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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 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 – – – – 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. 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 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. 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. ***************************************************