Sertraline

Liver test abnormalities have been reported to occur in up to 1% of patients on sertraline, but elevations are usually modest and infrequently require dose modification or discontinuation. Rare instances of acute, clinically apparent episodes of liver injury with marked liver enzyme elevations with or without jaundice have been reported in patients on sertraline. The onset of injury is usually within 2 to 24 weeks and the pattern of serum enzyme elevations has varied from hepatocellular to mixed and cholestatic. Autoimmune (autoantibodies) and immunoallergic features (rash, fever, eosinophilia) are uncommon. Acute liver failure due to sertraline has been described but is very rare.

Likelihood score: B (likely but rare cause of clinically apparent liver injury).

◉ Summary of Use during Lactation

Because of the low levels of sertraline in breastmilk, amounts ingested by the infant are small and is usually not detected in the serum of the infant, although the weakly active metabolite norsertraline (desmethylsertraline) is often detectable in low levels in infant serum. Rarely, preterm infants with impaired metabolic activity might accumulate the drug and demonstrate symptoms similar to neonatal abstinence. No adverse effects on development have been found in infants followed for up to 5 years of age. Most authoritative reviewers consider sertraline a preferred antidepressants during breastfeeding.

Mothers taking an SSRI during pregnancy and postpartum may have more difficulty breastfeeding, although this might be a reflection of their disease state. These mothers may need additional breastfeeding support. Breastfed infants exposed to an SSRI during the third trimester of pregnancy have a lower risk of poor neonatal adaptation than formula-fed infants.

◉ Effects in Breastfed Infants

Benign neonatal sleep myoclonus occurred in one 4-month-old infant and agitation that spontaneously resolved whose mother was taking sertraline 75 mg daily.

None of 26 infants with an average age of 16.6 weeks (range 4 to 28 weeks) whose mothers were receiving an average of 124 mg sertraline daily had any detectable acute adverse reactions to sertraline in breastmilk. All had been breastfeeding for at least 3 weeks.

Whole blood serotonin levels were measured in 14 mothers and their breastfed infants after 6 to 16 weeks of sertraline therapy. Maternal dosages ranged from 25 to 200 mg daily. Although maternal serotonin levels were decreased from 159 mcg/L to 19 mcg/L by sertraline therapy, infant serotonin levels averaged 227 mcg/L before and 224 mcg/L after maternal therapy. The authors concluded that these findings indicate that the amount of sertraline ingested by the infants was not sufficient to affect platelet serotonin uptake in breastfed infants. Platelets and neurons both have the same serotonin transporter, so this lack of effect was seen as indirect evidence of safety of sertraline use during breastfeeding. None of the infants experienced any adverse effects from sertraline in breastmilk, including 6 exclusively breastfed infants under 3 months of age.

Twenty-five mothers who took an average sertraline dosage of 82.4 mg daily breastfed their infants exclusively for 4 months and breastfed at least 50% during months 5 and 6. Their infants had 6-month weight gains that were normal according to national growth standards and the mothers reported no abnormal effects in their infants.

In 6 infants aged 5 to 34 weeks whose mothers were taking sertraline 50 to 100 mg daily, no adverse reactions were noted clinically at the time of the study.

No adverse effects were seen in 7 infants who were 4 weeks old and whose mothers had been taking sertraline 50 mg daily since day 4 postpartum.

One study of side effects of SSRI antidepressants in nursing mothers found no adverse reactions that required medical attention among 2 infants whose mother was taking sertraline. No specific information on maternal sertraline dosage, extent of breastfeeding or infant age was reported.

A small study compared the reaction to pain in infants of depressed mothers who had taken an SSRI during pregnancy alone or during pregnancy and nursing, to a control group of unexposed infants of nondepressed mothers. Infants exposed to an SSRI either prenatally alone or prenatally and postnatally via breastmilk had blunted responses to pain compared to control infants. Four of the 30 infants were exposed to sertraline. Because there was no control group of depressed, nonmedicated mothers, an effect due to maternal behavior caused by depression could not be ruled out. The authors stressed that these findings did not warrant avoiding drug treatment of depression during pregnancy or avoiding breastfeeding during SSRI treatment.

An uncontrolled online survey compiled data on 930 mothers who nursed their infants while taking an antidepressant. Infant drug discontinuation symptoms (e.g., irritability, low body temperature, uncontrollable crying, eating and sleeping disorders) were reported in about 10% of infants. Mothers who took antidepressants only during breastfeeding were much less likely to notice symptoms of drug discontinuation in their infants than those who took the drug in pregnancy and lactation.

In a telephone follow-up study, 124 mothers who took a benzodiazepine while nursing reported whether their infants had any signs of sedation. One mother who was taking sertraline 50 mg daily, zopiclone 2.5 mg about every 3 days as needed, and also took alprazolam 0.25 mg on 2 occasions, reported sedation in her breastfed infant.

A mother was taking sertraline 150 mg daily during gestation, at delivery and postpartum while exclusively breastfeeding her infant. Her preterm infant born by cesarean section at 33 weeks gestation developed hyperthermia, muscle tone regulation disorders, and high-pitched crying during the first 24 hours after birth. The symptoms worsened on the 4th day of life, but breastfeeding was continued. On day 5, the infant had serum concentrations of sertraline and its metabolite that are in the reported therapeutic range in adults. Breastfeeding was discontinued on day 9 postpartum and the infant's symptoms dissipated, serum drug levels decreased, and the infant thrived over several months. The infant was later found to have genetically intermediate metabolism of two of the CYP450 enzymes involved in sertraline metabolism. The authors attributed the infant's symptoms to serotonergic overstimulation caused by persistently high sertraline levels from breastfeeding and reduced metabolism. The reaction was probably caused by sertraline.

An infant was being breastfed (extent not stated) by a mother who began taking sertraline 50 mg daily and methylphenidate after 5 weeks postpartum. Dosage was started at 10 mg daily with an immediate-release product and gradually increased to 72 mg daily of an extended-release product. At 14 weeks of age, the infant was developing normally with no feeding difficulties. Examinations at 6 months and 1 year of age found no developmental problems in the child.

In a study of sertraline for postpartum depression, 11 women completed the full 7-week duration of the study out of 36 who were entered. Six mothers reported breastfeeding their infants (extent not stated) and 5 did not breastfeed their infants. The average sertraline dose in week 7 was 100 mg daily. No side effects were reported for any of the infants in the sertraline or placebo groups at this time.

Authors of a meta-analysis on sertraline reported 25 infants who were breastfed by mothers taking sertraline. Ten of the infants were exclusively breastfed, two were 80% breastfed and the breastfeeding status of the others was not reported. No adverse reactions occurred.

A cohort of 247 infants exposed to an antidepressant in utero during the third trimester of pregnancy were assessed for poor neonatal adaptation (PNA). Of the 247 infants, 154 developed PNA. Infants who were exclusively given formula had about 3 times the risk of developing PNA as those who were exclusively or partially breastfed. Sixty-eight of the infants were exposed to sertraline in utero.

A retrospective study of 30 nursing mothers who had been seen at a psychiatric outpatient facility, followed for at least 8 weeks, and prescribed sertraline found that adverse effects were reported in 5 (13%) of their infants. One mother was taking 25 mg daily; 3 mothers were taking 50 mg daily and 1 was taking 100 mg daily. The most commonly reported adverse events in the infants were insomnia and restlessness; constant crying and poor feeding were less commonly reported. All of the adverse effects developed within the first 2 weeks after initiation of maternal treatment and disappeared within the 3 days after drug discontinuation. Adverse effects failed to disappear in one infant after reducing the maternal dosage from 50 mg daily to 25 mg daily. There was no difference in prevalence of adverse effects between these infants and those in the same study whose mothers were prescribed paroxetine.

A 12-day-old exclusively breastfed male infant presented with severe weight loss and hypernatremic dehydration because of inadequate milk intake and a 30% weight loss since birth. The infant's mother was being treated for bipolar disorder with lamotrigine 250 mg orally once daily, aripiprazole 15 mg orally once daily, and sertraline 100 mg orally once daily. She was also taking levothyroxine 50 mcg once daily, a prenatal multivitamin, and folic acid. On initial evaluation in the emergency department, he was pale, with marbled skin, dry mucous membranes, decreased skin turgor, and bluish feet with prolonged capillary refill. The right foot eventually became darker with blackened toes, and he developed gangrene of the right lower limb, which did not respond to medical therapy and required amputation of all five toes and surgical debridement of the metatarsals. Necrosis was attributed to arterial microthrombi caused by disseminated intravascular coagulation after severe dehydration. The authors considered the mother's medications as a possible cause of the dehydration and related problems.

A mother who was exclusively breastfeeding a 2-month-old infant began taking sertraline 50 mg daily for depression. Six days later, restlessness and a dramatic decrease in the duration of sleep in the baby was reported. Sertraline was discontinued and the symptoms completely resolved within 3 days. No abnormalities were seen on physical examination or laboratory tests. The infant subsequently developed severe constipation with maternal paroxetine use, but tolerated maternal citalopram use.

A mother who was 3 months postpartum was treated for depression with sertraline 50 mg in the morning and olanzapine 1.25 mg at night at night for sleep. After 2 weeks, the sertraline dosage was increased to 25 mg in the morning and 50 mg at night. Five days after the dosage increase, her breastfed infant began having diarrhea about 15 minutes after each feeding. She continued the medication and provided oral rehydration solution to the infant. The diarrhea resolved after 2 weeks. The diarrhea was probably caused by sertraline in breastmilk.

Nine women treated with sertraline 25 to 75 mg daily (7 were taking 50 mg daily) during the third trimester of pregnancy and during breastfeeding. Pediatric evaluations including neurologic assessments and brain ultrasound were conducted during the first 24 hours postpartum. Further follow-up was conducted at 6 or more months of age. Infant clinical status was comparable to unexposed infants from the same pediatric department.

A case-control study in Israel compared 280 infants of nursing mothers taking long-term psychotropic drugs to the infants of 152 women taking antibiotics. Infant sleepiness at 3 days of age was reported by 1 mother taking sertraline during pregnancy and breastfeeding and by none taking antibiotics. The sleepiness resolved within 24 hours with no developmental effect.

A prospective study of nursing mothers who called to a lactation service in Poland found 4 with sertraline-induced adverse effects in breastfed infants. These included 3 with infant colic that were rated possible and one probable case of sinus tachycardia in a 3-week-old exclusively breastfed infant whose mother was taking 50 mg daily.

In a retrospective cohort study of 5,079 newborns whose mothers took an SSRI during pregnancy, 1.5% of breastfed newborns had neonatal withdrawal compared with 2.3% among the formula-fed newborns, although this did not reach statistical significance. Breastfed newborns had a reduced risk of transfer to the NICU than formula-fed newborns; however, this finding did not persist in sensitivity analysis. Thirty percent of women in the study were taking sertraline.

A mother was taking sertraline and levothyroxine. She reported that her 2.5-month-old infant who was exclusively breastfed experienced a rash. The reaction was rated as possible or probable, but relatively mild.

A secondary analysis of a population study evaluated infant IQ scores with SSRI use postpartum during nursing (n = 22), non-SSRI exposed breastfed infants (n = 37), and non-breastfed infants (n = 38). Of the entire group of mothers, 81 mothers were treated with fluoxetine, 9 with sertraline, 8 with paroxetine, and 2 with citalopram. Children had IQ testing at a mean age of 4.9 years. There were no significant differences in any adjusted mean IQ scores between breastfed children with and without postnatal SSRI exposure.

A pilot study compared the stool of breastfed infants whose mothers were taking an SSRI antidepressant to those of infants whose mothers were not taking an SSRI. Six of the 10 women taking an SSRI were taking sertraline. The stools of infants exposed to an SSRI in milk had increases in the genera Gemella, Staphylococcus and Corynebacterium and a decrease in Lactobacillus.

◉ Effects on Lactation and Breastmilk

Sertraline has caused galactorrhea in nonpregnant, nonnursing patients, sometimes with normal serum prolactin. However, in a study of cases of hyperprolactinemia and its symptoms (e.g., gynecomastia) reported to a French pharmacovigilance center, sertraline was not found to have an increased risk of causing hyperprolactinemia compared to other drugs. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

A midwife observed 6 patients who reported a decrease in milk supply after starting sertraline (dosages not reported). One of the mothers had been taking sertraline since the 6th month of pregnancy. She reported an increase in milk supply when she stopped sertraline for one week at 4 months postpartum. When she restarted sertraline, her milk supply reportedly decreased. In all of the women, the milk supply increased in 2 to 3 days after increasing fluid and the frequency of nursing.

In a small prospective study, 8 primiparous women who were taking a serotonin reuptake inhibitor (SRI; 3 taking fluoxetine and 1 each taking citalopram, duloxetine, escitalopram, paroxetine or sertraline) were compared to 423 mothers who were not taking an SRI. Mothers taking an SRI had an onset of milk secretory activation (lactogenesis II) that was delayed by an average of 16.7 hours compared to controls (85.8 hours postpartum in the SRI-treated mothers and 69.1 h in the untreated mothers), which doubled the risk of delayed feeding behavior in the untreated group. However, the delay in lactogenesis II may not be clinically important, since there was no statistically significant difference between the groups in the percentage of mothers experiencing feeding difficulties after day 4 postpartum.

A case control study compared the rate of predominant breastfeeding at 2 weeks postpartum in mothers who took an SSRI antidepressant throughout pregnancy and at delivery (n = 167) or an SSRI during pregnancy only (n = 117) to a control group of mothers who took no antidepressants (n = 182). Among the two groups who had taken an SSRI, 33 took citalopram, 18 took escitalopram, 63 took fluoxetine, 2 took fluvoxamine, 78 took paroxetine, and 87 took sertraline. Among the women who took an SSRI, the breastfeeding rate at 2 weeks postpartum was 27% to 33% lower than mother who did not take antidepressants, with no statistical difference in breastfeeding rates between the SSRI-exposed groups.

An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 37% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge. The antidepressants used by the mothers were not specified.

A retrospective cohort study of hospital electronic medical records from 2001 to 2008 compared women who had been dispensed an antidepressant during late gestation (n = 575; sertraline n = 200) to those who had a psychiatric illness but did not receive an antidepressant (n = 1552) and mothers who did not have a psychiatric diagnosis (n = 30,535). Women who received an antidepressant were 37% less likely to be breastfeeding at discharge than women without a psychiatric diagnosis, but no less likely to be breastfeeding than untreated mothers with a psychiatric diagnosis.

In a study of 80,882 Norwegian mother-infant pairs from 1999 to 2008, new postpartum antidepressant use was reported by 392 women and 201 reported that they continued antidepressants from pregnancy. Compared with the unexposed comparison group, late pregnancy antidepressant use was associated with a 7% reduced likelihood of breastfeeding initiation, but with no effect on breastfeeding duration or exclusivity. Compared with the unexposed comparison group, new or restarted antidepressant use was associated with a 63% reduced likelihood of predominant, and a 51% reduced likelihood of any breastfeeding at 6 months, as well as a 2.6-fold increased risk of abrupt breastfeeding discontinuation. Specific antidepressants were not mentioned.

◈ What is sertraline?

Sertraline is a medication that has been used to treat depression, anxiety, obsessive-compulsive disorder, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder (a severe form of premenstrual syndrome), and social phobia. Sertraline belongs to the class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs). A brand name for sertraline is Zoloft®.Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take your medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.Stopping this medication suddenly can cause some people to have withdrawal symptoms. It is not known if or how withdrawal might affect a pregnancy. If you plan to stop this medication, your healthcare provider may suggest that you slowly lower the dose instead of stopping all at once. Some people may have a return of their symptoms (relapse) if they stop this medication during pregnancy. If you stop taking this medication, it is important to have other forms of support in place (e.g. counseling or therapy) and a plan to restart the medication after delivery, if needed.

◈ I take sertraline. Can it make it harder for me to get pregnant?

It is not known if sertraline can make it harder to get pregnant. One study found that people who take SSRIs have a slightly lower chance of getting pregnant. However, some conditions, including depression, can make it harder to get pregnant. This makes it hard to know if the medication, the condition being treated, or other factors might affect fertility. For more information on depression, please see our fact sheet at https://mothertobaby.org/fact-sheets/depression-pregnancy/.

◈ Does taking sertraline increase the chance of miscarriage?

Miscarriage is common and can occur in any pregnancy for many different reasons. Use of sertraline and the chance of miscarriage has not been well studied. One study found no differences in the chance of miscarriage in people who filled prescriptions for sertraline during the first 35 days of pregnancy and those who stopped filling prescriptions before pregnancy. Also, some conditions, including depression, may increase the chance of miscarriage. This makes it hard to know if the medication, the condition being treated, or other factors might affect the chance of miscarriage.

◈ Does taking sertraline increase the chance of birth defects?

Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. There are reports of more than 25,000 pregnancies exposed to sertraline. Some studies have suggested an increased chance for heart defects or other birth defects. However, most studies have not found an increased chance of birth defects when sertraline is used in pregnancy. Overall, the available data does not suggest that sertraline increases the chance of birth defects above the background risk.

◈ Does taking sertraline in pregnancy increase the chance of other pregnancy-related problems?

Some studies suggest a higher chance for pregnancy-related problems, such as preterm delivery (birth before week 37) or low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth) with the use of sertraline in pregnancy. However, research has also shown that when conditions such as depression or anxiety are untreated or undertreated during pregnancy, there could be an increased chance for pregnancy complications. This makes it hard to know if it is the medication, the underlying condition, or other factors that might increase the chance for these problems.Some, but not all, studies have suggested that when people who are pregnant take SSRIs during the second half of pregnancy, their babies might have an increased chance for a serious lung condition called persistent pulmonary hypertension (PPH). PPH happens in 1 or 2 out of 1,000 births. A recent report that combined results from several studies suggested the chance for PPH might be increased if an SSRI was used during pregnancy. However, it was not clear if this was due to medication exposure or to other exposures that people who take SSRIs have in common, such as higher rates of smoking. Data from studies suggest the overall chance for PPH when an SSRI is used in pregnancy is less than 1/100 (less than 1%).

◈ I need to take sertraline throughout my entire pregnancy. Will it cause withdrawal symptoms in my baby after birth?

The use of sertraline during pregnancy can cause temporary symptoms in newborns soon after birth. These symptoms are sometimes referred to as withdrawal. Symptoms can include irritability, jitteriness, tremors (shivering), constant crying, changes in sleep patterns, lower muscle tone (hypotonia), skin discoloration (cyanosis), problems with eating, trouble controlling body temperature, and problems with breathing (apnea). In most cases, these symptoms are mild and go away within a couple weeks with no treatment required. Some babies may need to stay in the nursery or NICU until the symptoms go away. Not all babies exposed to sertraline will have these symptoms. It is important that your healthcare providers know you are taking sertraline so that if symptoms do occur, your baby can get the care that is best for them.

◈ Does taking sertraline in pregnancy affect future behavior or learning for the child?

One study on a small number of children who were exposed to SSRIs during pregnancy reported a lower score on motor skill tests than other children. Another small study looked at behaviors in children ages 4-5 years old. This study found no difference in behavior between children who were exposed to sertraline or other SSRIs during pregnancy and those children who were not.

◈ Breastfeeding while taking sertraline:

Sertraline gets into breastmilk in small amounts. Most reports show no problems for babies who are exposed to sertraline through breast milk. Babies who were also exposed to sertraline in the third trimester of pregnancy may have a lower chance of withdrawal after birth if they are breastfed. Be sure to talk to your healthcare provider about all your breastfeeding questions.

◈ If a male takes sertraline, could it affect fertility or increase the chance of birth defects?

Some studies have shown that SSRIs might have sexual side effects, like low sexual desire or problems with ejaculation, which might affect male fertility (ability to get partner pregnant). Also, people with conditions such as depression may have lower sex drive. An increased chance of birth defects is not expected when a male takes sertraline. In general, exposures that fathers or sperm donors have are unlikely to increase risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposure at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.National Pregnancy Registry for Psychiatric Medications: There is a pregnancy registry for people who take psychiatric medications, such as sertraline. For more information you can look at their website: https://womensmentalhealth.org/research/pregnancyregistry/.

SSRIs, considered a newer class of antidepressants, are better tolerated than tricyclic antidepressants or monoamine oxidase inhibitors. The primary side effects of sertraline include syncope, lightheadedness, diarrhea, nausea, sweating, dizziness, xerostomia, confusion, hallucinations, tremor, somnolence, impotence, a disorder of ejaculation, fatigue, rhinitis, and female sexual disorder.

There is a bleeding risk associated with sertraline, as it may inhibit platelet aggregation.

Sertraline can prolong the QT interval; however, the prolongation is dose-dependent and is very modest. Furthermore, this risk is higher in citalopram rather than sertraline or other SSRIs.

Sertraline may rarely produce symptoms of serotonin syndrome, though this generally happens when combining it with another serotonergic medication. These symptoms include myoclonus, muscle rigidity, diaphoresis, tremor, hyperreflexia, agitated delirium, and hyperthermia.

Sertraline, like other antidepressants, may increase the risk of suicidal ideation and behavior in children, adolescents, and young adults with major depression.

Sertraline use requires caution in patients 65 years and older. It is identified in the Beers Criteria as a high-risk medication in geriatric patients, as it may induce a syndrome of inappropriate antidiuretic hormone or hyponatremia.

Sertraline use in the first trimester of pregnancy increases the risk of cardiovascular-related malformations such as atrial and/or ventricular septal defects in infants.

Neonates exposed to sertraline late in the third trimester have been reported with complications requiring prolonged hospitalization, tube feeding, and respiratory support.