Some doctors are concerned that too much emphasis is being placed on the relatively small risk of taking Prozac during pregnancy vs. the health of the mother.

In April, the National Toxicology Program's Center for the Evaluation of Risks to Human Reproduction, established by the NTP and the National Institute of Environmental Health Sciences, issued a final report on the reproductive and developmental toxicity of fluoxetine (Prozac). The report concluded that "third-trimester exposure to therapeutic doses of fluoxetine ... is associated with an increased incidence of poor neonatal adaptation," which includes jitteriness, tachypnea, poor tone, and other symptoms, "as well as increased admissions to special care nurseries."

Having reviewed the report in draft and final form and having testified at the meeting of the expert panel convened to write the report, my greatest concern is what patients and some clinicians may do with the panel's conclusions. Information in the report, while comprehensive and technically correct in most cases, might easily be misconstrued by women and their families.

The report provides a summary and review of existing data, with a thorough review of the animal and human literature on reproductive safety of fluoxetine. It does not adequately address the clinical context in which fluoxetine or other selective serotonin reuptake inhibitors (SSRIs) are used. While this may not be the aim of the project, failure to address this issue limits the report's value with respect to its ability to inform clinical care; the absence of a clinical context with which to interpret the report may lead to incorrect conclusions and clinical treatment decisions, putting women at risk for the sequelae of untreated or relapsing depressive illness.

The report criticizes much of the literature regarding reproductive safety of fluoxetine, which is understandable because controlled studies of exposures to any medication during pregnancy are not done for ethical reasons. Conclusions regarding reproductive safety of medications come from various sources, such as case series, postmarketing surveillance registries, and teratovigilance programs. These sources can sometimes provide large enough numbers of drug exposures to allow for useful conclusions regarding reproductive safety.

The panel's conclusions regarding the risk for major congenital malformations associated with prenatal exposure to fluoxetine are consistent with the literature and suggest an absence of increased risk with first-trimester exposure to the medicine. The report also addresses the risk for "perinatal toxicity," which typically includes symptoms of jitteriness and autonomic reactivity in the newborn.

Enough literature has accumulated suggesting that third-trimester exposure to SSRIs may be tied to an increased risk of transient symptoms as noted above. Most reports have not associated such exposure with adverse longer-term sequelae. Fluoxetine is the only SSRI for which we have long-term neurobehavioral data, including follow-up of exposed children through ages 4-7 years. No differences in long-term neurobehavioral outcome between exposed and un ­exposed children were noted.

One of the greatest failures of the NTP report is that an important confounding factor with regard to outcome of SSRI use in pregnancy is neglected: maternal mood. In the recent literature, one can find the same "toxicity," such as lower Apgar scores or obstetric complications, in children of mothers who have untreated depression during pregnancy. Failure to address this adequately in the report is a significant omission.

Fluoxetine is used to treat a serious illness; it is not a potential environmental toxin, such as those reviewed by other NTP panels. The report does not indicate that decisions about whether to use fluoxetine during pregnancy are clinical choices made by patients in the context of some risk-benefit analysis made collaboratively between the patient, her family, and the physician. My colleagues and I have described high rates of relapse in women with a history of recurrent major depression who discontinue antidepressants in pregnancy. Depression during pregnancy is associated with compromised fetal and neonatal outcomes-risks that are not reflected in the report. Discontinuation of antidepressant medication near the end of pregnancy appears to increase the risk for postpartum depression.

The panel notes in the report that it recognizes that any risks of fluoxetine need to be weighed against the risks of untreated disease. But this brief statement embedded in a lengthy document that describes fluoxetine as "a reproductive toxin" is inadequate. One has to wonder how this report will impact what actually goes on as patients make decisions about using these compounds.

Dr. Lee Cohen is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston. He is a consultant for and has received research support from manufacturers of several SSRIs. He is also a consultant to Astra Zeneca, Lilly and Jannsen - manufacturers of atypical antipsychotics. He originally wrote this article for ObGyn News.

Antidepressant package inserts now warn of complications to the baby from mothers who took antidepressants during pregnancy. Is there reason for extreme concern?

Physicians and patients may be alarmed by recent changes to the product labels of the selective serotonin reuptake inhibitors (SSRIs) and the selective norepinephrine reuptake inhibitor venlafaxine (Effexor) with respect to their use during pregnancy.

The labels now describe clinical findings in newborns exposed to these drugs late in the third trimester, including respiratory distress, jitteriness, irritability, hypoglycemia, feeding difficulties, cyanosis, hypotonia, hypertonia, hyperreflexia, and constant crying. Complications requiring "prolonged hospitalization, respiratory support and tube feeding" are also mentioned.

Prompting these changes were postmarketing adverse event reports made to the Food and Drug Administration over several years, suggesting a constellation of symptoms associated with third trimester exposure. Because these spontaneous reports were uncontrolled, it is impossible to know with certainty whether they are secondary to the medicine. Some of the symptoms-such as jitteriness, irritability, and feeding difficulties-are consistent with anecdotal reports and case series in the literature, which support at least transient jitteriness and irritability associated with maternal use of these antidepressants, particularly late in the third trimester.

But more serious problems such as prolonged hospitalization and the need for respiratory support are not well supported by any objective data in the medical literature. Listing these in the label may do little but alarm patients and physicians.

One theoretical rationale for mandating the label change derives from the assumption that these symptoms are consistent with antidepressant discontinuation symptoms now well described in older patients who abruptly stop treatment with these compounds, particularly those that are shorter-acting. While the description of these symptoms as a "neonatal discontinuation syndrome" is an interesting clinical hypothesis, it is untested and not supported by data.

The label also now advises physicians to "carefully consider the potential risks and benefits of treatment" in patients and suggests that clinicians should consider tapering or discontinuing the medicine late in the third trimester before labor and delivery. One has to wonder about the wisdom of suggesting a taper or discontinuation of an antidepressant during this critical time, considering that the risk for relapse among women who discontinue antidepressants during pregnancy is high and that depression during pregnancy is one of the strongest predictors of postpartum depression.

There are no data to suggest that tapering the drug near term attenuates the risk for toxicity in the newborn. In our earlier work, we actually suggested the peripartum taper of antidepressants; the approach was intuitive as it avoided even the potential risk for neonatal toxicity. However, we then observed high relapse rates among women around labor and delivery, prompting us to shift our recommendation to continue antidepressant therapy across the peripartum period.

The labeling changes will likely create alarm about a potential clinical syndrome that has an extremely low incidence and modest clinical significance. Nonetheless, the label change has the potential to affect scores of women for whom depression remains a significant medical problem.

These changes may increase the threshold for using antidepressants during pregnancy not only during the peripartum period but also during other stages of pregnancy-despite data suggesting that depression in pregnancy has an independent adverse effect on fetal well-being and is the strongest predictor of postpartum depression. The text of the label change lacks this context and puts the clinician in the situation of prescribing counter to the new language if the decision is made to treat during at least the third trimester of pregnancy. The label change is an example of blanket, non-evidence-based recommendations that not only fail to thoughtfully inform clinical care, but also may do more harm than good.

Clinicians confused by these changes should weigh the risks and benefits of antidepressant use near delivery. No psychotropic drug is approved for use in pregnancy, so decisions about using these medicines are made on a case-by-case basis. For women who have experienced depression during pregnancy, particularly those who have had residual symptoms of depression, discontinuing antidepressant therapy may lead to significant worsening or relapse of depression. These issues should be discussed with patients in the context of the patient's individual clinical situation. Only in that context can truly thoughtful treatment decisions be made pending better controlled data.

Dr. Lee Cohen is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston. He is a consultant for and has received research support from manufacturers of several SSRIs. He is also a consultant to Astra Zeneca, Lilly and Jannsen - manufacturers of atypical antipsychotics. He originally wrote this article for ObGyn News

With limited research data on the impact of newer atypical antipsychotics during pregancy, pregnant women with bipolar disorder or schizophrenia may be better off with the older antipsychotics.

The reproductive safety of the older typical antipsychotics, such as haloperidol, is supported by extensive data that have accumulated over the past 40 years, at least with respect to teratogenic risk. Much of the data come from their use in treating nausea, particularly with prochlorperazine (Compazine). While long-term neurobehavioral data have been somewhat sparse, no particular indications of risk have been raised in over four decades of use.

We have far less reproductive safety data on the newer "atypical" class of antipsychotics that have become widely used over the past decade because they lack some of the longterm side effects associated with the typical antipsychotics. These drugs - olanzapine (Zyprexa), risperidone (Risperdal), quetiapine Seroquel), aripiprazole (Abilify), riprasidone (Geodon), and clozapine (Clozaril) - are approved for schizophrenia; several are approved for acute mania indications as well.

But they are also being used widely across psychiatric disease states, including anxiety, agitation in the elderly, generalized anxiety disorder, and obsessive compulsive disorder), and as adjunctive treatment of depression.

Because reproductive safety data on the atypicals have been sparse, clinicians are again faced with the difficult situation where a relatively new class of medicine is being used frequently in a population of reproductive age women. What data are available have been largely limited to manufacturers' accumulated case series or spontaneous reports, which have their inherent biases with respect to over-reporting of adverse outcomes.

To date, such information has not suggested any "signals" with respect to specific concerns regarding their use during pregnancy but we can make only limited conclusions on such information. Thus, clinicians have been in a bind with respect to use of the atypicals during pregnancy. A study published in April - the first prospective study of the reproductive safety of the atypicals in the literature - provides some reassuring data regarding the risk of malformations, albeit in a relatively small sample of 151 patients. Investigators from the Motherrisk Program in Toronto prospectively followed these women who took olanzapine, risperidone, quetiapine, or clozapine during pregnancy. All of the women had taken one of these agents during the first trimester, and 48 were exposed throughout pregnancy. A total of 151 pregnant women who had taken a non-teratogenic drug also were followed.

In the atypical-exposed group, one child was born with a major malformation (0.9%) a rate lower than the 1%-3% background rate in the general population; compared with two (1.5%) babies in the control group - an insignificant difference.

Differences between groups in the rate of spontaneous abortions, stillbirths, or gestational age at birth were not statistically significant. Women taking atypical antipsychotics did have significantly higher rates of low birth weight babies (10% vs. 2%) and therapeutic abortions (10% vs. 1%) (J. Clin. Psychiatry 2005; 66:444-449).

As the authors point out, the sample was relatively small, the study was statistically underpowered, and long-term neurobehavioral outcomes were not evaluated. Still, this is the first prospective study that complements spontaneous reports from the manufacturers.

The authors included the number of spontaneous reports of pregnancy exposures to atypicals, provided by the respective manufacturers, with the exception of the newer atypicals. Among the 242 reports of olanzapine-exposed pregnancies, there was no increase of major malformations or other abnormal outcomes above baseline. Of the 523 clozapine exposed pregnancies reported, there were 22 "unspecified malformations." Of the 446 quetiapine-exposed pregnancies, 151 outcomes were reported, of which 8 were different congenital anomalies. Eight malformations were reported among the approximately 250 reports of pregnancies and lactation exposed to risperidone, but no pattern of abnormalities was noted.

Obviously, if a patient can do without the medication, then it would be appropriate to discontinue it, but this is frequently not the case and these decisions have to be made on a case-by-case basis weighing the relative risks versus benefits.

For a patient planning a pregnancy who has a severe psychiatric illness and who is maintained on an atypical antipsychotic to sustain functioning, switching to a typical antipsychotic may be prudent. However, we often see women who present when they are already pregnant and on an atypical agent. At this point a switch may not be the wisest decision, if she is at a risk of relapse. For those women, the Motherrisk data are not a guarantee of safety but provide information that is at least moderately reassuring to clinicians. Although this small study is encouraging, given the prevalence of reproductive age women on these agents, it would be ideal if industry performed post-marketing surveillance studies that would rapidly provide the amount of cases we need to reliably estimate reproductive risks. Such studies may soon be mandated by the Food and Drug Administration in this post-Vioxx era with increased emphasis on the safety of marketed drugs.

Dr. Lee Cohen is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston. He is a consultant for and has received research support from manufacturers of several SSRIs. He is also a consultant to Astra Zeneca, Lilly and Jannsen - manufacturers of atypical antipsychotics. He originally wrote this article for ObGyn News.

Examination of the safety data available on taking SSRI antidepressant medications during pregnancy.

Over the past few years, several studies have addressed the reproductive safety of the selective serotonin reuptake inhibitors (SSRIs). Recent studies have focused on the risk for neonatal discontinuation syndrome or symptoms of perinatal jitteriness associated with maternal use of SSRIs during the latter portions of pregnancy. Estimates of risk of first-trimester exposure to SSRIs derive from data accumulated over the last 15 years, which support the absence of major congenital malformations associated with first-trimester exposure. Data on the teratogenicity of SSRIs come from relatively small cohort studies and larger, international teratovigilance programs, and they have cumulatively supported the reproductive safety of fluoxetine (Prozac) and certain other SSRIs. These include a Scandinavian-based registry study of 375 women exposed to citalopram (Celexa) in the first trimester, which failed to indict SSRI as a teratogen. A recent meta-analysis conducted by researchers at the Motherisk Program in Toronto supported the absence of teratogenicity associated with first-trimester exposure to a number of SSRIs.

Another recent report from the Swedish Medical Birth Registry failed to identify higher rates of congenital malformations associated with prenatal exposure to a number of SSRIs, including fluoxetine, citalopram, paroxetine (Paxil), and sertraline (Zoloft). But at the Teratology Society's annual meeting in June, investigators from the University of British Columbia, Vancouver, reported an increased risk of omphalocele and craniosynostosis associated with first-trimester exposure to SSRIs. Using data from the National Birth Defects Prevention study, they compared data on 5,357 infants with selected major birth defects with 3,366 normal controls and interviewed mothers about exposures during pregnancy and other possible risk factors. Children with chromosomal anomalies or known syndromes were excluded.

They found an association between exposure to any SSRI during the first trimester and omphalocele (odds ratio of 3). Paroxetine accounted for 36% of all SSRI exposures and was associated with an odds ratio of 6.3 for omphalocele. Use of any SSRI during the first trimester was also associated with having an infant with craniosynostosis (odds ratio of 1.8). No association was noted between SSRI use and the other classes of major malformations studied.

This preliminary unpublished report is also described in a letter to physicians from GlaxoSmithKline, which markets paroxetine as Paxil. The letter also includes additional data from an uncontrolled study of SSRI use during pregnancy, which noted a twofold increased risk in overall congenital malformations and cardiovascular malformations (most were ventricular septal defects) in offspring exposed to paroxetine, compared with other SSRIs. These data were derived from an HMO claims database.

Many clinicians who prescribe SSRIs may be confused by the volley of new reports that suggest some potential teratogenic risk associated with this class of compounds. Indeed, previous reports fail to describe such an association. Many more recent findings derive from either retrospective data sets taken from HMO claims data or from case-control studies, which also have certain methodologic limitations, compared with prospective cohort studies.

These recent findings of increased risk with prenatal SSRI exposure are inconsistent with earlier findings. Nevertheless, large case-control studies can uncover an association not previously identified because of the inadequate statistical power of previous cohort studies, which were not large enough to detect an infrequent anomaly.

Even if we assume the associations from the new case-control study are true and that they are indeed causal, an odds ratio of 6.4 is associated with an absolute risk for omphalocele of only 0.18%. Absolute risk is of far greater clinical value than relative risk and should be taken into account before patients are arbitrarily counseled to discontinue antidepressants during pregnancy.

The new findings are not necessarily cause for alarm. Patients who are planning to conceive and are at significant risk for depressive relapse associated with antidepressant discontinuation may benefit from switching to an antidepressant for which there are the most data supporting reproductive safety. These include fluoxetine, citalopram, escitalopram (Lexapro), as well as the older tricyclics.

However, for women who present when pregnant and still taking SSRIs, including paroxetine, discontinuation should not be arbitrarily pursued. Abrupt discontinuation of antidepressants can threaten maternal affective well-being. That is an unacceptable outcome, which can be stated absolutely.

Dr. Lee Cohen is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston. He is a consultant for and has received research support from manufacturers of several SSRIs. He is also a consultant to Astra Zeneca, Lilly and Jannsen - manufacturers of atypical antipsychotics. He originally wrote this article for ObGyn News.

More information is needed regarding medications used to treat ADHD during pregnancy and while nursing. Learn about the effects of ADHD medications during pregnancy.

Over the past decade, adults have been increasingly diagnosed with attention-deficit hyperactivity disorder (ADHD), including many women in their childbearing years. ADHD patients can be successfully treated with medications such as stimulants, the mainstay of treatment, followed by tricyclic antidepressants and bupropion (Wellbutrin). Women who have been stabilized on one of these medications and want to become pregnant often come to see us with questions about whether they should remain on the drug. What we advise these patients depends in part on the severity of their disorder. For women with mild to moderate symptoms that do not interfere dramatically with their life, we frequently recommend a switch to a nonpharmacologic intervention even though there's a fair amount of information on the reproductive safety of one therapeutic option, the tricyclic antidepressants. For these women, the risk of not being treated does not justify fetal exposure to a drug that we do not know much about or even a drug for which we have reassuring reproductive safety data.

The more difficult clinical scenario is with women who unequivocally have severe ADHD that, if left untreated, could dramatically interfere with their functioning and potentially affect the outcome of their pregnancy. Stimulants such as methylphenidate (Ritalin) do not appear to be teratogenic as a class. But there are some data suggesting an association between in utero exposure to psychostimulants and poor fetal or neonatal outcomes, such as small for gestational age or intrauterine growth retardation. These data, however, are not from reports of women with ADHD, but largely from women abusing stimulants such as amphetamines who had other risk factors for poor neonatal or fetal outcomes. This makes it difficult to discern the independent risk associated with fetal exposure to stimulants.

When we see patients with more severe symptoms who have done well on a stimulant, we share these data with them, pointing out that it's not entirely clear whether exposure is associated with impaired fetal outcome. For women who need treatment in pregnancy, we often recommend a switch to a tricyclic antidepressant because of the robust data supporting the efficacy of these agents for treating ADHD and solid data supporting their reproductive safety. These data include studies showing no increased rate of major congenital malformations with first-trimester exposure. Another study followed exposed children through age 6 and found no differences in long-term neurobehavioral effects between those exposed to tricyclics in utero and those who weren't.

A switch to a tricyclic antidepressant would also be preferable for a woman on Wellbutrin despite evidence supporting its effectiveness in treating ADHD. Because there are only sparse data on its reproductive safety, we discourage use of this drug during pregnancy. Wellbutrin is a pregnancy category B compound, meaning that it has been categorized as fairly safe in pregnancy. However, this categorization is based on limited information that does not indicate a risk but is insufficient to rule risk out entirely. There are some data suggesting that selective serotonin reuptake inhibitors (SSRIs) are effective for ADHD in some people, but most studies do not show efficacy. For those who have responded to an SSRI, the safest such agents to use during pregnancy are fluoxetine (Prozac) or citalopram (Celexa). Still, the use of a stimulant is not absolutely contraindicated during pregnancy. We occasionally have a treatment-dependent woman with ADHD who did not tolerate or respond to treatment with an antidepressant but was stabilized on a stimulant. We have not observed any problems using stimulants in pregnancy over the past 15 years, but the sample size is small and we have not investigated this question in a controlled fashion.

There are no data on the postpartum course of ADHD, but since worsening of psychiatric disorders during the postpartum period is the rule, we typically reintroduce medications at this time in women who went off them before or during pregnancy. We do not counsel women who have remained on stimulants, tricyclics, or Wellbutrin to defer breast-feeding. The data on stimulant use during breast-feeding are incomplete. At our center we would not consider a stimulant as absolutely contraindicated in women who are breast-feeding, because the amount of the drug secreted into breast milk is small.

Dr. Lee Cohen is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston. He is a consultant for and has received research support from manufacturers of several SSRIs. He is also a consultant to Astra Zeneca, Lilly and Jannsen - manufacturers of atypical antipsychotics. He originally wrote this article for ObGyn News.

Interview

With several years of experience as a psychotherapist in community mental health and inpatient psychiatric settings, Linda Chapman has practiced in individual, family, and group modalities, and has special expertise in existential group therapy for adults, including trauma survivors. As a writer and feminist activist on issues concerning survivors of abuse and trauma, Linda voluntarily maintains a number of websites on related topics, including The Wounded Healer Journal, an award-winning healing community for psychotherapists and abuse survivors since 1995. Linda is a 1986 graduate of the University of Oklahoma School of Social Work and is the mother of a teenage son.

Tammie: What prompted you to create the "Wounded Healer Journal?"

Linda: Many strands are woven into that thread. Primarily, I created it out of a desire to meet my own needs as a survivor and a therapist. I wanted a place where I could express myself creatively, use some computer expertise I had picked up along the way, and test the possibilities of the new medium of the world-wide web. As the saying goes, "Like attracts like," and soon I found myself engaged in a dynamic survivor community.

Tammie: Why the title, "The Wounded Healer"?

Linda: I recall reading Henri Nouwen's book, "The Wounded Healer" a few decades ago. Nouwen used the term as a synonym for Christ. At the time I named the website, however, I chose it because it was simply descriptive of myself and my recent experience.

Since then, I have learned that the notion of "The Wounded Healer" is a Jungian archetypal concept springing from the ancient mythological Chiron or "Quiron," who was the penultimate healer and a teacher of healers.

A friend once quoted her therapist as saying, "The deeper the pain, the better the therapist." I was coming to terms with my own woundedness, and it was inspiring to think that something good could come from the pain and brokenness inside. Judging from my contacts with colleagues, I knew that this phenomenon was not unique to me. I wanted to establish community with others who were wounded -- and healing. It can be such an isolating experience and so needlessly filled with shame.

Tammie: You wrote in the Journal that people can become bonded to their pain. Would you talk more about this?

Linda: Most students of child development are aware that a child's personality and character develop rapidly in the first few years of life. In the first year or two, we develop a picture or a "schema" of how the world is, and more powerfully, how we believe it must continue to be in order for us to survive.

So whatever our world looks like tends to become our roadmap for life. If I primarily live in a fair world, then I am probably going to be the most comfortable in relationships which reflect that. If I primarily live in an abusive or neglectful world, I may come to experience that as my "comfort zone," odd as it may be, and seek it out, unconsciously, in an effort to re-create the conditions I believe are most favorable to my survival.

So it's about adaptation and survival. It's not a conscious process or choice. It most likely operates at some very basic, instinctual level. It's not so much a bonding to pain, per se, but a bonding to "the known."

It's important to keep in mind that this is just a theory, and is subject to scrutiny and change. It's been useful to many people whom I have worked with as a therapist to help them consider the possibility that many behaviors which seem, on the surface, to be self-defeating are likely to be rooted in an effort to re-create a world that makes sense to them and to survive.

Once a person can make that leap, it is possible for the motivations behind problem behaviors to become more conscious and more addressable. But we're not programmed robots; I always leave room for elements of synchronicity and grace in the equation. And there is also room for additional theories to be considered and integrated, such as Prof. Jennifer Freyd's "Betrayal Trauma" theory.

Tammie: You also write about a treatment model for survivors of abuse based on the work of the late Dr. Richard Wienecke. Can you share a bit about how his ideas influenced your work?

Linda: It's what I describe above, formerly known as "the masochism model." Two of my supervisors were trained by the late Dr. Wienecke, who was a very humble, kind, and generous soul from all reports. Part of the beauty of his theory, which he never published, was that it provided a kind of framework which each person could flesh out in their own way.

I have a kind of thumbnail sketch of how I used to present the theory to clients on my website. I used to tell in-patients (with tongue-in-cheek) that a condition for discharge was that they had to master the theory, explain how it applied to their own lives, and teach it to another patient. Several took me up on the challenge and never failed to amaze me with their grasp of it and with they way that they personalized it from their own experiences. It's an elegant theory, and it makes sense. (For all its simplicity, however, I resisted it for a full year before I "got it." My clients were generally much quicker to catch on.)

Tammie: Would you consider pain to be a teacher? If so, what are some of the lessons your own pain has taught you?

Linda: Pain is. Pain is a teacher.

In one of her poems, Dr. Clarissa Pinkola Estes, a powerful healer whom I revere, says "A wound is a door. Open the door." It's an opening to understanding. If we pass up the opportunity to learn its lessons, whatever they may be, then suffering becomes meaningless and loses its transformative potential. And life becomes flattened out and dried up somehow.

An important lesson for survivors, however, is that pain need not be the only teacher. You don't have to be in pain to learn and grow. It certainly commands our attention when it happens, however, and we might as well use it, for what it's worth.

Tammie: Can you talk a little about your own healing journey?

Linda: It's an ongoing process. I conceptualize the healing journey as circular, like the rings on a tree, because many times when I think I have dealt with an issue, I find myself facing it again from yet another perspective. My journey has had many stops and starts, lapses, undoings and "do-overs". It's turned me every which way but loose. I've often said that it feels like it has a life of its own, and I am just along for the ride!

The hardest part of my journey has been the experience of re-traumatization by a therapist who had cultivated my trust for several years, then betrayed it. That's why I believe that it's so vitally important that therapists practice ethically (especially in terms of honoring therapeutic boundaries); that we seek psychotherapy, and that we avail ourselves of skilled consultation on a regular basis to deal with transference and countertransference issues, which are the at the core of the therapeutic relationship.

It's a sacred privilege to be invited into a client's world. Some people abuse this power. They shouldn't be practicing. And some people, like my childhood art teacher, are not therapists at all but can exert a tremendous therapeutic power in relationship. Remembering the force of good she had in my life helps me heal from my experience of re-traumatization, and inspires me to be the kind of healer she was in my life.

Tammie: What do you consider to be the most important step in healing?

Linda: The most important step in healing is always the next step. The step up out of despair and into hope. The step into the abyss, with a wild prayer that somehow I can find a hand-hold. So far, I have. Or it has found me.

Tammie: Thanks so much Linda.... Appreciate your wonderful wisdom

Linda: Thank-you, Tammie, for the chance to speak these things. Thank-you for asking, and for hearing me out. I so appreciate your thoughtful questions.

interviews index

next:Interviews: An Interview with Dru Hamilton at "Book Talk" with Tammie Fowles

Discontinuing mood stabilizers during pregnancy leads many bipolar women to relapse. Some mood stabilizers are toxic to the baby, but others are relatively safe.

Bipolar disorder is a chronic relapsing illness with a deteriorating course over time, particularly if there have been multiple episodes. This creates a bind for women in their reproductive years because stopping the medication increases their relapse risk.

Complicating the matter is the trend away from treatment with lithium and divalproex sodium (Depakote), toward newer anticonvulsants and atypical antipsychotics. We know more about the reproductive safety of lithium and divalproex sodium, even though both are teratogenic. But data on newer antimanic drugs are sparse, putting the clinician between a teratologic rock and a clinical hard place.

Last month at the American Psychiatric Association's annual meeting, we reported on the first prospective study of bipolar women who had discontinued mood stabilizers at about the time they got pregnant. Within 3 months, half of the 50 women had relapsed, and by 6 months about 70% had relapsed. This supports the findings of our earlier study, a chart review, which found a high relapse rate among women who had stopped taking lithium during pregnancy.

Lithium is clearly safer during pregnancy than divalproex sodium (Depakote). Many of us learned in medical school that lithium is a known teratogen and should not be used in pregnancy, but we now know that its teratogenicity is relatively modest: The risk of Ebstein's anomaly is about 0.05% among babies exposed to lithium in the first trimester.

Divalproex sodium, which is increasingly used as first-line therapy, is about 100 times more teratogenic than lithium, with a 5% risk for neural tube defects among children exposed to this anticonvulsant during the first 12 weeks of gestation. This makes it a less-than-ideal choice for women during the childbearing years.

The anticonvulsants that are being used increasingly are topiramate (Topamax), gabapentin (Neurontin), and lamotrigine (Lamictal). These drugs are sometimes used as monotherapy and often as adjunctive therapy, raising concerns because there are almost no reproductive safety data on these agents.

There are no human studies of topiramate and gabapentin. The manufacturer of lamotrigine has a pregnancy registry, and preliminary data do not suggest that risk of malformations is increased when this drug is used as monotherapy, but it is too early to reach conclusions.

Atypical antipsychotics are being used as adjuncts to mood stabilizers and as monotherapy: risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), and ziprasidone (Geodon). We are getting more and more calls with questions about the use of these drugs during pregnancy, and obstetricians should expect to see more women on these as well as the newer anticonvulsants.

The manufacturer of olanzapine has data on a small number of pregnancy exposures, but with fewer than 100 cases, no safety estimates can be made.

The atypicals often cause weight gain, and maternal adiposity may increase the risk for neural tube defects. This was noted in a recent study of patients with schizophrenia taking atypical or typical antipsychotics by Dr. Gideon Koren and his associates at the University of Toronto. More than half of the female patients were overweight, and intake of folate was poor. The investigators concluded that women who take atypical antipsychotics are therefore at a greater risk of having a baby with a neural tube defect (Am. J. Psychiatry 159[1]:136-37, 2002).

As obstetricians see more patients in their reproductive years who are on these medications, these issues need to be considered in the context of relative risk. The absence of data does not imply safety, and the arbitrary use of these medications in women of reproductive age is the largest uncontrolled trial in the history of medicine.

The newer treatments may be more effective but may pose greater risks. What we know leaves us to conclude that lithium is the safest treatment for those who need a mood stabilizer.

We advise that if a woman has not responded to lithium but has had an excellent response to a mood stabilizer such as lamotrigine (Lamictal) or gabapentin, she would be better off staying on that drug. But patients who have not tried effective mood stabilizers like lithium should consider a trial of lithium before they get pregnant, if possible.

What about the patient who conceives while taking one of those medications that we know nothing about? The clinician has the option to switch the patient to lithium, but this gets tricky because she may not respond. This may be the type of situation where you keep a patient on the drug if she is doing well to avoid a relapse.

Physicians can report pregnancies exposed to any of these drugs to the manufacturers and, in the case of antiepileptics, to the antiepileptic drug pregnancy registry at 888-AED-AED4.

Dr. Lee Cohen is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston. He is a consultant for and has received research support from manufacturers of several SSRIs. He is also a consultant to Astra Zeneca, Lilly and Jannsen - manufacturers of atypical antipsychotics. He originally wrote this article for ObGyn News.

Is it safe and effective to switch from a psychiatric medication to an alternative treatment while trying to conceive or during pregnancy?

Safety of Herbs, Supplements for Mental Health Conditions Questionable During Pregnancy

A common scenario seen on our consultation service is a woman with an anxiety disorder or mood disorder who is stabilized on a drug and who wants to switch to an alternative medicine during pregnancy or while trying to conceive. The compounds people ask the most about are St. John's wort, SAMe (S-adenosyl-L-methionine), and omega-3 fatty acids. We also get questions about the use of kava supplements as an alternative treatment for anxiety.

Many women make the intuitive leap that some of these widely used complementary or alternative therapies represent a more "natural" and therefore safer alternative to a more standard pharmacologic treatment during pregnancy or while they are trying to conceive. The problem is that we have very little, if any, reproductive safety data on these natural compounds. Many of these products do not contain just the specific herbal compound, but fillers and other components used for compounding, about which we know very little.

Moreover, efficacy data for many of the herbals are limited. For example, there is still an ongoing debate about the efficacy of St. John's wort for depression. Although there are no data indicating that it's dangerous, not much is known about the reproductive safety of hypericum, its active ingredient.

While omega-3 fatty acids are not presumed to be teratogenic, the data supporting their efficacy in patients with bipolar disorder have been based primarily on adjunctive use with other mood-stabilizing medications. There are very little data on monotherapy; even the experience with adjunctive therapy was based on an extremely small sample of people.

Based on these uncertainties, an arbitrary switch to an alternative treatment may represent a failed risk-benefit decision, exposing a pregnant woman to both an unknown reproductive safety risk and an increased risk for relapse. A woman, therefore, will not be in a much better position regarding safety with one of these products than with a drug for which there are only limited reproductive safety data but which is known to be effective.

The growing array of newer antidepressants and anticonvulsants increases the possibility that more women will be successfully treated, although not much is yet known about their reproductive safety. More is known about the older medications, like lithium and divalproex sodium (Depakote), which are known to be teratogenic.

Some antidepressants, including fluoxetine (Prozac) and the tricyclics, are not teratogenic. There are neurobehavioral data following children through age 7 years showing no adverse impact of in utero exposure to these agents, but there is still more to be learned about their long-term neurobehavioral effects.

My biggest concern is the risk of relapse in women who switch to an alternative treatment under the presumption that it will invariably work. What has become increasingly clear, however, is that across psychiatric disorders pregnancy is not protective against relapses or onset of new illness, so more patients are being treated with pharmacologic therapies.

A common scenario we see is a woman who has had multiple episodes of major depression and has been treated with multiple antidepressants. She has been stabilized on a selective serotonin reuptake inhibitor like fluoxetine, for which there is a lot of reproductive safety information, or a medicine like mirtazapine, nefazodone, or bupropion, for which we have very little reproductive safety information. This is the type of patient who is at high risk of relapse if she stops taking medication, and many of these patients do relapse.

An untreated mood disorder during pregnancy is not something to discount. There is a growing literature illustrating the impact of untreated depression during pregnancy, including adverse outcomes on perinatal well-being in terms of Apgar scores, birth weight, and other basic neonatal outcomes. The most dramatic example is with bipolar patients who, without proper treatment, may relapse into severe recurrent mania or depression, placing the fetus and mother at increased risk.

As a clinician and a researcher, I appreciate the efforts to identify safe treatments during pregnancy. Unfortunately, the science to support the belief that natural treatments are safer, held by so many women (and some clinicians) who are concerned about prenatal exposure to any psychiatric medicines, is not substantiated.

While we have pregnancy registries for some psychiatric medications and there are animal data on these medications, we may never have such reproductive safety data on some of the naturally occurring compounds, because to date they remain unregulated.

Dr. Lee Cohen is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston. He is a consultant for and has received research support from manufacturers of several SSRIs. He is also a consultant to Astra Zeneca, Lilly and Jannsen - manufacturers of atypical antipsychotics. He originally wrote this article for Ob-gyn News.

Even 20 years ago, researchers started noticing that antidepressant use during pregnancy sometimes produced antidepressant discontinuation like symptoms in the newborn baby.

Complications From Taking Antidepressants During Pregnancy

The increasing number of reproductive-age women who are on antidepressants has raised concerns about the potential risks of teratogenicity, perinatal toxicity, and the long-term neurobehavioral sequelae of prenatal exposure to these medications. Literature over the last decade supports the absence of teratogenicity of selective serotonin reuptake inhibitors (SSRIs) and the older tricyclics.

Still, questions remain about the risks of short-term perinatal toxicity in newborns when antidepressants are used around the time of labor and delivery. These concerns date back 20 years when case reports suggested that maternal use of tricyclics near term was associated with problems in the newborn such as difficulty feeding, restlessness, or jitteriness.

More recent studies have suggested that peripartum exposure to SSRIs may be associated with poor perinatal outcomes. One study found an association between the use of fluoxetine (Prozac) during the third trimester and a greater risk of neonatal complications (N. Engl. J. Med. 335:1010-15, 1996).

Concerns have been raised about the study's methodology, however: The study was not blinded so examiners knew the babies had been exposed to medication. In addition, the study did not control for maternal mood disorder during pregnancy.

Two more recent studies of perinatal effects associated with third-trimester exposure to antidepressants have generated many questions. The first, conducted by investigators at the Motherisk Program at the University of Toronto, compared 55 newborns exposed to paroxetine (Paxil) late in pregnancy with a control group of newborns exposed to paroxetine early in pregnancy and newborns exposed to nonteratogenic drugs. There was a significantly higher rate of neonatal complications among paroxetine-exposed newborns, resolving in 1-2 weeks. Respiratory distress was the most common adverse effect (Arch. Pediatr. Adolesc. Med. 156:1,129-32, 2002).

The authors posit that the unexpectedly high rate of symptoms in these newborns may be the neonatal equivalent of the discontinuation syndrome commonly seen in adults who develop a variety of somatic symptoms after rapidly stopping paroxetine. While this is an interesting study consistent with some but not all previous reports, it has obvious methodologic limitations: Information was obtained through telephone interviews rather than direct blinded observation, and the well-described effects of maternal mood during pregnancy on neonatal outcome were not considered. Depression during pregnancy has been independently associated with adverse neonatal effects, including low birth weight, small-for-gestational-age babies, and increased obstetrical complications.

The second study compared neonatal outcomes following in utero exposure to tricyclics and SSRIs using a large database from a group-model HMO. The malformation rate was not increased among those exposed to antidepressants in utero, but there was an association between third-trimester exposure to SSRIs and lower 5-minute Apgar scores and decreases in mean gestational age and birth weights; these differences were not observed among tricyclic-exposed newborns (Am. J. Psychiatry 159:2055-61, 2002). At ages 6 months and up, there were no significant differences between the groups, despite the differences noted at birth, and exposure to SSRIs or tricyclics was not associated with developmental delays through age 2. As in the previous study, maternal mood during pregnancy was not assessed.

Given the methodologic weaknesses of these studies, one cannot conclude that the use of antidepressants is associated with compromised perinatal outcomes. The findings from these two studies may be a signal of a potential problem. But pending more controlled study, appropriate vigilance of exposed newborns is good clinical care versus arbitrary discontinuation of antidepressants during the peripartum period.

Treatment decisions need to be made in the context of yet to be qualified relative risk (if any) for perinatal sequelae exposure to antidepressants at term versus the increased risk for adverse neonatal outcomes and postpartum depression associated with pregnancy-associated maternal depression. Accumulated data regarding potential risks of perinatal exposure to antidepressants do not appear to justify lowering the dose of these agents or stopping these medicines around labor and delivery. Doing so may increase the risk for depression in the mother and the impact of affective dysregulation on the newborn.

The findings of the two studies are clearly of interest and demand further prospective inquiry. Until results of such studies are available, clinicians should share available information with patients, so together they can make informed decisions regarding the use of antidepressants across pregnancy.

Dr. Lee Cohen is a psychiatrist and director of the perinatal psychiatry program at Massachusetts General Hospital, Boston. He is a consultant for and has received research support from manufacturers of several SSRIs. He is also a consultant to Astra Zeneca, Lilly and Jannsen - manufacturers of atypical antipsychotics. He originally wrote this article for ObGyn News.

Guidelines for determining which ADHD medication your child should be taking plus how to determine if the medication treatment is helping your child's ADHD symptoms.

"What are the guidelines that are used to determine which medicines a child should be on for ADD? And which guidelines are used to let parents and teachers know if the ADHD medication is working properly?" These are really important questions because although there is considerable research evidence that medication is quite helpful for the vast majority of children with ADHD, it is frequently prescribed and monitored in such a way that prevents children from getting the maximum benefit possible.

In regards to the first question raised above, there is simply no way to predict in advance which of several medications will be most helpful for a child with ADHD, or what the optimal dose will be. Physicians generally start with Ritalin, which is certainly reasonable since it is the most extensively researched. A child who does not respond well to Ritalin, however, may do very well on another stimulant (e.g. Adderall, Cylert, Concerta, and Dexedrine or Strattera.). Similarly, a child who does not do well on the initial doses tried may do very well on a different dose. In some cases, side effects that are prominent with one medicine may be absent with another.

The bottom line is that because there is no way to know in advance what will be best for an individual child, the child's response needs to be monitored very carefully. One very useful procedure is to begin a child on medication for ADHD using a careful trial in which a child is tried on different doses during different weeks, and is also put on a placebo for one or more weeks during the trial. The child's teacher is asked to complete weekly ratings of the child's behavior and academic performance, and side effects forms are completed by both parents and teachers.

Why have a child receive a placebo during the trial? This is important because no matter how good one's intentions are; it is very difficult to be objective about a child's behavior when one knows the child is on medication. Thus, one study found that when children with ADHD were given a placebo, the child's teacher reported significant improvement over half the time. This is probably because teachers expect the child to do better which can color what they see. Also, when children believe they are on meds they actually may do a bit better, at least for a period of time. By using the placebo procedure outline above, the information obtained is less likely to be effected by such potential biases because the teacher does not know when the child is getting medicine and when he or she is not.

By comparing the teacher's ratings for the different medication weeks with the placebo week, one has a more objective basis for deciding if the medicine really helped, whether it helped enough to be worth continuing, what dose produced the greatest benefits, whether there were adverse side effects, and what problems may remain to be addressed even if the medicine was helpful.

Compare this type of careful trial with what is often done: the doctor prescribes ADHD medication and asks the parent to let him know what happened. Parents ask the teacher for feedback about how their child did on medication, and passes this along to the physician who then decides whether to continue, try a different dose, or try a different medication. Here are possibilities that are much more likely to occur with this procedure:

1. Because of the "placebo" effect, medication may be reported to have been helpful even though no real benefit was produced. The child then continues to take medicine even though he or she is not really benefiting.
2. Because a systematic comparison of different doses is not made, the child is maintained on a non-optimal dose, and thus fails to get al the benefits that are possible.
3. Medication is discontinued because of "side effects" that actually had nothing to do with the medication (see below).
4. Because a careful assessment was not made of how the child did on medicine, problems that may have remained even though the medicine was helpful are not targeted for adjunctive forms of treatment.

Let me say something about side effects of medications for ADHD. I do these types of trials all the time and often find that what would otherwise be assumed to be side effects of medication actually occur during the placebo week! Several carefully controlled studies have reported similar findings, as well as the fact that problems presumed to be side effects of medicine are often present prior to starting medication. Suppose a good trial has been done and the proper dose selected - now what?

After this has been done, it is VERY important to monitor how the child is doing on a regular basis. In fact, guidelines published by the American Academy of Child and Adolescent Psychiatry, recommend that at least weekly ratings from teachers be obtained. This is because a child's response to medication can change over time, so what starts out as being very helpful may become less helpful over time. Some of you may have already had the unfortunate experience of believing that things were going along pretty well, and then finding out at report card time that this was not the case.

With regular, systematic feedback from teachers about how well a child's ADHD symptoms are being managed, the quality of work being completed, peer relations, etc.; this type of unpleasant surprise does not need to occur. This is not difficult to do, but in my experience, is rarely done. (Editor's note: the Concerta website has forms that can be used for both ongoing parent and teacher evaluations of a child with ADHD.)

Dr. Rabiner is a research psychologist at Duke University and publisher the ADHD newsletter "Attention Research Update."

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