Razširjenost, klinična slika in posledice za plod
Obsesivno kompulzivna motnja (OKM) je izredno heterogena motnja z obsesijami v obliki ponavljajočih se neprijetnih vsiljivih misli, podob, impulzov, ki povzročajo hudo tesnobo. Oseba lahko to tesnobo lajša s kompulzijami, ki so vedenja ali dejanja, katera prepozna kot svoja lastna, a nesmiselna in se ne more upreti potrebi po njihovemu po-navljanju. Običajno ima kroničen potek, prevalenca v splošni populaciji je okoli 1 % (68, 69), življenjska prevalenca znaša 2,3 % (5).
Prevalenca v nosečnosti znaša okoli 2 %, v prvem letu po porodu okoli 2,5 % (68). Po podatkih drugih avtorjev prevalenca v celotnem obporodnem obdobju znaša med 4 in 9
% (70). Ženske v obporodnem obdobju imajo torej v primerjavi z ostalimi življenjskimi obdobji večje tveganje za OKM. Takrat bodo bolj verjetno doživele začetek ali relaps OKM kot splošna populacija.
Nosečnost in porod sta povezana s poslabšanjem OKM ali njenim začetkom. Na to kaže podatek, da se je pri približno tretjini žensk z OKM ta začela v perinatalnem obdobju – pri slabi polovici v nosečnosti, pri polovici po porodu in pri malo več kot 1 % po spon-tanem splavu. V nosečnosti se lahko simptomi že obstoječe OKM poslabšajo pri dobri tretjini žensk, izboljšajo pri dobri petini, pri ostalih pa ni sprememb. V raziskavah so ugotavljali, da so se pri večini žensk z začetkom OKM v nosečnosti oziroma perinatal-nim poslabšanjem, poslabšanja simptomov dogajala že pred menstruacijo, zato sklepajo, da je v to dogajanje vpleten tudi hormonski mehanizem (70, 71).
V nosečnosti so najpogostejše obsesije kontaminacije in simetrije/natančnosti ter kom-pulzije umivanja, čiščenja in preverjanja. Po porodu je največ ego-distoničnih obsesij o poškodovanju otroka, ki jih spremljajo izogibajoče vedenje in/ali kompulzije preverjanja (72). Misli o poškodovanju otroka se ženska ustraši. Njeno stisko poveča prepričanje, da dobra in skrbna mama takšnih misli ne bi smela imeti. Vendar pri OKM ni želje po
uresničenju teh misli in nevarnosti za otroka ni. Prisotni so strah, sram in občutki krivde, zato o tem redko spregovorijo same. Obvezno je treba izključiti duševne motnje, pri katerih bi te ideje lahko bile ogrožajoče za otroka (poporodna psihoza).
Tako kot novorojenčki žensk z anksioznimi motnjami, imajo lahko tudi novorojenč-ki žensk z OKM nižjo porodno težo. V popkovnični krvi so našli povišane vrednosti faktorja nekroze tumorja alfa (TNF-α), provnetnega citokina, ki lahko spodbuja vnetne procese v možganih fetusa in tako vpliva na njegov razvoj (73). Posamezni simptomi OKM pogosto spremljajo katerokoli duševno motnjo. Pri okoli polovici žensk s po-porodno depresijo se pojavljajo obsesivne misli agresivnih vsebin, ki so usmerjene na otroka (74).
Priporočila za zdravljenje OKM v obporodnem obdobju
Če je OKM blago do zmerno izražena, je ustrezna oblika zdravljenja kognitivno vedenj-ska terapija. Če je močno izražena, obsesije in kompulzije vzamejo veliko časa in so velika ovira v vsakodnevnem življenju, je priporočljivo zdravljenje z zdravili.
Zdravila prvega izbora za zdravljenje OKM so zaradi dobre prenosljivosti tako kot pri anksioznih motnjah antidepresivi iz razreda SSRI, običajno v višjih odmerkih kot pri depresiji in anksioznih motnjah, tudi do 400 mg sertralina dnevno ali do 50 mg escita-loprama ali 80 mg fluoksetina (75, 76). V primeru neučinkovitosti zdravljenja nekateri dokazi podpirajo dodajanje antipsihotika, drugi pa visoke odmerke SSRI (77).
V nosečnosti ob že prisotni motnji, ki je dobro stabilizirana z zdravili, preverimo nji-hov vpliv na plod. Za zamenjavo se odločimo glede na tveganja in koristi. Predpišemo najnižji še učinkovit odmerek. Med napredovanjem nosečnosti se zaradi večjega po-razdelitvenega volumna in spremenjenega metabolizma učinkovitost zdravil običajno zmanjša. To se pokaže s poslabšanjem simptomatike.
Če se v nosečnosti OKM pojavi prvič in je potrebno zdravljenje z zdravili, najprej pred-pišemo antidepresiv iz skupine SSRI. Sertralin, escitalopram in citalopram so najboljša izbira pri zdravljenju OKM v nosečnosti (78). Ob delnem ali nobenem odzivu odmerek antidepresiva postopoma povišamo do še sprejemljivega za nosečnost. Če še ni želenega odziva, lahko antidepresiv zamenjamo, ali pa dodamo atipični antipsihotik, prvi izbor naj bi bil risperidon. Zdravilo drugega izbora je fluvoksamin, tretjega fluoksetin in četrtega paroksetin, klomipramin ali venlafaksin.
V prvem trimesečju nosečnosti ni priporočljivo jemanje fluoksetina in paroksetina, prav
tako se ju odsvetuje ženskam, ki bi lahko nenačrtovano zanosile, ker sta povezana s tve-ganjem za prirojene napake (79). Sicer naj antidepresivi ne bi bili povezani s povečanim tveganjem za prirojene malformacije, statistično pomembna je povezava paroksetina s srčno žilnimi napakami (80). Paroksetin je varen za uporabo ob dojenju.
Zaključek
Kljub temu, da anksiozne motnje uspešno zdravimo z zdravili in psihoterapijo, so po-gosto spregledane in nezdravljene, pomoč poišče le petina oseb, ki trpi zaradi njih. Pri ženskah so dvakrat pogostejše kot pri moških, prisotne so v skoraj celotnem rodnem obdobju. Hormonska nihanja vplivajo na pojav in potek motnje v primeru občutljivosti centralnega živčevja nanje. V nosečnosti jih je treba zdraviti, ker preko kroničnega stres-nega odziva materistres-nega telesa vplivajo na potek nosečnosti in razvoj ploda, po porodu pa na materino nadaljnje duševno zdravje in na razvoj otroka. V vsakdanji klinični praksi se pri zmerno izraženih motnjah zaradi slabe dostopnosti psihoterapije pogosteje odlo-čamo za zdravljenje z zdravili, a v času nosečnosti in laktacije moramo skrbno pretehtati koristi in tveganja njihove uporabe tako za žensko kot za plod. Številni antidepresivi so dovolj varni, da koristi močno presegajo tveganja njihove uporabe. V Sloveniji nastaja nacionalni presejalni program za nosečnice in ženske po porodu, s katerim bomo lahko prepoznali tiste s tveganjem za duševne motnje, jih vključili v diagnostiko in obravnavo ter morda tako nekoliko prispevali k boljšemu duševnemu zdravju prebivalstva.
Literatura
1. Alonso J, Lepine JP, Committee ESMS. Overview of key data from the European Study of the Epide-miology of Mental Disorders (ESEMeD). J Clin Psychiatry 2007; 68 (suppl 2): 3–9.
2. Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci 2015; 17(3): 327–35.
3. Hantsoo L, Epperson CN. Anxiety Disorders Among Women: A Female Lifespan Approach. Focus 2017; 15(2): 162–72. doi: 0.1176/appi.focus.20160042.
4. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). National Comorbidity Survey Replication. JAMA 2003; 289: 3095–105.
5. Kessler RC, Petukhova M, Sampson NA, Zaslavsky AM, Wittchen HU. Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. Int J Methods Psychiatr Res 2012; 21(3): 169–84. doi:10.1002/mpr.1359.
6. Nolen-Hoeksema S. Emotion regulation and psychopathology: the role of gender. Annu Rev Clin Psychol 2012; 8: 161–87. doi: 10.1146/annurev-clinpsy-032511-143109.
7. Schmidt PJ, Nieman LK, Danaceau MA et al. Differential behavioral effects of gonadal steroids in women with and in those without premenstrual syndrome. N Engl J Med 1998; 338: 209–16.
8. Field T. Postnatal anxiety prevalence, predictors and effects on development: A narrative review. In-fant Behav Dev 2018; 51: 24–32. doi: 10.1016/j.infbeh.2018.02.005.
9. Dennis CL, Falah-Hassani K, Shiri R. Prevalence of antenatal and postnatal anxiety: systematic revi-ew and meta-analysis. Br J Psychiatry 2017; 210: 315–23.
10. Wynter K, Rowe H, Fisher J. Common mental disorders in women and men in the first six months after the birth of their first infant: a community study in Victoria, Australia. J Affect Disord 2013; 151:
980–5.
11. Wenzel A, Haugen EN, Jackson LC, Brendle JR. Anxiety symptoms and disorders at eight weeks postpartum. J Anxiety Disord 2005; 19: 295–311.
12. Brockington IF, Macdonald E, Wainscott G. Anxiety, obsessions and morbid preoccupations in preg-nancy and the puerperium. Arch Womens Ment Health 2006; 9: 253–63.
13. Matthey S, Barnett B, Howie P, Kavanagh DJ. Diagnosing postpartum depression in mothers and fathers: whatever happened to anxiety? J Affect Disord 2003; 74: 139–47.
14. Robertson E, Grace S, Wallington T, Stewart DE. Antenatal risk factors for postpartum depression: A synthesis of recent literature. Gen Hosp Psychiatry 2004; 26: 289–95.
15. Heron J, O'Connor TG, Evan J. The course of anxiety and depression through pregnancy and the postpartum in a community sample. J Affect Disord 2004; 80: 65–73.
16. O'Connor TG, Heron J, Golding J, Beveridge M, Glover V. Maternal antenatal anxiety and children's behavioural/emotional problems at 4 years. Report from the Avon Longitudinal Study of Parents and Children. Br J Psychiatry 2002; 180: 502–8.
17. Glover V, O'Connor TG, Heron J, Golding J. Antenatal maternal anxiety is linked with atypical han-dedness in the child. Early Hum Dev 2004; 79: 107–18.
18. Field T. Prenatal anxiety effects: A review. Infant Behav Dev 2017; 49: 120–8. doi: 10.1016/j.in-fbeh.2017.08.008.
19. Huizink AC, Mulder EJ, Buitelaar JK. Prenatal stress and risk for psychopathology: specific effects or induction of general susceptibility? Psychol Bull 2004; 130: 115–42.
20. O'Connor TG, Heron J, Glover V, ALSPAC Study Team. Antenatal anxiety predicts child behavio-ral/emotional problems independently of postnatal depression. J Am Acad Child Adolesc Psychiatry 2002; 41: 1470–7.
21. O'Connor TG, Heron J, Golding J, Glover V, ALSPAC Study Team. Maternal antenatal anxiety and behavioural/emotional problems in children: a test of a programming hypothesis. J Child Psychol Psychiatry 2003; 44: 1025–36.
22. Teixeira JM, Fisk NM, Glover V. Association between maternal anxiety in pregnancy and increased uterine artery resistance index: cohort-based study. BMJ 1999; 318: 153–7.
23. Barker DJ. The fetal origins of adult disease. Proc R Soc Lond B Biol Sci 1995; 262: 37–43.
24. Henshaw C, Cox J, Barton J. Childbearing in women with existing mental disorders. V: Henshaw C, Cox J, Barton J. Modern management of Perinatal Psychiatric Disorders. 2nd ed. London: RCPsych Publications; 2017; 93.
25. Miranda A, Sousa N. Maternal hormonal milieu influence on fetal brain development. Brain Behav 2018; 8(2): e00920. doi:10.1002/brb3.920.
26. Salvante KG, Milano K, Kliman HJ, Nepomnaschy PA. Placental 11 β-hydroxysteroid dehydrogena-se type 2 (11β-HSD2) expression very early during human pregnancy. J Dev Orig Health Dis 2017; 8:
149–54. doi: 10.1017/S2040174416000611.
27. Glover V, Bergman K, Sarkar P, O'Connor TG. Association between maternal and amniotic fluid cor-tisol is moderated by maternal anxiety. Psychoneuroendocrinology 2009; 34: 430–5. doi: 10.1016/j.
psyneuen.2008.10.005.
28. Kane HS, Dunkel Schetter K, Glynn LM, Hobel CJ, Sandman CA. Pregnancy Anxiety and Prenatal Cortisol Trajectories. Biol Psychol 2014; 100: 13–9. doi: 10.1016/j.biopsycho.2014.04.003.
29. Reck C, Muller M, Tietz A, Mohler E. Infant distress to novelty is associated with maternal anxiety disorder and especially with maternal avoidance behavior. J Anxiety Disord 2013; 27: 404–12. doi:
10.1016/j.janxdis.2013.03.009.
30. Glasheen C, Richardson GA, Fabio A. A systematic review of the effects of postnatal maternal anxiety on children. Arch Womens Ment Health 2010; 13: 61–74. doi: 10.1007/s00737-009-0109-y.
31. Ramchandani PG, Stein A, Hotopf M, Wiles NJ. Early parental and child predictors of recurrent abdominal pain at school age: results of a large population-based study. J Am Acad Child Adolesc Psychiatry 2006; 45(6): 729–36.
32. Buist A, Gotman N, Yonkers KA. Generalized anxiety disorder. Course and risk factors in pregnancy.
J Affect Disord 2011; 131: 277–83. doi: 10.1016/j.jad.2011.01.003.
33. Adewuya AO, Ola BA, Aloba OO, Mapayi BM. Anxiety disorders among Nigerian women in late pregnancy: a controlled study. Arch Womens Ment Health 2006; 9: 325–8.
34. Misri S, Abizadeh J, Sanders S, Swift E. Perinatal Generalized Anxiety Disorder: Assessment and Treatment. J Womens Health (Larchmt) 2015; 24: 762–70. doi: 10.1089/jwh.2014.5150.
35. Wenzel A, Haugen EN, Jackson LC, Brendle JR. Anxiety symptoms and disorders at eight weeks postpartum. J Anxiety Disord 2005; 19: 295–311.
36. Goodman JH, Chenausky KL, Freeman MP. Anxiety disorders during pregnancy: a systematic revi-ew. J Clin Psychiatry 2014; 75(10): e1153-84. doi: 10.4088/JCP.14r09035.
37. Weisberg RB, Paquette JA. Screening and treatment of anxiety disorders in pregnant and lactating women. Womens Health Issues 2002; 12: 32–6.
38. Coelho HF, Murray L, Royal-Lawson M, Cooper PJ. Antenatal anxiety disorder as a predictor of postnatal depression: a longitudinal study. J Affect Disord 2011; 129: 348–53. doi: 10.1016/j.
jad.2010.08.002.
39. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S et al. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the Nati-onal Comorbidity Survey. Arch Gen Psychiatry 1994; 51: 8–19.
40. Güler O, Sahin FK, Emul HM, Ozbulut O, Gecici O, Uguz F, Gezginc K, Zeytinci IE, Karatayli S, Askin R. The prevalence of panic disorder in pregnant women during the third trimester of pregnancy.
Compr Psychiatry 2008; 49: 154–8. doi: 10.1016/j.comppsych.2007.08.008.
41. Güler O, Kaya V, Gezgi̕nç K, Kayhan F, Çi̕çek E, Sönmez Ö et al. Pregnancy-Onset Panic Disor-der: Incidence, Comorbidity and Associated Factors. Arch Neuropsychiatr 2015; 52: 216–220. doi:
10.5152/npa.2015.7565.
42. Ross LE, McLean LM. Anxiety disorders during pregnancy and the postpartum period: A systematic review. J Clin Psychiatry 2006; 67: 1285–98.
43. Dannon PN, Iancu I, Lowengrub K, Grunhaus L, Kotler M. Recurrence of panic disorder during pregnancy: a 7-year naturalistic follow-up study. Clin Neuropharmacol 2006; 29: 132–7.
44. Cohen LS, Sichel DA, Faraone SV, Robertson LM, Dimmock JA, Rosenbaum JF. Course of panic disorder during pregnancy and the puerperium: a preliminary study. Biol Psychiatry 1996; 39: 950–4.
45. Marchesi C, Ampollini P, Paraggio C, Giaracuni G, Ossola P, De Panfilis C et al. Risk factors for panic disorder in pregnancy: a cohort study. J Affect Disord 2014; 156: 134–8. doi: 10.1016/j.
jad.2013.12.006.
46. Rambelli C, Montagnani MS, Oppo A, Banti S, Borri C, Cortopassi C, Ramacciotti D, Camilleri V, Mula M, Cassano GB, Mauri M. Panic disorder as a risk factor for post-partum depression: Results from the Perinatal Depression-Research & Screening Unit (PND-ReScU) study. J Affect Disord 2010;
122: 139–43.
47. Chen YH, Lin HC, Lee HC. Pregnancy outcomes among women with panic disorder—do panic attacks during pregnancy matter? J Affect Disord 2010; 120: 258–62. doi: 10.1016/j.jad.2009.04.025.
48. Stinson FS, Dawson DA, Patricia Chou S, Smith S, Goldstein RB, June Ruan W et al. The epidemi-ology of DSM-IV specific phobia in the USA: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Psychol Med 2007; 37: 1047–59.
49. Räisänen S, Lehto SM, Nielsen HS, Gissler M, Kramer MR, Heinonen S. Fear of childbirth pre-dicts postpartum depression: a population-based analysis of 511 422 singleton births in Finland.
BMJ Open 2013; 3(11): e004047. Dostopno dne 2. 12. 2017 na: https://www.ncbi.nlm.nih.gov/pub-med/24293208.
50. Sydsjö G, Sydsjö A, Gunnervik C, Bladh M, Josefsson A. Obstetric outcome for women who received individualized treatment for fear of childbirth during pregnancy. Acta Obstet Gynecol Scand 2012;
91: 44–9.
51. O'Connell MA, Leahy-Warren P, Khashan AS, Kenny LC, O'Neill SM. Worldwide prevalence of tocophobia in pregnant women: systematic review and meta-analysis. Acta Obstet Gynecol Scand 2017; 96(8): 907–20. doi: 10.1111/aogs.13138.
52. Demšar K, Svetina M, Verdenik I, Tul N, Blickstein I, Globevnik Velikonja V. Tokophobia (fear of childbirth): prevalence and risk factors. J Perinat Med 2018; 46: 151–4. doi: 10.1515/jpm-2016-0282.
53. Bhatia MS, Jhanjee A. Tokophobia: A dread of pregnancy. Ind Psychiatry J. 2012; 21: 158–9. doi:
10.4103/0972-6748.119649.
54. van Veen JF, Jonker BW, van Vliet IM et al. The effects of female reproductive hormones in genera-lized social anxiety disorder. Int J Psychiatry Med 2009; 39: 283–95.
55. Coelho HF, Murray L, Royal-Lawson M, Cooper PJ. Antenatal anxiety disorder as a predictor of postnatal depression: a longitudinal study. J Affect Disord 2011; 129(1-3): 348–53. doi: 10.1016/j.
jad.2010.08.002.
56. International Statistical Classification of Diseases and Related Health Problems 10th Revision. Dosto-pno dne 10. 2. 2018 na: http://apps.who.int/classifications/icd10/browse/2016/en#/VII.
57. American Psychiatric Association: Diagnostic and statistical manual of mental disorders: DSM-V, 5th edition. American Psychiatric Association 2013.
58. Seng JS, Rauch SA, Resnick H, Reed CD, King A, Low LK et al. Exploring posttraumatic stress disorder symptom profile among pregnant women. J Psychosom Obstet Gynaecol 2010; 31: 176–87.
doi: 10.3109/0167482X.2010.486453.
59. Ayers S. Delivery as a traumatic event: prevalence, risk factors, and treatment for postnatal posttrau-matic stress disorder. Clin Obstet Gynecol 2004; 47: 552–67.
60. Adewuya AO, Ologun YA, Ibigbami OS. Post-traumatic stress disorder after childbirth in Nigerian women: prevalence and risk factors. BJOG 2006; 113: 284–8. doi:10.1111/j.1471-0528.2006.00861.x.
61. Andersen LB, Melvaer LB, Videbech P, Lamont RF, Joergensen JS. Risk factors for developing post--traumatic stress disorder following childbirth: a systematic review. Acta Obstet Gynecol Scand 2012;
91: 1261–72. doi: 10.1111/j.1600-0412.2012.01476.x.
62. Sentilhes L, Maillard F, Brun S, Madar H, Merlot B, Goffinet F et al. Risk factors for chronic post--traumatic stress disorder development one year after vaginal delivery: a prospective, observational study. Sci Rep 2017; 7: 8724. doi: 10.1038/s41598-017-09314-x.
63. Rowan C, Bick D, Bastos MH. Postnatal debriefing interventions to prevent maternal mental health problems after birth: exploring the gap between the evidence and UK policy and practice. Worldviews Evid Based Nurs 2007; 4: 97–105.
64. Bosquet Enlow M, Kitts RL, Blood E, Bizarro A, Hofmeister M, Wright RJ. Maternal posttraumatic stress symptoms and infant emotional reactivity and emotion regulation. Infant Behav Dev 2011; 34:
487–503. doi: 10.1016/j.infbeh.2011.07.007.
65. Lim L, Chan HN, Chew PH, Chua SM, Ho C, Kwek SK et al. Ministry of Health Clinical Practice Gu-idelines: Anxiety Disorders. Singapore Med J. 2015 Jun; 56(6): 310–5. doi: 10.11622/smedj.2015088.
66. Butler AC, Chapman JE, Forman EM, Beck AT. The empirical status of cognitive-behavioral therapy:
a review of meta-analyses. Clin Psychol Rev 2006; 26: 17–31.
67. Bandelow B, Reitt M, Röver C, Michaelis S, Görlich Y, Wedekind D. Efficacy of treatments for anxiety disorders: a meta-analysis. Int Clin Psychopharmacol 2015; 30(4): 183–92. doi: 10.1097/
YIC.0000000000000078.
68. Russell EJ, Fawcett JM, Mazmanian D. Risk of obsessive-compulsive disorder in pregnant and postpartum women: a meta-analysis. J Clin Psychiatry 2013; 74: 377–85.
69. Challacombe FL, Wroe AL. A hidden problem: consequences of the misdiagnosis of perinatal ob-sessive-compulsive disorder. Br J Gen Pract 2013; 63: 275–6. doi: 10.3399/bjgp13X667376.
70. McGuinness M, Blissett J, Jones C. OCD in the perinatal period: is postpartum OCD (ppOCD) a distinct subtype? A review of the literature. Behav Cogn Psychother 2011; 39: 285–310. doi: 10.1017/
S1352465810000718.
71. Forray A, Focseneanu M, Pittman B, McDougle CJ, Epperson CN. Onset and exacerbation of ob-sessive-compulsive disorder in pregnancy and the postpartum period. J Clin Psychiatry 2017; 8:
1061–8. doi: 10.4088/JCP.09m05381blu.
72. Abramowitz JS, Schwartz SA, Moore KM, Luenzmann KR. Obsessive-compulsive symptoms in pregnancy and the puerperium: a review of the literature. J Anxiety Disord 2003; 17: 461–78.
73. Uguz F, Onder Sonmez E, Sahingoz M, Gokmen Z, Basaran M, Gezginc K et al. Neuroinflammation in the fetus exposed to maternal obsessive-compulsive disorder during pregnancy: a comparative study on cord blood tumor necrosis factor-alpha levels. Compr Psychiatry 2014; 55: 861–5. doi:
10.1016/j.comppsych.2013.12.018.
74. Wisner KL, Peindl KS, Gigliotti T, Hanusa BH. Obsessions and compulsions in women with postpar-tum depression. Clin Psychiatry 1999; 60: 176–80.
75. Ninan PT, Koran LM, Kiev A, Davidson JR, Rasmussen SA, Zajecka JM et al. High-dose sertraline strategy for nonresponders to acute treatment for obsessive-compulsive disorder: a multi-center dou-bleblind trial. J Clin Psychiatry 2006; 67: 15–22.
76. Rabinowitz I, Baruch Y, Barak Y. High-dose escitalopram for the treatment of obsessive-compulsive disorder. Int Clin Psychopharmacol 2008; 23: 49–53.
77. Fineberg NA, Reghunandanan S, Simpson HB, Phillips KA, Richter MA, Matthews K et al.
Accreditation Task Force of The Canadian Institute for Obsessive Compulsive Disorders. Obsessi-ve-compulsive disorder (OCD): Practical strategies for pharmacological and somatic treatment in adults. Psychiatry Res 2015; 227: 114–25.
78. Uguz F. Pharmacotherapy of obsessive-compulsive disorder during pregnancy: a clinical approach.
Rev Bras Psiquiatr 2015; 37: 334–42.
79. Myles N, Newall H, Ward H, Large M. Systematic meta-analysis of individual selective serotonin re-uptake inhibitor medications and congenital malformations. Aust NZ J Psychiatry 2013; 47: 1002–12.
doi: 10.1177/0004867413492219.
80. Grigoriadis S, VonderPorten EH, Mamisashvili L, Roerecke M, Rehm J, Dennis CL et al. Antidepre-ssant exposure during pregnancy and congenital malformations: is there an association? A systematic review and meta-analysis of the best evidence. J Clin Psychiatry 2013; 74: e293–308. doi: 10.4088/
JCP.12r07966.