Use of Psychotropic Medications Among Pregnant Women With Bipolar Disorder

Use of Psychotropic Medications Among Pregnant Women With Bipolar Disorder: Patterns, Determinants, and Impact on Perinatal Outcomes

The objectives of the proposed project are:

1. To describe the patterns of mood stabilizer, antipsychotic, antidepressant, and anxiolytic prescriptions during pregnancy over a period of 12 years (2002-2014) in women aged 13 to 50 years who are diagnosed with bipolar disorder in Ontario.
2. To identify the factors associated with use of antipsychotics, antidepressants, and antipsychotic-antidepressant polytherapy in pregnant women diagnosed with bipolar disorder.
3. To assess the impact of antipsychotics, antidepressants, and antipsychotic-antidepressant polytherapy on the risk of maternal, neonatal, and labour and delivery outcomes in women with bipolar disorder.
4. To assess the impact of antipsychotics, antidepressants, antipsychotic-antidepressant polytherapy on psychiatric readmission rates during the early postpartum period in women with bipolar disorder.

Study Overview

• Status: Completed
• Conditions: Pregnancy Complications; Bipolar Disorder
• Intervention / Treatment: Drug: Antipsychotic; Drug: Antidepressant; Drug: Antipsychotic and Antidepressant

• Study Type: Observational
• Enrollment (Actual): 3357

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Women between the ages of 13 and 50 years who were hospitalized for a singleton obstetrical delivery between 2002-2014. Additionally, these women must be covered under the provincial drug benefit plan during index pregnancy, which is defined as having filled a drug prescription in the period from six months prior to pregnancy to six months after delivery. For women who had multiple pregnancies over the study period, we will select their first pregnancy as the index pregnancy.

Description

Inclusion Criteria:

Women were included in our study cohort if they met at least one of the following criteria: (i) an inpatient hospitalization with a primary discharge diagnosis of BD prior to the index pregnancy; (ii) an outpatient OHIP fee code for a mood disorder plus a prescription of a mood stabilizer prior to the index pregnancy (note that the outpatient OHIP fee code (296) without a prescription would not have been sufficient to identify BD patients because the fee code is used concurrently used for diagnosis of unipolar depression). Additionally, women were included in the study cohort if they were continuously covered for ODB throughout their pregnancy, defined as having filled any provincially funded drug prescription within six months prior to conception and another either during their pregnancy or within six months after delivery.

Exclusion Criteria:

(1) women with gestational weeks less than 20 and more than 45 at delivery; (2) pregnancies with multiple overlapping records over the study time period; (3) any data with inconsistencies and duplicate records for pregnancy; (4) any woman sharing the newborn's IKN, given that we would be unable to differentiate between the two persons; (5) observations with missing birth date for the baby and the time period between the mother's admission and discharge date greater than 14 days (since we were unable to determine the conception date for these women; and (6) women who filled a treatment prescription up to 30 days prior to pregnancy and none during the period of pregnancy.very

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Bipolar disorder-treated; Individuals in this group are taking any medication (mood stabilizer, antipsychotic, antidepressants, antianxiety) during pregnancy	Drug: Antipsychotic; Antipsychotic monotherapy; Drug: Antidepressant; Antidepressant monotherapy; Drug: Antipsychotic and Antidepressant; Polytherapy
Bipolar Disorder-Not Treated; Individuals in this group are not taking any medications during pregnancy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal Outcomes (pregnancy)	Venous Thromboembolism, gestational diabetes, gestational hypertension, preeclampsia or eclampsia, placental abruption, placental infarction	2002-2014
Neonatal Outcomes	Preterm birth, small for gestational age, large for gestational age, sepsis, mortality, infection, neonatal adaption syndrome, respiratory distress syndrome, seizure, intraventricular haemorrhage	2002-2014
Fetal Outcomes	Stillbirth, congenital malformation	2002-2014
Labour and Delivery Outcomes	Caesarean, forceps/ventouse, induced labour, episiotomy or delivery with tear (3rd or 4th degree)	2002-2014
Psychiatric Readmission	Readmission for mental health reasons ≤ 7 days post-delivery, readmission for mental health reasons within 1 to 12 weeks post-delivery	2002-2014

Collaborators and Investigators

• Sponsor: Western University, Canada

Publications and helpful links

General Publications

• Boden R, Lundgren M, Brandt L, Reutfors J, Andersen M, Kieler H. Risks of adverse pregnancy and birth outcomes in women treated or not treated with mood stabilisers for bipolar disorder: population based cohort study. BMJ. 2012 Nov 8;345:e7085. doi: 10.1136/bmj.e7085.
• Vigod SN, Gomes T, Wilton AS, Taylor VH, Ray JG. Antipsychotic drug use in pregnancy: high dimensional, propensity matched, population based cohort study. BMJ. 2015 May 13;350:h2298. doi: 10.1136/bmj.h2298.
• Broeks SC, Thisted Horsdal H, Glejsted Ingstrup K, Gasse C. Psychopharmacological drug utilization patterns in pregnant women with bipolar disorder - A nationwide register-based study. J Affect Disord. 2017 Mar 1;210:158-165. doi: 10.1016/j.jad.2016.12.001. Epub 2016 Dec 8.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: November 18, 2016
• First Submitted That Met QC Criteria: November 18, 2016
• First Posted (Estimate): November 22, 2016

Study Record Updates

• Last Update Posted (Actual): May 11, 2018
• Last Update Submitted That Met QC Criteria: May 3, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: bipolar disorder; readmission; polytherapy; adverse outcomes
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Bipolar and Related Disorders; Disease; Bipolar Disorder; Pregnancy Complications; Physiological Effects of Drugs; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Antidepressive Agents; Antipsychotic Agents
• Other Study ID Numbers: 108217