Medication, Pregnancy and Lactation

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This page will attempt to provide information on safe prescribing patterns of psychiatric medications that can be used during pregnancy, and also during lactation. I will try to stick to generic names of medication, that is the name of the chemical not the brand name, as these can vary from one country to another (as can availability). If I do use brand names, it will refer to brands available here, in Australia.


1. Why may we wish to use medications during pregnancy? As a general rule it is very important to avoid the use of any medication during pregnancy. Whilst most medications on the market (at least here in Australia) have been tested for teratogenicity, that is the ability to produce congenital malformations, testing of new drugs on human beings has obviously been limited for ethical reasons. We can therefore be fairly sure of a medication's safety on the basis of results from animal testing (I'm sorry animal liberation supporters, is there any other way?) but we cannot be absolutely positive that a medication is safe in humans. Our best guide to safety is from studying the effects of medications on women who have been taking them when they became pregnant, and who have remained on them throughout the pregnancy. There are obvious reasons why psychiatric medications, that is medication that acts on the brain to treat depression, anxiety or psychosis should not be given to a pregnant woman unless absolutely necessary. Those medications, after crossing the placenta, will also be present in the developing brain of the embryo, and it is possible that they may affect this developing organ in a different way from the intended effects on an adult brain.

The decision to recommend medication should therefore not be taken lightly. It is my experience, and that of many others around the world, that this is a situation where there is no 'right' answer. Rather, a decision must be made after weighing up the risks and benefits of each course of action. Ultimately, of course, the decision must rest with the parent/s of the unborn child. What we do know is that:

The decision to use medication should always be part of a comprehensive plan for recovery that also involves psychotherapy (talking and listening treatments) and social interventions, such as relationship support, family and community support and education. It should be recommended as part of this range of treatments when the anticipated risks of not treating outweigh the potential risks of using medication.

If you are not clear about this ask your doctor to clarify this for you. Once again the final decision can only be yours to make.


2. What medications are used safely during pregnancy? Antidepressants have been available in the Western world since the mid 1950s. Initially there were 2 classes of drugs: MAOInhibitors, and Tricyclic antidepressants. MAOInhibitors are effective antidepressants but are not safe to use during pregnancy so I will not discuss them further, other than to say 'don't take them'.

Tricyclic antidepressants have been used extensively, and there are reports of their use during pregnancy in literally thousands of women. There are some conflicting data that suggest a possible higher rate of miscarriage in early pregnancy, but this has not been shown consistently. There are no studies that show a rate of birth abnormality any higher that 1-2% which is the normal rate of birth abnormality. This is a very important point, because tricyclic antidepressants will not protect you from having a child with a birth abnormality, but neither are they likely to cause them. There is some theoretical risk of tricyclics interfering with the normal pattern of labour, however this risk is probably more theoretical than real. If you are concerned, discuss this with your doctor. You can always lower the dose prior to your expected date of birth. There are some reports of some babies becoming irritable after birth, and perhaps in some babies there may be a drug withdrawal syndrome, however this is not universal or even common. Whilst not ignoring the problem, some babies are going to be irritable anyway.


Newer Antidepressants in pregnancy and lactation
There are several newer classes of antidepressants that have become available during the 80s and 90s. The best known of these are the SSRIs, the best known example of which is Fluoxetine. This is the chemical in Prozac. Other SSRIs that are used here in Australia are Sertraline (Zoloft) and Paroxetine (Aropax). The only SSRI that appears to be as safe as tricyclics is Sertraline, although this drug has not been studied in as many women as tricyclic antidepressants, and this statement is based on the results of fairly small studies. It may also be that Fluoxetine is safe to use during pregnancy, however some studies have shown that after birth, it can be secreted in variable, but relatively high levels in breast milk. This does not necessarily rule out it's use, because we don't know that this is dangerous, however there should be a sound reason why Fluoxetine should be used in breastfeeding women, and the baby should be monitored carefully for signs of toxicity. Some studies have shown that even if it is secreted in breast milk, perhaps only 1% of that dose may be absorbed. There have been a few case reports claiming that babies exposed to Fluoxetine prior to birth became 'jittery' and 'agitated ' after the birth. These are case reports only, and babies may be 'jittery' for many reasons that are unrelated to Fluoxetine. Indeed, even in those case reports there was no detectable level of antidepressant present in the baby.

A recent study published in the New England J Medicine (1997;336:258-62) showed no diiference (compared to the control group) in developmental milestones , behaviour and IQ of children exposed to tricyclics or Fluoxetine for a followup period of 7 years. This study is a welcome addition to the few longer term followup studies of children exposed to antidepressants in-utero, which all seem to have produced similar findings so far. However I'm a cautious fellow, and I still recommend that the newer antidepressants be used with caution, and of course with full informed consent.

Paroxetine is secreted in quite high doses in breastmilk and should be avoided if breastfeeding, however there is no evidence that it causes harm during pregnancy.

Moclobemide(Aurorix) is a reversible MAOInhibitor that is not available in the USA, but is available in Australia. Whilst there is evidence that orthodox MAOIs are teratogenic, (that is they cause birth abnormalities) there is no evidence that Moclobemide is teratogenic. There are studies currently that may indicate that Moclobemide may be used in breastfeeding, and indeed it appears to be secreted in breastmilk in lower levels than Sertraline.

Remember however that there is just not the same weight of evidence regarding safety for these newer medications, and that there has not been possible to assess the long-term effects of any antidepressants. There may be problems that only come to light in generations to come. Any decision to use or not use medications must be made on the balance of risk versus benefit.

Mood Stabilisers

Commonly used mood stabilising medications available in Australia include Lithium Carbonate, Carbamazepine (Tegretol) and Sodium Valproate (Epilim).

Lithium has been reported to include cardiac endocardial cushion defects in the developing hearts of 10% of foetuses in some studies. This figure is much lower in some recent studies ( as low as 1:1,000) and the abnormality may not be serious even if present. This appears to be a problem that is confined to the first trimester, the period of cardiac development. Foetuses at risk can be checked by ultrasound scan. There is no clear evidence for other teratogenicity, but of course Lithium levels must be monitored throughout pregnancy to avoid the risks of toxicity to mother and baby. Alternatively, all women taking Lithium should be warned of the risks of birth abnormality and should be encouraged to use regular contraception. Pregnancy should be planned if possible, and follow a cessation of Lithium. Please discuss this with your doctor first! If you are taking Lithium during pregnancy then it is recommended that you have frequent blood monitoring of your Li level. Lithium requirements increase throughout the 2nd and third trimester (related to it's higher excretion rate), and that the dosage be reduced by 50% prior to delivery. Whilst there are definitely problems that have occured with Lithium use during pregnancy, remember that this must be balanced against the risk of relapse if the medication was ceased.

Lithium has been shown to be secreted in variable levels in breast milk, and often the levels can be high. If, on the balance of risk, Lithium treatment should be continued whilst breastfeeding, Lithium levels in the baby should be monitored and extra care should be taken to avoid dehydration in the baby.

Carbamazepine and Valproate have both been reported as causing a greater rate of birth abnormalities. Some caution must be drawn from these findings however, as the data were collected from women taking this medication for epilepsy, not mood control, and other studies have shown that women with a history of epilepsy have a higher rate of birth abnormalities. There is some additional evidence that Carbamazepine also causes birth abnormalities during the first trimester - specifically neural tube defects such as spina bifida. The risk of neural tube defects is highest in the first trimester, so these medications should be used cautiously during this time. Pregnant women should probably take folate supplements, a B group vitamin known to reduce the risk of neural tube defects.

Carbamazepine has been reported to cause sedation, hepatitis and hyperbilirubinaemia in babies when used by breastfeeding mothers. It has been measured at a level in breastmilk of 50-75% of the mother's blood level. It seems most likely that Sodium Valproate is the safest mood stabiliser to use during pregnancy and with breastfeeding, although it is certainly not without risk. It has been measured at a low 1-4% of maternal blood levels.




5 Antipsychotic medication

There are few studies on the use of antipsychotics in pregnant women. Whilst some reports have suggested an increased risk of birth abnormalities with phenothiazines, this is not a consistent finding. There is some evidence that phenothiazines may resrict uterine blood flow, and may also compromise the foetus if it causes postural hypotension in the mother. there have been some reports of extrapyramidal symptoms in babies soon after birth, but once again these are mainly case reports. Thioridazine (Melleril in Australia ) should be avoided in pregnancy as some French syudies have reported a higher incidence of limb malformation. It seems likely that high potency antipsychotics such as Haloperidol are the safest antipsychotics to use in pregnancy. Oral medication should be used in preferance to depot medication. Pimozide (Orap) is an alternative when compliance is doubtful as the drug has a long half life.

Some studies have now followed children exposed to intrauterine antipsychotics for 5 years and they have normal milestones.

Haloperidol is probably the safest in breastfeeding but there is little hard data to support this. Low doses should be used and the baby monitored for side effects, although they have rarely been reported.

Benzodiazepines

As a general rule benzodiazepines should be avoided during pregnancy, and certainlt avoided during breastfeeding. There have been some reports of a higher incidence of cleft lip and palate in babies exposed to Diazepam (Valium) during the first trimester. There have been no specific reports assosiated with the use of Clonazepam. All benzodiazepines are excreted in breastmilk, and there have been reports of babies developing sedation and temperature dsyregulation.


Anticholinergics

These medications are used both as 'side effects medication' for some people who take antipsychotics, and is also found in many common cough medicines such as Benadryl. There is little information on the safety of these medications although there have been reports of cleft palates in babies exposed to Benadryl. The safety in breastfeeding is unknown.

Prophylaxis

This is also an area of some controversy. If there is a clear history of recerrent postpartum mood disturbance or otherwise a strong likelihood of depression there is some evidence that prophylactic use of antidepressants may lower the risk of relapse. In a small study of women who were treated this way the relapse rate was reduced from 8:10 to 1:10. this was only a small study and cannot be generalised to apply to everybody. Discuss this with your doctor.


ECT

Electoconvulsive therapy is a safe, quick and effective treatment for both depression and postpartum psychosis. It can relieve symptoms in some cases bu the time medication begins to work. It can be used safely during pregnancy with appropriate monitoring of the foetus, and of course has no effects on breastmilk. It also has 'side effects', the most disabling of which are temporary memory disturbance and headache and short term confusion. A general anaesthetic is given for ECT.

This treatment has attracted some strident opposition from people who see it as punishment, a weapon of state mind control , brain damaging, or torture. I don't believe it is any of these things have any basis of truth whatsoever, but read what they say if you wish and decide for yourself. I've seen many severely depressed people rapidly return to a normal life with ECT. Once again please discuss this with your doctor.


Side Effects
All medications cause side effects. It is also a sad but important fact to remember that even inert sugar tablets cause side effects in 30% of people who take them. Please read Dr. Valerie Raskin's article on side effects of antidepressants used to treat perinatal psychiatric disorders.

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