Antidepressant treatment during pregnancy: between Scylla and Charybdis
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- "The current study augments this recent investigation of early life CSS associated changes in central gene expression through the analysis of plasma hormones (OXT, estradiol, PRL, and corticosterone ) and the inclusion of milk intake to assess lactation and saccharin preference as an abstract measure of anhedonia. Changes in female gonadal hormones are involved in the etiology of mood disorders in women (Rubinow, 2006), and it has been postulated that exogenous estradiol is a valid target for the treatment of postpartum mood disorders through its effects on normalizing estradiol sensitive maternal neural circuits (Bloch et al., 2000; Moses-Kolko et al., 2009). Estradiol is involved in the expression of both OXT and AVP receptors in the vertebrate brain (Bale and Dorsa, 1995; Champagne et al., 2001; Ochedalski et al., 2007) and has also been linked to maternal depression (Dennis et al., 2008; Gregoire et al., 1996; Moses- Kolko et al., 2009; Studd, 2011). "
ABSTRACT: Exposure to early life stress is a predictor of mental health disorders, and two common forms of early life stress are social conflict and impaired maternal care, which are predominant features of postpartum mood disorders. Exposure of lactating female rats to a novel male intruder involves robust social conflict and induces deficits in maternal care towards the F1 offspring. This exposure is an early life social stressor for female F1 pups that induces inefficient lactation associated with central changes in oxytocin (OXT), prolactin (PRL), and arginine vasopressin (AVP) gene expression in adult F1 females. The mothers of the rats in the current study were either allowed to raise their pups without exposure to a social stressor (control), or presented with a novel male intruder for 1 hour each day on lactation days 2-16 (chronic social stress). The effects of this early life chronic social stress (CSS) exposure on subsequent peripheral endocrinology, maternal behavior, and physiology were assessed. Exposure of female pups to early life CSS resulted in persistent alterations in maternal endocrinology at the end of lactation (attenuated prolactin and elevated corticosterone), depressed maternal care and aggression, increased restlessness and anxiety-related behavior, impaired lactation, and decreased saccharin preference. The endocrine and behavioral data indicate that early life CSS has long-term effects which are similar to changes seen in clinical populations of depressed mothers, and provide support for the use of the chronic social stress paradigm as an ethologically relevant rodent model for maternal disorders such as postpartum depression and anxiety. http://www.sciencedirect.com/science/article/pii/S0018506X13001657Hormones and Behavior 09/2013; In Press. DOI:10.1016/j.yhbeh.2013.08.011 · 4.51 Impact Factor
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- "Such drugs are nowadays the antidepressant drugs (ADs) most frequently prescribed both in specialist as well as in primary care setting (Hirshefeld, 2001; Bellantuono et al., 2002). However, the overall safety profile of these drugs in pregnancy is, so far, not well-established and the risk/benefit of a pharmacological management of the depressed mother is a recurrent matter of debate (Hampton, 2006; Rubinow, 2006). A number of reports, in fact, indicate that intrauterine exposure to SRIs can be associated with poor neonatal adaptation (including low birth weight and mild respiratory distress), withdrawal syndromes and serotoninergic symptoms (Gentile, 2005a; Sanz et al., 2005); it should be noted, however, that these neonatal adverse events were predominantly mild and self-limiting (Austin, 2006). "
ABSTRACT: To review studies conducted to establish the risk of major congenital malformations in women exposed to serotonin reuptake inhibitors (SRIs) during the first trimester of pregnancy. A literature search [corrected] was conducted within PsycINFO [corrected] EMBASE, MEDLINE and Cochrane databases from 1966 to October 2006, to identify studies assessing the risk of major malformations in infants whose mother was taking SRIs (SSRIs and SNRIs) during the first trimester of pregnancy. Fifteen studies were selected for the analysis: seven adopted a prospective cohort design and seven a retrospective design, of these one was a case-control study. The reviewed studies suggest that exposure to fluoxetine, sertraline, citalopram and venlafaxine in early pregnancy is not associated with an increased risk of major congenital malformations. For paroxetine, recent data call for caution in prescribing such a drug in early pregnancy. For the other SRIs, the risk remains substantially undetermined, as data are so far scanty. Given this background, large prospective cohort studies are urgently needed to better assess the risk/benefit ratio of SRIs-treatment during pregnancy.Human Psychopharmacology Clinical and Experimental 04/2007; 22(3):121-8. DOI:10.1002/hup.836 · 1.85 Impact Factor
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ABSTRACT: Concerns regarding antidepressant drug use during pregnancy I have several concerns with the re-cent editorial by Dr. Blier regarding antidepressant drugs and pregnancy. 1 In his editorial, Dr. Blier failed to ade-quately discuss the association of the selective serotonin reuptake inhibitors (SSRIs) with congenital anomalies; he failed to discuss the neonatal syn-drome associated with maternal SSRI use; and he failed to comment on the association of SSRIs with numerous pregnancy complications. A review of the studies he referenced reveals the absence of vital studies on this issue from some of the world's most respected journals. 2–4 The SSRIs may be associated with congenital malformations. Paxil, for example, has been associated with cardiac defects. On September 29, 2005, GlaxoSmithKline, in discussions with Health Canada, warned health professionals about this association. 5 In December 2005, at the Food and Drug Administration's (FDA) request, GlaxoSmithKline changed paroxe-tine's pregnancy category from C to D. 6 Why didn't Dr. Blier mention this major issue in his editorial, and how does he justify his statement: "SSRIs do not increase the risk of major and minor malformations?" He also failed to reference a study published in the New England Journal of Medicine (N Engl J Med) showing that fluoxetine exposure was associated with increased rates of 3 or more minor malformations. 2 SSRI use in pregnancy has been as-sociated with low birth weight, 2,7 preterm birth 2,7 and neonatal neurobe-havioural problems. 2–4 Additionally, fetal death and seizures have been shown to be increased. 7 Surely, these complications merited some mention in a discussion on antidepressant use in pregnancy. Although some people have argued that depression itself ac-counts for the above-mentioned associations, recent work by Oberlander and others 8 suggests that SSRI use may account for such pregnancy complications. I found Dr. Blier's discussion of Dr. Chambers' study on the association between maternal SSRI use and persis-tent pulmonary hypertension of the newborn (PPHN) 9 inadequate. He spent approximately one-third of his editorial criticizing her study and con-cluded: "The purported role of SSRI exposure in PPHN after the first 20 weeks of pregnancy appears doubt-ful." The association may appear doubtful to Dr. Blier. However, the ed-itors and reviewers at the N Engl J Med did not doubt the association nor did their editorialist, Dr. Mills. 10 Health Canada and the FDA have issued ad-visories concerning PPHN based on Chambers' study. 11,12 In sum, in various studies, SSRI use during pregnancy has been associated with increased rates of spontaneous abortion, 13 congenital malforma-tions, 2,5,6 preterm birth, 2,7 low birth weight, 2,7 fetal death, 7 seizures, 7 neona-tal withdrawal syndrome, 2–4 PPHN 9 and a possible predisposition to psy-chopathology. 14 Dr. Blier inadequately covered these complications. An edito-rial, such as his, on antidepressant drug use and pregnancy that fails to discuss major Health Canada and FDA public health advisories and sev-eral important pregnancy complica-tions is potentially misleading for readers, as well as for pregnant women with depression, their obstetri-cal providers and the public.