is a ceiling effect for buprenorphine on euphoria and respiratory depression . 7 , 8 The risk for overdose death is thus minimized in comparison to other opioids , including methadone . 7 In addition , buprenorphine itself is unlikely to result in cardiac arrhythmias when there is no predisposition . 9
In the maintenance treatment of OUD , buprenorphine is typically administered sublingually , which avoids the first-pass effect on the drug . 4 It can also be administered once monthly , in a depot form , by subcutaneous injection . 4 The typical sublingual maintenance dose of buprenorphine is 8-16 mg / day . 4 Buprenorphine is combined with naloxone , a mu-opioid receptor antagonist , in commonly prescribed formulations to minimize diversion or misuse . 7
Reasons for converting from maintenance methadone to buprenorphine vary but include side effect profile , individual preference , and logistical considerations . Rapid buprenorphine micro-dosing typically begins with the administration of a sublingual buprenorphine dose of < 2.0 mg / day on day one . 10 , 11 The daily dose of buprenorphine is then gradually increased over three to 10 days until a daily maintenance dose , typically 8-16 mg / day , is achieved . 10 , 11 The initial full methadone dose is administered on each day of the micro-dosing regimen until a buprenorphine maintenance dose is achieved . 10 , 11 The methadone is then discontinued , commonly without significant withdrawal symptoms , as reported by several published articles . 10 , 11 Other methods to convert from methadone use to buprenorphine maintenance without significant withdrawal symptoms have been described . These methods include use of bridge medications such as fentanyl , hydromorphone , or slow-release morphine to replace methadone and avoid precipitated withdrawal while the sublingual buprenorphine is being titrated . 12-14 Other literature describes the use of a buprenorphine patch to deliver the medication rather than sublingual buprenorphine . 15
The cases reported here suggest that even at very high initial doses of methadone , rapid micro-dosing to convert to buprenorphine maintenance can be achieved with minimal withdrawal symptoms . In the literature , there is one article that reports buprenorphine micro-dosing starting at 220 mg / day of methadone . 16 The complete methadone taper and buprenorphine induction process took 123 days to complete , which is impractical in most settings . 16 The starting methadone dose for our patient in Case Report 1 of 195 mg / day appears to be the highest starting methadone dose ever presented using a rapid micro-dosing method .
CONCLUSION
Our cases support the approach of using a rapid micro-dosing method to switch patients from high dose methadone to buprenorphine maintenance therapy . The utility of this treatment is corroborated by the absence of significant withdrawal symptoms . Further well controlled trials to evaluate and compare various transition methods should be considered .
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