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Psychotropic Drug Use Before, During, and After Pregnancy: A Population-Based Study in A Canadian Cohort (2001-2013)
Psychotropic Drug Use Before, During, and After Pregnancy: A Population-Based Study in A Canadian Cohort (2001-2013)
Psychiatric Association
Abstract
Objective: To describe the extent of increase in use and the rate of continuation versus discontinuation of psychotropic
agents before, during, and after pregnancy.
Methods: Rates of psychotropic use (antidepressants, anxiolytic/sedative-hypnotics, antiepileptics, antipsychotics, lithium,
stimulants) among women with a hospital-recorded pregnancy outcome were assessed using databases at the Manitoba
Centre for Health Policy. Rate of use was defined as 1 prescription over the total number of pregnancies in the 3-12 months
before pregnancy, 0-3 months before pregnancy, during pregnancy, or 3 months after pregnancy. Continued use was defined
as 2 prescriptions with gap 14 days. Poisson regression was used to analyze trends.
Results: Over the study period, a psychotropic drug was used before, during, or after pregnancy in 41,923 of 224,762
pregnancies. From 2001 to 2013, psychotropic use increased 1.5-fold from 11.1% to 16.2% (p < 0.0001) in the 3-12 months
before pregnancy, 1.6-fold from 6.4% to 10.5% (p < 0.0001) in the 3 months before pregnancy, 1.8-fold from 3.3% to 6.0% (p <
0.0001) during pregnancy, and 1.5-fold from 6.2% to 9.5% (p < 0.0001) in the 3 months postpartum. Among the 13,579 women
who received at least 1 psychotropic agent in the 3 months prior to pregnancy, 38.5% stopped the agent prior to pregnancy
and only 10.3% continued use throughout pregnancy. Continued use throughout pregnancy was higher (56.9%) among the
6693 women who received at least 2 prescriptions for a psychotropic agent and were at least 80% adherent in the 3 months
prior to pregnancy.
Conclusion: The use of psychotropic agents increased over 12 years. The safety of continuing versus discontinuing these
agents during pregnancy remains uncertain, but we observed a decrease in psychotropic drug use during the pregnancy period.
Keywords
drug use, pregnancy, pharmacoepidemiology, psychotropic drugs
As many as 10% of women of childbearing age experience challenging for many clinicians. It is therefore important to
mental illness and may be exposed to a psychotropic medi- study the pattern of psychotropic exposure in order to
cation prior to becoming pregnant.1-4 However, the relative address the clinical implications associated with the use of
risk of continuing versus discontinuing drug therapy during
pregnancy on maternal and child health outcomes remains 1
College of Pharmacy, Rady Faculty of Health Sciences, University
uncertain.5 Although not treating mental illness in pregnant of Manitoba, Winnipeg, Manitoba
women may pose a higher risk of maternal relapse, poor 2
Manitoba Centre for Health Policy, Department of Community Health
obstetric care, and pregnancy complications,6 the perceived Sciences, University of Manitoba, Winnipeg, Manitoba
risk of psychotropic drug use during pregnancy may contrib-
ute to nonadherence and discontinuation of these agents.5,7 Corresponding Author:
Christine Leong, BSc, BScPharm, PharmD, College of Pharmacy, Rady
Clinicians are provided with limited guidance on how to Faculty of Health Sciences, University of Manitoba, 750 McDermot
best manage patients who are stable on medication during Avenue, Winnipeg, MB, R3E 0T5, Canada.
the perinatal period, and this decision is controversial and Email: christine.leong@umanitoba.ca
544 The Canadian Journal of Psychiatry 62(8)
(99.8)
(0.04)
(0.01)
(0.02)
(0.1)
(0.1)
Stimulant
examined the impact of continuing versus discontinuing psy-
(n,%)
chotropic agents during pregnancy, and findings on the risk
288
82
104
25
<6*
<6*
45
224,197
of continuing drug therapy during pregnancy are conflict-
ing.8-11 Surveys have reported that up to 60% of women had
poor adherence to chronic medication therapy during preg-
(99.0)
(0.03)
Antiepileptic
(0.4)
(0.1)
(0.3)
(0.1)
(0.1)
(0.1)
nancy.5,7 Previous studies have examined the extent of psy-
(n,%)
chotropic medication use and discontinuation during
880
246
666
232
73
121
125
222,419
pregnancy11-24; however, few studies have used large admin-
istrative databases that distinguished between regular and
intermittent users of these agents, and even fewer studies
224,540 (99.9)
20 (0.01)
48 (0.02)
24 (0.01)
13 (0.01)
examined these trends in a Canadian population. We also
106 (0.1)
Lithium
have limited knowledge about the intentional use of certain
(n,%)
<6*
<6*
psychotropic classes, such as stimulants, anxiolytics, and
mood stabilizers, from a population perspective. Manitoba
has one of the most comprehensive databases with which to
study psychotropic drug use from a population perspective.
221,747 (98.7)
75 (0.03)
Antipsychotic
1,284 (0.6)
273 (0.1)
494 (0.2)
395 (0.2)
361 (0.2)
133 (0.1)
We aimed to describe the extent of increase in use of select
(n,%)
psychotropic agents before, during, and after pregnancy and
Table 1. Overall psychotropic use (receipt of at least 1 prescription) before, during, and after pregnancy (N ¼ 224,762).
Drug
Note: Before pregnancy exposure is defined as 12 months before pregnancy; Post-partum exposure is defined 3 months after delivery.
to examine the rate of continued and discontinued use of
these agents during pregnancy between 2001 and 2013.
Antidepressant
197,494 (87.9)
11,417 (5.2)
2,817 (1.3)
5,424 (2.4)
3,556 (1.6)
706 (0.3)
1,371 (0.6)
1,977 (0.9)
*Values <6 could not be reported due to restrictions on reporting small cell counts by the health information privacy laws.
(n,%)
Methods
Data Sources
This was a retrospective, population-based, cohort study to Sedative-Hypnotic
examine the frequency of psychotropic prescriptions dis-
196,391 (87.4)
12,795 (5.7)
2,466 (1.1)
4,210 (1.9)
3,819 (1.7)
701 (0.3)
2,839 (1.3)
1,541 (0.7)
pensed before, during, and after pregnancy between April
Anxiolytic/
(n,%)
1, 2001, and March 31, 2013. Data were obtained from the
administrative database of the Population Health Research
Data Repository located at the Manitoba Centre for Health
Policy (MCHP), which includes administrative data for 1.2
million individuals living in Manitoba.
All Psychotropics
182,839 (81.4)
Figure 1. Weighted percentage of pregnant women who filled at least 1 prescription for a psychotropic medication (2001-2013).
Table 2. Baseline demographic and clinical characteristics of pregnant women (birth outcome of livebirth, stillbirth, or intrauterine death
only) who had 1 psychotropic drug prescription dispensed in the 3 months prior to start of pregnancy.
Age (y), mean (SD) 28.4 (5.6) 27.5 (5.8) 27.0 (5.8) 29.7 (5.1) 27.8 (5.8)
Age group, n (%)
20 years 311 (8.5) 303 (12.0) 721 (15.1) 45 (3.7) 1380 (11.4)
21-29 years 1801 (49.5) 1260 (50.0) 2434 (50.9) 547 (45.2) 6042 (49.7)
30-39 years 1449 (39.8) 915 (36.3) 1551 (32.4) 584 (48.2) 4499 (37.0)
40 years 81 (2.2) 41 (1.6) 75 (1.6) 35 (2.9) 232 (1.9)
Year of start of pregnancy, n (%)
2000 125 (3.4) 121 (4.8) 281 (5.9) 27 (2.2) 554 (4.6)
2001 174 (4.8) 140 (5.6) 371 (7.8) 50 (4.1) 735 (6.0)
2002 211 (5.8) 175 (6.9) 371 (7.8) 67 (5.5) 824 (6.8)
2003 260 (7.1) 201 (8.0) 373 (7.8) 84 (6.9) 918 (7.6)
2004 280 (7.7) 200 (7.9) 376 (7.9) 75 (6.2) 931 (7.7)
2005 326 (9.0) 205 (8.1) 405 (8.5) 84 (6.9) 1020 (8.4)
2006 282 (7.7) 192 (7.6) 409 (8.6) 87 (7.2) 970 (8.0)
2007 320 (8.8) 211 (8.4) 424 (8.9) 98 (8.1) 1053 (8.7)
2008 346 (9.5) 220 (8.7) 407 (8.5) 122 (10.1) 1095 (9.0)
2009 367 (10.1) 245 (9.7) 381 (8.0) 143 (11.8) 1136 (9.3)
2010 392 (10.8) 262 (10.4) 408 (8.5) 158 (13.0) 1220 (10.0)
2011 432 (11.9) 272 (10.8) 461 (9.6) 174 (14.4) 1339 (11.0)
2012a 127 (3.5) 75 (3.0) 114 (2.4) 42 (3.5) 358 (2.9)
Income quintile, n (%)
Quintile 1 1272 (34.9) 879 (34.9) 1487 (31.1) 375 (31.0) 4013 (33.0)
Quintile 2 717 (19.7) 508 (20.2) 946 (19.8) 247 (20.4) 2418 (19.9)
Quintile 3 590 (16.2) 460 (18.3) 879 (18.4) 213 (17.6) 2142 (17.6)
Quintile 4 531 (14.6) 376 (14.9) 772 (16.1) 200 (16.5) 1879 (15.5)
Quintile 5 507 (13.9) 280 (11.1) 664 (13.9) 168 (13.9) 1619 (13.3)
Not found 25 (0.7) 16 (0.6) 33 (0.7) 8 (0.7) 82 (0.7)
Rural, n (%) 1397 (38.4) 1085 (43.1) 1912 (40.0) 405 (33.4) 4799 (39.5)
Primiparous, n (%) 1041 (28.6) 823 (32.7) 1654 (34.6) 378 (31.2) 3896 (32.1)
Health care utilization in year prior to
start of pregnancy, n (%)
Psychiatric services hospitalization 218 (6.0) 120 (4.8) 156 (3.3) 77 (6.4) 571 (4.7)
Inpatient hospitalization 870 (23.9) 561 (22.3) 1009 (21.1) 279 (23.0) 2719 (22.4)
Emergency visitb 1124 (30.9) 657 (26.1) 1179 (24.7) 401 (33.1) 3361 (27.7)
Co-medication in 3 months prior to start
of pregnancy, n (%)
Anxiolytic/sedative 1057 (29.0) 650 (25.8) 386 (8.1) 428 (35.3) 2521 (20.7)
Antipsychotic 194 (5.3) 75 (3.0) 42 (0.9) 98 (8.1) 409 (3.4)
Antidepressant 1702 (46.7) 1114 (44.2) 937 (19.6) 753 (62.2) 4506 (37.1)
Lithium 14 (0.4) 11 (0.4) s (s) s (s) 38 (0.3)
Antiepileptic 202 (5.5) 44 (1.7) 44 (0.9) 156 (12.9) 446 (3.7)
Stimulant 19 (0.5) 37 (1.5) 20 (0.4) 13 (1.1) 89 (0.7)
Opioid 768 (21.1) 439 (17.4) 333 (7.0) 271 (22.4) 1811 (14.9)
Psychiatric diagnosis in 3 yearsc prior to
start of pregnancy, n (%)
Mood/anxiety 3184 (87.4) 2130 (84.6) 3288 (68.8) 1062 (87.7) 9664 (79.5)
Schizophrenia 95 (2.6) 37 (1.5) 33 (0.7) 41 (3.4) 206 (1.7)
Substance use disorder 669 (18.4) 444 (17.6) 656 (13.7) 234 (19.3) 2003 (16.5)
Self-harm 81 (2.2) 50 (2.0) 68 (1.4) 35 (2.9) 234 (1.9)
Nonpsychiatric comorbidities in 3 yearsc
prior to start of pregnancy, n (%)
Cancer 21 (0.6) 23 (0.9) 36 (0.8) 17 (1.4) 97 (0.8)
Diabetes 190 (5.2) 110 (4.4) 167 (3.5) 43 (3.6) 510 (4.2)
Headache 530 (14.6) 352 (14.0) 543 (11.4) 156 (12.9) 1581 (13.0)
Epilepsy 181 (5.0) 29 (1.2) 34 (0.7) 121 (10.0) 365 (3.0)
a
2012 includes data only up to March 31, 2012.
b
Emergency department database only for Winnipeg emergency department visits from April 1, 1999, to March 31, 2013. Population for characteristics was
limited to those whose start of pregnancy was on or after April 1, 2000, and end of pregnancy was on or before December 31, 2012.
c
There are 4.3% (523 pregnancies) with less than 3 years of coverage prior to start of pregnancy.
La Revue Canadienne de Psychiatrie 62(8) 547
Figure 2. Comparison of discontinued (before first trimester and before second trimester), intermittent, and continued users among
pregnant patients (birth outcome of livebirth, stillbirth, intrauterine death only) who had 1 psychotropic drug prescription dispensed in the
3 months prior to start of pregnancy. Denominator is population who received at least 1 prescription for each class of drug in 3 months prior
to conception (shown in parentheses). Continuous use was defined as no gap greater than 14 days.
Restricted to women who filled at least 2 consecutive prescriptions for the psychotropic agent in the 3 months prior to pregnancy with a medication possession ratio of at least 80% based on the additive day
Stimulant,
22 (24.4)
35 (38.9)
29 (32.2)
n (%)
prior to their first and second trimesters, respectively.
Approximately 30.5% (n ¼ 4140) of patients were consid-
<6
ered intermittent users of these agents throughout pregnancy.
Antidepressant, Antipsychotic, Lithium, n Antiepileptic, The proportions of patients who continued, discontinued,
51 (11.1)
66 (14.4)
293 (63.7)
50 (10.9)
n (%) and intermittently used their agents by psychotropic drug
class are shown in Figure 2. When the population was
restricted to only those who filled at least 2 consecutive
Table 3. Pattern of continued and discontinued psychotropic use among pregnant women resulting in a livebirth, stillbirth, or intrauterine death (n ¼ 6693)a.
12 (36.36)
10 (30.3)
pregnancy who were at least 80% adherent (80% MPR) (n ¼
(%)
59 (17.9)
159 (48.3)
57 (17.3)
820 (20.1)
1837 (44.9)
610 (14.9)
Discussion
hypnotic, n (%)
201 (11.3)
448 (25.2)
745 (41.9)
384 (21.6)
1105 (16.5)
1020 (15.2)
3808 (56.9)
760 (11.4)
N/A
N/A
medications.
N/A
N/A
N/A
of pregnancy
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