Buprenorphine Treatment

History of Buprenorphine for Opioid Addiction Treatment

Buprenorphine is a semi-synthetic opioid which was first marketed in the 1980s by Reckitt & Colman (now Reckitt Benckiser) as an analgesic. It was available in the form of both a sublingual tablet and an injectable solution. In 2002, the Food and Drug Administration (FDA) approved two buprenorphine products for use in opioid addiction treatment in the United States. The two medications approved were Subutex®, the medication containing only buprenorphine, and Suboxone®, the buprenorphine/naloxone combination medication. In 2007, Suboxone (buprenorphine/naloxone) was approved by Health Canada for the treatment of opioid-related disorders, joining methadone as one of the two drugs to be offered as a treatment option for opioid addiction in Canada.

How Buprenorphine Treatment Works for Opioid Treatment

Buprenorphine is an opioid partial agonist, meaning that although buprenorphine is an opioid and can produce typical opioid agonist effects such as euphoria and respiratory depression, its effects are less than those of full agonists like heroin and methadone. When taken at low doses, buprenorphine produces sufficient agonist effect that allows opioid-addicted individuals to discontinue the use of other opioids without experiencing withdrawal symptoms. The agonist effects of buprenorphine increase with increasing doses of the drug until at moderate doses, in the range of 16-32mg for sublingual tablets. At this dose range, the agonist effects of buprenorphine reach a plateau and no longer continue to increase with further increases in dose. This is phenomenon is commonly known as the ‘ceiling effect.’ Buprenorphine is metabolized by the liver and has a half-life of 24-60 hours. This long duration of action may allow some patients to be able to dose every other day, as opposed to the daily dosing required in methadone treatment.

Buprenorphine has a poor oral bioavailability and a moderate sublingual bioavailability. Currently, all formulations of buprenorphine authorized for used in the treatment of opioid addiction are in the form of sublingual tablets. Due to its low bioavailability and ceiling effect, buprenorphine carries a lower risk of abuse, addiction, and side effects compared to full opioid agonists. If administered at a high dose to an opioid-addicted individual while a full agonist is in the bloodstream, buprenorphine can actually block the effects of full opioid agonists and produce withdrawal symptoms. This is an intense form of opioid withdrawal and is commonly called ‘precipitated withdrawal.’ This does not occur in everyone who has a tolerance to full-agonist opioids, but rather depends on the severity of dependence and time elapsed from the last dose.

Buprenorphine maintenance treatment commonly involves three phases: induction, stabilization, and maintenance. The induction phase is the medically monitored start-up of buprenorphine therapy. Buprenorphine is first administered when an opioid-addicted individual has abstained from using opioids for 12-24 hours and is in the early stages of opioid withdrawal. This is done to ensure that the buprenorphine does not cause the patient to enter into acute precipitated withdrawal. Treatment may continue as an observed therapy in the physician’s office or the patient may be prescribed up to an one-month supply for self-administration, depending on the judgement of the physician. During the stabilization phase, the dose is adjusted until a patient has either discontinued or greatly reduced the use of other opioids and is no longer experiencing cravings. Once a steady dose is reached, the patient enters the maintenance phase. The length of time of the maintenance phase will vary from patient to patient and for some it may continue indefinitely.

After spending some time in buprenorphine maintenance at a stable dose, a patient may decide they are ready to gradually taper off of the buprenorphine. As described, the length of time this requires varies considerably from one patient to the next and a percentage of individuals will continue treatment indefinitely. Determining to taper off buprenorphine and eventually discontinue treatment is definitely a large decision and it is important that you have the right mindset about it.

The Purpose of Naloxone for Opioid Addiction Treatment

Due to its opioid agonist effects, buprenorphine is abusable, especially by individuals who aren’t physically dependent on opioids. In buprenorphine/naloxone medications such as Suboxone, the drug naloxone is combined with buprenorphine to decrease the likelihood of diversion and abuse of the combination product. Sublingual buprenorphine has a moderate bioavailability, while the bioavailability of sublingual naloxone is very poor. Consequently, when the buprenorphine/naloxone tablet is definitely administered sublingually by an opioid-dependent individual, the buprenorphine opioid agonist effect predominates, while the naloxone does not precipitate opioid withdrawal.

However, when naloxone is definitely administered via injection, it has a very good bioavailability. If the sublingual buprenorphine/naloxone tablets are crushed and injected by an opioid-dependent individual, the naloxone effect predominates and may trigger acute precipitated withdrawal. Buprenorphine by itself can also cause precipitated withdrawal in opioid-dependent individuals. However, this will only occur under certain conditions, such as a short time interval between a dose of opioid agonist (e.g., methadone) and a dose of buprenorphine, and with higher doses of buprenorphine.