Should Pregnancy and Infertility Patients Receive Psychotropics ?

By Lynn Shapiro

Women suffering from mood disorders like anxiety or depression often find cold comfort from the average gynecologist when pregnancy is in the offing. The typical advise is Get off Prozac. But cutting-edge psychopharmacologists more familiar with the current research say the issue is less black and white than that.

Some of these physicians are willing to prescribe psychotropic drugs to a pregnant woman, even in the first trimester, if the benefits to her clearly outweigh the risks to her fetus. Others are more cautious. They say the data on drugs such as Prozac and the benzodiazepine, Klonopin while encouraging are not conclusive. (Many more doctors feel confident prescribing medication later in pregnancy when the baby is simply growing.)  Fertility treatment involves less guesswork. Most everyone on the cutting-edge agrees that giving such a patient the medicine she needs is not only kosher but advisable and that denying her treatment may actually keep her from becoming pregnant.

A leading proponent of drug therapy during pregnancy is Lee Cohen, director of the Perinatal Clinical Psychiatry Research Service at Massachusetts General Hospital. Dr. Cohen ventured into the terra incognito of pregnancy research in the mid-80s, starting what he calls a small consulting service to help women and their doctors weigh the risks of taking mood-altering medicines versusthe risks posed by a possible return of their illnesses.

Now, with the help of National Institutes of Health funding, he is following women on medication throughout their pregnancies and during the postpartum period. And this year, his team has begun tracking babies whose mothers were given psychotropics data his peers say theyre anxiously awaiting.

Asked if he believes it is dangerous for a pregnant woman to use medication, Dr. Cohen says, Is it dangerous? Its more dangerous to have malignant recurrent depression and to become more treatment resistant over time and then to have an impaired mother. Im as concerned about untreated psychiatric illness during pregnancy as about the use of drugs.

Still, the Mass. General physicianwho also teaches at Harvard says he never prescribes drugs to women as a first line of treatment. Instead, he routinely refers all his pregnant patients for cognitive behavioral therapy (CRT), as evidence mounts that the treatment works. But for many patients it doesnt work. In Dr. Cohens experience, some patients with moderate mood disorders can discontinue drugs and use CRT, while other more severely ill patients either fail to respond to the therapy, or dont succeed for the duration of pregnancy and the postpartum period. For these women, medication with a good safety record may be the best course of action, Dr. Cohen says, even during the first trimester when its traditionally shunned.

He provides a case in point: A woman has a history of depression. Shes been on a number of drugs and has responded exquisitely to Prozac. Shes tried on three occasions to stop Prozac and each time she becomes severely depressed. On one of those occasions she ends up in the hospital. And so she comes to see us because shes very concerned about staying on Prozac but shes as concerned about becoming ill during pregnancy.

In this case, Dr. Cohen says he would feel fairly confident putting his patient back on Prozac, as the most recent data suggest it does not increase the risk of fetal malformations, even when used in the first trimester.  Indeed, of the 2,000 woman hes seen on the drug, he reports there is no greater incidence of malformation than in the general population. (No such evidence exists yet for Zoloft or any of the newer serotenergic drugs, he says.)

He cites one caveat, though. A study published in The Journal of the American Medical Association followed 138 women in the first 12 weeks of regnancy who were taking Prozac or the tricyclic antidepressant, nortriptylene. The study found there was a non-significant increase in miscarriage during the first trimester with both types of antidepressants versus the drug-free control group. While Dr. Cohen believes this study is too small to be meaningful in any case, others cite it as a reason for caution.

Miscarriage aside, several psychiatrists say they are not persuaded that Prozac on the market for a mere 8 years has been proven safe. If I had to give a pregnant patient a drug Id choose the oldest one available, says Jennifer Downey, research psychiatrist at New York State Psychiatric Institute. Instead of treating a depressed patient with Prozac, shed prescribe one of the tricyclics antidepressants, since these drugs have been around for more than 50 years and thousands upon thousands of pregnant women have used them.

If she were forced to treat a pregnant anxiety disorder patient with medication, Dr. Downey says shed prescribe a small dose of a major tranquilizer like Thorazine or Haldol also very old drugs rather than any of the benzodiazepines, including Ativan, Librium or Klonopin. While Klonopin probably is the safest drug in its class and the one most often prescribed to pregnant women its safety record is still questionable, she says. Other physicians agree with her: they say they are steering clear of the benzos because they have been linked with spina bifida and various limb deformations both in animals and humans.

Surprisingly, Klonopin manufacturer Hoffman La Roche is willing to rebut this claim. A company spokesman says that after exhaustive research, the company has found no data in the literature to support a higher than normal rate of congenital malformation as the result of the administration of Klonopin.

Dr. Cohens research affirms this finding. So far, he says hes seen several hundred woman who have taken Klonopin during pregnancy and all have had healthy babies. Moreover, he says preliminary data show that on dosages of anywhere from one-half to 1.5 milligrams, there is no evidence of fetal distress, of more lengthy labor, of neonatal irritability or of withdrawal symptoms in infants. (Hes not sure Klonopin is safer than the other benzodiazepines, hes just had more experience with it.)

Just as important, he says, anxiety left untreated during pregnancy is not a benign event: He cites data suggesting high levels of anxiety during gestation is associated with a higher incidence of pre-term labor, children with low APGAR scores and a greater number of obstetric complications. Manhattan psychiatrist Robert Levine is also willing to prescribe Klonopin to those women who cant function without it. He notes since hes never seen a human being whos had any organ deformation due to this drug, he has given it to some of his patients during the last two trimesters and some during all three.

Thats not something he advocates because of the unknowns. However, he says while some women are willing to discontinue Klonopin and endure severe discomfort, others, especially those with full blown panic disorder, just arent. Some women suffer three to four panic attacks a week and are afraid to leave the house for fear of having another attack, he points out. Is it fair to deny these women treatment with a drug that apparently does no harm? He thinks not.

Recently, Dr. Levine treated two pregnant panic attack sufferers with Klonopin, 1 milligram a day in one case and 2 milligrams in the other. He reports: Both woman are highly intelligent and had been warned that there were risks. But both decided to go through the entire pregnancy with medication. One women did extensive research, consulted a genetic counseling service, was supervised very closely during pregnancy it was probably the most sonogrammed fetus that ever was. But at least at the time of delivery, the babies were perfectly normal. And both women reported their pregnancies were joyful experiences.

But heres the pin that punctures the balloon. While the psychotropics apparently cause no organ defects, there are no long term neurobehavioral studies proving they dont impair cognitive function. For this reason, Jack Gorman, chief of clinical psychobiology at the New York State Psychiatric Institute, is adamantly opposed to giving most patients drugs while theyre pregnant.

Calling himself the most conservative physician in this world, he admits the evidence is against his argument that shunning drugs during pregnancy is the right thing to do. Even with lithium, where doctors were certain there was a risk of cardiac abnormalities, theres some debate whether this is true, he says.Yet, my question is always do these drugs present a subtle change in brain development so that when the child is five yearsold, say, he or she doesnt read easily, or his fine motor coordination is impaired. To find this out, youd have to do an enormous study and its unlikely anyone is ever going to deliberately expose a large group of pregnant woman to a drug and another group of pregnant woman to a placebo and then follow their babies throughout childhood.

Psychopharmacologists feel infinitely more confident treating would-be pregnant patients. Here, many of the same doctors who blanch at giving drugs to an already pregnant woman say it is a mistake to deny an infertility patient the medicine she needs, as long as she is diligent about taking early pregnancy tests; that is, taking a beta HCG even before she misses a period.Just the process of getting pregnant can be extremely taxing, says Manhattan psychiatrist Peter Kaplan. And lots of studies have shown that a mothers mental status is definitely going to affect her ability to ovulate and to conceive, so we must take mental status into account. Once the pregnancy test comes back positive, Dr. Kaplan says he immediately takes the patient off the drug shes using. At this stage, there would be no damage to the fetus because the maternal-fetal circulatory system is not yet formed.

He says hes extremely sympathetic toward patients who say fertility drugs have caused their mood disorders in the first place. Clomid is a real culprit in that it affects the hypothalamus which also governs mood. Dr. Kaplan has seen it trigger depression, anxiety, flushing and even panic. So when a woman is on Clomid unless theres a reason not to give one of the anti-panic disorder drugs or anxiolytics, its cruel and unnecessary not to, he says, adding, Why suffer if youre not already pregnant?

Dr. Cohen agrees. The hot issue today, he says, is what is the impact of infertility treatment on fertility itself? In other words, what does the stress, depression, anxiety, do to the hypothalamus/gonadal axis? Theres no answer to that, but I think the message ought to be conveyed that treating depression and anxiety disorders need not be deferred just because a woman is trying to get pregnant.

If theres one sure thing about the pregnancy/drug quandary, it is that those couples that approach their physicians beforethey get pregnant are well ahead of the game, says Psychiatric Institutes Jennifer Downey. In other words, husband and wife shouldcome in together, don their own white coats, so to speak, and analyze their predicament. For example, the wife might argue she can do without medication while the husband says, Yes, honey, but the last time you stopped your medicine you spent a year sitting on the floor in the bedroom and I cant take it. In this way the three of us will weigh the risks of medication versus the benefits and decide on a course of action.

And after pregnancy? Here, even the most cautious believes a woman suffering from a mood disorder should resume treatment so she can better care for her child. Breast feeding is a little overrated, anyway, says Psychiatric Institutes Jack Gorman. He adds: Women with a history of bipolar illess should resume drug treatment immediately after pregnancy while still in the hospital since the incidence of postpartum depression is very high in women with mood swings. And for those with a history of psychosis, the incidence is 40 times higher during the first month after pregnancy and that risk extends for two years after, according to the most recent literature.


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