domingo, 2 de noviembre de 2008

Articulo antidepresivos y lactancia

Pregnancy, depression, antidepressants
and breast-feeding
Pierre Blier, MD, PhD
University of Ottawa Institute of Mental Health Research, Ottawa, Ont.
“Pregnancy protects against depression.” This is a common
belief, perhaps based in part on some women experiencing a
heightened feeling of emotional well-being during pregnancy.
However, the evidence indicates otherwise. In particular,
pregnancy is a high-risk period for a relapse of depression.
A recent prospective study, conducted on 201 patients
who had been euthymic for at least 3 months, examined relapse
rates over the course of pregnancy.1 Women who discontinued
their medication had more frequent relapses when
compared with women who maintained their medication,
with a hazard ratio of 5.0. Moreover, in the women who discontinued
their antidepressant, the reintroduction of medication
decreased the risk of relapse, but to a much lesser extent
than if medication was continued throughout pregnancy.
Therefore, transient interruption of medication may still predispose
pregnant women to a negative outcome. In addition,
allowing major depression to occur during pregnancy may
result in a negative impact on fetal conditions. Because the
placental barrier is limited in its capacity to protect the fetus
against the systemic perturbations that depression can produce,
it appears imperative to prevent depressive relapses
from occurring. The endogenous substances that can be produced
in greater concentrations during depression, and
could have a negative impact, include cortisol and catecholamines.
The former can lead to increased corticotropinreleasing
factor production, which can induce premature
labour, whereas the latter can alter uterine blood flow and induce
uterine irritability.2,3 Finally, depressed mothers may
have a decreased appetite and may be more at risk of using
alcohol or illicit drugs, factors that can have a negative impact
on the fetus.4,5 Therefore, it is important to weigh the
benefits of not allowing depression to occur during pregnancy
against the risks of using antidepressants during this
period. The use of antidepressants clearly offers a protective
influence against such relapse.
“Antidepressants increase the risk of congenital malformations
and perturb organ development.” Again, the evidence
indicates otherwise. Reviews of the literature indicate that
antidepressants, especially selective serotonin reuptake inhibitors
(SSRIs), do not increase the risk of major and minor
malformations.6–9 However, there would appear to be a small,
but statistically significant, increased risk of spontaneous
abortions with SSRIs. The role of depression itself cannot be
eliminated as a contributing factor to this increase from 8.7%
to 12.4%.10 More troublesome is a recent study reporting an
increase of persistent pulmonary hypertension of the newborn
(PPHN) in babies whose mothers were exposed to SSRIs
after the first 20 weeks of gestation.11 This study reported that
14 infants with PPHN had been exposed to an SSRI (3.7%)
versus 6 control infants (0.7%). Nevertheless, it is important
to mention that the crude risk of PPHN at any time in pregnancy
was not increased by SSRI exposure. This seemed to
result from an apparent, though not significant (p = 0.08),
protective effect of SSRIs in the first 20 weeks. It is also possible
that the finding resulted from studying a small number of
subjects. As an illustration of the latter possibility, the number
needed to treat to obtain 1 PPHN was 200. This study
cannot establish causality, as pointed out by the authors
themselves, but it is well known that serotonin has mitogenic
and comitogenic effects on pulmonary smooth-muscle cells
that can produce pulmonary hypertension (PH).12,13 It was
thus postulated that elevated circulating levels of serotonin,
presumably resulting from reuptake inhibition by the SSRIs,
could be responsible for the proliferation of smooth-muscle
cells seen in PH.11 The problem with this hypothesis is that
SSRIs have been shown to protect against smooth-muscle hyperplasia
in the pulmonary bed.14 This is because serotonin
reuptake inhibition in the periphery decreases circulating levels
of serotonin, since platelets can no longer store serotonin
through reuptake,15 thereby decreasing any potential release.
Correspondence to: Dr. Pierre Blier, University of Ottawa Institute of Mental Health Research, Royal Ottawa Hospital, LG 2043,
1145 Carling Ave., Ottawa ON K1Z 7K4; fax 613 761-3610;