Psychiatric Drugs, Pregnancy and Lactation: Atypical Antipsychotics
June 15, 2005 from
ObGynNews
By Lee S. Cohen, M.D.
The reproductive safety of the older typical
antipsychotics, such as
haloperidol, is supported by extensive data that have accumulated over the past
40 years, at least with respect to teratogenic risk. Much of the data come from
their use in treating nausea, particularly with prochlorperazine (Compazine).
While long-term neurobehavioral data have been somewhat sparse, no particular
indications of risk have been raised in over four decades of use.
We have far less reproductive safety data on the newer "atypical" class of
antipsychotics that have become widely used over the past decade because they
lack some of the longterm side effects associated with the typical
antipsychotics. These drugs - olanzapine (Zyprexa),
risperidone (Risperdal),
quetiapine (Seroquel),
aripiprazole (Abilify), riprasidone (Geodon), and clozapine (Clozaril) - are approved for
schizophrenia; several are approved for
acute mania indications as well.
But they are also being used widely across psychiatric disease states,
including anxiety, agitation in the elderly, generalized anxiety disorder, and
obsessive compulsive disorder), and as adjunctive treatment of depression.
Because reproductive safety data on the atypicals have been sparse,
clinicians are again faced with the difficult situation where a relatively new
class of medicine is being used frequently in a population of reproductive age
women. What data are available have been largely limited to manufacturers'
accumulated case series or spontaneous reports, which have their inherent biases
with respect to over-reporting of adverse outcomes.
To date, such information has not suggested any "signals" with respect to
specific concerns regarding their use during pregnancy but we can make only
limited conclusions on such information. Thus, clinicians have been in a bind
with respect to use of the atypicals during pregnancy. A study published in
April - the first prospective study of the reproductive safety of the atypicals
in the literature - provides some reassuring data regarding the risk of
malformations, albeit in a relatively small sample of 151 patients.
Investigators from the Motherrisk Program in Toronto prospectively followed these
women who took olanzapine, risperidone, quetiapine, or clozapine during
pregnancy. All of the women had taken one of these agents during the first
trimester, and 48 were exposed throughout pregnancy. A total of 151 pregnant
women who had taken a non-teratogenic drug also were followed.
In the atypical-exposed group, one child was born with a major malformation
(0.9%) a rate lower than the 1%-3% background rate in the general population;
compared with two (1.5%) babies in the control group - an insignificant
difference.
Differences between groups in the rate of spontaneous abortions, stillbirths, or
gestational age at birth were not statistically significant. Women taking
atypical antipsychotics did have significantly higher rates of low birth weight
babies (10% vs. 2%) and therapeutic abortions (10% vs. 1%) (J. Clin. Psychiatry
2005; 66:444-449).
As the authors point out, the sample was relatively small, the study was
statistically underpowered, and long-term neurobehavioral outcomes were not
evaluated. Still, this is the first prospective study that complements
spontaneous reports from the manufacturers.
The authors included the number of spontaneous reports of pregnancy exposures
to atypicals, provided by the respective manufacturers, with the exception of
the newer atypicals. Among the 242 reports of olanzapine-exposed pregnancies,
there was no increase of major malformations or other abnormal outcomes above
baseline. Of the 523 clozapine exposed pregnancies reported, there were 22
"unspecified malformations." Of the 446 quetiapine-exposed pregnancies, 151
outcomes were reported, of which 8 were different congenital anomalies. Eight
malformations were reported among the approximately 250 reports of pregnancies
and lactation exposed to risperidone, but no pattern of abnormalities was noted.
Obviously, if a patient can do without the medication, then it would be
appropriate to discontinue it, but this is frequently not the case and these
decisions have to be made on a case-by-case basis weighing the relative risks
versus benefits.
For a patient planning a pregnancy who has a severe psychiatric illness and
who is maintained on an atypical antipsychotic to sustain functioning, switching
to a typical antipsychotic may be prudent. However, we often see women who
present when they are already pregnant and on an atypical agent. At this point a
switch may not be the wisest decision, if she is at a risk of relapse. For those
women, the Motherrisk data are not a guarantee of safety but provide information
that is at least moderately reassuring to clinicians. Although this small study
is encouraging, given the prevalence of reproductive age women on these agents,
it would be ideal if industry performed post-marketing surveillance studies that
would rapidly provide the amount of cases we need to reliably estimate
reproductive risks. Such studies may soon be mandated by the Food and Drug
Administration in this post-Vioxx era with increased emphasis on the safety of
marketed drugs.
Dr. Lee Cohen is a psychiatrist and director of the
perinatal psychiatry program at Massachusetts General Hospital, Boston. He is a
consultant for and has received research support from manufacturers of several
SSRIs. He is also a consultant to Astra Zeneca, Lilly and Jannsen -
manufacturers of atypical antipsychotics.
continue: Neonatal Withdrawal
Syndrome and SSRIs . drugs during
pregnancy index
top .
pages 1
2 3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18 .
send to friend .
mental health site
map
Reviewed: 03/2006
|
REALMENTALHEALTH
CARE PROVIDER
DIRECTORY
Find a Local Therapist
|
|
del.icio.us
Digg
Furl
Google
StumbleUpon
Yahoo