Am J Psychiatry 158:10, October 2001
Pregnancy Outcome Following Gestational Exposure to
Venlafaxine: A Multicenter Prospective Controlled Study
Adrienne Einarson, R.N.
Bumn Fatoye, M.D.
Moumita Sarkar, B.Sc.
Sharon Voyer Lavigne, M.Sc.
Christina Chambers, M.P.H.
Pierpaolo Mastroiacovo, M.D.
Antonio Addis, Pharm.D.
Doreen Matsui, M.D.
Lavinia Schuler, M.D., M.Sc.
Thomas R. Einarson, Ph.D.
Gideon Koren, M.D.
Objective: Because there are no studies available on the safety
of venlafaxine during pregnancy, the authors’ goal in this study
was to determine whether venlafaxine increases the risk for
Method: Data on 150 women exposed to venlafaxine during
pregnancy in seven pregnancy counseling centers were com-
pared with data from studies of pregnant women who 1) re-
ceived selective serotonin reuptake inhibitor antidepressants (SS-
RIs) (N=150) and 2) who received nonteratogenic drugs (N=150).
Results: Among the 150 women who were exposed to ven-
lafaxine during pregnancy, 125 had live births, 18 had sponta-
neous abortions, and seven had therapeutic abortions; two of
the babies had major malformations. There were no significant
differences between these women and the two comparison
groups on any of the measures analyzed.
Conclusions: These results suggest that the use of venlafaxine
during pregnancy does not increase the rates of major malfor-
mations above the baseline rate of 1%–3%.
(Am J Psychiatry 2001; 158:1728–1730)
T o date, to our knowledge there are no studies on the
safety of venlafaxine during human pregnancy. In animal
studies (rats and rabbits), venlafaxine did not cause mal-
formations in doses 11–12 times the maximum recom-
mended human daily dose (1). The manufacturer of ven-
lafaxine has a number of spontaneous case reports of
women exposed to venlafaxine during pregnancy, docu-
menting both birth defects and healthy babies with no
specific pattern of defects (2). It is important to recognize
the inherent bias of spontaneous reporting to drug com-
panies, as our group commented in a recent report (3), be-
cause companies are much more likely to receive reports
of adverse birth outcomes than healthy babies.
Data obtained by the U.K. Drug Safety Research Unit (4)
revealed known outcomes of the pregnancies of 39 women
who took venlafaxine. There were 26 live births, seven
spontaneous abortions, and six therapeutic abortions in
this group and no reports of malformations.
A substantial number of women of child-bearing age
suffer from depression. Coupled with the fact that at least
50% of pregnancies are unplanned (5), the likelihood of
depression during pregnancy means that women will use
this drug in early pregnancy. We have found that some
women may choose to abort a wanted pregnancy because
there is no information on the safety of a particular drug
(6). In another one of our studies (7), we found that a num-
ber of women elected to discontinue needed antidepres-
sants abruptly after their pregnancy was diagnosed be-
cause there was no information on the safety of the drugs.
Because of the paucity of information on venlafaxine,
we elected to carry out this study to assess its safety or risk
potential during pregnancy. Our main objective was to as-
certain whether venlafaxine use during pregnancy raised
the baseline risk of 1%–3% for major malformations. Sec-
ondary outcomes of interest included rates of spontane-
ous and therapeutic abortions, mean gestational age, and
The Motherisk Program and the other participating pregnancy
counseling centers provide similar services for pregnant and lac-
tating women and their health professionals. Information is given
on the safety or risk potential during pregnancy of drugs, chemi-
cals, radiation, and infectious diseases. For the purpose of this
study, we ascertained the outcome of the pregnancy of women
who had called each service requesting information about the
safety of venlafaxine when they were in the first trimester of the
On successful contact, information on each woman’s exposure
history and pregnancy outcome were obtained, along with other
measures of interest, with the aid of a structured questionnaire.
The exposure history included medical indication for drug use,
dose, and frequency and timing of administration, as well as ma-
ternal demographics and obstetrical history. At follow-up, women
were questioned regarding the course of their pregnancy, the
health of their child, and specific details of their exposure to ven-
lafaxine and any other drugs or exposure to other risk factors dur-
ing their pregnancy. Outcomes were confirmed by sending a let-
ter to the child’s primary care physician to corroborate the
The primary outcome of interest was the incidence of major
malformations, which are defined by the presence of any anom-