Should you take antidpressants while pregnant? What does the latest research say about antidepressants and pregnancy? Sadly there isn't much literature on antidpressants and being pregnant. One has to use caution. The following are the lastest research abstracts I have found on antidpressants and pregnancy
Psychiatr Clin North Am. 2003 Sep;26(3):547-62. :
Assessment and treatment of depression during pregnancy: an update.
Nonacs R, Cohen LS.
Perinatal and Reproductive Psychiatry Clinical Research Program, Clinical Psychopharmacology Unit, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
rnonacs@partners.org
Depression occurs commonly during pregnancy, and women with recurrent depression are at particularly high risk for depressive illness in this setting. Though the use of psychotropic medications during pregnancy raises concerns, there are data to support the use of certain antidepressants, including fluoxetine and the tricyclic antidepressants. Data on the newer SSRI antidepressants is gradually accumulating and is encouraging.
None of the SSRIS or TCAs have been associated with an increased risk of congenital malformation. However, information on the long-term neurobehavioral effects of these medications still remains limited. As depression during pregnancy carries risk for both the mother and child, it is crucial to diagnose depression in this setting and to provide appropriate treatment strategies. Further data on nonpharmacologic and pharmacologic strategies is needed to aid in the treatment of this challenging clinical population. The clinician must weigh the relative risks of various treatment options and take into account individual patient wishes. Such a process will lead to thoughtful treatment choices, which with close clinical follow-up can minimize the risk for maternal morbidity.
J Clin Psychiatry. 2003 Aug;64(8):966-8. :
The safety of St. John's wort (Hypericum perforatum) during breastfeeding.
Lee A, Minhas R, Matsuda N, Lam M, Ito S.
Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
BACKGROUND: We examined the safety of St. John's wort to nursing mothers and their infants. METHOD: A prospective, observational, cohort study was conducted. Thirty-three breastfeeding women receiving St. John's wort (Group 1) who contacted our teratogen/toxicant counseling service regarding the safety of St. John's wort during breastfeeding were followed up between May 1999 and April 2001. These women were compared with 101 disease-matched (Group 2) and 33 age- and parity-matched nondisease controls (Group 3). Information collected included maternal and neonatal demographics, breastfeeding duration, use of St. John's wort, maternal and infant adverse events, infant weight over the first year of life, and whether or not the mother experienced a decrease in lactation. RESULTS: There were no statistically significant differences found in maternal or infant demographics or maternal adverse events. Whereas only 1 infant each in Groups 2 and 3 was reported to be colicky, there were 2 cases of "colic," 2 of "drowsiness," and 1 of "lethargy" in Group 1 (p <.01; Group 1 vs. Group 2, p <.01; Group 1 vs. Group 3, p =.20). Although 3 of these women in Group 1 consulted their doctor, specific medical treatment was not required. No significant difference was observed in the frequency of maternal report of decreased milk production among the groups, nor was a difference found in infant weight over the first year of life. CONCLUSION: These results provide a framework for the management of breastfeeding women receiving St. John's wort.
J Pediatr. 2003 Apr;142(4):402-8.
Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy.
Casper RC, Fleisher BE, Lee-Ancajas JC, Gilles A, Gaylor E, DeBattista A, Hoyme HE.
Division of Medical Genetics, Department of Pediatrics, Stanford University and Stanford University School of Medicine, Stanford, California 94305-5723, USA.
rcasper@stanford.edu
OBJECTIVE: To compare the structural growth and developmental outcome of children born to mothers diagnosed with major depressive disorder during pregnancy who were exposed or not exposed to selective serotonin reuptake inhibitors (SSRIs) in utero. STUDY DESIGN: Children whose mothers were diagnosed with major depressive disorder in pregnancy and elected not to take medication (n = 13) were compared with children of depressed mothers treated with SSRIs (n = 31) on birth outcomes and postnatal neurodevelopmental functioning between ages 6 and 40 months. Children underwent blinded standardized pediatric and dysmorphology examinations and evaluations of their mental and psychomotor development with the use of the Bayley Scales of Infant Development (BSID II). RESULTS: The Bayley mental developmental indexes were similar in both groups. Children exposed to SSRIs during pregnancy had lower APGAR scores and scored lower on the Bayley psychomotor development indexes and the motor quality factor of the Bayley Behavioral Rating Scale than unexposed children.
CONCLUSIONS: The findings that SSRIs during fetal development might have subtle effects on motor development and motor control are consistent with the pharmacologic properties of the drugs.
1: Clin Pharmacol Ther. 2002 Aug;72(2):184-91.:
Citalopram in pregnancy and lactation.
Heikkinen T, Ekblad U, Kero P, Ekblad S, Laine K.
Department of Pharmacology and Clinical Pharmacology, University Central Hospital, University of Turku, Itainen Pitkakatu 4, FIN-20520 Turku, Finland.
tuija.heikkinen@utu.fi
BACKGROUND: Although citalopram has gained wide acceptance in the treatment of depression and anxiety disorders, its use during pregnancy and lactation has been poorly characterized. The aim of this study was to examine the efficacy and safety of citalopram in relation to concentrations of citalopram and its metabolites during pregnancy and lactation. METHODS: Eleven mothers taking citalopram and their infants were enrolled in the study, and a control group of 10 women who were not taking medication were prospectively matched for confounding obstetric characteristics at the time of delivery. Plasma and breast milk samples were collected from mother/infant pairs during pregnancy, at delivery, and for up to 2 months after delivery. Trough plasma and breast milk concentrations of citalopram, desmethylcitalopram, and didesmethylcitalopram were measured by HPLC. The pregnancy outcome was recorded, and the neurodevelopment of children was monitored for up to 1 year. RESULTS: Although the citalopram dose of 20 mg to 40 mg once daily resulted in low maternal trough plasma concentrations (range, 46-214 nmol/L) and metabolites during pregnancy, only one subject required an increase of daily dose. The mean didesmethylcitalopram-desmethylcitalopram metabolic ratio was significantly higher during pregnancy (54%, P <.001) than at 2 months after delivery, indicating induction of cytochrome P450 (CYP) 2D6 during pregnancy. At delivery, the trough plasma citalopram, desmethylcitalopram, and didesmethylcitalopram concentrations in the infants were 64%, 66%, and 68% of the maternal concentrations, respectively. The citalopram and metabolite concentrations in the milk were 2- to 3-fold higher compared with maternal plasma concentrations, but the infant citalopram and metabolite plasma concentrations were very low or undetectable. The delivery outcome and the neurodevelopment of all infants up to the age of 1 year were normal. CONCLUSION: Even though the sample size was limited, results from this prospective clinical trial suggest uncomplicated pregnancy outcome in mothers using citalopram during pregnancy and minimal exposure of the infants to citalopram during lactation. However, maternal therapeutic drug monitoring of citalopram should be recommended to minimize fetal exposure.
: Prescrire Int. 2002 Feb;11(57):17. :
Drugs and breast-feeding.
[No authors listed]
(1) Report of severe adverse effects in infants from drugs passing into breast milk are rare. (2) Two reports of neurological disorders in infants due to doxepin, a tricyclic antidepressant, necessitating hospitalisation, serve as a reminder that this risk exists. (3) Epidemiological data are almost non existent. A prospective follow-up study of more than 800 breast-fed infants whose mothers were taking medicinal drugs showed minor adverse effects in 11% of the children (mainly diarrhoea, drowsiness and irritability). None of the mothers sought medical advice. (4) When a breast-feeding mother requires drug therapy, all available information should be weighed up before advising her to switch to bottle feeding.
Am J Psychiatry. 2002 Nov;159(11):1889-95. :
Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study.
Nulman I, Rovet J, Stewart DE, Wolpin J, Pace-Asciak P, Shuhaiber S, Koren G.
Motherisk Program, Division of Pediatrics and Psychology and the Reseaarch Institute, The Hospital for Sick Children, Toronta, Ont. Canada.
OBJECTIVE: Previous work suggested that first-trimester exposure to tricyclic antidepressants or fluoxetine does not affect adversely child IQ and language development. However, many women need antidepressants throughout pregnancy to avoid morbidity and suicide attempts. Little is known about the fetal safety of tricyclic antidepressants and fluoxetine when taken throughout pregnancy. The goal of this study was to assess the effects of tricyclic antidepressants and fluoxetine used throughout gestation on child IQ, language, and behavior. METHOD: In a prospective study, mother-child pairs exposed throughout gestation to tricyclic antidepressants (N=46) or fluoxetine (N=40) and an unexposed, not depressed comparison group (N=36) were blindly assessed. The three groups were compared in terms of the children's IQ, language, behavior, and temperament between ages 15 and 71 months. The authors adjusted for independent variables such as duration and severity of maternal depression, duration of pharmacological treatment, number of depression episodes after delivery, maternal IQ, socioeconomic status, cigarette smoking, and alcohol use. RESULTS: Neither tricyclic antidepressants nor fluoxetine adversely affected the child's global IQ, language development, or behavior. IQ was significantly and negatively associated with duration of depression, whereas language was negatively associated with number of depression episodes after delivery. CONCLUSIONS: Exposure to tricyclic antidepressants or fluoxetine throughout gestation does not appear to adversely affect cognition, language development, or the temperament of preschool and early-school children. In contrast, mothers' depression is associated with less cognitive and language achievement by their children. When needed, adequate antidepressant therapy should be instituted and maintained during pregnancy and postpartum
Am J Psychiatry. 2002 Dec;159(12):2055-61.
Outcomes of prenatal antidepressant exposure.
Simon GE, Cunningham ML, Davis RL.
Center for Health Studies, Group Health Cooperative, 1730 Minor Avenue #1600, Seattle, WA 98101, USA.
simon.g@ghc.org
OBJECTIVE: This study evaluated the effects of prenatal antidepressant exposure on perinatal outcomes, congenital malformations, and early growth and development. METHOD: Within a group-model health maintenance organization, all infants with apparent prenatal exposure to tricyclic or selective serotonin reuptake inhibitor (SSRI) antidepressants were frequency matched to an unexposed comparison group by year of birth, maternal age, and mother's lifetime use of antidepressant drugs and mental health care. A structured blind review of mothers' and infants' medical records examined perinatal outcomes, congenital malformations, and developmental delay. RESULTS: Tricyclic antidepressant exposure was not associated with any significant difference in perinatal outcomes. Exposure to SSRIs was associated with a 0.9-week decrease in mean gestational age, a 175-g decrease in mean birth weight, and a 0.29 decrease in mean Apgar score at 5 minutes, but differences in birth weights and Apgar scores were not significant after adjustment for gestational age. Differences in gestational age and birth weights were unrelated to length of exposure, but differences in Apgar scores were limited to those with third-trimester exposure. Neither tricyclic antidepressant nor SSRI exposure was significantly associated with congenital malformations or developmental delay. CONCLUSIONS: The authors found no association between tricyclic antidepressant or SSRI exposure and either congenital malformations or developmental delay. SSRI exposure during pregnancy was associated with earlier delivery and consequent lower birth weight. Third-trimester SSRI exposure was also associated with lower Apgar scores. Women considering taking SSRIs during pregnancy may balance any higher fetal risk against the risk of persistent or recurrent depression
Psychopharmacol Bull. 2003 Spring;37 Suppl 1:148-66. :
Clinical management of perinatal depression: focus on paroxetine.
Newport DJ, Stowe ZN.
Department of Psychiatry, Emory University School of Medicine, Atlanta, GA 30322, USA.
The literature on antidepressant use during pregnancy and lactation is replete with review articles and clinical decision algorithms. Remarkably, a limited number of such articles include the methodological advances that have served to define the extent of fetal and neonatal exposure to antidepressants. For this review, MEDLINE search for original research articles focusing on obstetrical, neonatal, and infant outcomes associated with antidepressant use was conducted. These articles were scrutinized to include those with data on the selective serotonin reuptake inhibitors (SSRIs) and limited to breast-feeding studies that included infant serum concentrations.Sixty-seven articles were identified that included a total of 3050 cases of SSRI use during pregnancy and 240 cases of use during lactation. The amount of obstetrical outcome data available for each SSRI was proportional to the duration of time each medication has been available. In contrast, the lactation data were heavily weighted toward sertraline and paroxetine relative to other antidepressants. The myriad of confounds, failure to control for maternal depression, lack of prospective documentation of other medications, and environmental exposures preclude any definitive conclusions. There was no clear association between SSRI exposure and obstetrical complications or poor outcome. In contrast, the amniotic fluid, umbilical cord, and nursing infant sera literature demonstrated significantly different exposures to individual medications.
Am J Obstet Gynecol. 2003 Mar;188(3):812-5.
Comment in:
Am J Obstet Gynecol. 2003 Dec;189(6):1810-1; author reply 1811.
Birth outcomes after prenatal exposure to antidepressant medication.
Hendrick V, Smith LM, Suri R, Hwang S, Haynes D, Altshuler L.
UCLA Neuropsychiatric Institute and Hospital, Los Angeles, Calif, USA. vhendric@ucla.edu
OBJECTIVE: The purpose of this study was to examine prospectively the incidence of congenital anomalies and neonatal complications after prenatal exposure to antidepressant medication. STUDY DESIGN: Birth outcomes were obtained from a review of obstetric and neonatal records of 138 women who were treated with selective serotonin reuptake inhibitor antidepressant medications (SSRIs) during pregnancy. RESULTS: The incidence of congenital anomalies in this study was 1.4%, comparable to general population rates. Rates of low birth weight and preterm births were low, occurring in 2.9% and 6.5% of births, respectively. The low birth weight infants had been exposed to relatively high doses of fluoxetine (40-80 mg/d) throughout pregnancy. Average maternal weight gain in pregnancy was comparable across the three major medication categories (fluoxetine, paroxetine, sertraline). CONCLUSION: After prenatal use of selective serotonin reuptake inhibitor antidepressant medications, neonatal complications and congenital anomalies appear to occur within general population rates.
However, maternal use of high doses of fluoxetine throughout pregnancy may be associated with a risk for low birth weight
J Clin Psychiatry. 2003 Apr;64(4):410-2.
Weight gain in breastfed infants of mothers taking antidepressant medications.
Hendrick V, Smith LM, Hwang S, Altshuler LL, Haynes D.
Department of Psychiatry and Behavioral Sciences, UCLA Neuropsychiatric Institute and Hospital, Los Angeles, CA 90095, USA.
vhendric@ucla.edu
BACKGROUND: Little is known about the physical development of infants who are exposed to antidepressant medications through breast milk. METHOD: Seventy-eight breastfeeding women taking antidepressant medications were included in the study. Maternal mood was prospectively evaluated at 6, 12, and 18 months postpartum. Infants' weights were obtained from review of pediatric records. Data were gathered from 1997 to 2002. RESULTS: Infants' weights were not significantly different from weights of 6-month-old breastfed infants from normative populations. However, infants of mothers who relapsed to relatively long-lasting major depressive episodes (lasting 2 months or more) following delivery weighed significantly (p =.002) less when compared with infants of mothers who relapsed to brief depressive episodes (< 2 months) and infants of mothers who did not relapse to depression in the postpartum period. This finding remained after including medication dosage and infant birth weight as covariates. CONCLUSION: Exposure to antidepressant medications through breast milk does not appear to affect infants' weight. However, infants exposed to maternal depression lasting 2 months or more appear to experience significantly lower weight gain than infants of euthymic mothers or mothers who experience brief (< 2 months) major depressive episodes. Maternal depression following delivery may influence behaviors that, over the course of 2 months or more, affect infants' weight gain.
Ned Tijdschr Geneeskd. 2003 Jul 12;147(28):1370-2. :
Comment in:
Ned Tijdschr Geneeskd. 2003 Sep 20;147(38):1885-6; author reply 1886.
[Withdrawal symptoms in a neonate following exposure to venlafaxine during pregnancy]
[Article in Dutch]
de Moor RA, Mourad L, ter Haar J, Egberts AC.
Afd. Kindergeneeskunde, TweeSteden ziekenhuis, Postbus 90.107, 5000 LA Tilburg.
rdmoor@tsz.nl
Withdrawal symptoms occurred in a male neonate after maternal use of venlafaxine for depression during pregnancy. The symptoms were restlessness, hypertonia, jitteriness, irritability and poor feeding. The diagnosis was confirmed by a temporary improvement after administration of a low dose (1 mg) of venlafaxine to the boy. Eventually the symptoms began to decline spontaneously, and ceased after 8 days. Exposure to venlafaxine and other antidepressants which inhibit serotonin reuptake during the third trimester of pregnancy carries the risk of a neonatal withdrawal syndrome
fluoxetine-Prozac venlafaxine-Effexor
Can Fam Physician. 2004 Feb;50:227-9. :
New antidepressants in pregnancy.
Einarson A, Koren G.
Hospital for Sick Children, Toronto, Ont.
QUESTION: I have read that fluoxetine is the drug of choice for treating depression during pregnancy. One of my patients, who did not respond to the "old" selective serotonin reuptake inhibitors, is doing well on venlafaxine and is now 6 weeks pregnant. What advice should I give her? ANSWER: Fluoxetine is recommended because to date it has the most evidence of its safety. It is important that women be treated appropriately for depression during pregnancy, and some research on the newer antidepressants, such as venlafaxine, will be useful to you and your patient in making an informed decision regarding treatment.
Can Fam Physician. 2004 Jan;50:37-9.:
Risks of untreated depression during pregnancy.
Bonari L, Bennett H, Einarson A, Koren G.
Motherisk Team, Hospital for Sick Children, Toronto, Ont.
QUESTION: One of my patients who was taking an antidepressant for major depression is now pregnant and does not wish to take it any more. I believe she needs to continue her medication. She, however, is adamant about stopping it because she believes it would put her baby at risk. Is there evidence that not treating depression during pregnancy puts babies at risk? ANSWER: A growing body of literature investigating the effects of not treating depression on mother and developing fetus suggests that untreated depression is associated with adverse fetal outcomes and a higher risk of maternal morbidity, including suicide ideation and attempts, and postpartum depression.
Drug Alcohol Rev. 2003 Jun;22(2):191-202.
Pharmacotherapies to enhance smoking cessation during pregnancy.
Oncken CA, Kranzler HR.
Department of Medicine, University of Connecticut School of Medicine, Farmington 06030, USA.
oncken@nso2.uchc.edu
Smoking during pregnancy is a significant public health concern. Maternal smoking increases the risk of spontaneous abortion, low birth weight, premature delivery, sudden infant death syndrome and learning and behavioral problems in the offspring. Unfortunately, the majority of pregnant women do not quit smoking during pregnancy. Although pharmacotherapy may improve smoking cessation rates in pregnancy, very few studies exist that have studied the safety and efficacy of medications to treat pregnant smokers. This article reviews the available safety and efficacy data for the use in pregnancy of the five first-line therapies and two second-line therapies that are recommended for smoking cessation in non-pregnant smokers. Other promising nicotine replacement therapies are also reviewed. Ultimately, the choice whether to use pharmacotherapy for smoking cessation should be made jointly by the pregnant smoker and her health care provider. This article reviews factors that may be considered when prescribing pharmacotherapy to pregnant smokers (i.e. the role of behavioral counseling, identification of appropriate patients, potential advantages and disadvantages of each of the pharmacotherapies, proposed monitoring strategies, dose and duration and goals of treatment). More research regarding the safety and efficacy of pharmacotherapy during pregnancy is needed to define the risk/benefit profile of each medication for use in smoking cessation in pregnant women.
citalopram=celexa, fluoxetine=prozac, paroxetine-paxil, or sertraline =zoloft
Am J Psychiatry. 2003 May;160(5):993-6.
Placental passage of antidepressant medications.
Hendrick V, Stowe ZN, Altshuler LL, Hwang S, Lee E, Haynes D.
Mood Disorders Research Program, UCLA Neuropsychiatric Institute and Hospital, University of California-Los Angeles, 300 Medical Plaza, Suite 2345, Los Angeles, CA 90095, USA.
vhendric@ucla.edu
OBJECTIVE: This study determined the placental transfer of antidepressants and their metabolites. METHOD: A total of 38 pregnant women taking citalopram, fluoxetine, paroxetine, or sertraline participated. Maternal and umbilical cord blood samples were obtained to determine antidepressant and metabolite concentrations. RESULTS: Antidepressant and metabolite concentrations were detectable in 86.8% of umbilical cord samples. The mean ratios of umbilical cord to maternal serum concentrations ranged from 0.29 to 0.89. The lowest ratios were for sertraline and paroxetine; the highest were for citalopram and fluoxetine. Maternal doses of sertraline and fluoxetine correlated with umbilical cord concentrations of these medications. CONCLUSIONS: Umbilical cord concentrations of antidepressants and their metabolites were almost invariably lower than corresponding maternal concentrations. Maternal doses predicted umbilical concentrations of fluoxetine and sertraline.
Mean umbilical cord to maternal serum ratios were significantly lower for sertraline than fluoxetine, suggesting that sertraline may produce less fetal medication exposure than fluoxetine near delivery.
J Womens Health (Larchmt). 2003 May;12(4):373-80.
Depressive symptoms among pregnant women screened in obstetrics settings.
Marcus SM, Flynn HA, Blow FC, Barry KL.
Department of Psychiatry, Women's Mood Disorders Program, University of Michigan Depression Center, University of Michigan Medical School, 900 Wall Street, Ann Arbor, MI 48109-0722, USA.
smmarcus@umich.edu
OBJECTIVES: This study aimed to describe the prevalence of depressive symptomatology during pregnancy when seen in obstetric settings, the extent of treatment in this population, and specific risk factors associated with mood symptoms in pregnancy. METHODS: A total of 3472 pregnant women age 18 and older were screened while waiting for their prenatal care visits in 10 obstetrics clinics using a brief (10 minute) screening questionnaire. This screen measured demographics, tobacco and alcohol (TWEAK problem alcohol use screening measure), and depression measures, including the Center for Epidemiological Studies-Depression scale (CES-D), use of antidepressant medications, past history of depression, and current treatment (i.e., medications, psychotherapy, or counseling) for depression. RESULTS: Of women screened, 20% (n = 689) scored above the cutoff score on the CES-D, and only 13.8% of those women reported receiving any formal treatment for depression. Past history of depression, poorer overall health, greater alcohol use consequences, smoking, being unmarried, unemployment, and lower educational attainment were significantly associated with symptoms of depression during pregnancy. CONCLUSIONS: These data show that a substantial number of pregnant women screened in obstetrics settings have significant symptoms of depression, and most of them are not being monitored in treatment during this vulnerable time. This information may be used to justify and streamline systematic screening for depression in clinical encounters with pregnant women as a first step in determining which women may require further treatment for their mood symptoms. As elevations in depressive symptomatology have been associated with adverse maternal and infant outcomes, further study of the impact of psychiatric treatment in gravid women is essential.
3e
nefazodone-Serzone
Can J Psychiatry. 2003 Mar;48(2):106-10.
A multicentre prospective controlled study to determine the safety of trazodone and nefazodone use during pregnancy.
Einarson A, Bonari L, Voyer-Lavigne S, Addis A, Matsui D, Johnson Y, Koren G.
Motherisk Program, Division of Clinical Pharmacology, Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8.
einarson@sickkids.on.ca
OBJECTIVES: Trazodone and nefazodone are phenylpiperazine antidepressants. Currently, there are no adequate, well-controlled studies on the fetal safety of these drugs. Our primary objective was to determine whether the use of trazodone or nefazodone during pregnancy is associated with an increased risk for major malformations. Secondary outcomes of interest included rates of spontaneous and therapeutic abortions, rates of premature labour, and birth weight. METHODS: Pregnant women from 5 centres who had been exposed to these drugs (n = 147) were enrolled in the study during their first trimester. We compared the women with 2 groups of women who took either other antidepressant drugs (n = 147) or nonteratogenic drugs (n = 147). All the women were followed up after delivery to ascertain pregnancy outcome and the health of the baby. RESULTS: We have completed 147 follow-ups. There were 121 (82.4%) live births, 20 (13.6%) spontaneous abortions, and 6 (4%) therapeutic abortions. Of the live births, there were 2 (1.6%) major malformations. In all cases, drug exposure occurred during the first trimester, with 52 (35%) of the women using these drugs throughout pregnancy. The mean gestational age at birth was 38 weeks (SD 4.2), and the mean birth weight was 3306.34 g (SD 655). We found no statistically significant differences among the 3 groups in any of the endpoints of interest that we examined. Of the sample, 58 women were exposed to trazodone, and 89 were exposed to nefazodone. CONCLUSION:
Our results suggest that these drugs do not increase the rates of major malformations above the baseline rate of 1% to 3%.
Therapie. 2002 Jul-Aug;57(4):397-401.
[New antiepileptic drugs in pregnancy: outcome of 12 exposed pregnancies]
[Article in French]
Cissoko H, Jonville-Bera AP, Autret-Leca E.
Centre Regional de Pharmacovigilance et d'Information sur le Medicament, Service de Pharmacologie, CHRU, Tours, France.
There is currently little evidence available concerning the risks of foetal exposure to new anti-epileptic drugs such as lamotrigine, vigabatrin, gabapentine, topiramate. A small number of malformations without organ specificity have been described and are not easy to interpret because of the existence of concomitant treatments. We have reported a series of 12 pregnancies with exposure to recent anti-epilepticdrugs and that were reported to the Post-marketing Surveillance office in Tours, France. Five concerned Lamictal of which 2 related to monotherapy, one concerned Epitomax used in monotherapy and there were 6 cases of polytherapy including Sabril. Associated drug therapies were Depakine, Tegretol, Rivotril and Urbanyl. Six of the patients were on folic acid supplements. The average age of the women was 26.5 years. In each case, treatment had been initiated before conception and was continued for at least 3 months. Of the 12 babies born, only one presented with a malformation (aplasia of the muscle of the left lower lip and asymmetrical abduction of the hips) following exposure to Lamictal and Depakine. Four infants, two of whom were premature, showed signs of neonatal stress: transient respiratory distress and difficulty in taking feeding-bottles following exposure throughout the pregnancy to Epitomax; suction disorders, hypotonia and vomiting were observed after exposure to Sabril, Tegretol and Rivotril throughout the pregnancy; respiratory distress and apnoea--bradycardia were observed after exposure throughout the pregnancy to Lamictal and Urbanyl; respiratory distress and thrombocytopaenia were observed after exposure throughout the pregnancy to Lamictal". This small series confirms that the current data concerning the teratogenicity of new anti-epileptic drugs are as yet insufficient to exclude any teratogenic risk. Consequently, strict adherence to current recommendations relating to drug use during pregnancy is essential. The treatment of all patients wishing to become pregnant should be discussed.
Seishin Shinkeigaku Zasshi. 2003;105(9):1136-44.
[Treatment strategy for women with puerperal psychiatric disorders--psychopharmaco-therapy and its impact on fetus and breast-fed infants]
[Article in Japanese]
Yoshida K, Yamashita H.
Department of Neuropsychiatry, Kyushu University Hospital.
Women have the most possibility of suffering from mental disorders during pregnancy and postpartum periods in their whole life time. Especially, postnatal depression is not uncommon with an incidence of 10-20%, fortunately a screening system has been developed, and in Japan the Edinburgh Postnatal Depression Scale (EPDS) is now practically used in both hospitals and community health service centers. Additionally most mental disorders during this period are not severely disturbed, so they do not have to be necessarily treated by psychiatrists. Severely disturbed cases, however, which include postnatal depression with self or infant harm thought or puerperal psychosis are to be treated by psychiatrists and tend to have psychopharmaco-therapy. In using psychotropic drugs attention must be paid for both women and their babies. Impact on breast-fed babies while mothers take psychotropic drugs have been reported, mostly as case reports. We have reported the controlled studies, (1) The 25 mothers with postnatal depression were treated by tricyclic antidepressants, of which 10 breast-fed and 15 did not. The drugs were amitriptyline, imipramine, clomipramine, dothiepine, (2) The 30 mothers with puerperal psychosis were treated by antipsychotic drugs, of which 12 breast-fed and 18 did not. The drugs were chlorpromazine, trifluoperazine, perphenazine and haloperidol. Both antidepressants and neuroleptics were transferred through breast-milk and a few % of maternal dose per kilogram were injected to their babies by calculating drug concentration ratios of in breast-milk/in serum. None of the breast-fed infants had adverse effects, and no developmental difference was found compared to bottle-fed infants using the Bayley Development Scale during infancy. Furthermore, the breast-fed infants were followed up as long as possible up to 30 months and no significant developmental delay was found. In addition, we reported a case study on four breast-fed babies whose mothers took fluoxetine. The infants had no adverse effects. Pregnant women and their fetuses need to be more carefully monitored. Three preliminary cases were reported here; the pregnant women took clomipramine, sulpiride, haloperidol and chlorpromazine. Drug concentrations in maternal plasma in late pregnancy and postnatally and in umbilical cords were almost the same, which meant they were freely transferred from mothers to babies. Regarding the neonate's outcome, all were full turn born with normal birth weight with good Apgar scores. Weight gain in one month was normal which meant all babies had normal sucking without hypotonic muscle. Psychiatrists must accumulate these date and contribute as one of specialists in perinatal mental health in multi-disciplinary team.
Methotrexate formerly Amethopterin
Obstet Gynecol. 2002 Apr;99(4):599-602. :
Multiple anomalies in a fetus exposed to low-dose methotrexate in the first trimester.
Nguyen C, Duhl AJ, Escallon CS, Blakemore KJ.
Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
BACKGROUND: Methotrexate has multiple therapeutic uses in women of reproductive age including treatment for ectopic pregnancy, neoplastic disease, autoimmune disorders, and inflammatory conditions. More frequent use of methotrexate may result in an increased number of exposures in pregnant women and their fetuses. CASE: A 16-year-old gravida 1, para 0 used oral methotrexate treatment of 7.5 mg per day for psoriasis for 2 days at 3.5 weeks postconception. Multiple anomalies were noted on an 18-week ultrasound. Fetopsy revealed craniofacial, axial skeletal, cardiopulmonary, and gastrointestinal abnormalities. CONCLUSION: A minimal, low-dose, brief exposure to methotrexate in the first trimester resulted in a fetus with multiple internal and external malformations. Some of the anomalies (craniofacial and skeletal) have been previously reported with first- trimester methotrexate exposure. This case depicts the association of cardiopulmonary and gastrointestinal abnormalities with methotrexate exposure.
Stress. 2002 Sep;5(3):167-76.
Can the behaviour abnormalities induced by gestational stress in rats be prevented or reversed?
Weinstock M.
Department of Pharmacology, Hebrew University Hadassah School of Medicine, EIN Kerem, Jarusalem, Israel.
martar@cc.huji.ac.il
Gestational stress increases circulating maternal hormones that produce changes in behaviour and impair the feedback regulation of the hypothalamic pituitary adrenal axis of the offspring. Prenatally-stressed (PS) rats also release more corticotropin-releasing hormone (CRH) in the limbic system in response to stimulation than controls. This contributes to their exaggerated fear of intimidating situations and depressive-like behaviour. By using different treatments given to the pregnant mother, to neonatal or adult offspring, it has been possible to learn more about the mechanisms underlying the behavioural abnormalities induced by gestational stress. Many of these treatments were also able to prevent or reverse the abnormalities. They included maternal adrenalectomy and replacement of her basal hormone levels to avoid the prolonged elevation of plasma corticosterone, administration of anti-anxiety agents to reduce her reactions to the stress and continuous blockade of opioid receptors to prevent down-regulation of the foetal opioid system and subsequent alterations in behaviour. Hyperanxiety in the adult PS offspring could also be avoided if, as neonates, they were handled daily for 10 days, or given an antidepressant, amitriptyline for 4-5 weeks in the prepubertal period. Increased fear of novelty in adult PS rats could also be abolished by the intracerebro-ventricular administration of a CRH antagonist. This suggests that the new non-peptide CRH1 receptor antagonists that enter the brain might provide an effective treatment for the behaviour abnormalities in the offspring arising as a result of gestational stress.
1: Pediatr Res. 2002 Apr;51(4):433-42.
Comment in:
Pediatr Res. 2002 Apr;51(4):424-5.
Effect of maternal fluoxetine administration on uterine blood flow, fetal blood gas status, and growth.
Morrison JL, Chien C, Riggs KW, Gruber N, Rurak D.
Department of Obstetrics and Gynaecology, British Columbia Research Institute for Children's & Women's Health, Vancouver, BC, Canada.Clinical depression, diagnosed in 5-15% of women during pregnancy, increases the risk of negative pregnancy outcomes including an increased incidence of low birth weight newborns and preterm delivery. Fluoxetine, a selective serotonin reuptake inhibitor, is often prescribed to treat depression due to its efficacy, high margin of safety, and mild side effects. However, fluoxetine initially increases plasma serotonin concentration, and serotonin causes uterine vasoconstriction in sheep, which could result in fetal hypoxemia. To assess fetal fluoxetine effects, late-gestation pregnant sheep were surgically prepared for the measurement of blood gases, heart rate, blood pressure, and uterine artery blood flow (n = 29). Ewes received a 70-mg bolus i.v. infusion of fluoxetine over 2 min in 10 mL of sterile water followed by continuous infusion at a rate of 100 microg/min for 8 d (n = 14), or continuous infusion of sterile water (n = 15). Transient decreases in uterine artery blood flow, fetal PO(2), and oxygen saturation were observed within the first 15 min after fluoxetine exposure, which did not return to normal values by 24 h. Fetal pH decreased and PCO(2) increased over the first 4 h with a return to normal by 24 h. However, there were no differences in uterine artery blood flow, blood gas status, or cardiovascular measures between the control and fluoxetine group over the rest of the 8-d infusion period. Thus, fluoxetine exposure during pregnancy has transient effects on fetal status that may be of developmental consequence if they occur repetitively.
Eur J Obstet Gynecol Reprod Biol. 2002 Mar 10;101(2):147-54.
A population-based case-control teratologic study of nitrazepam, medazepam, tofisopam, alprazolum and clonazepam treatment during pregnancy.
Eros E, Czeizel AE, Rockenbauer M, Sorensen HT, Olsen J.
Department of Human Genetics and Teratology, National Center for Epidemiology, Budapest, Hungary.
OBJECTIVE: To study the association between nitrazepam, medazepam, tofisopam, alprazolum and clonazepam treatments during pregnancy and prevalence of different congenital abnormalities (CAs). MATERIALS AND METHODS: A matched case-control study using cases with CAs and population controls from the dataset of the nationwide Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA), 1980-1996. RESULTS: Of 38,151 pregnant women who had babies without any defects (population control group), 75 (0.20%) were treated with these five benzodiazepines during pregnancy. Of 22,865 pregnant women who delivered offspring with CAs, 57 (0.25%) had benzodiazepine treatment. The occurrence of five benzodiazepine treatments during the second and third months of gestation, i.e. in the critical period for most major CAs did not show significant differences in matched case-control pairs. CONCLUSION: Treatment with five benzodiazepines studied during pregnancy did not present detectable teratogenic risk to the fetus in humans but the amount of information was limited for different CAs.
Acta Paediatr. 2001 Mar;90(3):288-91. :
Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors.
Nordeng H, Lindemann R, Perminov KV, Reikvam A.
Department of Pharmacotherapeutics, University of Oslo, Oslo, Norway.
h.m.e.nordeng@farmasi.uio.no
Selective serotonin reuptake inhibitors (SSRIs) are a new group of antidepressants used in mild to moderate cases of depression. In studies evaluating the safety of SSRIs during pregnancy, no increase in major anomalies has been reported. This might have led to increasing off-label prescription of SSRIs to pregnant women. Neonatal withdrawal syndrome commonly occurs in infants exposed during the third trimester to drugs known to cause addiction. We report five cases of neonatal withdrawal syndrome after third trimester in utero SSRI exposure. In three cases the mother used paroxetine in doses from 10 to 40 mg, one mother used citalopram 30 mg, and one mother fluoxetine 20 mg. Withdrawal symptoms occurred within few days after birth and lasted up to one month after birth. Four of the infants needed treatment with chlorpromazine. Symptoms were irritability, constant crying, shivering, increased tonus, eating and sleeping difficulties and convulsions. CONCLUSION: Neonatal withdrawal syndrome can occur after third trimester in utero SSRI exposure. Further research should focus on whether it is safe to use SSRIs during the last trimester. All neonates exposed to SSRIs during the last trimester should be followed-up closely for withdrawal symptoms after birth.
Epilepsia. 2000 Jun;41(6):709-13. :
Lamotrigine in pregnancy: pharmacokinetics during delivery, in the neonate, and during lactation.
Ohman I, Vitols S, Tomson T
.
Departments of Clinical Pharmacology and *Clinical Neuroscience, Section of Neurology, Karolinska Institute at Karolinska Hospital, Stockholm, Sweden.
inoeh@mb.ks.se
PURPOSE: To investigate the pharmacokinetics of lamotrigine (LTG) during delivery, during the neonatal period, and lactation. METHODS: High-performance liquid chromatography was used to determine plasma and milk levels of LTG in nine pregnant women with epilepsy treated with LTG, and plasma levels in their 10 infants. Samples were obtained at delivery, the first 3 days postpartum, and at breast-feeding 2-3 weeks after delivery. RESULTS: At delivery, maternal plasma LTG concentrations were similar to those from the umbilical cord, indicating extensive placental transfer of LTG. There was a slow decline in the LTG plasma concentration in the newborn. At 72 h postpartum, median LTG plasma levels in the infants were 75% of the cord plasma levels (range, 50-100%). The median milk/maternal plasma concentration ratio was 0.61 (range, 0.47-0.77) 2-3 weeks after delivery, and the nursed infants maintained LTG plasma concentrations of approximately 30% (median, range 23-50%) of the mother's plasma levels. Maternal plasma LTG concentrations increased significantly during the first 2 weeks after parturition, the median increase in plasma concentration/dose ratio being 170%. CONCLUSIONS: Our data demonstrate a marked change in maternal LTG kinetics after delivery, possibly reflecting a normalization of an induced metabolism of LTG during pregnancy. LTG is excreted in considerable amounts in breast milk (the dose to the infant can be estimated to >/=0.2-1 mg/kg/day 2-3 weeks postpartum), which in combination with a slow elimination in the infants, may result in LTG plasma concentrations comparable to what is reported during active LTG therapy. No adverse effects were observed in the infants, however.
Depress Anxiety. 2000;11(2):51-7.
Dose of selective serotonin uptake inhibitors across pregnancy: clinical implications.
Hostetter A, Stowe ZN, Strader JR Jr, McLaughlin E, Llewellyn A.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
The use of antidepressants during pregnancy has undergone considerable scrutiny with respect to safety issues, though limited data with respect to dose management and symptom resolution is available. Previous reports on tricyclic antidepressants (TCAs) have demonstrated the need to adjust maternal dose later in pregnancy to maintain therapeutic serum concentrations. However, there is no data on the dosage of selective serotonin uptake inhibitors (SSRIs) required to maintain symptom resolution in women treated for major depression during pregnancy. The purpose of this study, then, was to assess the medication dosage requirements of SSRIs during this time. In this naturalistic study, pregnant women with a primary diagnosis of major depression were followed prospectively through pregnancy at monthly intervals with symptom assessment. Subjects were included in data analysis if they presented prior to 28 weeks gestation, were treated with SSRI monotherapy, received all psychiatric treatment during the pregnancy at the Emory Pregnancy and Postpartum Mood Disorders Program, and achieved euthymia after initial treatment intervention (CGI = 1 and Beck Depression Inventory (BDI) < 9) during pregnancy or failed to respond after eight weeks of treatment. Medication selection was based on personal treatment history or family treatment history (if any), and the published data on SSRIs in pregnancy. All medication dose adjustments were based on depressive symptoms as measured by the BDI and a psychiatric interview (ZNS). Thirty-four pregnant women were included in final analysis. Two thirds of the subjects (n = 22) required an increase in their daily dose of medication to maintain euthymia. The dose increases occurred at 27.1 +/- 7.1 weeks gestation, with mean BDI scores of 16.4 +/- 9.6, compared to a mean treatment response BDI of 6.9 +/- 5.4. Subject's age, education, past personal and familial psychiatric history were not significantly associated with dose adjustment. These novel data on SSRI daily dose in pregnancy parallels the extant literature with tricyclic antidepressants (TCA). Further work to determine the predictors of dose adjustments will provide guidelines for minimizing fetal exposure to both medication and maternal mental illness.
Prescrire Int. 1999 Oct;8(43):157-9. :
Serotonin reuptake inhibitor antidepressants and pregnancy: many unanswered questions.
[No authors listed]
(1) Serotonin reuptake inhibitor antidepressants are not teratogenic in animals. (2) Human data are limited, and most involve fluoxetine. (3) No data pointing to a teratogenic effect after fluoxetine exposure during the first trimester have been reported. (4) Self-resolving neurological signs have been observed in newborns exposed to fluoxetine at the end of pregnancy. (5) The paucity of data requires all prescribers of antidepressants to pregnant women to report any adverse events occurring in a child or mother to a teratogenicity or pharmacovigilance centre
Drug Saf. 1999 Feb;20(2):171-86. :
Treatment of anxiety during pregnancy: effects of psychotropic drug treatment on the developing fetus.
McGrath C, Buist A, Norman TR.
University of Melbourne, Heidelberg, Victoria, Australia. c.mcgrath@medicine.unimelb.edu.au
Pregnancy is a time of great emotional change for a woman, producing increased stress and anxiety. Medication may be required for the treatment of anxiety disorders at this time. Given the fact that psychotropic drugs readily cross the placenta and could have important implications for the developing fetus, it is necessary to balance the possible effects of medication against the potential effects to both the mother and fetus if the anxiety disorder is left untreated. Despite the widespread use of psychotropic drugs such as benzodiazepines and antidepressants during pregnancy, there is a paucity of information regarding the effect of such exposure on the developing fetus. From a review of the literature it is clear that the issue of safety of psychotropic drugs during pregnancy is far from resolved. While some of the findings from animal studies are alarming, these studies cannot be directly extrapolated to humans. In addition, varying sample sizes and multiple drug exposures further complicate interpretation of human studies. Nonpharmacological treatments such as cognitive behavioural therapy should be employed whenever possible for the treatment of anxiety disorders during pregnancy. However, if medication is required pregnant women should be prescribed the lowest dosage for the minimum amount of time.
