|Year : 2018 | Volume
| Issue : 1 | Page : 58-60
Risks associated with psychotropic drugs during pregnancy
Supriya Agarwal1, Malvika Dahuja1, Mamta Tyagi2
1 Department of Psychiatry and Obstetrics, Subharti Medical College, Meerut, Uttar Pradesh, India
2 Department of Gynaecology, Subharti Medical College, Meerut, Uttar Pradesh, India
|Date of Web Publication||8-May-2018|
Department of Psychiatry and Obstetrics, Subharti Medical College, Meerut, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Unplanned pregnancies in women with psychiatric illness are common and result in exposure of the fetus to multiple psychotropics during the first trimester. Literature reveals that olanzapine may rarely cause major malformations and selective serotonin reuptake inhibitors may be associated with primary pulmonary neonatal hypertension. We present a rare case of 39-year-old (middle-aged) female Gravida 4 para 2 abortion 1 live 2, with bipolar affective disorder with gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) presenting in the third trimester of her pregnancy. The patient continued 5 mg olanzapine and 150 mg sertraline throughout pregnancy unsupervised. Ultrasonographic findings revealed multiple congenital anomalies in the fetus, and emergency cesarean was conducted in the 32nd week of pregnancy, which was followed by neonatal complications including bradycardia, gasping, absent birth cry and reflexes, and weak gross motor activity and early neonatal death. The anomalies observed in the fetus are similar to the anomalies that have been observed and discussed with psychotropics in the past. Thus, we report this case to understand in naturalistic setting – the complications and risks associated with psychotropic medications in pregnancy along with other physical morbidities including GDM and PIH in the female suffering from bipolar disorder.
Keywords: Bipolar disorder, pregnancy, psychotropic drugs, teratogenesis
|How to cite this article:|
Agarwal S, Dahuja M, Tyagi M. Risks associated with psychotropic drugs during pregnancy. Ann Indian Psychiatry 2018;2:58-60
| Introduction|| |
Pregnancy can be a very challenging time for women with long-term mental illnesses. Bipolar affective disorder (BPAD) is a common mental disorder affecting women of childbearing age group. Women have 50% increased risk of developing BPAD symptoms in the first trimester of pregnancy. Multiple risks are associated when a patient with mental illness becomes pregnant, either due to the illness itself or also due to the exposure of the mother and fetus to the psychotropics medications used during pregnancy, especially when the pregnancy is unplanned or the psychotropics are continued unsupervised, and hence, timely monitoring for the fetal well-being and treatment on the basis of risk and benefit ratio becomes very relevant in the management of psychiatric illness in pregnancy.
The use of various antidepressants and antipsychotics during pregnancy has been reported to be associated with four types of risks – risk of pregnancy loss or miscarriage, risk of organ malformation syndromes during acute neonatal period, and the risk of long-term neurobehavioral sequelae.
Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and sertraline can cause spontaneous abortions, primary pulmonary neonatal hypertension (PPNH), and neurobehavioral syndrome which includes jitteriness, poor muscle tone, weak or absent cry, respiratory distress, hypoglycemia, and low APGAR score and possibly seizures as reported by various case reports.
All second-generation antipsychotics (SGA), except clozapine, are category C drugs. Less than 20% of olanzapine crosses placenta and also that it is rarely been seen to cause spontaneous abortions and major malformations. In comparison with haloperidol, olanzapine has been reported to be associated with an approximately 50% increase in the risk of diabetes; however, the hazard ratio of olanzapine-induced diabetes mellitus (DM) is almost equal with both haloperidol and olanzapine.
There is no evidence to reflect on the teratogenic risk of the combination of SSRIs with SGAs, but in a naturalistic setting, it is more common to see a patient on polytherapy in comparison to a monotherapy, and thus, reporting of such cases becomes relevant. Since there has been a trend of increasing usage of psychotropic drugs in pregnant women; the chances of unfolding of various other teratogenic effects are a possibility and should be carefully monitored. Most difficult part in managing psychiatric patients during pregnancy other than the choice of medications is the plethora of physiological and metabolic changes that a female undergoes, for example, hyperglycemia, which might blur the clear picture of identifying any teratogenic effects that psychotropic drugs might cause to the fetus and making it difficult to zero in on one particular cause for fetal malformations. However, weighing the existent literature and comparison of various possible factors can help in ruling out the confounders. Nevertheless, vigilance regarding the risk of psychotropic-induced maternal and fetal complications should be the norm in any case of pregnancy with mental illness.
| Case Report|| |
A 39-year-old woman presented to the obstetric outpatient department with a history of gravid 4, para 2, abortion 1, live births 2 (G4, P2, A1, L2) with 28 weeks and 3 days' pregnancy with increasing physical exhaustion and weakness. The family also reported significant mood disturbances that were worsening over few weeks, with patient becoming irritable, talking excessively, sleeping poorly and deteriorating self-care. Psychiatric opinion was sought and detailed assessment revealed prior history of total duration of 13 years of BPAD with present episode being 5th episode. Before conceiving the patient was on 150 mg sertraline once daily, olanzapine 5 mg at night dosage which she continued during pregnancy without any psychiatric advice. All her earlier medications were tapered and stopped and she was on quetiapine 200 mg at night because of its safety profile during pregnancy and also because she had already crossed her first trimester of the pregnancy. The patient had been on 10 mg of olanzapine for 4 years before this pregnancy and delivered 2 healthy children during this period. Her abortion happened at the age of 24 years when she was drug naive. There was no history of hypertension, DM, or any other medical or surgical illness in the patient before the current pregnancy. Her prior pregnancies have been uneventful with no significant contributory family history. On physical examination, patient's blood pressure (BP) was found to be raised to 140 mmHg systolic BP and 94 mmHg diastolic BP. Her blood investigations were all within normal limit except for the raised fasting sugar levels of around 130 mg/dl. The patient was being monitored and managed for gestational DM (GDM) as well as hypertension. The patient did not go for any antenatal evaluation in this pregnancy till the third trimester. Thus, the anomalies were detected third trimester, and hence, medical termination of the pregnancy could not be planned for the patient in spite of multiple malformations. In patient's Doppler studies, umbilical artery showed increased resistance with intermittent absence of end-diastolic flow and reversal of flow was also absent. Level 2 scan showed an anomalous fetus followed by nonstress test for 20 min bi-weekly till delivery. The patient was taken up for emergency cesarean, and the fetus postdelivery on examination was found to have micrognathia, limb deformities, calipo-talus-equinovarus (CTEV), short neck, single umbilical artery, polyhydramnios, choroid plexus cyst, subcutaneous edema, right thumb absent, bilateral flexed wrist joint, subgaleal bleed, and cyanosis. His heart rate was <60/min, with birth cry and reflexes absent, and gross motor activity was found to be very weak. The baby was shifted to nursery and expired on the 3rd day of delivery.
| Discussion|| |
In our case advanced age of the mother, metabolic disturbances in pregnancy including GDM and pregnancy-induced hypertension (PIH), genetics of the previous abortion, and exposure to olanzapine in prior pregnancies were some of the factors that needed to be evaluated before considering the psychotropics as a possible cause for the fetal malformations and neonatal death.
Considering the advanced age of the mother literature review revealed that limb deformities have been reported in the fetuses of older mothers; however, similar limb deformities have also been observed and reported with olanzapine exposure; thus, none of the two factors can be singularized as far as limb deformities are concerned. Exposure to olanzapine is also observed to be associated with CTEV, flexed joints, absent fingers, and other anomalies. In a recent review, Gentile reviewed the data of 248 reported cases on olanzapine maintained by the manufacturer (Eli Lilly) up to December 2006. One case each of bilateral talipes, clubfoot, and absent fingers was found.  GDM and PIH have been associated with retromicrognathia, short neck, single umbilical artery, and subcutaneous edema, and polyhydramnios have been associated with GDM. It has been seen that mothers with GDM with choroid plexus cyst have higher chances of developing polyhydramnios. Subglial bleed occurs due to trauma during delivery, especially in mothers with GDM. Thus, these factors could be safely ruled out.
Our patient despite being on olanzapine in her earlier two pregnancies had normal children suggesting that olanzapine exposure to the fetus in utero may not cause fetal malformations in every case of exposure even though the risk may remain same in all pregnancies.
Similar to our case, various other research studies have also observed similar PPNH such as picture, after prolonged SSRIs such as fluoxetine and sertraline exposure during early fetal life. A case–control retrospective study looked at SSRIs (such as citalopram, fluoxetine, paroxetine, and sertraline) exposure after 20 weeks of gestation in which it was found that normal risk of PPNH of 1/700 increases to 7/1000 with the use of SSRIs. The absolute risk though small is of concern because it may be fatal in 10%–20% of newborns. Based on this study in April 2006, the United States Food and Drug Administration recommended a label change to formally include SSRIs increasing the risk of pulmonary hypertension.
Low-potency dopamine blockade (D2 blockade) neuroleptic drugs have been associated with an increased rate of congenital anomalies. High-potency dopamine blockade (D2 blockade) antipsychotic medications have not been associated with congenital abnormalities.
Newport et al. measured placental passage of medication from mother to fetus by measuring levels in umbilical cord serum and documented neonatal outcomes in 54 women followed through pregnancy. They concluded that olanzapine has the highest rate of placental passage, compared with haloperidol, risperidone, and quetiapine. Neonates exposed to olanzapine showed trends toward other birth weights and more neonatal Intensive Care Unit admissions than neonates exposed to other antipsychotic medications.
| Conclusion|| |
The evidence for the psychotropic-related risks in pregnancy to the fetus is mostly in the form of case reports is limited and inconclusive. Thus, any case of exposure of the fetus to drugs, in spite of multiple confounders, needs to be evaluated and is worthwhile discussing.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Vladmirova R, Stoyanova V, Milanova V. Bipolar affective disorder, pregnancy and childbirth: Clinical characteristics and heredity. Biotechnol Biotechnol Equip 2015;30:1.
Sharma I, Parial S, Tripathi MN, editors. Management of depression in women during pregnancy and lactation. In: Women Mental Health- Treatment of Psychiatric Disorders in Women During Pregnancy and Lactation. Recommendations for Psychiatrists in India- National Workshop Held. Ch. 2. Varanasi: Indian Psychiatric Society Committee on Women Mental Health; 2009. p. 59.
Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C, Jones KL, et al.
Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N
Engl J Med 2006;354:579-87.
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.
Sadock BJ, Sadock VA, Ruiz P. Comprehensive Textbook of Psychiatry. 9th
ed. Vol. 1. Wolters Kluwer; 1802.
Lambert BL, Cunningham FE, Miller DR, Dalack GW, Hur K. Diabetes risk associated with use of olanzapine, quetiapine, and risperidone in veterans health administration patients with schizophrenia. Am J Epidemiol 2006;164:672-81.
Zīle I, Villeruša A. Maternal age-associated congenital anomalies among newborns: A retrospective study in Latvia. Medicina (Kaunas) 2013;49:29-35.
Gentile S. Antipsychotic therapy during early and late pregnancy. A systematic review. Schizophr Bull 2010;36:518-44.
Chen CP. Congenital malformations associated with maternal diabetes. Taiwan J Obstet Gynecol 2005;44:1-7.
Newport DJ, Calamaras MR, DeVane CL, Donovan J, Beach AJ, Winn S, et al.
Atypical antipsychotic administration during late pregnancy: Placental passage and obstetrical outcomes. Am J Psychiatry 2007;164:1214-20.