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1 Report Information from ProQuest 17 May :36 17 May 2015 ProQuest

2 Table of contents 1. Antidepressants in pregnancy May 2015 ii ProQuest

3 Document 1 of 1 Antidepressants in pregnancy Author: George, Jacqueline ProQuest document link Abstract (Abstract): There may actually be more concerns about the use of SSRI or SNRI antidepressants in the second half of pregnancy. About 20-30% of infants exposed to SSRIs or SNRIs in the latter part of pregnancy may require admission to a special care nursery to manage 'neonatal adaptation problems', which include poor feeding, hypotonia and minor respiratory problems. It is not clear whether these effects are manifestations of withdrawal or prolonged drug effect in the neonate. Links: Check for fulltext Full text: MISCONCEPTIONS: Choosing the appropriate treatment regimen for pregnant women with depression can prevent harm to the baby and the mother. DEPRESSION affects up to 20% of women of childbearing age. Therefore GPs need to feel confident about managing women with depression during pregnancy. Untreated depression can be a significant obstetric risk factor, with several studies showing an increased incidence of adverse pregnancy outcomes, including: * Spontaneous abortion. * Preterm delivery. * Intrauterine growth restriction. * Small head circumference. * Low Apgar scores. * The need for special neonatal care. * Elevated neonatal cortisol levels at birth. Women with untreated depression during pregnancy may not look after themselves properly, obtain appropriate antenatal care or receive adequate nutrition. They may also undertake risky behaviours, such as attempting suicide or self-harm or self-medicating with cigarettes, alcohol or illegal drugs. It is clear that the risks associated with untreated depression continue postnatally and these women are at increased risk of postpartum depression. Studies have also shown that women with untreated depression are less capable of carrying out maternal duties and bonding with their children. There is a tendency to try to discontinue antidepressant use in the third trimester of pregnancy because of the risks of neonatal withdrawal and adaptation problems. Although stopping medication seems logical to avoid neonatal symptoms, it may not be the most sensible option for the woman with depression. In general, women who have required medication until the third trimester are not likely to experience a sudden resolution of their depression. It is also well known that the peripartum period is a time of increased risk for depression. Hormonal changes, the major life event of having a new baby, and disrupted sleep and daily routines are all factors likely to exacerbate depression, even in women with no history of depression. If a woman has stopped her medication and needs to restart her antidepressant the benefits may take several weeks to become apparent. She and her family may suffer through a time that could be far more enjoyable if she had continued her medication. It is important to emphasise that the management of depression is about more than just prescribing an antidepressant. Women benefit from other therapeutic modalities, including counselling/psychotherapy, exercise and relaxation techniques. However, it is clear that some women will require medication in addition to these supportive measures and they need to feel confident and reassured about their medication options. [sup]1,2 17 May 2015 Page 1 of 4 ProQuest

4 TRICYCLIC ANTIDEPRESSANTS Tricyclic antidepressants have been available for more than 30 years and are 'tried and true' with regard to use in pregnancy. Their use has not been associated with an increased incidence of birth defects or other adverse pregnancy outcomes. There have been reports of neonatal symptoms after maternal use of tricyclics during pregnancy but these tend to be transient and are probably less frequent than those seen after SSRI or serotonin noradrenaline reuptake inhibitor (SNRI) exposure. It is also worth noting that pulmonary hypertension has not been seen in infants exposed to tricyclic antidepressants at any time during the pregnancy (as opposed to SSRI exposure in the second half of the pregnancy). Long-term neurodevelopmental follow-up studies have also been reassuring. Many women do not tolerate the side effects of tricyclics, which include dry mouth and blurry vision. Psychiatrists are often reluctant to prescribe tricyclics to patients at risk of self-harm because the risks of fatal overdose are far higher than with SSRIs. Despite these problems they may be the drug of choice to treat depression in pregnancy. The sedating tricyclic antidepressants, such as Prothiaden, are a good option in women for whom insomnia is a significant symptom of depression because the risks of neonatal withdrawal are reduced when the mother uses only one psychotropic agent. Therefore a sedating tricyclic antidepressant may be a better option than the combination of an SSRI and a hypnotic and/or anxiolytic. SSRI AND SNRI ANTIDEPRESSANTS Fluoxetine is the oldest of the SSRI antidepressants and there has been more data published about its use in pregnancy than any other SSRI. Because fluoxetine has been available for a longer time there is more neurodevelopmental follow-up data available. This has been reassuring because no significant differences have been noted in terms of neurodevelopment or behaviour in exposed vs unexposed controls tested up to about seven years. There have been some reports suggesting a slight increase in the risk of cardiac defects in infants exposed to SSRI antidepressants, in particular paroxetine and fluoxetine, although other studies have failed to show this. However, putting this cardiac defect data into perspective, the baseline risk for any couple to have a baby with a birth defect is 3% and specifically a cardiac defect 0.5-1% (making heart defects the most common group of defects). So even if there is a doubling of this risk (that is, a relative risk of two) the absolute risk of a cardiac defect for a woman taking an SSRI is still only 1-2%. It is important to emphasise absolute vs relative risk when counselling a patient regarding possible effects on a pregnancy. There is no other evidence of adverse pregnancy outcome such as miscarriage, prematurity or low birthweight after using SSRIs or SNRIs (such as venlafaxine) in early pregnancy. [sup]3 There may actually be more concerns about the use of SSRI or SNRI antidepressants in the second half of pregnancy. About 20-30% of infants exposed to SSRIs or SNRIs in the latter part of pregnancy may require admission to a special care nursery to manage 'neonatal adaptation problems', which include poor feeding, hypotonia and minor respiratory problems. It is not clear whether these effects are manifestations of withdrawal or prolonged drug effect in the neonate. These symptoms tend to be self-limiting and appear to have no longterm sequelae. Patients are counselled that these symptoms are not a reason to discontinue antidepressant therapy if it is needed but that women and their doctors should be aware of the possibility of complication and therefore should plan to deliver at a hospital with appropriate special care nursery facilities. It is also important to emphasise that these symptoms do not appear to be dose related provided the dose is within the normal therapeutic range. Therefore, it is not logical for women to lower their antidepressant dose to try to avoid this problem. The lower dose may not adequately control their symptoms, yet they are still exposing their baby to medication without obtaining the maximum therapeutic benefit. As with the tricyclics, the main risk factor for neonatal symptoms appears to be maternal use of more than one psychotropic drug. A study published in early 2006 suggested an increased risk (relative risk of six) of persistent pulmonary 17 May 2015 Page 2 of 4 ProQuest

5 hypertension in infants exposed to SSRIs in the second (but not first) half of pregnancy. The absolute risk for this has not been elucidated and this issue clearly warrants further study. Of note was the fact that tricyclic antidepressant use at any time during pregnancy was not implicated in the increased risk of pulmonary hypertension. [sup]4 With regard to breastfeeding, sertraline is probably regarded as the SSRI of choice because its level in infants and breastmilk is essentially undetectable. Fluoxetine has a long half-life and an active metabolite, and its levels may remain elevated in infants, particularly neonates, for some time. Although not absolutely contraindicated, caution should be used and infants observed for adequate feeding and weight gain. Mothers may need to be switched to a shorter-acting SSRI if breastfed infants are displaying effects related to fluoxetine use. OTHER ANTIDEPRESSANTS Mirtazapine is a newer tetracyclic antidepressant that is being increasingly used to treat depression. There is outcome data available on more than 150 pregnancies, with no increase in birth defects or other adverse pregnancy outcomes noted. [sup]5 Of interest is the fact that mirtazapine acts on the same 5-HT3 receptors as the antiemetic drug ondansetron. Some women have taken the drug to treat both hyperemesis and depression with good effect, and normal pregnancy outcome in seven infants has been reported. [sup]6 Thus far there is no information available about long-term neurodevelopment in children exposed to mirtazapine in utero. SUMMARY It is important that GPs are comfortable managing depression in women of childbearing age and that they are able to discuss the risks and benefits of treatment of this common problem during pregnancy and lactation. Dr Kennedy is director of MotherSafe, Royal Hospital for Women, and conjoint lecturer at the school of women's and children's health, University of NSW, Randwick, NSW. REFERENCES 1. Kalra S, et al. Canadian Family Physician 2005; 51: Wisner KL, et al. American Journal of Psychiatry 2000; 157: Einarson TR, Einarson A. Pharmacoepidemiology and Drug Safety 2005; 14: Chambers C, et al. New England Journal of Medicine 2006; 354: Djulus J, et al. Journal of Clinical Psychiatry 2006; 67: Saks BR. Archives of Women's Mental Health 2001; 3: Subject: Pregnancy; Antidepressants; Medical treatment; Medical diagnosis; Location: Australia Classification: 9179: Asia & the Pacific; 8320: Health care industry Publication title: Australian Doctor Pages: 33 Publication year: 2007 Publication date: Aug 10, 2007 Section: News Publisher: Reed Business Information Pty Ltd, a division of Reed Elsevier Inc. Place of publication: Chatswood Country of publication: Australia Publication subject: Medical Sciences 17 May 2015 Page 3 of 4 ProQuest

6 ISSN: Source type: Trade Journals Language of publication: English Document type: News ProQuest document ID: Document URL: Copyright: Copyright Reed Business Information Pty Ltd, a division of Reed Elsevier Inc. Aug 10, 2007 Last updated: Database: ProQuest Central Contact ProQuest Copyright 2015 ProQuest LLC. All rights reserved. - Terms and Conditions 17 May 2015 Page 4 of 4 ProQuest