Journal of Clinical Psychopharmacology
&
Volume 34, Number 6, December 2014
Drs Cohen and Ravichandran as well as Ms Babb have no commercial supports or interests. Beth L. Murphy, MD, PhD Frazier Research Institute McLean Hospital Belmont, MA and Harvard Medical School Boston, MA [email protected]
Caitlin Ravichandran, PhD Harvard Medical School Boston, MA and Laboratory for Psychiatric Biostatistics McLean Hospital Belmont, MA
Suzann M. Babb, MS Bruce M. Cohen, MD, PhD Frazier Research Institute McLean Hospital Belmont, MA and Harvard Medical School Boston, MA
REFERENCES 1. Carlezon WA Jr, Be´guin C, Knoll AT, et al. Kappa-opioid ligands in the study and treatment of mood disorders. Pharmacol Ther. 2009;123:334Y343. 2. Spanagel R, Herz A, Shippenberg TS. Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci U S A. 1992;89:2046Y2050. 3. Barber A, Gottschlich R. Novel developments with selective, non-peptidic kappa-opioid receptor agonists. Expert Opin Investig Drugs. 1997;6:1351Y1368. 4. Carlezon WA Jr, Be´guin C, DiNieri JA, et al. Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats. J Pharmacol Exp Ther. 2006;316:440Y447. 5. Mague SD, Pliakas AM, Todtenkopf MS, et al. Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats. J Pharmacol Exp Ther. 2003;305:323Y330. 6. Brown ES, Beard L, Dobbs L, et al. Naltrexone in patients with bipolar disorder and alcohol dependence. Depress Anxiety. 2006;23:492Y495. 7. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382Y389. 8. Hamilton MA. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56Y62. 9. Young RC, Biggs JT, Ziegler VE, et al. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133:429Y435. 10. Brown ES, Carmody TJ, Schmitz JM, et al. A randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with
* 2014 Lippincott Williams & Wilkins
bipolar disorder and alcohol dependence. Alcohol Clin Exp Res. 2009;33:1863Y1869. 11. Sullivan MA, Nunes EV. New-onset mania and psychosis following heroin detoxification and naltrexone maintenance. Am J Addict. 2005;14:486Y487.
Selective Serotonin Reuptake Inhibitors Exposure During Pregnancy and Neonatal Outcomes To the Editors: read with interest the article by Grzeskowiak et al1 about the effect of late-gestation exposure to selective serotonin reuptake inhibitors (SSRIs) on the neonatal outcomes. Their study design was a retrospective cohort study carried out by gathering information from 33,965 pregnant women and their neonates for a period of 8 years. The total number of women prescribed with SSRIs (group A), number of women having psychiatric illness but not prescribed with SSRIs (group B), and number of women having no psychiatric illness and not prescribed with SSRIs (group C) were 221, 1566, and 32,004, respectively. The odds ratios (95% confidence intervals) for preterm delivery, low birth weight, admission to hospital, and length of hospital stay longer than 3 days were significantly higher for the neonates of the women in group A as compared with that for the neonates of the women in group B, being 2.68 (1.83Y3.93), 2.26 (1.31Y3.91), 1.92 (1.39Y2.65), and 1.93 (1.11Y3.36), respectively. From these results, they concluded the existence of positive associations between SSRI exposure during pregnancy (late-gestation period) and several adverse lneonatal outcomes. I appreciate their study design in the way that the control group was set, a valid method to elucidate the net effect of SSRIs on adverse neonatal outcomes. Namely, they presented the odds ratios in group A or group B against group C for several neonatal outcomes. I think that their study limitation for the lack of information on the severity of the psychiatric illness of the pregnant women and the limitation of the representativeness of their study participants should be explored in a further study. Recently, Stephansson et al2 reported the effect of exposure to SSRIs on 3 types of mortalityVstillbirth, neonatal death, and postneonatal death. In their study, the exposure period to SSRIs was also considered in their subanalysis. As their main
I
Letters to the Editors
result, there was no significant association between SSRI exposure and the risk of stillbirth or infant mortality, except for the significant increase of the stillbirth rate by SSRI exposure from 3 months before the start of pregnancy until the first trimester. Although it would be somewhat difficult to directly compare these 2 studies, the discrepancies between the 2 studies in respect of the effect of SSRI exposure during pregnancy on the neonatal outcomes were clearly observed. Namely, Grzeskowiak et al1 clarified the subclinical effects of SSRI exposure on the neonatal outcomes, and Stephansson et al2 reported no clear effect of SSRI exposure on the mortality. I strongly recommend that Grzeskowiak et al1 should conduct a further study to check the clinical manifestations of the infants, including fatal outcomes. Such an additional survey may be expected to more clearly reveal the effect of SSRI exposure during pregnancy (lategestation period) on the infant life prognosis. AUTHOR DISCLOSURE INFORMATION The author declares no conflicts of interest. Tomoyuki Kawada, MD, PhD Department of Hygiene and Public Health Nippon Medical School Bunkyo-Ku, Tokyo, Japan [email protected]
REFERENCES 1. Grzeskowiak LE, Gilbert AL, Morrison JL. Neonatal outcomes after late-gestation exposure to selective serotonin reuptake inhibitors. J Clin Psychopharmacol. 2012;32:615Y621. 2. Stephansson O, Kieler H, Haglund B, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality. JAMA. 2013;309:48Y54.
Reply to Dr Kawada Late-Gestation Selective Serotonin Reuptake Inhibitor Exposure and Perinatal Mortality Reply: e appreciate the interest by Dr Kawada1 in our study investigating neonatal outcomes after late-gestation exposure to selective serotonin reuptake inhibitors (SSRIs)2 and the call for additional analyses to examine clinical manifestations of the infants, in particular, fatal outcomes. Given the rarity of fatal outcomes, such as stillbirth (3.69 per 1000) and neonatal death
W
www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
751
&
Volume 34, Number 6, December 2014
Drs Cohen and Ravichandran as well as Ms Babb have no commercial supports or interests. Beth L. Murphy, MD, PhD Frazier Research Institute McLean Hospital Belmont, MA and Harvard Medical School Boston, MA [email protected]
Caitlin Ravichandran, PhD Harvard Medical School Boston, MA and Laboratory for Psychiatric Biostatistics McLean Hospital Belmont, MA
Suzann M. Babb, MS Bruce M. Cohen, MD, PhD Frazier Research Institute McLean Hospital Belmont, MA and Harvard Medical School Boston, MA
REFERENCES 1. Carlezon WA Jr, Be´guin C, Knoll AT, et al. Kappa-opioid ligands in the study and treatment of mood disorders. Pharmacol Ther. 2009;123:334Y343. 2. Spanagel R, Herz A, Shippenberg TS. Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci U S A. 1992;89:2046Y2050. 3. Barber A, Gottschlich R. Novel developments with selective, non-peptidic kappa-opioid receptor agonists. Expert Opin Investig Drugs. 1997;6:1351Y1368. 4. Carlezon WA Jr, Be´guin C, DiNieri JA, et al. Depressive-like effects of the kappa-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats. J Pharmacol Exp Ther. 2006;316:440Y447. 5. Mague SD, Pliakas AM, Todtenkopf MS, et al. Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats. J Pharmacol Exp Ther. 2003;305:323Y330. 6. Brown ES, Beard L, Dobbs L, et al. Naltrexone in patients with bipolar disorder and alcohol dependence. Depress Anxiety. 2006;23:492Y495. 7. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382Y389. 8. Hamilton MA. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960;23:56Y62. 9. Young RC, Biggs JT, Ziegler VE, et al. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. 1978;133:429Y435. 10. Brown ES, Carmody TJ, Schmitz JM, et al. A randomized, double-blind, placebo-controlled pilot study of naltrexone in outpatients with
* 2014 Lippincott Williams & Wilkins
bipolar disorder and alcohol dependence. Alcohol Clin Exp Res. 2009;33:1863Y1869. 11. Sullivan MA, Nunes EV. New-onset mania and psychosis following heroin detoxification and naltrexone maintenance. Am J Addict. 2005;14:486Y487.
Selective Serotonin Reuptake Inhibitors Exposure During Pregnancy and Neonatal Outcomes To the Editors: read with interest the article by Grzeskowiak et al1 about the effect of late-gestation exposure to selective serotonin reuptake inhibitors (SSRIs) on the neonatal outcomes. Their study design was a retrospective cohort study carried out by gathering information from 33,965 pregnant women and their neonates for a period of 8 years. The total number of women prescribed with SSRIs (group A), number of women having psychiatric illness but not prescribed with SSRIs (group B), and number of women having no psychiatric illness and not prescribed with SSRIs (group C) were 221, 1566, and 32,004, respectively. The odds ratios (95% confidence intervals) for preterm delivery, low birth weight, admission to hospital, and length of hospital stay longer than 3 days were significantly higher for the neonates of the women in group A as compared with that for the neonates of the women in group B, being 2.68 (1.83Y3.93), 2.26 (1.31Y3.91), 1.92 (1.39Y2.65), and 1.93 (1.11Y3.36), respectively. From these results, they concluded the existence of positive associations between SSRI exposure during pregnancy (late-gestation period) and several adverse lneonatal outcomes. I appreciate their study design in the way that the control group was set, a valid method to elucidate the net effect of SSRIs on adverse neonatal outcomes. Namely, they presented the odds ratios in group A or group B against group C for several neonatal outcomes. I think that their study limitation for the lack of information on the severity of the psychiatric illness of the pregnant women and the limitation of the representativeness of their study participants should be explored in a further study. Recently, Stephansson et al2 reported the effect of exposure to SSRIs on 3 types of mortalityVstillbirth, neonatal death, and postneonatal death. In their study, the exposure period to SSRIs was also considered in their subanalysis. As their main
I
Letters to the Editors
result, there was no significant association between SSRI exposure and the risk of stillbirth or infant mortality, except for the significant increase of the stillbirth rate by SSRI exposure from 3 months before the start of pregnancy until the first trimester. Although it would be somewhat difficult to directly compare these 2 studies, the discrepancies between the 2 studies in respect of the effect of SSRI exposure during pregnancy on the neonatal outcomes were clearly observed. Namely, Grzeskowiak et al1 clarified the subclinical effects of SSRI exposure on the neonatal outcomes, and Stephansson et al2 reported no clear effect of SSRI exposure on the mortality. I strongly recommend that Grzeskowiak et al1 should conduct a further study to check the clinical manifestations of the infants, including fatal outcomes. Such an additional survey may be expected to more clearly reveal the effect of SSRI exposure during pregnancy (lategestation period) on the infant life prognosis. AUTHOR DISCLOSURE INFORMATION The author declares no conflicts of interest. Tomoyuki Kawada, MD, PhD Department of Hygiene and Public Health Nippon Medical School Bunkyo-Ku, Tokyo, Japan [email protected]
REFERENCES 1. Grzeskowiak LE, Gilbert AL, Morrison JL. Neonatal outcomes after late-gestation exposure to selective serotonin reuptake inhibitors. J Clin Psychopharmacol. 2012;32:615Y621. 2. Stephansson O, Kieler H, Haglund B, et al. Selective serotonin reuptake inhibitors during pregnancy and risk of stillbirth and infant mortality. JAMA. 2013;309:48Y54.
Reply to Dr Kawada Late-Gestation Selective Serotonin Reuptake Inhibitor Exposure and Perinatal Mortality Reply: e appreciate the interest by Dr Kawada1 in our study investigating neonatal outcomes after late-gestation exposure to selective serotonin reuptake inhibitors (SSRIs)2 and the call for additional analyses to examine clinical manifestations of the infants, in particular, fatal outcomes. Given the rarity of fatal outcomes, such as stillbirth (3.69 per 1000) and neonatal death
W
www.psychopharmacology.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
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