Antidepressant Medication Use in Pregnancy

Barbara Hackley, CNM, MSN

Disclosures

J Midwifery Womens Health. 2010;55(2):90-100. 

In This Article

Treatment

During pregnancy, a health care provider will generally need to manage two different clinical scenarios: 1) starting medications, either for a woman with new-onset depression or for a woman experiencing a relapse of depression, or 2) management of a woman with current depression who is already receiving antidepressants.

In each of these cases, the provider will need to confirm the diagnosis, assess the acuity of the situation, identify any comorbidity that may complicate management, and decide on a treatment plan. After an in-depth discussion of available options, a woman may choose to use antidepressants, receive counseling, or use a combination of both modalities. She may also decide to have some or all of her care managed by her provider, or she may prefer to be referred to a mental health specialist. Providers should carefully evaluate women for other coexisting medical conditions, drug use, or psychiatric conditions that can mimic depression or complicate management when considering treatment options and before initiating antidepressants. Because the principles of management are similar in pregnant and nonpregnant women, and because the management of depression for nonpregnant women was covered in a recent article,[10] the discussion here will primarily focus on the medication management specifically for pregnant and lactating women. Readers interested in a description of SSRIs and their side effect profiles and dosages are referred to that article.[10]

Starting Medication

If the maternal condition permits, waiting to start an antidepressant until after the first trimester is ideal, because this minimizes the potential risk of miscarriage and teratogenesis associated with antidepressant use. The goal of treatment in pregnancy is remission, and using subtherapeutic doses of an antidepressant has not been shown to reduce neonatal risks and increases the risk of poor maternal self-care.[55] Indeed, higher doses may be needed in pregnancy, particularly in the third trimester, as drug serum levels fall secondary to the increased plasma volume and dilutional effects in pregnancy.[55] Therefore, starting an antidepressant at a low dose and titrating slowly upward until remission is achieved is the approach recommended by the American College of Obstetricians and Gynecologists (ACOG) and the American Psychiatric Association.[32,36] ACOG also recommends treatment with a single agent and the use of antidepressants with few active metabolites, lower placental transfer, and minimal interactions with other medications.[36] The largest amount of data on the safety of antidepressants in pregnancy is found for tricyclic antidepressants and SSRIs.[56] Tricyclic antidepressants are rarely used in the treatment of depression because of their problematic side effect profile and lethality in overdose. They are therefore not used as first-line agents in pregnancy. SSRIs are much more commonly used in the treatment of depression, and among SSRIs, paroxetine (Paxil), sertraline (Zoloft), and fluoxetine (Prozac) have been studied most.

Some authorities recommend sertraline (Zoloft) as the preferred first-line agent in pregnancy,[38] but it is not risk-free. It has been reported to increase the risk of cardiac septal defects (OR, 2.0; 95% CI, 1.2–4), but the absolute risk appears to be small.[44] Louik et al.[44] note that even if the risk increases by a factor of four, the risk of having an affected child would be only 0.2%. The use of sertraline in pregnancy has several advantages. First, it has lower maternal serum levels than other SSRIs.[56,57] Second, serum levels of sertraline in breastfed infants have been found to be almost undetectable.[55,56] While serum levels of women taking paroxetine (Paxil) in pregnancy and during lactation have also been found to be significantly lower than in those whose mothers taking fluoxetine (Prozac), paroxetine is not recommended for use in pregnancy because it has been reported to be associated with higher risks of congenital anomalies in some studies.[36,51,55,56] Other commonly used agents, such as NNRIs and atypical antidepressants, appear to be safe, but the data on their safety are much more limited.[51,55,56] Therefore, the use of sertraline might be particularly helpful for use in pregnant women who are considering breastfeeding.

A thorough review of the medication history is needed for those women who have used antidepressants in the past. In particular, those who needed multidrug regimens or who have used TCAs, MAOIs, or mood stabilizers may have more refractory depression or other comorbid psychiatric conditions. While beginning with sertraline (Zoloft) may be a good first approach, women with a more complex psychiatric history may benefit from consulting a psychiatrist to determine the most effective and safe regimen.

Women who are Currently Taking Medication

Women who are currently taking medication for depression also need a careful review of their psychiatric and medication histories. Treatment will need to be individualized. Some women may prefer to stop their medications if their depression is in remission or change their medication regimen to products for which safety data are more abundant. Those who have used paroxetine (Paxil) in early pregnancy should be offered a fetal echocardiogram, because the risk of cardiac defects may be increased with use of this medication in early pregnancy.[36]

The decision about whether to stop or change medications is complex. Women should be cautioned that the risk of relapse is high. Cohen et al.[58] found that risk of relapse was significantly higher in women who elected to stop antidepressants in the first trimester than in those who continued using antidepressants throughout pregnancy (hazard ratio, 5.0; 95% CI, 2.8–9.1; P < .001). Indeed, in another similar study, Cohen et al.[59] found that 42% of those who stopped taking antidepressants at conception restarted their medications later in pregnancy; 50% of these women restarted medications in the first trimester. If a woman chooses to stop taking medication, she should be weaned slowly in order to minimize the chance of relapse. Providers should reduce the dose by no more than 25% every 2 weeks until the woman is off medication.[32] Careful and regular follow-up is then warranted.

Generally, medications are not changed if depression is well controlled, because the risk of adverse effects in pregnancy is thought to be low with most of the commonly used antidepressants.[55,60] In addition, changing medications may lead to relapse. Therefore, women who desire to change their medication regimen to products for which safety data are more abundant need to do this under the guidance of a psychiatrist.

Weaning off medications at the end of pregnancy has been suggested by some as a way to minimize neonatal problems. However, not only is the risk of maternal relapse high, but also the response to medication after it is reintroduced may not be as positive as it would be if the medication had been continued. A small study of 104 depressed individuals suffering from a relapse of depression found that the response rate to medication declined as the number of previous depressive episodes increased.[61]

Postpartum Considerations

Because of the steep decline in the levels of many hormones immediately postpartum, treating postpartum depression with supplemental estrogen would seem to be a biologically plausible option. However, there is an insufficient number and quality of studies available to evaluate the effectiveness of this approach. To date, only one randomized trial has been conducted. Gregoire et al.[62] randomly assigned 61 women with major depression that began within 3 months of childbirth to either an active treatment group (n = 34; 3 months of transdermal 17b-oestradiol 200 mg daily alone, then 3 months with added cyclical dydrogesterone 10 mg daily for 12 days each month) or placebo (n = 27; placebo patches and tablets according to the same regimen). Women completed monthly self-ratings of depressive symptoms using the Edinburgh Postnatal Depression Scale. Women receiving estrogen improved rapidly compared to the women in the control group. The estimated overall treatment effect of estrogen was a reduction of Edinburgh Postnatal Depression Scale of 4.38 points (95% CI, 1.89–6.87). More studies of sufficient size are needed to confirm these findings before treatment with estrogen can be recommended. Consequently, postpartum treatment options are the same as those recommended for women in pregnancy—namely counseling, medication, or both.

Lactation

The only specific consideration during the postpartum period is if a woman is breastfeeding. SSRIs or TCAs are considered compatible with breastfeeding; little data are available about the safety of other antidepressants during lactation.[63] Of the SSRIs, fluoxetine (Prozac) and citalopram (Celexa) are thought by some to not be first-line options because of reports of adverse neonatal effects with their use.[63] Both sertraline (Zoloft) and paroxetine (Paxil) may be more appropriate, because they have been found to have lower serum levels and are considered acceptable for use during lactation.[37,56]

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