Yıl: 2011 Cilt: 21 Sayı: 2 Sayfa Aralığı: 161 - 173 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Gebelikte psikotrop ilaç kullanımı: Bir güncelleme

Öz:
Gebelik dönemi, hormonal ve psikososyal yaşam tarzı değişikliklerinin olduğu çalkantılı bir dönemdir. Bu nedenle gebelik döneminde depresyon, anksiyete bozuklukları, obsesif kompulsif bozukluk gibi hastalıklar başlayabildiği gibi; psikotrop ilaç kullanımındaki aşırı kısıtlılıklardan dolayı da mevcut ciddi psikiyatrik bozuklukların alevlenmeleri sıklıkla görülebilmektedir. Gebeliklerin büyük bir bölümünün plansız olduğu düşünüldüğünde bu problemlerin aşılması hem gebe yönünden hem de gebeye bakım veren sağlık ekibi yönünden zorluklar içermektedir. Psikotrop ilaçların güvenliği ve gebelikte psikiyatrik bozuklukların tedavisinde kullanılmaları ile ilgili çelişkili bulgular vardır. Gebelikte psikofarmakolojik tedavinin yararları ve riskleri dikkate alınmalıdır. Gebelere ilaç verildiğinde, bu ilaçlar anne ve plasenta kanı arasında hiçbir engel olmadığından rahatlıkla fetüsa ulaşırlar. Genellikle fetüs serumunda annenin serumunda tesbit edilen ilaç düzeylerinden daha yüksek oranda psikotrop ilaç düzeyleri oluşmaktadır. Bundan dolayı gebelikte ilaç kullanımına karar verilirken neonatal toksisite, prematüre ve ölü doğum ile morfolojik ve davranışsal teratojenite risklerinin dikkate alınması gerekmektedir.Teratojenite denince de, sadece anatomik malformasyonlar değil, aynı zamanda uzun vadeli davranışsal teratojenite de ilaçların güvenilirliği değerlendiriliken gözönüne alınmalıdır. Klasik antipsikotikler ve trisiklik antidepresanlar (klorimipramin hariç) fetüs için görece güvenlidirler. Neredeyse tüm prenatal dönemdeki antidepresan kullanımı anomali riski ile ilişkilidir. Özellikle bu risk paroksetin ve klorimipramine maruz kalanlarda daha da artmış gibi görünmektedir. Bir çok atipik antipsikotiğin gestasyonel diyabeti tetikleyerek fetal malformasyon oranında artış yaptıklarına ilişkin anlamlı veriler mevcuttur. Bu nedenle gebelikten önce atipik antipsikotik kullanımını sürdüren anne adaylarında gebelik başladığında mutlaka klasik antipsikotiklere geçiş yapılmalıdır. Mizaç dengeleyicileri (lityum, karbamazepin, valproat, v.b. gibi antikonvülzanlar)’nin yüksek teratojenik riskleri olduğu eskiden beri bilinmektedir. Bununla birlikte son zamanlarda lityum için bu teratojenite riski düşürülmüştür. Buna karşılık özellikle gebelikte valproat kullanımının fetal anomaliler ve otizm-spektrum bozuklukları riski ile güçlü ilişkileri vardır. Bu nedenlerle gebelikte, özellikle klomipramin, paroksetin, valproat ve atipik antipsikotiklerin kullanımının önlenmesi tavsiye edilir. İlk trimesterde kullanılan benzodiazepinler teratojenik olup; yenidoğanda da yüksek dozda yoksunluk belirtileri, hipotoni ve ajitasyona neden olabilirler. Yine uzun vadeli psikotrop ilaç kullanımına ihtiyaç var ise, tam bir değerlendirme yapılmalı ve polifarmasi, gereksiz ilaç kullanımı önlenmelidir. Kullanılacak psikotrop ilaçların dozları asgari ölçülerde tutulmalıdır. Çünkü, gebelik sırasında kullanılması mutlak gerekli olan ilaçları kesmek için çok fazla geçerli neden yoktur. Bu yazıda, günlük psikiyatri pratiğinde çok karşılaşılan ve önemli bir konu olan “gebelikte psikotrop ilaç kullanımı”nı son veriler ışığında güncelleştirmek istedik.
Anahtar Kelime:

Konular: Farmakoloji ve Eczacılık

Psychotropic drug use in pregnancy: An update

Öz:
Pregnancy is a turbulent period, during which hormonal and psychosocial lifestyle changes occur. Hence depression, anxiety disorders, or obsessive-compulsive disorders can be triggered and chronic psychiatric disorders can be exacerbated, particularly, due to limitations on the use of psychotropic drugs. Considering a large percentage of pregnancies are not planned, overcoming these challenges creates difficulties for both the pregnant women and the team providing health care services. There are contradictory findings about the safety of psychotropic drugs and their use in the treatment of psychiatric disorders during pregnancy. The benefits and risks of psychopharmacological treatment during pregnancy should be considered carefully. When psychotropic drugs are given to pregnant women they easily reach fetüs, as there are no barriers between maternal and placental blood. Generally higher serum drug levels are detected in newborns than in maternal serum. Therefore in deciding on psychotropic drug use during pregnancy, the risks of neonatal toxicity, premature and still births, and morphological and behavioral teratogenicity must be taken into account. In addition not only anatomical malformations, but also long-term behavioral teratogenicity of the drugs must be considered while evaluating the safety of drug use during pregnancy. The classical antipsychotics and tricyclic antidepressants (except chlomipramine) are relatively safe for the fetus. Antidepressant use is associated with the risk of anomalies during almost all of the prenatal period; however, the risk appears to be especially increased in fetüses that have been exposed to paroxetine and chlomipramine. There are significant findings that many atypical antipschotics cause an increase in the rate of fetal malformations by provoking gestational diabetes. Therefore, women who wish to become pregnant, who have been on ongoing atypical antipsychotic treatment before pregnancy, should always be switched to conventional antipsychotics upon the beginning of pregnancy. Benzodiazepines used during the first trimester can be teratogenic and can cause withdrawal symptoms in high doses in newborns, hypotonia, and agitation. The mood stabilizers (carbamazepine, valproate, similar anticonvulsants, and lithium) have been known to possess high teratogenic risk for a long time. However, the teratogenicity risk for lithium has recently been decreased. On the other hand, the use of valproate during pregnancy has a strong association with the risk of fetal abnormalities and autism-spectrum disorders. For these reasons, the uses of clomipramine, paroxetine, valproate, and atypical antipsychotics are recommended to be avoided during pregnancy. If there is a need for long-term use of psychotropic drugs during pregnancy, a full assessment should be conducted, polypharmacy and unnecessary medication use should be avoided, and the doses of psychotropic drugs should be kept to a minimum, because there are rarely valid reasons to discontinue medications that are necessary during pregnancy. In this paper, we aimed to update psychotropic drug use during pregnancy, an important and common issue in daily psychiatry practice, in the light of recent data.
Anahtar Kelime:

Konular: Farmakoloji ve Eczacılık
Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık
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  • 1. Akdeniz F, Gebelik ve mzirme Döneminde Psikotrop İlaç Kullanımı. İçinde Temel Psikofarmakoloji. Yüksel N, Tural,Ü,Soygür H, Demet M M. ( Editörler )Ankara, TPD BÇB Dizisi- No:11, 2010:1292-312.
  • 2. Erden AC, Bayhan G. Gebelikte psikotropik ilaçların kullanımı. Psikofarmakoloji Bülteni - Bulletin of Clinical Psychopharmacology 1999; 9:28-33.
  • 3. Marcus SM, Flynn HA, Blow FC, Barry KL. Depressive symptoms among pregnant women screened in obstetrics settings. J Womens Health (Larchmt) 2003;12:373-80.
  • 4. Oberlander TF, Warburton W, Misri S. Neonatal outcomes after prenatal exposure to selective serotonin reuptake inhibitor antidepressants and maternal depression using population-based linked health data. Arch Gen Psychiatry 2006;63:898-906.
  • 5. Stowe Z, Hostetter A, Newport D. The onset of postpartum depression: implications for clinical screening in obstetrical and primary care. Am J Obstet Gynecol 2005;192:522-26
  • 6. Cohen LS, Altshuler LL, Harlow BL. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. JAMA 2006;295:499-507.
  • 7. Blehar MC, DePaulo JR Jr, Gershon ES, Reich T, Simpson SG, Nurnberger JI Jr. Women with bipolar disorder: findings from the NIMH Genetics Initiative sample. Psychopharmacol Bull. 1998;34:239-43.
  • 8. Freeman MP, Smith KW, Freeman SA.The impact of reproductive events on the course of bipolar disorder in women. J Clin Psychiatry 2000; 63:284-7.
  • 9. Viguera AC, Nonacs R, Cohen LS, Tondo L, Murray A, Baldessarini RJ. Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance. Am J Psychiatry. 2000;157:179-84.
  • 10. Newport DJ, Stowe ZN, Viguera AC.Lamotrigine in bipolar disorder: efficacy during pregnancy. Bipolar Disord 2008;10:432-6.
  • 11. Viguera AC, Whitfield T, Baldessarini RJ, Newport DJ, Stowe Z, Reminick A, Zurick A, Cohen LS. Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry. 2007;164:1817-24.
  • 12. Glaze R, Chapman G, Murray D: Recurrence of puerperal psychosis during late pregnancy. Br J Psychiatry 1991;159:567-9.
  • 13. Miller LJ: Sexuality, reproduction, and family planning in women with schizophrenia. Schizophr Bull 1997;23:623-35.
  • 14. Neziroglu FN, Anemone MA, Yaryura-Tobias JA. Onset of obsessive-compulsive disorder in pregnancy. Am J Psychiatry 1992;149:947-50.
  • 15. Hertzberg T, Wahlbeck K.The impact of pregnancy and puerperium on panic disorder: a review. J Psychosom Obstet Gynecol 1999;20:59-64.
  • 16. Allen S. A quantitative analysis of the process, mediating variables, and impact of traumatic childbirth. J Reprod Infant Psychol 1998;16:107-31.
  • 17. Stowe ZN, Nemeroff CB.Women at risk for postpartum-onset major depression. Am J Obstet Gynecol 1995;173:639-45.
  • 18. McGorry P, Conell S. The nosology and prognosis of puerperal psychosis: a review. Compr Psychiatry 1990;31:519-34.
  • 19. Rutter, M. Maternal depression and infant development: cause and consequence, sensitivity and specificity. In Postpartum Depression and Child Development (eds L. Murray & P. J. Cooper), 1997 New York: Guilford Press,pp. 295-315.
  • 20. Newport DJ, Owens MJ, Knight DL, Ragan KA, Morgan N, Nemeroff CB and Stowe ZN. Alterations in platelet serotonin transporter binding in women with postpartum onset major depression. J Psychiatr Res 2004;38:467-73.
  • 21. Güz H, Dilbaz N.Gebelikte psikotrop ilaçların kullanımı . Psikofarmakoloji Bülteni - Bulletin of Clinical Psychopharmacology 1998; 8:1-7.
  • 22. Rubin, P. C. (ed.) Prescribing in Pregnancy (2nd ed.). London: BMJ Publishing,1995.
  • 23. Ornoy A. Valproic acid in pregnancy: how much are we endangering the embryo and fetus? Reprod Toxicol, 2009;28:1-10.
  • 24. Simon GE, Cunningham ML, Davis RL. Outcomes of prenatal antidepressant exposure. Am J Psychiatry 2002; 159:2055-61.
  • 25. Diav-Citrin O, Shechtman S, Weinbaum D, Wajnberg R, Avgil M, Di Gianantonio E, et al. Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational study. Br J Clin Pharmacol 2008;66:695-705.
  • 26. FDA Public HealthAdvisory. Paroxetine. http://69.20.19.211/cder/ drug/advisory/paroxetine200512.htm.(Accessed 10 May 2008)
  • 27. Kallen B, Olausson PO. Maternal use of selective serotonin re-uptake inhibitors and persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf 2008;17: 801-6.
  • 28. Cole JA, Ephross SA, Cosmatos IS Walker AM. Paroxetine in the first trimester and the prevalence of congenital malformations. Pharmacoepidemiol Drug Saf 2007;16:1075-85.
  • 29. Reis M, Källén B. Delivery outcome after maternal use of antidepressant drugs in pregnancy: an update using Swedish data. Psychol Med. 2010;40:1723-33.
  • 30. Einarson A, Choi J, Einarson TR, Koren G. Incidence of major malformations in infants following antidepresant exposure in pregnancy: results of a large prospective cohort study. Can J Psychiatry 2009;54:242-6
  • 31. Bérard A, Ramos E, Rey E, Blais L, St-André M and Oraichi D. First trimester exposure to paroxetine and risk of cardiac malformations in infants: the importance of dosage. Birth Defect Res B Birth Defect Res B 2007;80:18-27.
  • 32. Cole JA, Ephross SA, Cosmatos IS, et al: Paroxetine in the first trimester and the prevalence of congenital malformations. Pharmacoepidemiol Drug Saf 2007;16:1075-85.
  • 33. Hendrick V, Stowe ZN, Altshuler LL, et al: Placental passage of antidepressant medication. Am J Psychiatry 2003;160:993-6.
  • 34. US Food and Drug Authority. FDA Medwatch drug alert on Effexor and SGİs. 2004. www.fda.gov/MEDWATCH/SAFETY/2004/ efexxor_dear_hcp_june.pdf. (Accessed 13 April 2008)
  • 35. Health Canada. Health Canada advises of potential serious adverse effects of SGİs and other antidepressants on newborns (advisory). Ottawa: Health Canada; 2004. http://www.hc-sc.gc.ca/ahc-asc/ media/advisories-avis/_2004/2004_44_e.html. (Accessed 13 April 2008)
  • 36. Levin R. Neonatal adverse events associated with in utero SGİ/ SNGİ exposure. www.fda.gov/ohrms/dockets/AC/04/slides/2004- 4050S1_11_Levin.ppt. (Accessed 15 February 2008)
  • 37. Gentile S. SRI-induced perinatal complications. Paediatr Drugs 2007; 9:97-106.
  • 38. FDA ALERT (7/2006): Increased risk of neonatal persistent pulmonary hypertension. http://www.fda.gov/Drugs/DrugSafety/ PostmarketDrugSafetyInformationforPatientsandProviders/ DrugSafetyInformationforHeathcareProfessionals/ucm085313.htm. (Accessed 21 April 2010)
  • 39. Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C, Jones KL, Mitchell AA. Selective serotonin reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. New Engl J Med 2006; 354:579-87.
  • 40. Källén B, Otterblad-Olausson P. Maternal use of selective re-uptake inhibitors and persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf 2008; 17:801-6.
  • 41. Andrade SE, McPhillips H, Loren D, Raebel MA, Lane K, Livingston J,et al. Antidepressant medication use and the risk of persistent pulmonary hypertension of the newborn. Pharmacoepidemiol Drug Saf 2009; 18:246-52.
  • 42. Sanz EJ, De-las-Cuevas C, Kiuru A, Bate A, Edwards R. Selective serotonin reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet 2005; 365:482-7.
  • 43. Gentile S. On categorizing gestational, birth, and neonatal complications following late in utero exposure to antidepressants. The Prenatal Antidepressant Exposure Syndrome. CNS Spectr 2010; 15:167-85.
  • 44. Lund N, Pedersen LH, Henriksen TB. Selective reuptake inhibitor exposure in utero and pregnancy outcome. Arch Pediatr Adolesc Med 2009; 163:949-54.
  • 45. Lennestål R, Källén B. Delivery outcome in relation to maternal use of some recently introduced antidepressants. J Clin Psychopharmacol 2007; 27:607-13.
  • 46. Nulman I, Rovet J, Stewart DE, Wolpin J, Gardner HA, Theis JG, et al: Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997;336:258-62.
  • 47. Nulman I, Scolnik D, Chitayat D, Farkas LD, Koren G. Findings in children exposed in utero to phenytoin and carbamazepine monotherapy: independent effects of epilepsy and medications. Am J Med Genet 1997;68:18-24.
  • 48. Nulman I, Rovet J, Stewart DE, Wolpin J, Pace-Asciak P, Shuhaiber S, Koren G. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry 2002;159:1889-95.
  • 49. Casper RC, Fleisher BE, Lee-Ancajas JC, Gilles A, Gaylor E, DeBattista A, Hoyme HE. Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr 2003;142:402-8.
  • 50. Koren G, Matsui D, Einarson A, Knoppert D, Steiner M.Is maternal use of selective serotonin reuptake inhibitors in the third trimester of pregnancy harmful to neonates? CMAJ, 2005;172: 1457-9.
  • 51. Belik J . Fetal and neonatal effects of maternal drug treatment for depression. Semin Perinatol, 2008;32:350-4.
  • 52. Eggermont E: Withdrawal symptoms in neonates associated with maternal imipramine therapy. Lancet 1973;2(7830):680.
  • 53. Nordeng H, Lindemann R, Perminov KV, Reikvam A.Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors. Acta Paediatr. 2001;90:288-91.
  • 54. Newport DJ, Wilcox M, Stowe ZN: Antidepressants during pregnancy and lactation: defining exposure. Semin Perinatol 2001;25:177-90.
  • 55. Newport DJ, Hostetter A., Arnold A., Stowe Z. The treatment of postpartum depression: minimizing infant exposures. J Clin Psychiatry . 2002; 63(Suppl 7): S31-S44.
  • 56. Loughhead AM, Fisher AD, Newport DJ, et al. Antidepressants in amniotic fluid: another route of fetal exposure. Am J Psychiatry 2006; 163:145-7.
  • 57. Newport DJ, Stowe ZN, Nemeroff CB: Parental depression: animal models of an adverse life event. Am J Psychiatry 2002;159:1265-83.
  • 58. Louik C, Lin AE, Werler MM, et al. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. New Engl J Med 2007; 356:2675-83.
  • 59. Gentile S. Escitalopram use during pregnancy. Navigating toward international guidelines and the real world. Clin Drug Invest 2008; 28:735-9.
  • 60. Gentile S, Bellantuono C. SRI-exposure during early pregnancy and the risk of fetal major malformations: focus on paroxetine. J Clin Psychiatry 2009; 70:414-22.
  • 61. Einarson A, Fatoye B, Sarkar M, Lavigne SV, Brochu J, Chambers C,et al. Pregnancy outcome following gestational exposure to venlafaxine: a multicenter prospective controlled study. Am J Psychiatry 2001; 158:1728-30.
  • 62. Oberlander TF, Warburton W, Misri S, Riggs W, Aghajanian J, Hertzman C. Major congenital malformations following prenatal exposure to serotonin reuptake inhibitors and benzodiazepines using population-based health data. Birth Def Res Part B 2008; 83:68-76.
  • 63. Schatzberg A F and Nemeroff CB (eds). The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Ed. American Psychiatric Publishing, Inc. 2009, Arlington, VA
  • 64. Dannon PN, Iancu I, Lowengrub K, Gonopolsky Y, Musin E, Grunhaus L, Kotler M. A naturalistic long-term comparison study of selective serotonin reuptake inhibitors in the treatment of panic disorder. Clin Neuropharmacol 2007; 30:326-34.
  • 65. Watanabe N, Omori IM, Nakagawa A, Cipriani A, Barbui C, McGuire H, et al. MANGA (Meta-Analysis of New Generation Antidepressants) Study Group. Safety reporting and adverse-event profile of mirtazapine described in randomized controlled trials in comparison with other classes of antidepressants in the acute-phase treatment of adults with depression: systematic review and metaanalysis. CNS Drugs 2010; 24:35-53.
  • 66. Hewett K, Gee MD, Krishen A, Wunderlich HP, Le Clus A, Evoniuk G, Modell JG. Double-blind, placebo-controlled comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR. J Psychopharmacol 2010; 24:1209-16.
  • 67. Figueroa R. Use of antidepressants during pregnancy and the risk of attention-deficit/hyperactivity disorder in the offspring. J Dev Behav Pediatr 2010; 31:641-8.
  • 68. Yacobi S, Ornoy A . Is lithium a real teratogen? What can we conclude form the prospective versus retrospective studies? A review. Isr J Psychiatry Relat Sci, 2008;45: 95-106.
  • 69. Kozma C. Neonatal toxicity and transient neurodevelopmental deficits following prenatal exposure to lithium: Another clinical report and a review of the literature. Am J Med Genet A 2005;132:441-4.
  • 70. Williams K, Oke S. Lithium and pregnancy. Psychiatric Bulletin 2000; 24: 229-31.
  • 71. Goldberg HL, Nissim R.Psychotropic drugs in pregnancy and lactation. Int J Psychiat Med 1994:24: 129-47.
  • 72. Galbally M, Snellen M, Walker S, Permezel M. Management of antipsychotic and mood stabilizer medication in pregnancy: recommendations for antenatal care. Aust N Z J Psychiatry 2010; 44:99-108.
  • 73. Newport DJ, Viguera AC, Beach AJ, Ritchie JC, Cohen LS, Stowe ZN. Lithium placental passage and obstetrical outcome: implications for clinical management during late pregnancy. Am J Psychiatry 2005; 162:2162-70.
  • 74. Gentile S. Prophylactic treatment of bipolar disorder in pregnancy and breastfeeding: focus on emerging mood stabilizers. Bipol Disord 2006; 8:207-20.
  • 75. Nguyen HT, Sharma HT, McIntyre RS. Teratogenesis associated with antibipolar agents. Adv Ther 2009; 26:281-94.
  • 76. Ardinger HH, Atkin JF, Blackston RD, Elsas LJ, Clarren SK, Livingstone S, Flannery DB, Pellock JM, Harrod MJ, Lammer EJ, et al. Verification of the fetal valproate syndrome phenotype. Am J Med Genet. 1988;29:171-85.
  • 77. Morrow J, Russell A, Guthrie E, Parsons L, Robertson I, Waddell R, et al.Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register. J Neurol Neurosurg Psychiatry. 2006;77:193-8.
  • 78. Bescoby-Chambers N, Forster P, Bates G. Foetal valproate syndrome and autism: additional evidence of an association. Dev Med Child Neurol 2001;43:202-6.
  • 79. Moore SJ, Turnpenny P, Quinn A, Glover S, Lloyd DJ, Montgomery T, Dean JC. A clinical study of 57 children with fetal anticonvulsant syndromes. J Med Genet. 2000;37:489-97.
  • 80. Wyszynski DF, Nambisan M, Surve T, Alsdorf RM, Smith CR, Holmes LB. Increased rate of major malformations in offspring exposed to valproate during pregnancy. Neurology. 2005;64:961-5.
  • 81. Meador KJ, Baker GA, Finnell RH, Kalayjian LA, Liporace JD, Loring DW, Mawer G, Pennell PB, Smith JC, Wolff MC; NEAD Study Group. In utero antiepileptic drug exposure: fetal death and malformations. Neurology 2006;67:407-12.
  • 82. Harden CL, Pennell PB, Koppel BS, Hovinga CA, Gidal B, Meador KJ, et al. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): vitamin K, folic acid, blood levels, and breastfeeding: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009;73:142-9.
  • 83. Hernandez- Diaz S, Smith CR, Wyszynski DF, Holmes LB. Risk of major malformations among infants exposed to carbamazepine during pregnancy. Birth Defects Res A: Clin Mol Teratol 2007;79:357.
  • 84. Eroğlu E, Gökçil Z, Bek S, Ulaş UH, Odabaşi Z. Pregnancy and teratogenicity of antiepileptic drugs. Acta Neurol Belg. 2008;108:53-7.
  • 85. Dodd S, Berk M. The safety of medications for the treatment of bipolar disorder during pregnancy and the puerperium. Curr Drug Saf 2006;1:25-33.
  • 86. Gaily E, Kantola-Sorsa E, Hiilesmaa V, Isoaho M, Matila R, Kotila M, et al. Normal intelligence in children with prenatal exposure to carbamazepine. Neurology. 2004;62:28-32.
  • 87. Adab N, Kini U, Vinten J,Ayres, J,Baker,G, Clayton-Smith, J, et al. The long term outcome of children born to mothers with epilepsy. J Neurol Neurosurg Psychiatry 2004; 75: 1575-83.
  • 88. Sabers A, Dam M, A-Rogvi-Hansen B, Boas J, Sidenius P, Laue Friis M, et al.A. Epilepsy and pregnancy: lamotrigine as main drug used. Acta Neurol Scand 2004;109:9-13.
  • 89. Montouris G. Safety of the newer antiepileptic drug oxcarbazepine during pregnancy. Curr Med Res Opin 2005; 21: 693-701.
  • 90. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. ACOG Committee on Practice Bulletins-Obstetrics. Obstet Gynecol 2008; 111:1001-20.
  • 91. Cunnington M, Ferber S, Quartey G. Effect of dose on the frequency of major birth defects following fetal exposure to lamotrigine monotherapy in an international observational study. Epilepsia 2007; 48:1207-10.
  • 92. Holmes LB, Baldwin EJ, Smith CR, Habecker E, Glassman L, Wong SL, Wyszynski DF. Increased frequency of isolated cleft palate in infants exposed to lamotrigine during pregnancy. Neurology 2008;70:2152-8.
  • 93. Pennell PB, Peng L, Newport DJ, Ritchie JC, Koganti A, Holley DK, et al. Lamotrigine in pregnancy: clearance, therapeutic drug monitoring, and seizure frequency. Neurology 2008; 70:2130-36.
  • 94. Ehmer U, Vogel A, Schütte JK, Krone B, Manns MP, Strassburg CP Variation of hepatic glucuronidation: Novel functional polymorphisms of the UDP-glucuronosyltransferase UGT1A4. Hepatology. 2004;39:970-7.
  • 95. Tran TA, Leppik IE, Blesi K, Sathanandan ST, Remmel R. Lamotrigine clearance during pregnancy. Neurology 2002;59:251-5.
  • 96. de Haan GJ, Edelbroek P, Segers J, Engelsman M, Lindhout D, Devile-Notschaele M, Augustijn. Gestation-induced changes in lamotrigine pharmacokinetics: a monotherapy study. Neurology 2004; 63:571-3.
  • 97. Pennell P, Gleba J, Clements S. The impact of pregnancy and childbirth on the metabolism of lamotrigine. Neurology 2004;62:292- 5.
  • 98. Page B. Pennell PB. Antiepileptic drug pharmacokinetics during pregnancy and lactation. Neurology 2003; 61:(6 suppl) 2 S35-S42.
  • 99. Anderson J, Moor CC. Anti-epileptic drugs: a guide for the nonneurologist. Clin Med. 2010;10:54-8.
  • 100. Mawer G, Briggs M, Baker GA, Bromley R, Coyle H, Eatock J, Kerr L, et al. Pregnancy with epilepsy: obstetric and neonatal outcome of a controlled study. Seizure 2010;19:112-9.
  • 101. Diav-Citrin O, Shechtman S, Bar-Oz B, Cantrell D, Arnon J, Ornoy A. Pregnancy outcome after in utero exposure to valproate: evidence of dose relationship in teratogenic effect. CNS Drugs 2008; 22:325-34.
  • 102. Vajda FJ, Hitchcock AA, Graham J, O’Brien TJ, Lander CM, Eadie MJ. The teratogenic risk of antiepileptic drug polytherapy. Epilepsia 2010; 51:805-10.
  • 103. Tomson T, Battino D. Teratogenic effects of antiepileptic medications. Neurol Clin 2009; 27:993–1002.
  • 104. Holmes LB, Wyszynski DF, Baldwin EJ, Habecker E, Glassman LH, Smith CR. Increased risk for non-syndromic cleft palate among infants exposed to lamotrigine. Birth Defects Res A Clin Mol Teratol 2006;76:318.
  • 105. Sabers A, Tomson T. Managing antiepileptic drugs during pregnancy and lactation. Curr Opin Neurol 2009; 22:157-61.
  • 106. Meador KJ, Baker GA, Browning N, Clayton-Smith J, Combs-Cantrell DT, Cohen M. Cognitive functions at 3 years after fetal exposure to antiepileptic drugs. New Engl J Med 2009; 360:1597-605.
  • 107. Bromley RL, Mawer G, Clayton-Smith J, Baker GA, Liverpool and Manchester Neurodevelopment Group. Autism spectrum disorders following in utero exposure to antiepileptic drugs. Neurology 2008; 71:1923-4.
  • 108. Ebrinç S, Cetin M, Öner Ö. Özel gruplarda bipolar bozukluk tedavisinde atipik antipsikotikler. Klinik Psikofarmakoloji Bülteni - Bulletin of Clinical Psychopharmacology 2004; 14:236-5.
  • 109. Reis M, Källén B. Maternal use of antipsychotics in early pregnancy and delivery outcome. J Clin Psychopharmacol 2008; 28:279-88.
  • 110. McKenna K, Koren G, Tetelbaum M. Pregnancy outcome of women using atypical antipsychotic drugs: a prospective comparative study. J Clin Psychiatry 2005; 66:444-9.
  • 111. Gentile S. Antipsychotic therapy during early and late pregnancy. A systematic review. Schizophr Bull. 2010;36:518-44.
  • 112. Diav-Citrin O, Shechtman S, Ornoy S, Arnon J, Schaefer C, Garbis H, et al. Safety of haloperidol and penfluridol in pregnancy: a multicenter, prospective, controlled study. J Clin Psychiatry. 2005;66:317-22.
  • 113. Newport DJ, Calamaras MR, DeVane CL, Donovan J, Beach AJ, Winn S, Atypical antipsychotic administration during late pregnancy: placental passage and obstetrical outcomes. Am J Psychiatry. 2007;164:1214-20.
  • 114. Coppola D, Russo LJ, Kwarta RF Jr, Varughese R, Schmider J.Evaluating the postmarketing experience of risperidone use during pregnancy: pregnancy and neonatal outcomes. Drug Saf 2007; 30:247-94.
  • 115. Babu GN, Desai G, Tippeswany H, Chandra PS. Birth weight and use of olanzapine during pregnancy: a prospective comparative study. J Clin Psychopharmacol 2010; 30:331-2.
  • 116. Myllynen PK, Pienimaki PK, Vahakangas KH. Transplacental passage of lamotrigine in a human placental perfusion system in vitro and in maternal and cord blood in vivo. Eur J Clin Pharmacol 2003;58:677-82.
  • 117. Lin HC, Chen IJ, Chen YH, et al. Maternal schizophrenia and pregnancy outcome: does the use of antipsychotics make a difference? Schizophr Res 2010; 116:55-60.
  • 118. Einarson A, Boskovic R. Use and safety of antipsychotic drugs during pregnancy. J Psychiatry Pract, 2009;15:183-92.
  • 119. Mendhekar DN. Possible delayed speech acquisition with clozapine therapy during pregnancy and lactation. J Neuropsychiatry Clin Neurosci, 2007;19:196-7.
  • 120. Duran A, Ugur MM, Turan S, Emul M.Clozapine use in two women with schizophrenia during pregnancy. J Psychopharmacol. 2008;2:111-3.
  • 121. Kulkarni J, McCauley-Elsom K, Marston N, Gilbert H, Gurvich C, de Castella A, Fitzgerald P. Preliminary findings from the National Register of antipsychotic medication in pregnancy. Aust NZJ Psychiatry 2008;42:38-44.
  • 122. Gentile S. Infant safety with antipsychotic therapy in breast-feeding: a systematic review J Clin Pyschiatry, 2008;69:666-73.
  • 123. McKenna K, Koren G, Tetelbaum M, Wilton L, Shakir S, Diav- Citrin O, et al.Pregnancy outcome of women using atypical antipsychotic drugs: a prospective comparison study. J Clin Psychiatry. 2005;66:444-9.
  • 124. Reis M, Kallen B. Maternal use of antipsychotics in early pregnancy and delivery outcome. J Clin Psychopharmacol, 2008;28:279-88. Klinik Psikofarmakoloji Bülteni, Cilt: 21, Sayı: 2, 2011 / Bulletin of Clinical Psychopharmacology, Vol: 21, N.: 2, 2011 - www.psikofarmakoloji.org 173 M. Çetin
  • 125. Gentile S. Contributing factors to weight gain during long-term treatment with second-generation antipsychotics: a systematic appraisal and clinical implications. Obesity Rev 2009; 10:527-42.
  • 126. Gentile S. Long term atypical antipsychotics treatment and risk of weight gain: a literature analysis. Drug Saf 2006;29:303-19.
  • 127. Wikner BN, Stiller CO, Bergman U, Asker C, Källén B,Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congential outcome and congenital malformations. Pharmacoepidemipl Drug Saf 2007;16:1203-10.
  • 128. Iqbal MM, Sobhan T, Ryals T.Effects of commonly used benzodiazepines on the fetüs, the neonate, and the nursing infant. Psychiatr Serv, 2002;53:39-49.
  • 129. Edwards IR, Biriell C. Harmonization in pharmacovigilance. Drug Saf 1994; 10:93-102.
  • 130. Fejzo MS, Poursharif B, Korst LM, Munch S, MacGibbon KW, Romero R, Goodwin TM.Symptoms and pregnancy outcomes associated with extreme weight loss among women with hyperemesis gravidarum. J Womens Health (Larchmt) 2009; 18:1981-7.
  • 131. Davies GA, Maxwell C, McLeod L, Gagnon R, Basso M, Bos H, et al. Obesity in pregnancy. J Obstet Gynaecol Can 2010; 32:165-73.
  • 132. Davson SI. Long-term risk of malignant neoplasm associated with gestational glucose intolerance. Cancer 2004; 100:149-55.
  • 133. Amselem C, Puigdollers A, Azpiroz F, Sala C, Videla S, Fernández- Fraga X,et al. Constipation: a potential cause of pelvic floor damage? Neurogastroenterol Motil 2010; 22:150-3.
  • 134. National Institute of Diabetes, Digestive, and Kidney Diseases. Constipation. http://digestive.niddk.nih.gov/ddiseases/pubs/ constipation/. (Accessed 24 April 2004)
APA ÇETİN M (2011). Gebelikte psikotrop ilaç kullanımı: Bir güncelleme. , 161 - 173.
Chicago ÇETİN Mesut Gebelikte psikotrop ilaç kullanımı: Bir güncelleme. (2011): 161 - 173.
MLA ÇETİN Mesut Gebelikte psikotrop ilaç kullanımı: Bir güncelleme. , 2011, ss.161 - 173.
AMA ÇETİN M Gebelikte psikotrop ilaç kullanımı: Bir güncelleme. . 2011; 161 - 173.
Vancouver ÇETİN M Gebelikte psikotrop ilaç kullanımı: Bir güncelleme. . 2011; 161 - 173.
IEEE ÇETİN M "Gebelikte psikotrop ilaç kullanımı: Bir güncelleme." , ss.161 - 173, 2011.
ISNAD ÇETİN, Mesut. "Gebelikte psikotrop ilaç kullanımı: Bir güncelleme". (2011), 161-173.
APA ÇETİN M (2011). Gebelikte psikotrop ilaç kullanımı: Bir güncelleme. Klinik Psikofarmakoloji Bülteni, 21(2), 161 - 173.
Chicago ÇETİN Mesut Gebelikte psikotrop ilaç kullanımı: Bir güncelleme. Klinik Psikofarmakoloji Bülteni 21, no.2 (2011): 161 - 173.
MLA ÇETİN Mesut Gebelikte psikotrop ilaç kullanımı: Bir güncelleme. Klinik Psikofarmakoloji Bülteni, vol.21, no.2, 2011, ss.161 - 173.
AMA ÇETİN M Gebelikte psikotrop ilaç kullanımı: Bir güncelleme. Klinik Psikofarmakoloji Bülteni. 2011; 21(2): 161 - 173.
Vancouver ÇETİN M Gebelikte psikotrop ilaç kullanımı: Bir güncelleme. Klinik Psikofarmakoloji Bülteni. 2011; 21(2): 161 - 173.
IEEE ÇETİN M "Gebelikte psikotrop ilaç kullanımı: Bir güncelleme." Klinik Psikofarmakoloji Bülteni, 21, ss.161 - 173, 2011.
ISNAD ÇETİN, Mesut. "Gebelikte psikotrop ilaç kullanımı: Bir güncelleme". Klinik Psikofarmakoloji Bülteni 21/2 (2011), 161-173.