Updates on the management of psych meds during pregnancy and breastfeeding, with help from Anita Clayton, MD

Publication Date: 12/12/22

Duration: 14 mins, 30 seconds

Chris Aiken, MD, and Kellie Newsome, PMHNP have disclosed no relevant financial or other interests in any

Transcript: 

CHRIS AIKEN: Today we’ll cover the best and worst psych meds for pregnancy while keeping in mind that the safest scenario of all is a healthy mother.

Welcome to the Carlat Psychiatry Podcast, keeping psychiatry honest since 2003. I’m Chris Aiken, the editor in chief of the Carlat Report.

KELLIE NEWSOME: And I’m Kellie Newsome, a psychiatric NP and a dedicated reader of every issue.

 Last week we started to talk about psychiatric meds in pregnancy but the podcast was already getting too dense with new information so we’ll pick up on that here with pearls gleamed from Dr. Anita Clayton’s talk at the 9th annual Mood Disorders Summit. 

To recap, there are risks both ways – with medication, and with untreated depression - for the developing baby. Women with untreated depression have higher rates of preterm delivery, low birth rates, and delayed developmental milestones. They are less likely to take care of themselves – which means poor nutrition, substance abuse, alcohol, and nonadherence with prenatal care. 

And that’s not even counting the risk of active depression once the baby is delivered. The first thing a baby learns to see is two black dots – its mother’s eyes – and if those eyes are disengaged it’s going to take a toll on development. Untreated depression makes it more difficult to breastfeed, and it even changes the quality of the breast milk. Women with active depression have saltier breast milk, which often causes the infant to reject it.

But it’s not true that every woman with depression needs to stay on the antidepressant. The risk of relapse is low for some, and they can safely come off it while adding in some antidepressant activity like brisk walking, psychotherapy, Mediterranean diet, or a morning lightbox if there’s a seasonal component. 

Here are the situations where the risk is higher and it may be worth staying with the medication:

• Anyone who has had a severe past episode, like one that caused them to be unable to work, had suicidal or psychotic features, or lead to hospitalization
• Anyone with recurrent depression who has had more than one episode.
• Anyone with a history of postpartum depression
• Anyone with bipolar disorder

CHRIS AIKEN: In terms of the risks of medication, it’s the first trimester that we worry most about. That’s when the major organs are developing and teratogenic malformations can occur.  But only a few psych meds are associated with clear and relevant dangers that give us reason to avoid them in pregnancy; According to Dr. Clayton, those are: 

• Paroxetine (Paxil), valproate (Depakote), lithium, carbamazepine, tricyclic antidepressants (particularly clomipramine), benzodiazepines, and stimulants like Ritalin and Adderall.

Paroxetine, lithium, and tricyclic antidepressants: Cardiovascular malformations 

Valproate and carbamazepine: neural tube defects and – with valproate – lowered IQ in the offspring

Benzodiazepines: Various malformations, as well as neonatal flaccidity, respiratory and feeding difficulties, although  newer data suggest there may be little or no risk, most guidelines recommend discontinuing them if possible – with a taper – benzo withdrawal itself can be harmful to the mother and possibly the fetus.

Stimulants: Maternal hypertension, and a slightly increased risk of premature labor and delivery, and of preeclampsia 

KELLIE NEWSOME: For each of those medications, you have to weigh 3 risks – the risk of untreated psychiatric illness to the mother, to the fetus, and the risks of medications to the fetus. That’s not easy to compute. It might seem like untreated ADHD poses no risks to the fetus, but think again. What about traffic accidents? Or substance use – including excess caffeine – when ADHD goes untreated? If you do end up using stimulants in pregnancy, we recommend you site this article by Marlene Freeman from the American Journal of Psychiatry 2014. In it, she argues that stimulant use may be indicated in severe ADHD, where the risks of traffic accidents potentially outweigh the risks of the medication.

Of course, you would only use medications if they actually treated the psychiatric illness, and medications are not the only way to treat psych illness. Always think about psychotherapy, exercise, lightbox and – ECT and TMS are actually very safe for pregnancy. 

CHRIS AIKEN: Now for the safer meds. In bipolar disorder, that is lamotrigine and – surprisingly – the atypical antipsychotics.  In depression, the safest is technically fluoxetine, but this one is not ideal for breastfeeding in part because of its long half-life so if your patient plans to breastfeed and they have never been on an antidepressant before than sertraline (Zoloft) is your best choice. 

That information is good to know, but it leaves us in an uneasy position when it comes to lithium and bipolar disorder. 1 in 3 patients with bipolar disorder respond uniquely to lithium, these tend to be the ones with classic bipolar symptoms – pure euphoric manias or hypomanias with clean separation between the episodes, long periods of full recovery, and depressions that follow the highs as though they are following the law that what goes up must come down. For these patients lithium offers better protection against future episodes than any treatment we know of, while the peripartum period is the highest risk factor for future episodes than any other life event. But lithium is on the no fly list.

That doesn’t mean you can’t use it. The big fear with lithium in pregnancy was Epstein’s abnormality, a cardiac malformation that caused alarm when a string of reports first came out in the 1970’s. But those were just reports. What we need is good comparison groups in this area where controlled trials are understandably unethical. A new analysis from the American Journal of Psychiatry provides more accurate measures by pulling together multiple studies and comparing apples to apples: both groups of pregnant women had mood disorders, so the only difference between the two groups was that one took lithium. Only one risk stood out as significantly related to lithium: congenital anomalies, particularly cardiac abnormalities like Ebstein’s and atrioventricular septal defects. The paper also gives us usable numbers for those. The risk due to lithium for any congenital anomaly is 1 in 38, and the risk for cardiac anomalies is is 1 in 83. 

By congenital anomalies we’re talking about any structural defect, like neural tube defects where the spinal cord doesn’t close; or hypospadias in boys where the opening of the urethra is not located at the tip of the penis.

KELLIE NEWSOME: There are two ways to lower these risks with lithium. First, avoid exposure during the first trimester – that removed the risk of cardiac anomalies, though it didn’t completely eliminate the risk of all anomalies. Next, stick to the lowest dose of lithium that works, as the risk was dose dependent in this analysis. But Dr. Clayton emphasized that for other medications the risks are not dose-dependent, so you don’t gain anything – and do lose a lot – by lowering the dose of an antidepressant just to minimize the risks. Relapse rates are not as bad after lowering the dose as they are when women stop their antidepressant altogether; they are in the middle, about half way between staying on and stopping. And that puts these women into a whole new category – the ones who have depression despite taking an antidepressant. Outcomes for the infant were the worst for this group.

CHRIS AIKEN: The final thing you need to know about pregnancy many medications may need their doses raised in the third trimester. For one thing, the volume of distribution increases, diluting the medications in all that bloodflow. But pregnancy also increases the metabolism of some meds in the liver. For example lamotrigine may need to be as much as doubled during the third trimester. If your patient is doing well and has a long history of stability, you can keep it the same, but otherwise it’s best to raise lamotrigine.

KELLIE NEWSOME: As we end this podcast let’s make a list of some of the key drugs to know in pregnancy. All psychotropic medications cross the placenta, are present in amniotic fluid, and can enter breast milk, but they don’t all have the same risk, and just because a medication is high risk in pregnancy does not mean it’s high risk for breastfeeding.

First, the meds with the highest risk in pregnancy: 

Paroxetine (Paxil), valproate (Depakote), lithium, carbamazepine, tricyclic antidepressants, benzodiazepines, and stimulants like Ritalin and Adderall. But benzodiazepine withdrawal is also harmful for the mother and possibly the developing fetus, so if you are stopping that it’s best to taper it off.

The safest antidepressant – or at least the one with the most robust safety data – is fluoxetine, but this one is not ideal for breastfeeding so if your patient plans to breastfeed and they have never been on an antidepressant before than sertraline (Zoloft) is your best choice.

The following antidepressants are not as well studied, but we at least don’t know of any major risks with them: bupropion, trazodone, mirtazapine, and all the SSRIs/SNRIs.

CHRIS AIKEN: When it comes to pregnancy, we worry about teratogenicity as the organs develop, but when it comes to breastfeeding the risks are very different. There we worry about how much the medication passes into the breast milk and what the risks of toxicity are. Next week, we’ll pick up there and introduce you to the FDA’s new system for rating lactation risk with medications.

KELLIE NEWSOME: If you missed the Mood Disorders Summit,  catch it next September where they’ll return to a real, in-person conference in Scottsdale, Arizona. The conference will also be simulcast for a virtual audience, and admission is free for all attendees. 

You can earn continuing education credits for this episode through the link in the show notes, and you can get access to the full journal online.

We’ll see you next week, and if you get hungry for more psych updates before then, follow Dr. Aiken on LinkedIn – search Chris Aiken, MD, or twitter @chrisaikenmd - where he posts a new finding every day. Today’s study concerns an antidepressant that is moving closer to FDA approval and whose mechanism of action has nothing in common with the other 30 antidepressants on the market: Zuranolone.

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The Carlat CME Institute is accredited by the ACCME to provide continuing medical education for physicians. Carlat CME Institute maintains responsibility for this program and its content. Carlat CME Institute designates this enduring material educational activity for a maximum of one quarter (.25) AMA PRA Category 1 Credits^TM. Physicians or psychologists should claim credit commensurate only with the extent of their participation in the activity.