Guidelines for inducing pregnant patients to methadone have been well-established in several publications (CSAT, 1993
; Kaltenbach et al., 1998
). One must ensure the patient is not concurrently using other drugs that could increase the risk of over-sedation. Care should also be taken to avoid increasing the dose too quickly or slowly to minimize overdosing and to forestall potential premature termination from treatment due to the inability of the medication to alleviate withdrawal, respectively. The quality of the therapeutic alliance with the health care providers initially established during assessment can help with retention.
The initial daily dose of methadone should be 10 to 30 mg. The lower dose may be suitable for women who are primarily dependent on short acting oral opioids such as codeine, hydrocodone and oxycodone. If the patient should experience withdrawal within a few hours, additional doses of 5 to 10 mg every 4 to 6 hours while the patient is awake may be administered for breakthrough withdrawal. It is vital not to misinterpret nonspecific distress associated with life situation or pregnancy as withdrawal or withhold needed methadone if bone fide withdrawal is present. It takes 4–5 days to reach steady state for methadone. Thus, caution must be used to base dose increases on symptoms at peak methadone levels (i.e., 2–4 hours after administration) rather than how long the effects last; otherwise, as methadone accumulates over the first 3 to 7 days, overdose may occur (Srivastava & Kahan, 2006
). Therefore, total daily doses should not be increased any more frequently than every 3 to 5 days. The dose should be titrated up to the optimal dose where the patient experiences no withdrawal for at least 24 hours after a dose, uses no other opioid and experiences minimal or no cravings. A standardized assessment of withdrawal such as the Clinical Opiate Withdrawal Scale (COWS) (Wesson & Ling, 2003
) or Clinical Institute Narcotic Assessment Scale for Withdrawal Symptoms (CINA) (Peachey & Lei, 1988
) is helpful to quantify withdrawal. However, some withdrawal symptoms (e.g., nausea, back ache etc.) overlap with pregnancy symptoms and no instruments are currently available to disentangle the two medical conditions. This is where clinical judgment supersedes assessment tools. Often a patient who has experienced opioid withdrawal previously when not pregnant can guide the prescribing care provider with whom an effective therapeutic alliance has been established.
For buprenorphine, the more complex pharmacology (mu partial agonist/kappa antagonist) may make induction more challenging, especially if the patient is actively using at the time of first assessment. If the first dose of buprenorphine is administered too soon after the last opioid intake (prior to manifestation of clinical symptoms of opioid withdrawal which can be numerous hours if long acting opioids were used) or in too high a dose, there is a potential for significant precipitated withdrawal. As with methadone, if the buprenorphine dose is too low, it may not relieve withdrawal symptoms completely or for 24 hours until the next dose is due (e.g., Lintzeris et al., 2001). Unlike methadone, buprenorphine has the added complexity of possibly precipitating withdrawal.
In opioid-dependent pregnant patients in the second trimester, transition from slow-release morphine or methadone to buprenorphine resulted in a “transient dysphoric mood status” that was observed for two days, similar to reports in non-pregnant patients (Eder et al., 1998
). Similar to non-pregnant patients, allowing at least six hours between short-acting opioids and buprenorphine administration (i.e., a time when some objective signs of opioid withdrawal are present) was found to improve the tolerability of induction onto buprenorphine (Jones et al., 2005a).
Identifying the optimal timing of the initial buprenorphine dose for patients taking long-acting opioids (e.g., MS Contin®, OxyContin®, methadone) is more difficult. The few reports of transferring opioid-dependent pregnant women from methadone directly to buprenorphine (which we are not recommending at this time) indicate that it is possible (but not advised) to transition pregnant women in the second or third trimester from oral methadone (up to 85 mg) doses to sublingual buprenorphine (up to 12 mg). The major complaint due to this transition was dysphoric mood (Fischer et al., 1998
) and “clear headed” status (Jones et al., 2006b
Our own experience with pregnant women has shown that rapid induction onto 12–14 mg of buprenorphine in 2–3 days can be accomplished in pregnant women (e.g., Jones et al., 2005b
; Fischer et al., 2006
). Ideally, doses should be based upon the severity of opioid dependence. The safety of buprenorphine makes it less likely to result in sedation.
Regardless of whether patients are inducted onto methadone or buprenorphine, ancillary medications that are safe for use during pregnancy and may ease the common symptoms of withdrawal are listed. Acetaminophen (Tylenol®) is given for aches and pains. Antacids (Tums®) are given for indigestion. Loperamide (Imodium A–D®) may be given for diarrhea. Docusate sodium (Colace®) may be given for constipation. Hydroxyzine (Vistaril®) may be given for anxiety or restlessness. Diphenhydramine hydrochloride (Benadryl®) may also be given for anxiety and restlessness. Educating patients regarding behavioral methods to control some symptoms may minimize medication use.