January - February 2010
Therapeutics InitiativeThe University of British ColumbiaDepartment ofAnesthesiology, Pharmacology & Therapeutics2176 Health Sciences MallVancouver, BC Canada V6T 1Z3
Are antidepressants safe inpregnancy? A focus on SSRIs
relapsed in pregnancy, including 31% of ongoingusers and 68% of those discontinuing use. Theauthors do not report on withdrawal reactions, noprotocol is described for gradual dose reduction,and timing of many relapses suggests withdrawaleffects rather than a relapse. Quality of life, func-tioning, serious and total adverse events, and birthoutcomes were not reported.Publication bias has led to estimates of SSRI effi-cacy that are exaggerated by one-third indepressed non-pregnant adults.
SSRIs failed todiffer from placebo to a clinically distinguishableextent for mild or moderate depression.
A meta-analysis comparing drug and non-drug treatmentsfor depression found no difference in general;SSRIs were more effective than psychotherapy toa small, clinically meaningless extent, and psy-chotherapy was as effective for severe as formilder forms of depression.
What are the benefits to the infantof SSRIs in pregnancy?
Eight cohort studies with concurrent controlshave compared antidepressants to no treatment inwomen with depression. Three were population-based administrative database analyses, two inBritish Columbia
, and one in a U.S. healthplan, Group Health.
The other five studies weremainly clinic-based (n=44-107).
Thesestudies provide no evidence that SSRI useimproves infant health. Mortality was not exam-ined. Neonatal intensive care use did not differsignificantly (n=268; 4 studies): 16.6% on SSRIsvs. 8.6% no drug. Birth weight also did not sig-nificantly differ (n=2,279;6studies):mean3.36kgon SSRIs vs. 3.53 kg no drug. There were morepre-term births on SSRIs (n=548; 3 studies):11.8% vs. 4.7%, RR=2.2 (95% CI 1.2-4.1),
Catherine took paroxetine 20 mg daily 3 years ago at the age of 32 for symptoms of depression from a diffi-cult divorce. She only took it for 2 weeks as it made her feel nervous. Her depression lifted after 6 weeks. Shehas remarried and she and her new husband were dis-cussing whether to have children, when she discovered that she was 2 months pregnant. She is now experienc-ing the same symptoms she had 3 years ago and asksher family physician whether she should take an anti-depressant. What does the evidence show?
In British Columbia selective serotonin reuptakeinhibitor (SSRI) antidepressant use in pregnancy morethan doubled, from 2% in 1998 to 5% in 2001.
Use inQuebec also doubled over the same period,
and in 7U.S. health plans (n=118,935) use grew from 2% in1996 to 8% in 2004-5.
Are pregnant women at higher risk fordepression?
Pregnancy does not lead to higher rates of depression.
A systematic review estimates a point prevalence of 3.1%-4.9% per trimester, with 7.5% of women experi-encing a new episode of depression during pregnancy.
A nationally representative U.S. survey found similarrates of depression in pregnant and non-pregnantwomen: 5.6% vs. 8.1%.
Does depression in pregnancy lead toharm?
Depression in pregnancy is associated with an increasein prematurity, low birth weight, poor Apgar scores,need for neonatal intensive care, gestational hyperten-sion and pre-eclampsia, operative deliveries, postpar-tum depression, poor nutrition, smoking, alcohol anddrug use.
However, these studies fail to establishwhether depression leads to harm, or whether pooreroutcomes are due to an association of depression withfactors such as poverty, poor living conditions, lack of social support, and difficult previous pregnancies.
What are the benefits to the mother ofSSRIs in pregnancy?
There is no randomized controlled trial (RCT) evidenceof benefit; no RCTs have compared SSRIs in pregnan-cy with non-drug treatments, no treatment or other anti-depressants. One frequently cited cohort study (n=201)compared discontinuation of antidepressants for ≥1week with ongoing use in pregnancy.
Mean priordepression duration was >15 years; 43% of participants