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Pregnant patients with substance use disorder want to do what’s right for their pregnancy, and as clinicians, we need to be supportive and acknowledge our patients courage and vulnerability to seek help. But, what are the best treatments for the various substance use disorders in pregnant women, and which substances have the highest potential for producing negative pregnancy outcomes? 

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Published On: 12/10/2021

Duration: 18 minutes, 2 seconds

Referenced Article: “The Pregnant Patient With Substance Use Disorder,” The Carlat Addiction Treatment Report, July/August 2021

Noah Capurso, MD, MHS, and Ariadna Forray, MD, have disclosed no relevant financial or other interests in any commercial companies pertaining to this educational activity.

Transcript:

Dr. Capurso: Pregnant patients with substance use disorder want to do what’s right for their pregnancy, and as clinicians, we need to be supportive and acknowledge our patients courage and vulnerability to seek help. But, what are the best treatments for the various substance use disorders in pregnant women, and which substances have the highest potential for producing negative pregnancy outcomes? The latest issue of The Carlat Addiction Treatment Report contains an interview with Dr. Ariadna Forray. She’s an associate professor of psychiatry at Yale and does research on treatments for pregnant and postpartum patients with substance use disorders. Clinically, she’s the interim chief of the Section of Psychological Medicine at Yale New Haven Hospital, and works with patients in their adult sickle cell clinic In this podcast, Dr. Forray and I will unpack the aforementioned questions on how to treat substance use disorder in pregnant women, and the negative pregnancy outcomes associated with the use of different substances. 

Welcome to The Carlat Psychiatry Podcast. This is a special episode from the Carlat Report’s Addiction Treatment team.

I’m Noah Capurso, the Editor-in-Chief of The Carlat Addiction Treatment Report. I’m an assistant professor of psychiatry at the Yale University School of Medicine. I’m also the medical director of the Detoxification & Addiction Stabilization Service and the Psychosocial Residential Rehabilitation Program at the West Haven Veterans Administration Hospital.

Dr. Forray, can you describe the scope of addiction in pregnancy? What’s the prevalence of substance use in pregnancy?

Dr. Forray: So depending on what data you look at, in general, anywhere from 8 to 10% of women use alcohol during pregnancy. About a similar percentage use cigarettes. Historically, cigarette use is a little bit higher at about 16%, but over the last few years it has decreased. 

In terms of prescription opiates, around 2.5% of women use prescription opiates. So you can see from that that the majority of the substance use in pregnancy has to do with legal substances, and that’s not including cannabis. And in some states it’s legal, and that would actually probably make the majority of the substance use in pregnancy be alcohol, cigarettes, cannabis, followed by prescription opiates. But if we focus just on the federal, legally-defined illicit substances, we see that it’s about 6% of women use some illicit substance, predominantly marijuana followed by cocaine, heroin, and amphetamines, and much, much lower use of other substances like hypnotics and psychedelics, etc., and inhalants.

Dr. Capurso: Before we address the possible treatments for substance use disorders in pregnancy, Dr. Forray and I will present the potential negative pregnancy outcomes associated with certain substances. Let’s start with cigarette smoking in pregnancy. 

Dr. Forray: So this is the area that got me interested in treatment for substance use disorder right because it’s one of the most common substances used in pregnancy, and it has one of the worst outcomes in terms of pregnancy outcomes and actually some impacts in terms of the long-term cognitive effects, you know some attention deficits in children. There are some studies that show there’s an associated increased risk of schizophrenia for infants exposed to smoking in pregnancy. So again it’s one of those things that people are like “Oh, smoking is okay.” Well, no it’s one of the worst ones. And it’s one of the hardest ones for women to actually stop using.

So we did a prospective study following women who weren’t engaged in treatment over pregnancy and followed them for two years. We did a behavioral intervention which ultimately didn’t make much of a difference, unfortunately, in terms of outcomes. But that allowed us to actually look prospectively. And we saw that women who used alcohol, who had a cannabis use disorder or cocaine use disorder or tobacco use disorder the ones that used alcohol 96% of them managed to stop using; cocaine and marijuana were mid-70s. Only 32% of women that were smokers managed to achieve abstinence in pregnancy. A lot of them cut back significantly. Somebody might have been smoking a pack or half a pack a day; they might have cut back to like 2 or 3 cigarettes per day but they still couldn’t quite quit. And unfortunately, we don’t have any good treatments for it other than contingency management. So the gold standard is behavioral interventions or behavioral counseling. 

So the one thing actually that’s honestly not a teratogenic effect, but it’s actually one of the most concerning risk factors of women who smoke is actually postpartum. So smoking in the mother postpartum increases the risk of SIDS (sudden infant death syndrome) three fold. So it’s sort of one of the more well-known and well-established risk factors for SIDS. We don’t know much about sudden infant death syndrome, but we know that if you smoke you’re gonna increase your risk of having that happen.

The other things that you worry about, I mean there’s a lot of pregnancy-related outcomes that are related to smoking. So preterm delivery, ectopic pregnancy, placental abruption, and placental previa – all the risks are increased in women that smoke. And also one of the things that is most concerning is fetal growth restriction so the babies just don’t gain enough weight and don’t grow well. 

Dr. Capurso: What about THC and stimulants? How do they affect pregnancy outcomes? Let’s start with cannabis.

Dr. Forray: We do know that there are some adverse effects. A lot of them are related to the amount that women use. So the women who use regularly and heavily there’s definitely a correlation with developmental delays in the infant. With cannabis there’s also some concern about some birth outcomes. They are not as severe as say stimulants or tobacco, for example, but you do have an increased risk of preterm birth, low birth weight, small-for-gestational age, and a slightly increased risk for placental abruption. And there’s a recent study that looked at this and showed that there’s also an increased risk of NICU admission for infants exposed to cannabis that’s in some of the newer data in studies looking at you know in states where recreational marijuana use has been legalized.

Stimulants are the worst when it comes to pregnancy outcomes. 

So while, for example, smoking might increase the risk of placental abruption, you know, anywhere from it might double the risks – stimulants triple the risks right. So again you have a lot of more concerns and it’s just because of the nature of the stimulants right; they’re vasoconstrictors and that can cause a lot of trouble in terms of the placenta and placental blood flow, but you know you do have to have all the same things in terms of preterm delivery, placental abruption, placenta previa – those are all the same things that you see with stimulants. It’s just that the increase in that risk is much higher – and low birth weight. So it’s almost a four-fold increase in low birth weight and a much higher – it’s like 3.4 fold increase in preterm delivery.

And in terms of the stimulant in terms of long-term developmental effects, you again see a lot of the hyperactivity, behavioral dysregulation, and some of those issues – some cognitive delays as well with those infants that were exposed.

Dr. Capurso: Many prescribers, especially those without expertise, can be hesitant to prescribe medications for substance use disorders in pregnant patients. And their hesitancy is not without good reason. Other than for opioids, we don’t have studies that have evaluated the efficacy of most medications for addiction in pregnancy. In fact, the safety profile of many of these medications is, in a way, a secondary issue, because we don’t know if they work in pregnancy at all. 

For example, what can we do for pregnant patients with alcohol use disorder?

First things first, there’s a sense in the community that the recommendation for abstinence from alcohol during pregnancy is overblown. And we need to tell our patients that there is no time in pregnancy when it’s safe to drink; there simply is no amount of alcohol that has been shown to be safe. While critical organ formation occurs early in pregnancy, the brain continues to develop throughout pregnancy and beyond. A recent paper found that even light to moderate prenatal alcohol exposure was associated with increased psychopathology, attention deficits, and impulsivity compared to unexposed children. So the recommendation remains that there is no safe amount and no safe time for alcohol use in pregnancy. It’s also important to emphasize that the type of alcohol doesn’t matter either. Beer is no safer than wine, which is no safer than liquor; it is the overall amount of alcohol consumed that counts. 

But what can we do if our patients continue to drink while pregnant?

Well, unfortunately, none of the medications that we typically use for alcohol use disorder, such as naltrexone or acamprosate, have been studied for efficacy in pregnancy. That being said, naltrexone appears to at least be safe, and has been studied for efficacy in OUD during pregnancy. So naltrexone is a potential option, along with evidenced based psychotherapies such as Motivational Interviewing, Cognitive Behavioral Therapy, or mutual help groups such as AA. I would avoid disulfiram altogether given the physiological stress a disulfiram-alcohol reaction might put on the fetus.

Alcohol use is common in the United States, and a lot of reproductive age patients, who might not have an alcohol use disorder, still binge drink. To give you some background, about 45% of pregnancies in the U.S. are unplanned. For patients with a SUD, it’s 60% to 90% and many don’t find out that they’re pregnant until late in their first trimester, which is already past the critical period of exposure to alcohol. So it is very important for providers to consider birth control for reproductive age patients who binge drink.

Dr. Capurso: As I said before, we really only have quality evidence of efficacy for OUD medications in pregnancy. Dr. Forray, what is the evidence supporting the use of medications for OUD during pregnancy?

Dr. Forray: So for many decades, the only medication for opioid use disorder was methadone, and I think out of a lack of any treatments for pregnant women it was used in pregnancy. So for many decades it’s been the gold standard of treatment for pregnant women. It’s not thought to lead to any congenital malformations or any concerns of safety, and in fact is very beneficial for pregnant women. So many studies have looked at women who are on methadone and it helps them, you know, not only, you know, reduces their cravings like it does in nonpregnant patients and it also prevents them from using illicit substances and engaging in risky behavior, it also enhances prenatal care and enhances actually nutrition surprisingly. And so I think women who are on methadone just take better care of themselves. So historically, it’s been the gold standard.

So back in 2010 there was a sentinel paper that came out by Hendree Jones and the group of researchers worked with her on the MOTHER study that actually examined you know the role of buprenorphine in pregnancy. Specifically, the study was focusing on the impact of buprenorphine in pregnancy on neonatal adaptation syndrome which now we’re calling neonatal opiate withdrawal syndrome because it’s much more accurate to what’s happening to the infant. And that paper was really the paper that began to shift some of the paradigm in a way and really brought buprenorphine to the forefront. There was a concern about the naloxone and whether that would have any impact on fetal development at this point we aren’t concerned about that. And frequently, prescribers now use buprenorphine and naloxone together. The initial studies like I said only with buprenorphine alone. And they found that in terms of what the MOTHER study showed is that it improved outcomes with respect to length of stay. It decreased the length of stay by like almost 90%. It decreased the amount of morphine that infants needed to get treated with, and it also decreased the number of days that the infants were experiencing withdrawal symptoms which is what happens. 

So now I think they both essentially have become the standard of care and are both thought to be safe in pregnancy, and also in women who are on those medications are encouraged to breastfeed following delivery. So there is some transmission in the breast milk, but it is very low and the benefits of breastfeeding in women with an opioid use disorder in terms of helping manage any potential neonatal opiate withdrawal syndrome far outweigh the minimal exposure happening in the milk. And, again, the infants have already been exposed in utero to much, much higher doses anyway.

Dr. Capurso: I just want to highlight something you said about the use of co-formulated buprenorphine/naloxone, also known as Suboxone, versus the monoproduct buprenorphine, or Subutex. 

Traditionally, the recommendation had been for buprenorphine alone (Subutex). More recently, as we have gathered data on the safety of buprenorphine-naloxone, we have moved away from that strict recommendation. The inclusion of naloxone does not seem to have any negative impacts in pregnancy. In fact, some providers prefer to prescribe buprenorphine-naloxone if they have a particular concern for diversion. 

Okay, moving on to the dosing of methadone in pregnancy. How do we start a pregnant woman with OUD on methadone?

Dr. Forray: The initial starting dose for a woman who gets admitted for methadone induction would be anywhere between 10 and 30 mg depending on how much they are using at baseline. Often women might not be consistent about how much they say, so I often kind of default to the quantity just if I’m not sure. If I have a really good sense that they’re using more than I will go with the 30. I rarely start with the 10 just because you really want to avoid women experiencing withdrawal because that’s really the main thing we’re concerned about, and I can talk about why we’re concerned about that if you like. 

But in terms of you give them the 20 mg dose. Then you reassess in 2 to 4 hours. You really want to assess what the COWS and see what they’re COW score is. You really don’t want women to be experiencing COWS higher than 8 just because again you don’t want them to be experiencing withdrawal symptoms because that’s bad for the fetus. And so you monitor, like I said, in 2 hours and if they’re still having symptoms and they are at a 10 or above you really want to re-dose by another 5 or 10 mg depending on how they’re doing, and then reassess 4 hours later and you continue to do that for the first 24 hours and give any additional doses – again 5 to 10 mg for any breakthrough withdrawal symptoms. 

After the first 24 hours doing this you calculate the doses that they’ve received and that becomes their maintenance dose. And normally in the hospital we don’t go beyond that right because once you are kind of loading the women you don’t want to make any adjustments any more frequently than 3 to 5 days, so most women by then are kind of ready to transition to outpatient follow-up for treatment. So that’s how we would do a methadone induction for pregnant women in the hospital.

Dr Capusro: Now for the dosing of buprenorphine. Ideally, outpatient buprenorphine induction should be reserved for a pregnancy of less than 24 weeks gestation. If there is any medical comorbidity, or greater than 24 weeks gestation, it’s best to start buprenorphine inpatient, due to risks to the fetus during opioid withdrawal. In pregnancy, you want to start buprenorphine at a Clinical Opiate Withdrawal Scale score, or COWS score, of 8 with a dose of 2 or 4 mg. If the COWS is 10 or above, I favor the 4mg dose. From there, the protocol is the same as with methadone.

And when it comes to dose adjustments of medications for OUD as pregnancy progresses,  usually patients will need higher doses as pregnancy progresses due to increased volume of distribution and changes in hepatic metabolism. Patients in the late stages of the second or third trimester metabolize methadone and buprenorphine much more quickly, so they should receive split dosing to maintain a steady state. Some may require doses that are higher than you’d normally expect: frequently 100-120mg of methadone, or higher. 

Lastly, there’s no consensus on how to taper OUD medication doses after delivery. I recommend switching to once-a-day dosing soon after delivery. There is obviously a significant volume of distribution shift right away, but a lot of other physiologic changes take time, so for the first two weeks I will only decrease the dose slightly and taper more aggressively afterwards. Since there is no standardized protocol, doses should be adjusted according to the clinical picture. Let the signs and symptoms of the patient guide the taper. Cravings mean the dose is too low, for example, and sedation means the dose is too high. 

Before we go, I’d like to discuss some additional resources with quality information, per the advice of Dr. Forray. 

Reprotox is a really good specialist website with the latest evidence for medications during pregnancy and lactation, including commonly prescribed psychotropics (https://reprotox.org/). And don’t underestimate the power of Micromedex, which has a “Pregnancy & Lactation” section for all its medication listings (www.micromedexsolutions.com). In fact, providers who have institutional access to Micromedex also will have access to Reprotox. Other resources include the American Society of Addiction Medicine (ASAM) website, which has useful guidance for treating pregnant patients (www.asam.org). The CDC also has some fantastic resources under their reproductive health section (www.cdc.gov/reproductivehealth/maternalinfanthealth/substance-abuse/substance-abuse-during-pregnancy.htm). Finally, the Providers Clinical Support System (PCSS) which is a national training and clinical mentoring project, has online courses for providers specifically interested in learning more about MOUD in pregnancy (https://pcssnow.org/education-training/training-courses/treating-women-for-opioid-use-disorder-during-pregnancy-clinical-challenges/).The printed interview is available for subscribers to read in The Carlat Child Psychiatry Report. Hopefully people check it out. Subscribers get print issues in the mail and email notifications when new issues are available on the website. Subscriptions also come with full access to all the articles on the website and CME credits. 

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