Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Tuesday, January 11, 2011

Methadone and Buprenorphine Maintenance Treatment - Overview

Buprenorphine: HDB

High dose buprenorphine or HDB for short - involves the daily use of the opioid mixed agonist/antagonist buprenorphine in a 1 to 32 milligram dose range, to aid in promoting long term abstinence from traditional opioid agonists. The primary ends of HDB with Suboxone or Subutex are as follows:

1) To attenuate opioid withdrawal symptoms; by attatching tightly to opioid receptors and activating them partially thus providing some degree of narcotic effect. Using an agonist-active opioid such as buprenorphine as opposed to an opioid receptor blocking compound such as naltrexone, is more likely to incentivize compliance on the part of the 'patient', increasing the likelihood that he or she remains in "treatment" and continues taking the medication.

2) To reduce or block the effects of other opioids the subject may be likely to administer; buprenorphine attatches itself so strongly to the opioid receptor that most narcotics are unable to bind in its place, and are therefore less likely to produce effects. 

Buprenorphine, as I've discussed in previous entries, does not produce opioid tolerance past a certain level (specifically about 30mg methadone equivalent) due to its partial agonism and pharmacological ceiling. So unlike methadone, dose increase is not necessary past a certain level. This is a crucial consideration, as even after an extended period of use, there is no mechanism of diminishing returns (or clinical tolerance) to incentivize subjects to increase their dose. The law of diminishing returns experienced by those using opioid agonists often reinforces the compulsive pattern of dose escalation exhibited by many narcotic users.

Methadone: MMT

MMT (Methadone Treatment) is popularly assosiated with heroin addiction. This is increasingly no longer the case, and the assumption is for the most part false. Methadone is used to maintain addiction to various opioids; including morphine, heroin, oxycodone, hydromorphone, fentanyl, etc. MMT has been the classic clinical approach to serious narcotic addiction for over 40 years now, and is based on the principles of "harm reduction" and the "addictive disease" model. Like buprenorphine maintenance, MMT is beneficial in that it offers a socially legitimized means of maintaining a narcotic dependent lifestyle without fear of prosecution.

Methadone Maintenance Treatment, or MMT for short - involves the daily use of the opioid agonist methadone, to promote a reduction in high risk opioid use, particularly by the intravenous route. The ultimate ends of methadone maintentance treatment are as follows:

1) To keep opioid withdrawal symptoms at bay while reducing physiological or emotional craving for other opioids by providing a consistent degree of narcotic effect. Methadone is a mu opioid full agonist with effects similar to similar morphine and heroin.

2) To create a state of hyper tolerance (increased opioid tolerance to an excess point) - This reduces the risk of a fatal overdose in the case that a subject takes other opioids, and serves to disincentivize supplemental drug use by attenuating most of the "rush" produced by other narcotics. At doses of 40 to 70mg or greater, methadone inhibits the euphoric effect opioids taken by the intravenous route - Think of it this way; with methadone already saturating the brain's mu opioid receptors in excess and producing a relatively strong degree of narcosis itself, the introduction of heroin to the brain will do little to increase the current state. A 'rush' is perceived typically when opioid receptors rapidly change from a state of vacant non-activity to a state of moderate to full activity. In addition, as previously explained, tolerance has been increased by the methadone to the point that the typical dose of heroin or morphine would have little effect either way.

Additionally, the pharmacokinetic properties of methadone contribute to its blocking abilities - Taken in high doses, methadone may completely saturate available mu opioid receptors; due in part to its structural characteristics and its particlarly extensive lipophilic distribution. With all opioid receptors occupied and maximally activated, the addition of heroin or morphine is unlikely to produce any additional morphinomimetic effect.

Methadone, being a typical opioid agonist, will produce a steady level of tolerance which will continue to increase over time with each increase in dose. The need for upward dose escalation is perpetual, infinite. The primary problem this presents in my eyes would be; in the case of the dose ceilings that certain clinics or doctors have in place by their own policy. Fortunately, these limitations have become less common over time, and it is common to see patients on doses upwards of 300mg daily.

The decision to discontinue MMT should be reached mutually between the patient and the physician. MMT should be viewed as a means of long term palliation or "harm reduction" rather than a curative measure or even a "treatment". 

Regarding discontinuation of MMT, the product literature for methadone (Mallinckrodt) says the following:

"For Medically Supervised Withdrawal After a Period of Maintenance Treatment There is considerable variability in the appropriate rate of methadone taper in patients choosing medically supervised withdrawal from methadone treatment. It is generally suggested that dose reductions should be less than 10% of the established tolerance or maintenance dose, and that 10 to 14-day intervals should elapse between dose reductions. Patients should be apprised of the high risk of relapse to illicit drug use associated with discontinuation of methadone maintenance treatment."

Methadone VS Buprenorphine - Pros & Cons

Each appoach has its relative advantages and disadvantages. A choice between methadone or buprenorphine should generally not be based exclusively on an individual's tolerance level, however; buprenorphine may or may not provide sufficient attenuation of withdrawal in IV drug users, or in cases of severe dependence to potent opioids such as oxymorphone or fentanyl.

In terms of convenience, buprenorphine may provide a favorable option especially to those living in isolated areas without nearby methadone clinics. 

Buprenorphine is able to be prescribed in an office based, outpatient setting - for example, a family physician, psychiatrist, or internist; where as Methadone as a class II drug is highly regulated, and only authorized for us in a specially licensed facility such as a 'Methadone Clinic' - With new patients required to visit the clinic daily for each dose; and even after a solid patient history has been established, patients may recieve no more than 1 to 2 weeks worth of 'take home' medication with each visit (federal law puts the max supply at 30 days).

Treatment using buprenorphine may appeal to its own particular demographic due to the obvious fact that visiting a doctors office does not carry the stigma or stereotype of waiting in line at a methadone clinic.

Treatment with buprenorphine tends to be more expensive than the methadone route; Physicians who offer HDB often charge substantial fees, both for the initial visit and for subsequent regularly scheduled visits. Some Doctors require patients to visit the office bi-weekly or even weekly in some cases during the first several months of HDB; there is likely of course a profit motive in this.

Methadone is very cheap to manufacture and has been on the market for nearly 100 years, with a number of brand name and generic forms available in the US (and around the world). Prices of MMT tend to be lower than those of HDB treatment; though many methadone maintenance patients recieve treatment through Medicaid or by other federal/state funded means. 

Suboxone - The buprenorphine/naloxone preparation - has yet to see a generic released, and this is not likely to happen anytime soon.

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