Opioid substitution and withdrawal — induction, COWS, pregnancy (MEQ)

(i) COWS and immediate care. The COWS is a clinician-administered instrument that rates eleven common opiate withdrawal signs or symptoms, and the summed score assesses the level of withdrawal. Buprenorphine, a partial agonist, can precipitate withdrawal in highly dependent patients who are not yet in withdrawal.^[1]

Do not reach for an α2-agonist as the plan. NICE says methadone or buprenorphine should be offered as the first-line treatment in opioid detoxification, and clonidine should not be used routinely.^[9] The safety of lofexidine in pregnant women has not been established.^[14]

(ii) OAT choice. Methadone retains patients in treatment and decreases heroin use better than treatments without opioid replacement.^[2] Buprenorphine retains people at any dose above 2 mg and suppresses illicit opioid use at 16 mg or more; with flexible dosing, methadone retains more people than buprenorphine.^[3] NICE: if both drugs are equally suitable, methadone should be prescribed as the first choice, and both should be given daily under supervision for at least the first 3 months.^[10]

Methadone induction. Give the first dose under supervision when there is no sedation or intoxication and she shows withdrawal. An initial single dose of 20 to 30 mg will often suppress withdrawal, and the initial dose should not exceed 30 mg; for same-day adjustment, wait 2 to 4 hours, then give an additional 5 to 10 mg if needed. Methadone levels accumulate over the first several days, and deaths have occurred in early treatment from cumulative effects. Most commonly, clinical stability is achieved at 80 to 120 mg/day.^[11]

Buprenorphine induction. To avoid precipitated withdrawal, induct only when objective and clear signs of withdrawal are evident. For patients dependent on short-acting opioids who are in withdrawal: on Day 1, up to 8 mg/2 mg buprenorphine/naloxone in divided doses; on Day 2, a single dose of up to 16 mg/4 mg. The maintenance dose is generally 4 mg/1 mg to 24 mg/6 mg per day.^[12]

(iii) Pregnancy and the partner. NICE: for women who are opioid dependent during pregnancy, detoxification should only be undertaken with caution.^[9] Methadone clearance may be increased during pregnancy, so her dose may need to be increased or the dosing interval decreased.^[11]

Neonatal counselling. Neonatal opioid withdrawal syndrome is an expected and treatable outcome of prolonged opioid use in pregnancy; advise her of the risk and ensure that treatment will be available.^[12] In MOTHER (175 pregnant women), neonates exposed to buprenorphine needed less morphine (1.1 versus 10.4 mg), had a shorter hospital stay (10.0 versus 17.5 days) and a shorter duration of treatment for neonatal abstinence syndrome (4.1 versus 9.9 days) than those exposed to methadone; more women stopped buprenorphine (33% versus 18%).^[4] The Cochrane review concludes that methadone and buprenorphine may be similar in efficacy and safety for opioid-dependent pregnant women and their babies, but the evidence is too small for firm conclusions.^[5]

(iv) Naloxone and benzodiazepines. Strongly consider prescribing an opioid overdose reversal agent such as naloxone when buprenorphine/naloxone is started, because people treated for opioid use disorder can relapse and overdose.^[12] Use of opioids with benzodiazepines or other CNS depressants may cause profound sedation, respiratory depression, coma and death.^[11] If she is also benzodiazepine dependent, NICE says consider benzodiazepine detoxification.^[9]

(v) Mortality counselling. Pooled all-cause mortality was 11.3 versus 36.1 per 1000 person-years in and out of methadone treatment, and 4.3 versus 9.5 in and out of buprenorphine treatment. The induction phase onto methadone and the time immediately after leaving either treatment carry particularly increased mortality risk.^[6] After a non-fatal overdose, methadone maintenance (adjusted HR 0.47) and buprenorphine (adjusted HR 0.63) were associated with decreased all-cause mortality.^[15] NICE asks that people be told about the loss of opioid tolerance after detoxification and the increased risk of overdose and death that follows.^[9]