AT Forum: Your protocol for pregnant patients at the Bi-Valley clinic calls for giving split methadone take-home doses. How do you manage the safety issues involved?
Dr. McCarthy: Take-home doses clearly need to be monitored. What’s most important is to know every patient in the program, and her home situation. This is where a dedicated pregnancy counselor is invaluable. One counselor, closely in touch with the mother, can discuss the mother’s status with the physician every week, and they can work out the safety issues together.
We usually start split-dosing very early in treatment, because maternal metabolism is accelerated almost immediately after conception. That’s remarkable, but we’ve documented that it occurs.
Patients can be trained to split the take-home dose into two or three roughly equal doses. This is best done in a group setting, but it doesn’t have to be.
We obtain what’s known in regulatory language as an SMA-168 Exception Request. It allows a patient to take home part of her dose. Usually this “split-dosing” starts within a week or several weeks after the patient enters treatment, but in some cases we may decide to wait longer.
AT Forum: Do any special issues of trust emerge when you give take-home doses?
Dr. McCarthy: These women are not irresponsible when they have appropriate care, and they understand that the take-home dose is for their baby’s safety. So of course they can be trusted. They are not the bad people they are often portrayed as being. We can trust them if we work closely with them.
AT Forum: How often do the women return for clinic visits after they’re given take-home doses?
Dr. McCarthy: State and federal regulations determine the frequency of clinic visits. What our protocol changes is that we add split-dosing; we don’t add visits. So, technically, each woman has a take-home, but only for part of her daily dose. And she must comply with the clinic visit schedule set by regulations.
AT Forum: Can other opioid treatment programs follow your protocol for their pregnant patients?
Dr. McCarthy: Yes, absolutely. All programs can use multiple-dose regimens. Both federal and state regulators will approve special-exception take-homes—if they’re assured that the program physician is closely monitoring the patient, and if they’re given access to research showing that split doses are better for fetal health and stability.
To help document the need for split dosing, programs can send two references to regulatory authorities: 1.) Wittmann BK, Segal S. A comparison of the effects of single- and split dose methadone administration on the fetus: ultrasound evaluation. Int J Addict. 1991;26(2):213–218; and 2.) Bogen DL, Perel JM, Helsel JC, et al. Pharmacologic evidence to support clinical decision-making for peripartum methadone treatment. Psychopharmacology (Berl). 2013;225(2):441–451.)
AT Forum: The costs involved in treating NAS are another consideration, with total hospital charges estimated to be more than $40,000 for each newborn.
Dr. McCarthy: These cost figures are aggregate numbers. There is no way of knowing anything about who the mothers were, whether they were in treatment or not, pain patients or patients with substance use disorders. I suspect numbers for appropriately managed patients would be less. They would be much less if rooming-in was used for most mothers. That would avoid the emotional trauma to the mother of separation from her baby, and avoid the worsening of NAS that occurs when it the baby is also separated and placed in an NICU environment, which is not conducive to minimizing symptoms.
AT Forum: When OTPs follow your protocol, how often should they monitor pregnant patients’ methadone levels?
Dr. McCarthy: I suggest monitoring every four to six weeks during pregnancy—even though we’re making dose increases based solely on maternal symptoms. Frequent monitoring assures doctor and patient that the dose increases are necessary to compensate for an increase in maternal metabolism of methadone. They do not mean that the fetus is “getting more methadone.” The exact schedule depends on how often we need to increase the dose in order to keep mother and fetus out of the withdrawal stage.
We try to measure serum methadone levels again about one to three weeks before delivery. This allows us to anticipate the typical postpartum increase. And it enables us to compare prepartum and postpartum serum levels after delivery, and to use those levels as a guide to dose reductions.
AT Forum: You monitor the mothers’ methadone levels before the morning methadone dose—that is, you monitor the trough methadone levels only, is that correct?
Dr. McCarthy: Yes, morning levels, every four to six weeks, trough levels only, because we’re splitting the dose, to eliminate the big swings between peaks and troughs. We do not consider those swings of opiate exposure to represent a normal physiologic state for the fetus.
Measuring the mother’s serum levels helps us monitor maternal metabolism and fetal exposure. In fact, measuring the serum level—certainly not the dose—is the only way to monitor fetal exposure. Levels must stay below 600 ng/mL, the upper range Dr. Vincent Dole established many years ago.
We consider all maternal serum levels below 600 ng/mL to be safe for the fetus. So, within this range, we adjust the mother’s dose, based on her clinical symptoms. We don’t use arbitrary dose ceilings.
AT Forum: Does insurance cover the costs of monitoring methadone levels?
Dr. McCarthy: The measurements should be covered by insurance as therapeutic drug monitoring. Medicaid covered the cost for the eligible patients in our study. The measurements actually aren’t expensive, although some labs charge unconscionable fees. So it is best to contact the lab that does the clinic’s urine drug testing, or a local lab, to get the best rate.
Because this is an important quality-assurance issue, programs should pay for these blood tests if insurance doesn’t cover them. With the relatively small number of pregnant patients, total costs will be minimal. A potential problem is getting patients to a lab if an on-site phlebotomist isn’t available to draw blood. Scheduling the tests may need to be coordinated with scheduling routine obstetric lab tests.
AT Forum: The results of your study are impressive: Only 29 percent of the newborns needed treatment for neonatal abstinence syndrome, compared to 60 percent to 80 percent in previous studies that used single, lower doses of methadone. Looking back, what do you consider the most important finding from your study?
Dr. McCarthy: It’s the fact that our data, along with what others have learned separately and reported in the medical literature, simply do not support the use of single doses of methadone—at least not after the first trimester. After that time, the fetus is opiate-dependent and susceptible to intrauterine withdrawal problems.
Yet single-dose regimens are still common during pregnancy; they were used, for example, in the National Institute of Drug Abuse study comparing methadone and buprenorphine (the 2012 NIDA MOTHER study).
So, given the results of the current study, we can say that multiple daily doses, given frequently enough to minimize maternal withdrawal symptoms, appear to offer substantial benefits to both mother and child. Patients on the protocol very much appreciated the flexibility the protocol provided, allowing them to meet their individual dosing need. They had high recovery rates, and their babies had low rates of NAS treatment.
For information on the SMA-168 Exception Request: http://dpt.samhsa.gov/regulations/exrequests.aspx.