Download psychotropic medication in pregnancy and

PSYCHOTROPIC MEDICATION IN PREGNANCY AND
BREASTFEEDING
Introduction
The treatment of mental health problems during pregnancy and the postnatal
period poses a number of problems. The perinatal period is stressful
psychologically physically and socially. Some of our patients enter the period
already vulnerable.
Firstly the area is bedevilled with problems of diagnosis. When is an emotional
or behavioural problem in the perinatal period a mental health problem? There
is the issue of the failure to treat genuine illness which is accorded some form
of protection and cover by the parent’s perinatal status. On the other hand one
has to be aware of the risks of pathologising normal emotions and behaviour.
To what extent can our medical model of illness take account of the full range
of emotional phenomena in the perinatal period?
The perinatal period is a period of change and indeed upheaval. It is one of
the unique periods of transition in life’s journey. Some would say it presents
as a crisis promising great rewards for those who master its obstacles and
difficulties. Mothers and babies have profound effects on us all as onlookers
tending to polarise our thinking The two extremes are on the one hand seeing
all mental health difficulties as being a normal part of motherhood and hence
diminishing their importance and on the other hand being at a rush to
pathologise all forms of difficulty coping and assuming postnatal depression.
How do we offer help in this situation? Indeed is any specialised help
available and what resources are appropriate for the pregnant woman new
mother (or father) with a mental health problem?
There is still a stigma associated with mental illness and its treatment. In
contrast, the opposite is true of pregnancy, which in most cases is a subject
from which springs great hopefulness both for the individual and society. The
thought of recommending psychiatric treatment for the mother-to-be or the
breastfeeding mother uncovers deep unease and uncertainty in most people;
indeed it seems highly unnatural. As a result, there is a tendency to deny,
under-recognise and under-treat pregnant women and new mothers with
mental illness.
The general practitioner is in a unique position to help and yet is under a
number of competing pressures. Even when women are recognised as being
ill there is a strong tendency to undertreat the episode of illness or to
reconceptualise. This rationalising away of the woman’s distress rather than
grappling with the difficulties of treatment may have the effect of reducing a
clinician’s anxiety. They need not then be concerned about the effects of
medication on the neonate (ie by not prescribing) but there are still the
potential effects on the neonate of untreated psychiatric illness to be
considered.
Many clinicians’ feel ill equipped to deal with the clinical problem. They worry
about interfering in delicate, even hallowed, ground. Treatment decisions
require a comprehensive risk-benefit analysis. Unfortunately there are too few
clinicians who have been trained to do this adequately. Access to more
experienced clinicians is sometimes limited. Decisions have to be
individualised for each woman taking into account her own individual history of
health and illness. The risks have to be considered more specifically as the
risk for this woman.
The knowledge required includes:
a. the extent to which the foetus or a breast-fed baby is exposed to
medications via the placenta or breast milk.
b. the effects of such medication on the foetus generally in terms of
birth defects, toxicity, and obstetric outcomes
c. issues to do with the longer-term, neurobehavioural outcomes; the
effects on the developing brain (effects that are known or postulated)
Given that recent research has alerted us to the potential for SSRI’s to cause
some increase in birth defects (particularly ventricular septal defects) we
remain concerned about any as yet undiscovered potential for longer-term
negative effects of psychotropic drug exposure.
Some recent trends.
The increased age of mothers having a baby for the first time means that
there is a greater chance of pre-existing psychological illness especially
depression. This goes hand in hand with the increased recognition and
treatment of depression in women in childbearing years. There is the
increased detection of depression via screening programs both antenatally
and postnatally. There has been an increased recognition of antenatal
depression and an increased recognition of chronic depression.
There has been a trend for the increased recognition and treatment of anxiety
disorders and increased research and concern about the influence of maternal
(caregiver) psychopathology on the development of mother infant attachment
patterns and don infant psychological development including particularly
neurodevelopment.
Looking at conditions other than major depression there is a trend to the
increased use of atypical antipsychotics with their attendant reduced tendency
to diminish patient fertility. There has been a marked increase in the use of
mood stabilisers especially in the use of anticonvulsants. Many patients use
herbal remedies with quite some success especially St John’s Wort.
Some statistics.
Contrary to the long held belief pregnancy is now know to not protect against
mental illness. 70 % of women with a history of recurrent major depression will
relapse during pregnancy. About 50% of women with Bipolar Depression will
relapse during pregnancy. The recurrence rate for post partum psychosis is
very high varying between 50 and 70%.
There is significant depression and anxiety in 15% of women and prenatal
rates are often as high as postnatal rates. The risk of onset of psychiatric
illness is 2 to 3 times higher in the immediate post partum weeks compared to
any other time in a woman’s life and the risk of psychiatric hospitalisation is
…. ?20 times higher in these weeks.
Clinical situations.
Commonly the general practitioner will see the following situations:
1. During Pregnancy
2. Prior to Pregnancy
3. Postnatally
1. Prior to pregnancy
A woman will present (hopefully with her partner) and they are hoping to fall
pregnant but wish to discuss the ramifications of a past history of
psychological illness, which will include Major Depression or an Anxiety
Disorder or Bipolar disorder etc. The issue of management and prophylaxis
arises.
Similarly a woman may present who is currently taking a psychotropic
medication and considering a pregnancy.
2. During Pregnancy
Quite commonly, since 50% of all pregnancies are unplanned, a woman will
present to eth GP already taking a psychotropic medication and having fallen
pregnant.
A woman who is pregnant may present with a first onset of a psychological
illness or an exacerbation of a pre-existing psychological illness.
3. Postnatally
A woman, though currently well in her pregnancy, may have a previous history
of an illness such as Major Depression where postnatal prophylaxis may be
advisable. Perhaps she has had a history of postnatal psychosis or bipolar
disorder or her previous depression was so severe and involved such
disturbing behaviour that post partum prophylaxis is advisable.
There may be a new onset of psychiatric illness postnatally requiring
treatment with medication. Of course there is also the continuation of
medication used during pregnancy with perhaps some modifications due to
breastfeeding.
In terms of actual management we always try to tailor a treatment that draws
from all three domains of the bio-psycho-social model. Psychotherapy, be it
individual, couple or family therapy is always a necessity and of course some
women will only consider psychotherapy, medication being unacceptable to
them. Psychotherapy may be adequate for mild to moderate perinatal anxiety
or depression. CBT or supportive psychotherapy is very powerful, especially
when carried out by an expert and or a person highly valued by the woman.
It is important to respect a woman's position if she is anti-medication. There is
no place for ultimatums or manipulations involving guilt. Keep the door open.
We always say, “Let me know if you change your mind.” People can and do
change their mind.
As an aside, ongoing “talking” visits serve the purpose of providing
psychotherapy and allow for monitoring of mood and the re-evaluation of
symptoms, whichever treatment is being pursued. Powerful evidence-based
medicine involves reliability, consistency and continuity or care. This is not
mere talking. It is useful to schedule weekly or fortnightly appointments ahead
of time for the depressed woman. The appointments do not have to be
lengthy. The frequency and predictability of ongoing appointments may be
more important than the length of sessions. Don’t make the depressed woman
struggle with your secretary for an appointment. Similarly don’t make the
mother’s present her well baby as the only potential ticket into your consulting
room.
The Placenta as a Filter
The maternal placenta acts as a “filter”. It filters medication (to varying
degrees) and it also may filter to some degree the effects of mental illness in
terms of stress hormones such as cortisol. Therefore the question we ask is,
“What gets to baby?” Dr Zachary Stowe has recommended looking at the
problem in terms of exposure. The foetus/baby is exposed to something,
either medication or depression or in some instances, both. Non-exposure is
not an option.
Defining Exposure to Risk
The potential exposure in utero and breastfeeding is:
1. to medication
2. to maternal (and/or paternal) psychiatric illness
3. to both, as under-treatment is very common
Our role is to help the mother and her family decide which is the best path for
the family.
There are two basic assumptions from which to proceed. Firstly, that all
medications cross the placenta and enter the breast milk and secondly, that
we do not yet know all the potential risks from either medication exposure or
illness exposure.
We can only talk in terms of relative risks and hence the risk of treatment
versus the risk of non treatment.
Prenatal Maternal Psychiatric Illness
Effects on Mother and foetus
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poor compliance with obstetric/medical care
poor maternal health/nutrition
abuse of alcohol and cigarettes
abuse of other substances including over the counter remedies
suicidality, self-harm, recklessness
– reduced care of other children
– marital disturbance
What about the direct effects of maternal psychiatric illness on the foetus?
 These are potential effects on the foetus via changes in maternal blood
chemistry, hormones, catecholamines, immune function etc,
 What happens to the foetus in untreated maternal psychiatric illness??
 What are the long term consequences of untreated maternal
psychiatric illness (eg depression) for offspring into childhood,
adolescence, etc
Potential Direct Effects of Maternal Depression/Anxiety/Stress
Effects on foetus
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changes in the HPA axis especially with anxiety disorders
lower birth weight
prematurity
“behavioural teratogenicity” (experiments in pregnant rats)
What has been shown?
 Deleterious effect on obstetric outcome and later infant development.
 Severe Stress and Depression may:
– impede foetal growth
– smaller head circumference
– increased rate of preterm delivery and other complications
– long term behavioural problems eg aggression in boys
Postnatal Maternal Psychiatric Illness
Effects on Mother and baby.
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deficits in mother-infant attachment
Neuro-behavioural sequelae
increased failure to breastfeed
separations at home, possible psychiatric hospitalisation
abuse, neglect, self harm, recklessness
rarely, suicidality/infanticide
Further Effects on Family and Environment
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reduced care of other children
emotional neglect of other children
marital disturbance
occupational deterioration
reduced social network
other?
The risks of psychiatric Medication
Effects of Antidepressants on Foetus.
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Miscarriage
Malformations
Intra-uterine deaths
Low birth weight
Prematurity
Withdrawal syndromes
Behavioural sequelae
possible slight increase
? Increase VSD
no increase
slight increase
slight increase
can occur
as yet unknown
Until quite recently the data on SSRI’s was quite reassuring. We were able to
say as recently as 2005 that there were no risks of birth defects when using
SSRI’s (quote the paper)
Since then we have had a number of worrying reports to do with Ventricular
Septal Defects (hole in the heart) mostly involving the antidepressant
paroxetine. What we don’t yet know is if these adverse findings are limited to
paroxetine or whether they may turn out to be a class effect for all the SSRI’s.
The other possibility is that with larger, more accurate studies, the negative
findings may wash out.
Soon after the findings on VSD we were confronted earlier this year 2006 with
a finding implicating SSRI’s with Persistent Pulmonary Hypertension in the
Newborn (PPHN). This condition is believed to be related to the pulmonary
difficulties reported in babies whose mothers had been taking SSRI’s. Most of
these ventilatory difficulties have appeared self limiting but they may reflect
part of a continuum the worst cases of which may qualify for the diagnosis of
PPHN. This is a worrying report and follows the earlier reports which have
added a note of caution in the prescribing of antidepressants to depressed
mothers.
Indeed a controversy has predictably erupted with Dr Koren warning that an
overreaction is very likely and that much damage will be done by any major
move towards limiting the prescriptions of antidepressants to pregnant
woman. He counsels that the risks are low and that the risks of no treatment is
high. His group have been monitoring and reporting on the safety of
antidepressants for some time and so he is in a particular position to know
what the issues are.
Neonatal withdrawal syndromes.
There has long been concern about the potential for neonatal withdrawal
syndrome in babies born to mothers taking SSRI’s. Neonatologists seem to
take these difficulties in their stride. They see them as residing on the gentler
end of the spectrum of babies born with a tendency to increased difficulties in
physiological regulation. Nevertheless we worry about the short and long term
effects of such adverse reactions. In the short term there is the potential for
poor adaptation and effects on maternal contact and bonding and attachment
as well as breastfeeding and the beginnings of the sleep and settling pattern.
In the longer term one would wonder about neurological sequelae.
More recently the issue has been investigated with the revisited looking that
the question as to whether these so called withdrawal reactions may not be
instead aspects of serotonin excess and therefore toxicity. These authors
point to the immediacy of the reaction compared to the delay one would
expect in a withdrawal reaction and the issue arises as to whether this may
reflect a serotonin toxicity that is occurring in utero. Does the infant become
toxic subsequent to umbilical cord clamping? This would require the infant to
metabolise the SSRI by its own hepatic system and could thereby expose the
infant in the short term to a toxic reaction.
These questions remain the subject of research. In the meantime some
experts recommending reducing and ceasing antidepressant medication
SSRI’s in the weeks prior to delivery. In practice this is more difficult to do
than one would imagine. Firstly not all mother’s psychological conditions allow
this form of management. Some have past histories that preclude it. For
some, their current mood state is too fragile. For others the thought of no
longer taking medication and potentially relapsing at the point of facing the
stress of delivery seems counterintuitive if not outright foolishness. Hence
many women cannot be convinced that the potential benefits are useful.
Nevertheless in well selected cases there is a group of pregnant women who
are well and motivated and relish the thought of participating in such a
precautionary manoeuvre and for these women it can work well.
Approach to Pharmacotherapy of Depression in Pregnancy.
Try to pre-empt difficulties. Try to discuss the issues prior to pregnancy along
with any discussion of contraception and pre-pregnancy health. Planning
ahead is the key as this allows time for informed decisions.
Document your decision making. Document a plan based on the woman’s
past mental health as well as her current mental state and the “risk-befit ratio”.
Don’t underplay your reasons for recommending treatment.
Try to involve partners and families where appropriate. The woman and her
partner must ultimately decide based on all the information that we can
provide concerning the strengths and weakness of each treatment modality.
We should endeavour to communicate an attitude of optimism and
hopefulness while at the same time making it clear that our attempts can only
be aimed at “minimising exposures” and hence no decision can ever be risk
free.
If planning a pregnancy
Stop medications if possible while attempting conception. This is not always
possible and depends on the previous history of illness. Since it can take
some time for the couple to fall pregnant, stopping medication on becoming
pregnant may be a reasonable option. Again this depends on the history and
the willingness of the woman to test for pregnancy at the end of each cycle.
Certainly when pregnancy is discovered early, and medication ceased
immediately, the developing blastocycts is not exposed to the maternal
circulation and hence is unlikely to be affected by the medication. This allows
the not inconsiderable advantage of staying on medication that may be having
a prophylactic effect on mood for what may turn out to be many months or
even years of attempting pregnancy.
During early pregnancy
We try to avoid all medications in the first trimester. Again this may or may not
be possible. If medication becomes necessary we use mediations that have
been used frequently in pregnancy and have the most supportive data. If the
previous illness has been severe and there is a known previous response to
an antidepressant we might chose that medication despite a lack of data. At
this stage however it would seem unwise to use paroxetine without a second
opinion.
We avoid polypharmacy if at all possible. We avoid changes in medication as
this introduces a new or second exposure. For this reason we may start out
with a medication of known response for the patient rather than a medication
that has the most favourable data.
We avoid anticonvulsants unless absolutely necessary. In such case we add
high dose folate i.e. 5 mg per day and we monitor the baby’s morphology with
ultrasound.
We try to involve obstetric and medical and nursing carers where appropriate.
The approach in late pregnancy.
Try to promote a focus on the baby despite the effort engaged on the illness.
Attachment issues emerge in the last few months and we try to promote the
mother turning inward to focus on her relationships with the baby leading to
Primary Maternal Preoccupation. We try to foster that state despite our
concerns about the real world of the depression etc.
The pharmacokinetics of antidepressants can change in pregnancy and
relapses in depression or anxiety can occur requiring increases in the
medication dosage. This may occur around 16 to 24 weeks. It may be do to
changes in pharmacokinetics but other theories have been advanced to do
with the changes in sensitivity of serotonin receptors or their population
number related to changes in oestrogen levels. Whatever the cause be ready
in such cases to increase the dose.
To conclude:
In pregnancy and postnatal settings, new antidepressants are not likely to be
the answer. Learning to use what we have more intelligently and
systematically is the likely way forward.
Always remember the role of non-pharmacological management of mental
health issues.
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