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Perinatal Bipolar Disorder
Pharmacologic Considerations When Managing Pregnant Patients With Bipolar Disorder

Released: September 07, 2023

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Key Takeaways
  • Risperidone and paliperidone are both associated with teratogenic adverse events and are best avoided during pregnancy.
  • Among other second-generation antipsychotics, there are no absolutes when choosing a medication for a pregnant patient with bipolar depression; individual patient and disease factors need to be considered when adjusting treatment plans in the setting of pregnancy.
  • Patients with bipolar disorder are more prone to postpartum depression/psychoses than the general population, and they should be followed closely during and after pregnancy.

Many patients with bipolar depression are managed with second-generation antipsychotics (SGAs), some of which have been studied more than others in the context of pregnancy. Before reading this clinical commentary on considerations for bipolar depression management during pregnancy, keep in mind that although some of these options are considered “safe,” none are considered 100% without risk.

Two SGAs in particular are associated with teratogenic adverse events and are best avoided during pregnancy: risperidone and paliperidone. Aside from these, there are no absolutes when choosing an SGA to use during pregnancy. It is wise to choose medications with the most published research and lowest rate of teratogenic complications, as well as to stay in the lowest efficacious dose range.

As for SGAs that have been studied greatly in the settings of pregnancy and lactation, clozapine, olanzapine, aripiprazole, and lurasidone generally are considered safe options. Quetiapine, although considered safe in pregnancy, also is associated with low placental passage rates. Another consideration to keep in mind is that olanzapine may increase the risk of gestational diabetes. 

A Quick Note on Mood Stabilizers
Mood stabilizers during pregnancy are another tricky topic to tackle because of conflicting evidence, but my personal practice is to try to avoid their use in patients who are planning to become pregnant, and I will prescribe them to patients with childbearing potential only if they are taking a long-acting birth control (ie, injections or implant).

However, the focus of this clinical commentary is not to provide specific recommendations for bipolar depression medications to use in pregnancy, but rather to provide guidance on using patient factors and clinical judgment to modify treatment plans to optimize patient and fetus safety.

Ultimately, from a psychiatric standpoint, any medication changes in the setting of pregnancy should mitigate the risks of either adverse events or worsening presentation. The individual risks and benefits have to be weighed with consideration to each patient’s presentation and history. In addition to weighing the risk–benefit profile, it is important to educate your patient on these risks and your rationale for making changes (if applicable) to their medication regimen.

Clinic Visit Frequency
I follow my pregnant patients very closely—initially I like to see them weekly or biweekly—because, aside from any mood instability that may result from medication changes, there is also the risk of mood instability from hormonal changes. However, just like medication choice, the decision about visit frequency should be individualized based on patient presentation. For example, if I see signs of mood instability during a visit, I will arrange to see the patient again within the next week to make sure I can intervene in a timely manner. If the patient seems stable, I still follow them closely in the first trimester; if they continue to be stable and express that they is doing well, I reduce the visit frequency to monthly. Trust and experience also play a role in this decision-making process. If I trust that a patient will call me if their mood changes, I am more comfortable with less frequent visits. If the patient has had multiple children and we know how they did on the medication regimen, I am more comfortable with less frequent visits. In the opposite scenarios, I prefer a more frequent appointment schedule.

Aside from psychiatric visits, I also recommend that pregnant patients with bipolar depression see a therapist to help them manage their mood and any emotions that come up while pregnant. A therapist also serves as extra support and a person to check in on them.

Postpartum Considerations
Now, what happens when the patient has given birth? Do we resume the previous regimen or continue the patient on the new regimen? Again, patient factors and presentation play a huge role in making this decision.

I have an open conversation to give my patients some autonomy here: If they are feeling well from a mental standpoint on their new regimen, we can leave it as is and see how they feel going forward. For patients who express that they felt better on their previous regimen, we can resume their previous regimen—depending on their decision about breastfeeding—as soon as they are healthy enough to do so. During the postpartum time, regardless of medication regimen, we still want to follow a patient closely to catch any development of postpartum depression or psychosis—to which patients with bipolar disorder can be vulnerable.

Breastfeeding
Breastfeeding, although important to consider in the choice of medication, is a difficult topic to navigate. It seems that for every study you find to support a specific medication that is “safe,” you are going to find one that refutes it. Collaboration plays an important role here. The pediatrician and obstetrician should be included in this decision-making process.

Personally, I never discourage breastfeeding, but if the patient is experiencing severe mood instability and I have to use high‑dose medication, I suggest that the patient strongly consider using formula. 

Your Thoughts?
In summary, no SGA or mood stabilizer for bipolar disorder is considered 100% safe for use during pregnancy and breastfeeding. This means that we need to rely heavily on patient input and clinical judgment when making medication adjustments in the setting of pregnancy. How confident do you feel in your ability to manage a pregnant patient with bipolar depression? Answer the polling question and join the conversation in the comments.

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