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Sertraline

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 Sertraline:

  • Licensed in NZ for the treatment of depression, obsessive compulsive disorder (OCD), panic disorder, post traumatic stress disorder (PTSD), social phobia and premenstrual dysphoric disorder (PMDD).
  • Available as Zoloft.
  • Last updated in May 2013.

Summary

Sertraline:

  • Is one of the better studied SSRIs in pregnancy with reports of over 2000 pregnancies exposed to sertraline in the first trimester.
  • Some studies have found associations between sertraline use during pregnancy and particular birth defects.  However, data is limited and findings are conflicting.  Overall, the available information does not suggest sertraline increases the risk of birth defects above the background risk (3-5% of all births) in the general population.
  • As with the SSRI group as a whole, sertraline is likely to be associated with a small, but not necessarily clinically significant tendency to shorten the gestation period and lower the birth weight.
  • As with the SSRI group as a whole, sertraline has a lower incidence of neonatal adaption syndrome compared with paroxetine and venlafaxine.
  • Has a relatively low plasma milk transfer with a relative infant dose of up to 2.2%, therefore is considered compatible with breast feeding in full term infants.

The decision to use psychotropic medication in pregnancy and breast feeding should be made weighing up the risk versus the benfits in each individual case.  It should involve informed choice, with the mutual agreement between patient and clinician.

 

Use in Pregnancy

Category B

  • Many reviews have suggested that SSRIs as a class do not increase the risk of common birth defects, although individual SSRIs may confer a small increased risk of congenital malformations.  The number of cases of sertraline studied specifically are too small for the data to demonstrate clearly whether a congenital malformation or other effect is due to the drug or not.
  • A study in 2007 (1) suggested an association with omphalocele and cadiac septal defects, another 2007 study (2) suggested an association with anencephaly.
  • On the other hand, two recent studies in 2011 (3) and 2012 (4) demonstrated no statistically significant increase of any specific birth defects with sertraline.
  • The outcome of several studies suggest that the SSRIs as a group may be linked to pre-term birth and lower birth weight.  Once again the data is conflicting, with one retrospective cohort study in 2003 (5) demonstrating an increased risk of pre-term birth and low birth weight, with a second study in 2002 (6) not showing any association. 
  • The size of the effect even in the positive studies is small, for example a study in 2010 (7) found delivery dates of 38.5 weeks for those on SSRIs, versus 39.4 weeks for depressed mothers not on medications, and 39.7 weeks for controls.  It is unclear how clinically significant this result is.
  • Several studies have identified an association between SSRIs and spontaneous abortion, but a recent meta-analysis in 2013 (8) concluded there was no overall significant association.
  • Neonatal Adaptation Syndrome (NAS) has been found in 10-30% of newborns exposed to a SSRI in utero (9) and consists of increased muscle tone, tremulousness, jitteriness, temperature dysregulation, feeding and sleep problems, respiratory problems and low APGARS.  However, the majority of SSRI exposed infants experienced mild and transient effects that only required supportive care, and with symptoms that spontaneously resolved.  Similar symptoms are also seen in non-exposed infants but at a lower frequency.  The median length of hospital stay was four fold greater in SSRI or SNRI exposed pre-term infants versus non-exposed pre-term infants.
  • Pulmonary hypertension of the newborn(PPHN) is a serious but rare disorder. A study by Chambers et al, in 2006 (10) demonstrated an increased risk of PPHN linked to SSRI use in the third trimester, with an odds ratio of 6.1. However this study only included 14 cases and relied on retrospective patient interviews and incomplete records. Five follow-up studies showing an association (though less strongly than in Chambers paper) and three not. These studies were reviewed by Ochiogrosso  in 2012 (11). In this review, many of the risk factors for PPHN, such as obesity and smoking, are outlined. Many of these risk factors are increased in depressed mothers making it difficult to differentiate the relative contribution of an SSRI. He concludes that the data supporting a link between SSRI exposure and pulmonary hypertension is weak.
  • As a consequence of the lack of clear findings regarding pulmonary hypertension and SSRI use in pregnancy the FDA downgraded their previous warning about the risk in late 2011, concluding "it is premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN". (12)
  • There has only been one study linking SSRI exposure to prolonged QT in the ECG of newborns. The significance of this finding in unclear as the ECG abnormalities reverted to normal within 24 hours, but is worthy of further study.
  • A small number of case reports have noted a possible association between SSRIs and cerebral haemorrhage in the newborn. This is a plausible association as SSRIs decrease platelet serotonin and therefore decrease platelet aggregation. It remains unclear if there is an increased risk or not.  
  • There is a theoretical risk of long-term neurobehavioural effects in infants following exposure to SSRIs in utero. The available data are limited and conflicting. One prospective study showed no difference in development between exposed and non-exposed infants over a 4-5 year period. However, another study found small delays in milestones in sitting, walking and the ability to occupy themselves at 18 months. The size of the effect was small and the exposed infants were still within the normal range of development.
  • A population based study in 2011 (13), found an association with the use of SSRIs in pregnancy and the subsequent development of autism (odds ratio 2.2). The author of the study noted that these results should be viewed with caution, and that further studies were needed to clarify if there was a causal link or not.

References

(1) Louik et al. First trimester use of selective serotonin reuptake inhibitors and the risk of birth defects. N Eng J Med 2007;356:2675-2683.

(2) Alwan S et al. Use of selective srotonin-reuptake inhibitors in pregnancy and the risk of birth defects. New England Journal of Medicine 2007;356:2684-92.

(3) Colvin L et al. Dispensing patterns and pregnancy outcomes for women dispensed selective serotonin reuptake inhibitors in pregnancy. Birth Defects Research Part A - Clinical and Molecular Teratology 2011; 91:142-152.

(4) Nordeng H et al. Pregnancy outcomes after exposure to antidepressants and the role of maternal depression:Results from the Norwegian mother and child cohort study. Journal of Clinical Psychophamacology 2012;32:186-194

(5)  Hendrick V et al. Birth outcomes after prenatal exposure to antidepressant medication. American Journal of Obstetric Gynaecology 2003:188:812-815

(6) Simon GE et al.Outcomes of prenatal antidepressant exposure. Am J Psych 2002;159:2055-2061

(7) Grote et al. A meta analysis of depression during pregnancy and the risk of preterm birth, low birth weight and intrauterine growth restriction. Arch Gen psych 2010:76:1012-1024

(8) Ross et al. Selected Preganacy and Delivery Outcomes after exposure to Antidpressant Medication;A Systematic Review and Analysis JAMAPsychiatry. published online February 27th 2013

(9) Moses-Kalko et al. Neonatal signs after late in utero exposure to serotonin reuptake  inhibitors. JAMA 2005;293:2372-2383

(10) Chambers et al. Selective serotonin reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Eng J Med. 2006: 354:579-587 

(11) Occhiogrosso et al. Persisten Pulmonary Hypertension of the newborn and selective serotonin reuptake inhibitors:lessons from clinical translational studies. Am J Psychiatry 2012;169(2):134-140

(12) Kieler H, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of persisten pulmonary hypertension in the newborn population. 

(13) Croen et al. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psych 2011

 

 

 


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