process of tolerance testing enables clients to be inducted onto a 'holding dose' of methadone which prevents withdrawal symptoms, within a period of one week. This is in contrast to the duration of the induction period with GP prescribing, which can take weeks or even months. During this extended period, clients are likely to be using illicit opiates on-top of their prescription in order to prevent withdrawal symptoms, thereby putting themselves at risk and decreasing their GP's willingness to continue the prescription. The provision of a specialist tolerance testing service is thus likely to both directly improve clinical outcomes and the engagement of GPs with shared-care schemes.

The objective of the induction period is to prescribe a dose of methadone which prevents withdrawal symptoms, and to do this as safely and as rapidly as possible. This is in contrast to the stabilisation period (which follows the induction period and aims to ameliorate the euphoric effects of heroin through the prescription of doses larger than those merely required to prevent withdrawal).

The tolerance testing procedure has evolved as a consequence of the pharmaco-kinetic profile of methadone; the variables of note are the elimination half-life of 10

to 150 hours (most commonly between 24 and 40 hours), and the time to peak plasma concentration following a single dose which is 3 to 4 hours. The long half-life means that with a daily dosing schedule, the next day's dose will add to the remnants of the previous day's dose; thus plasma methadone levels for a given daily dose, will continue to rise until steady state is reached after about one week.Awareness of the time to peak plasma concentration after a single dose (3 hours) is useful in that it enables judgments regarding the client's overall response to be made at this time, thus directing the need for dose changes. In particular, the fact that that trough levels at steady-state will nearly always be greater than plasma levels at 3 hours after the first dose, indicates that clients not withdrawing at this point should achieve a satisfactory initial stabilisation within a week or so, without further dose increases.

IN PATIENT TOLERANCE TESTING

In-patients may be started on a maximum of 30mg methadone, which can then be topped up 4 hourly by increments of 10mg until they are no longer in withdrawal.

The total dose given in the first 24 hours can then be given on a once daily basis thereafter, or split to provide a twice-daily regime.

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The above information is copyright of Dr Bruce Trathen MBBS MRCPsych (2006). ISBN 0-9545164-0-0. The author grants permission for these guidelines to be downloaded, copied and distributed freely, but does not grant permission for their sale.