SCIENTIFIC
Rapid Micro-dosing to Convert High Dose Methadone to Buprenorphine Maintenance
AUTHORS :
Alexander E . Morgan , MD , Addiction Medicine Fellow , Rockefeller Neuroscience Institute , Department of Behavioral Medicine and Psychiatry , West Virginia University School of Medicine
James H . Berry , DO , Professor , Rockefeller Neuroscience Institute , Chair of the Department of Behavioral Medicine and Psychiatry , West Virginia University School of Medicine
Dorothy Van Oppen , MD , Assistant Professor , Rockefeller Neuroscience Institute , Department of Behavioral Medicine and Psychiatry , West Virginia University School of Medicine
Jeremy D . Hustead , MD , Assistant Professor , Rockefeller Neuroscience Institute , Department of Behavioral Medicine and Psychiatry , West Virginia University School of Medicine
CASE REPORT 1
A 33-year-old female , well known to our inpatient dual diagnosis service for polysubstance use and depression , was admitted for worsening suicidal ideation . She discontinued her duloxetine and aripiprazole for depression at approximately the same time her suicidal ideation developed . She also reported an increase in illicit substance use ( intravenous methamphetamine and heroin / fentanyl ) over the past week despite remaining on a therapeutic dose of methadone ( 195 mg daily ) obtained from a nearby opioid treatment program ( OTP ). The urine drug screen was positive for cannabinoids , methadone , amphetamines , and fentanyl with no other significant laboratory abnormalities .
ABSTRACT
The gold standard of opioid use disorder treatment is the use of medications , specifically maintenance methadone or buprenorphine . The ability to transition patients from methadone to buprenorphine has often proved difficult due to the differing full mu-opioid receptor agonist and partial agonist receptor activity of these respective medications . Over the past decade , micro-dosing methods have been developed , which involve a gradual increase in daily buprenorphine dose with no reduction in the initial daily methadone dose . Once a therapeutic buprenorphine level is achieved , the methadone is discontinued , usually with minimal or no withdrawal symptoms . The cases presented here utilized rapid
The patient had a psychiatric history of recurrent major depressive disorder and multiple substance use disorders ( SUD ), such as opioid , stimulant , sedative , and cannabis . The presentation was complicated by a history of epilepsy . She denied a family history of a mood or psychotic disorder but indicated that her mother had a history of alcohol and stimulant use disorder . After verification of her dose , the patient was restarted on methadone ( 195 mg / day ). The patient was placed back on phenytoin ( 300 mg daily ), gabapentin ( 600 mg twice daily ), and aripiprazole ( 2 mg daily ). Given her stimulant use and depression , she was prescribed mirtazapine ( 15 mg nightly ).
The patient reported prior abstinence from opioids for several years by using sublingual buprenorphine-naloxone ( SL BUP-NX ) before switching to methadone treatment . She admitted to using heroin and fentanyl in increasing amounts despite methadone maintenance . Given her opioid relapses on methadone , she stated an interest in returning to SL BUP-NX . On the third day of admission , she stated she felt symptoms of opioid withdrawal ( chills , nausea , and anxiety ) despite receiving methadone . She was reluctant to stop methadone for several days and then try to be rescued with a buprenorphine induction as per standard conversion practice . Given this reluctance and the typically short nature of inpatient dual diagnosis admissions ,
micro-dosing to convert high-dose methadone ( up to 195mg / day ) to buprenorphine maintenance . Initially , a very low dose ( 0.5- 1.0 mg / day ) of sublingual buprenorphine was administered and rapidly titrated up over six to eight days to a typical sublingual buprenorphine maintenance dose of 16 mg / day . Methadone was then discontinued with minimal withdrawal symptoms noted . These results further support rapid micro-dosing to convert high dose methadone to buprenorphine maintenance . To our knowledge , the starting methadone dose of 195 mg / day in our patient in Case Report 1 is the highest starting methadone dose ever reported using a rapid micro-dosing method .
she was offered a micro-dosing regimen to rapidly convert from high dose methadone to SL BUP-NX maintenance . She consented to the regimen ( Table 1 ), and it was initiated the next day .
On regimen day four , she experienced mild agitation that resolved with oral clonidine . Otherwise , she denied withdrawal symptoms or adverse effects during induction . Additionally , her depression stabilized , and the suicidal thoughts resolved . She was discharged on regimen day eight on the following medications : SL BUP-NX ( 8-2 mg twice daily ), aripiprazole ( 10 mg daily ), gabapentin ( 600 mg twice daily ), phenytoin ( 300 mg daily ), and mirtazapine ( 30 mg nightly ). She was discharged with an outpatient appointment the following week which was maintained on SL BUP-NX .
CASE REPORT 2
A 39-year-old male was admitted to our inpatient dual diagnosis service for paranoia and delusions . The patient was agitated but denied suicidal or homicidal ideation . He had been off his 140 mg / day methadone maintenance dose for 72 hours but had stopped heavy illicit opioid and methamphetamine use approximately
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