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maj 3 janvier 2008

     questions   élements de réponse  conférence de consensus  pratique  références



La conférence de consensus a été publiée dans le numéro d'avril 2004 de L'american journal of psychiatry. p608 Jonkers & co.
Avertissement : les éléments statistiques sur les anomalies de la grossesse (fausses couches, développement anormaux) peuvent choquer les personnes non averties.  La mentalité actuelle à vouloir ignorer tous les risques naturels et à vouloir trouver une faute à l'origine de chaque anomalie ne correspond pas à la réalité.

 
QUESTIONS POUR UNE GROSSESSE
"Les troubles bipolaires ont une origine biologique. Il y a aussi une forte évidence d'une base génétique pour cette maladie. C'est aussi un fait que le lithium, le thymorégulateur le plus employé dans le traitement, peut être la cause d'anomalies dans le développement du foetus.. Que doit penser de ces complications une femme qui désire avoir des enfants ? Si j'arrête de prendre le lithium et devient enceinte qu'arrivera-t-il si j'ai un épisode d'exaltation durant ma grossesse ? Si le continue à prendre mon traitement durant la grossesse, qu'arrivera-t-il si mon foetus en est affecté ?  Si j'ai un enfant sera-t-il lui aussi bipolaire ? Quelle sorte de mère serais-je si je suis malade ? Eventuellement, une autre question pourrait être posée : si un test génétique indique que mon foetus a les génes pour la bipolarité dois-je avorter ? Ajouter à ces dilemnes, le commentaire d'un psychiatre qui me dit que je ne dois même pas penser avoir d'enfant, si je ne veux pas avoir ma place réservée en Enfer"
(RT Caroll, dans un commentaire fouillé sur le livre de mémoire de  Kay Redfield Jamison, cité en référence).
  
ELEMENTS DE REPONSE
a).  L'eugénisme une voie erronée pour les maladies polygénétiques.
   
Les génes de susceptibilités aux troubles bipolaires sont situés sur 11 chromosomes,  prés de la moitié des chromosomes humains.
     La stérilisation ou l'extermination des malades mentaux, pratiquée dans le passé (première moitié du XXème siécle), est considérée aujourd'hui comme proche du crime contre l'humanité.
b).  L'eugénisme priverait l'humanité d'une part de son potentiel créateur.
   
Les génies créateurs de l'humanité sont pour une grande part des bipolaires, comme le démontre le livre de K.JAMISON "touched with fire".
c).  L'approche risque / bénéfice.
  
Il est rare qu'un traitement médical ou chirurgical  soit exempt d'effets secondaires ou de risques opératoires (l'aléa thérapeutique). L'art ou la science du médecin consiste à peser le plus objectivement possible les deux plateaux de la balance et à l'indiquer honnêtement à son patient, qui prend le risque.
   Les analyses de cohortes (groupes statistiques) de patients permettent une analyse statistique des risques et des bénéfices ( pour autant que les bonnes questions aient été posées et les cohortes choisies sans biais). Les conférences de consensus, réunissant les spécialistes d'une discipline, permettent de dégager à un instant donné l'état de l'art sur une question.  Leurs résultats sont publiées ensuite dans les revues spécialisées pour donner l'information à tous les praticiens.  
d). Un exemple de démarche pratique d'un psychiatre compétent.
  
Voici un exemple de démarche expliquée  par un psychiatre spécialisé  :
"La meilleure voie pour contrôler les désordres bipolaires dépend de nombreux facteurs. Le plus important est l'historique des épisodes précédents et les résultats dans le passé de l'arrêt de la prise du lithium. Pour beaucoup de femmes, la grossesse est une période de fonctionnement mental amélioré (une exaltation modérée), tandis que le post-partum est souvent une période ou la dépression peut être un problème.
  Si l'histoire de la femme inclut relativement peu d'épisodes qui ont été séparés par de longues périodes de normalité, le TRES GRADUEL arrêt du lithium (sur deux mois) peut précéder l'attente de la grossesse. Si des  arrêts précédents de la prise du lithium ont été suivis par une rapide rechute dans des épisodes dépressifs ou maniaques, l'arrêt du lithium avant de devenir enceinte n'a pas de sens.
  Il fut un temps ou l'on pensait que le lithium était extrêmement toxique pour le développement du foetus et que approximativement  1% des bébés exposés au lithium in-utero développeraient de sévéres et parfois mortelles malformations cardiaques. De plus récentes recherches  ont déterminé que le risque de tels défauts n'était que de 0,1 % plutot que des 1%  précédemment calculés.  Les autres médicaments utilisés comme alternative au lithium pouvant aussi causer de sévéres anomalies congénitales, ils ne peuvent être considérés comme des alternatives durant la grossesse. Quatre de mes patientes ont accouché de cinq enfants en parfaite santé après avoir pris du lithium durant leur grossesse" .
e). Lithium et allaitement.
 
L'allaitement maternel est découragé par les consensus médicaux actuels lorsque la mère a un traitement comprenant des sels de lithium, en dépit l'absence de données cliniques. Une récente étude a permis de quantifier l'exposition au lithium des enfants.Les niveaux du lithium dans le sang des enfants sont bas et bien tolérés. Aucun effet clinique génant ou comportemental n'a été relevé chez les enfants. Ces constatations vont dans le sens de la modification des recommandations décourageant l'allaitement et soulignent l'importance d'un suivi particulier des enfants.
f). Risques d'arrêt du lithium pendant la grossesse.
 
Un éditorial de décembre 2007 de l'American Journal of Psychiatry analyse le risque de récurrence du trouble bipolaire en cas d'arrêt du thymorégulateur. Il est constaté à 85% dans l'étude de Viguera et col..  Il faut espérer que cette étude permettra d'éviter l'arrêt systématique des médicaments par les gynécologues pour les patientes bipolaires sans évaluation du bénéfice-risque, qui est malheureusement l'habitude actuelle, et qui, hélas, conduit parfois à un avortement "thérapeutique" imposé par le gynécologue après déclenchement d'un cycle durant la grossesse suivant l'arrêt du thymo imposé par le même gynécologue.


CONFERENCE DE CONSENSUS : "Gestion du trouble bipolaire durant la grossesse et le post-partum"

( Traduction de quelques extraits significatifs.)

"Un panel d'expert a examiné les articles [de recherche] ayant pour sujet la gestion des troubles bipolaires et les conséquences de l'usage des stabilisateurs d'humeur durant la grossesse et produit un document de consensus.
Le traitement du trouble bipolaire chez les femmes enceintes implique des décisions difficiles. Quelques thymorégulateurs, i.e sodium valproate (depakote) et carbamazépine(tégrétol) sont tératogénes. D'un autre côté la tératogenicité associée avec le lithium peut avoir été surestimée par le passé."

Risques associées avec les thymorégulateurs durant la grossesse


Le risque de malformation foetale associé avec la prise de médicaments pendant la grossesse dépend des propriétés du médicament et de la période ou le foetus à été exposé. Dans les 32 jours après la conception, c'est le développement du tube neural qui peut être affecté. Entre 21 et 56 jours c'est le développement du coeur et entre 42 et 63 jours la bouche et le palais. Après le premier trimestre, c'est le tour des anomalies cranio-faciales et du développement du cerveau. La synthèse qui suit est organisée par domaine de toxicité, incluant les malformations structurelles , le retard  de la croissance, la  toxicité périnatale et les séquelles neurobiologiques.

Lithium
 Malformations d'organes
 Effets sur la croissance intrauterine
 Effets sur les fonctions cérébrales
 Toxicité neonatale
  Usage durant la grossesse.

Valproate (dépakote)

Carbamazépine (tégretol)

Lamotrigine (lamictal)

Antipsychotiques de première génération.
  C'est la plus grosse base de données disponible.

Recommandations pratiques extraites de la conférence.
   En résumé (sauf erreurs de traduction et ommissions) :
  Le lithium est le moins dangereux de tous les thymorégulateurs. Son action sur le foetus a été surestimée dans les études antérieures (registre des bébés lithium portant sur 50 ans d'usage !). Il n'y a aucune raison que cela ne se passe pas mieux ou moins bien que dans une grossesse ordinaire.

  Quelques recommandations extraites du texte du consensus :

1). Le risque de faire un cycle bipolaire en cas d'arrêt du lithium est majeur. Une période à trés très haut risque est celle du post-partum.  Le maintien du lithium doit absolument être pesé avec ses bénéfices/risques.
2). Le relatif risque de l'anomalie d'Epstein(anomalie cardiaque) avec la prise du lithium en prénatal (3 premiers mois) est plus élevé que dans la population générale, mais le risque absolu reste très petit. 
3). Les bébés lithium ont un poids normal.
4). Le neurodéveloppement  des bébés lithium est absolument identique à ceux de la population générale.
5). Le suivi du taux de lithium dans le sang (lithiémie) doit être plus fréquent que d'habitude en particulier durant le labeur, il doit être monitoré.  Le lithium a une demi-vie relativement courte (8-10 heures) et il se produit des pics substanciels de lithium dans le sang.. Le fractionnement de la dose quotidienne en 3 ou 4 prises est recommandé.  Quand la grossesse avance, en général l'excretion rénale augmente et nécessite un accroissement de la dose.
6). Une hydratation adéquate doit être maintenue en intraveineuse en cas de patientes avec un labeur prolongé.
7). En cas d'exposition au lithium durant le premier trimestre, les anomalies peuvent être identifiées entre la 16ème et la 18ème semaine  par un examen précis aux ultrasons et par une electrocardiographie foetale. Ces examens aident les parents à prendre une décision éventuelle d'interruption de grossesse ou d'intervention périnatale après la délivrance.
8). Pour une grossesse non planifiée, la reconnaissance de la grossesse arrive pendant ou après la période maximale de risque avec le lithium. L'arrêt de la médication à ce moment peut placer le bien-être de la femme  à risque pour un bénéfice potentiel très minime. Une haute dose d'acide folique (3mg/joour) peut être prescrite pour la femme.

  Quelques remarques aussi sur le contexte médical :

1). L'ignorance du corps médical est élevée, voire très élevée sur ce sujet. Voir le témoignage d'Alexine sur le forum Angie..
2). Le paradigme actuel ( le principe structurant) concernant la grossesse est d'éviter tout médicament non indispensable et tout facteur extérieur pouvant influencer le foetus : alcool, cigarette, drogues, etc.. Le lithium pour les bipolaires stabilisés est un médicament indispensable. 



Références.

Management of Bipolar Disorder During Pregnancy and the Postpartum Period
http://ajp.psychiatryonline.org/cgi/content/abstract/161/4/608

Kimberly A. Yonkers, M.D., Katherine L. Wisner, M.D., Zachary Stowe, M.D., Ellen Leibenluft, M.D., Lee Cohen, M.D., Laura Miller, M.D., Rachel Manber, Ph.D., Adele Viguera, M.D., Trisha Suppes, M.D., Ph.D., and Lori Altshuler, M.D.

OBJECTIVE: Bipolar disorder affects 0.5%–1.5% of individuals in the United States. The typical age at onset is late adolescence or early adulthood, placing women at risk for episodes throughout their reproductive years. General guidelines for the treatment of bipolar disorder are available from the American Psychiatric Association, but additional issues arise when these guidelines are applied in the treatment of peripartum women. The authors summarize knowledge regarding the management of bipolar disorder during pregnancy and the postpartum period, with a focus on managing mania, hypomania, and the psychotic components of the illness. METHOD: An expert panel reviewed articles that address the management of bipolar disorder and the consequences of the use of mood stabilizers during pregnancy, and a consensus document was generated. RESULTS: The treatment of bipolar disorder in pregnant women involves significant challenges. Some mood stabilizers, e.g., sodium valproate and carbamazepine, are human teratogens. On the other hand, the teratogenicity associated with lithium may have been overestimated in the past. CONCLUSIONS: Since treatment can be managed most effectively if pregnancy is planned, clinicians should discuss the issue of pregnancy and its management with every bipolar disorder patient who has childbearing potential, regardless of future reproductive plans. Additional research should address the risks of disturbed sleep to pregnant and postpartum women with bipolar disorder, as well as structural and behavioral consequences to offspring when mood stabilizers are used during pregnancy. Longitudinal and cohort studies can promote these efforts. Given the rate of bipolar disorder in the general population, research efforts will need to be broad based and include multiple collaborating centers.
 

The Skeptic's Dictionnary Robert Todd Caroll   Analyse du livre de K.Redfield JAMISON  "An Unquiet Mind A Memoir of Moods and Madness"
Traduit en français sous le titre "De l'exaltation à la dépression"

Manic depression is a disease which is biological in its origins. There is also strong evidence that there is a genetic basis for the illness. There is also evidence that lithium, the most common drug used in treatment for the disease, can cause birth defects. Think of the complications this means for a woman who wants to have children. If I go off the drug and get pregnant, what will happen if I have a manic episode during the pregnancy? If I stay on the drug while pregnant, what will happen if my fetus is adversely affected? If I have a child, will the child be manic depressive? What kind of mother can I be if I am ill? Eventually, perhaps another question will be askable: if a genetic test indicates my fetus has the gene for manic depression, should I abort? Add to these dilemmas, the comment of a psychiatrist who tells you that you should not even think about having children and you have a blueprint for a condo in Hell.

Hell is fueled not only by the fire in the brain. Jamison herself was the child of a mentally ill father, one who functioned quite well for many years before becoming hopelessly mad. Not only would Jamison not exist if her father had taken the advice of this psychiatrist, but the world would be a much duller place, less creative and diverse, certainly the worse for it if the mentally ill did not reproduce. The desire for a "pure" race of balanced brains is a vision of Lilliputian proportions, worthy of a small mind living in small, tidy, dull world. It does not take long to whip up a list of great artists, poets, writers, athletes, etc. who have suffered from neurochemical dysfunction. It is obvious that the species and human culture have benefited from the mentally ill and their progeny. To suggest that anyone with a neurochemical dysfunction should not even think of having children is an idea so preposterous as to deserve laughter rather than the rage it is likely to evoke from a mentally ill woman of Jamison's character and disposition. Who knows what great achievements would not have been conceived much less attempted but for mania? And who knows what foolish endeavors have been avoided because of the depression of world leaders? What would our libraries and museums look like if we removed everything created by a mentally ill person or the descendent of a mentally ill person? But while laughing at the suggestion that we should practice eugenics with the mentally ill, we should not get so carried away as to think that somehow having a neurochemical problem is a ticket to creativity or genius. Even if it were, the pain and suffering that accompany the diseases of the brain would not justify a policy of breeding creative geniuses.

The reason it is easy to come up with a list of great insane people is probably not because the genes which are major causal factors in neurochemical problems are also the genes which are the major causal factors in creativity or intelligence. The reason is much more mundane. There are lots of famous people and there are lots of people with neurochemical problems; that the two lists should overlap a great number of times is to be expected. The vast majority of the mentally ill are probably of ordinary intelligence and creativity. We never hear of them because they are not eloquent, do not create great works of art, etc. We only hear about mental illness from eloquent people: either the highly educated professionals who care for them or the highly articulate and creative ones among them, or, as in Dr. Jamison's case, both. Studies which claim there are a disproportionate number of poets, artists, composers, etc., who suffered from depression or manic depression may be accurate, though it is difficult to establish just what percentage of any population is "mentally ill." Also, I don't know how many poets would appreciate being told that their affinity for alliterative allusions may be due to a neurotransmitter malfunction.

Many of the "ordinary" mentally ill persons roam our streets and sleep in ditches. They scavenge the trash bins in our cities and towns. Some of them have children and it is monstrous to suggest that none of these people should have been born or given birth. The shame on humanity is not from its mentally ill, but from the rest of us because of the way we treat them...or rather because of the way we mistreat or fail to treat the less fortunate among us. But the lack of proper treatment for a large percentage of the mentally ill is a social problem and is not Jamison's area of specialization. Clinical problems, however, are her specialty.

Dr IVAN
The best way to control of bipolar disorder during pregnancy depends on a number of factors. Most important are the history of prior episodes, and the past results of discontinuing lithium. For many women, prengancy is a time of improved mental functioning, while the post-partum period is often a time when depression may be a problem.

If a woman's history includes relatively few mood episodes that have been separated by long periods of euthymia, the VERY gradual discointinuation of lithium (over a couple of months) might precede attempts to become pregnancy. If prior attempts to gradually discontinue lithium have resuled in the rapid onset of a depressive or manic episode, discontinuation prior to trying to get pregnant does not make sense.

At one time it was thought that lithium was extremely toxic to the developing fetus, and that approximately 1% of babies exposed to lithium in-utero would develop severe, possibly lethal, heart defects. More recent research has determined that the risk of such defects is actually one-tenth of a percent rather than the 1% previously estimated. As the anti- convulsant drugs used as lithium alternatives can also cause severe congenital abnormalities, they cannot be considered as alternatives to lithium duing pregnancy. Four of my patients have delivered five healthy babies after taking lithium though- out their pregnancies.

Ref: Sachs GS & Cohen LS Update on pharmacologic treatment of mood disorders: Bipoolar disorder and management through preg- nancy and postpartum. Psychiat Clin N Amer 1995, 2, 21-75.

 

Lithium in breast milk and nursing infants: clinical implications.

Viguera AC, Newport DJ, Ritchie J, Stowe Z, Whitfield T, Mogielnicki J, Baldessarini RJ, Zurick A, Cohen LS.Am J Psychiatry. 2007 Feb;164(2):342-5.

    Perinatal and Reproductive Psychiatry Clinical Research Program, Department of Psychiatry, Massachusetts General Hospital, Simches Research Bldg., Second Fl., Suite 2200, 185 Cambridge St., Boston, MA 02114, USA. aviguera@partners.org

 OBJECTIVE: Current practice guidelines discourage use of lithium during breast-feeding, despite limited data. This study aimed to quantify lithium exposure in nursing infants.

 METHOD: In 10 mother-infant pairs, the authors obtained assays of lithium in maternal serum, breast milk, and infant serum and indices of infant renal and thyroid function.
RESULTS: Maternal serum, breast milk, and infant serum daily trough concentrations of lithium averaged 0.76, 0.35, and 0.16 meq/liter, respectively, each lithium level lower than the preceding level by approximately one-half. No serious adverse events were observed, and elevations of thyroid-stimulating hormone, blood urea nitrogen, and creatinine were few, minor, and transient.

CONCLUSIONS: Serum lithium levels in nursing infants were low and well tolerated. No significant adverse clinical or behavioral effects in the infants were noted. These findings encourage reassessment of recommendations against lithium during breast-feeding and underscore the importance of close clinical monitoring of nursing infants.

Bipolar Disorder Recurrence in Pregnancy :

Women with bipolar disorder who stopped mood stabilizer treatment before becoming pregnant had an 85% rate of recurrence during pregnancy.

Bipolar Disorder and Pregnancy: Risks Revealed
Marlene P. Freeman, M.D.

 Am J Psychiatry 164:1771-1773, December 2007

In this issue of the Journal, Viguera et al. report findings from a prospective study of the course of bipolar disorder during pregnancy. Retrospective studies have identified the postpartum period as a particularly high-risk time for relapse in women with bipolar disorder (1, 2). A prospective study by Cohen et al. demonstrated that the postpartum is a period of high risk for mood episodes in women with bipolar disorder, with markedly higher rates of mood episodes in women who were not treated with mood stabilizers compared with those who continued or restarted medication (3). Mood stabilizers are a complicated class of medication to consider using during pregnancy, due to the known teratogenic risks posed by some and the lack of safety data for use in pregnancy for others (4). Presently, due to inadequate data, it is difficult to offer patients who are pregnant a definitive and comprehensive account of the risks of untreated bipolar disorder, the risks and benefits of medication, and the predictors of relapse during pregnancy.

In general, untreated maternal mood disorders during pregnancy are serious risk factors for the fetus, with impacts on pregnancy outcomes and infant/child development. Untreated depressive episodes are known to pose risks to the fetus (5). The specific risks of untreated maternal bipolar disorder are poorly understood and have received little study. By definition, untreated mania poses clear risk to the individual due to impulsivity and impaired judgment. Mania often results in poor self-care, which is dangerous to both mother and child.

In their current article, Viguera et al. compare relapse rates and time to recurrence for mood episodes between women who continue taking mood stabilizers during pregnancy and women who discontinue medication. The investigators enrolled 89 women with bipolar I or bipolar II disorder who were planning pregnancy and seeking psychiatric consultation in a specialized perinatal psychiatry program. Pregnant women were enrolled prior to 24 weeks gestation and included if they 1) were euthymic for at least 1 month prior to conception, 2) were receiving treatment with a mood stabilizer, or 3) had discontinued pharmacotherapy at least 6 months prior to pregnancy or within the first trimester. Women were followed through pregnancy and the postpartum year, and patients decided themselves whether to continue or discontinue medication. A majority of women experienced at least one mood episode during pregnancy (70.8%). The risk of recurrence was significantly higher in women who discontinued treatment with mood stabilizers. Women who discontinued medication also spent more time ill during pregnancy compared with women who continued medication. Several history of illness and treatment factors were associated with relapse during pregnancy. One of the treatment factors associated with increased relapse rates was rapid mood stabilizer discontinuation. The only pregnancy-related predictor of relapse was if the pregnancy was unplanned.

This study is groundbreaking, in that it is the largest prospective study of the course of bipolar disorder during pregnancy to our knowledge. The risk of recurrence was demonstrated to be extremely high during pregnancy, and greatest when medications were discontinued.

The finding that relapse rates were higher after rapid versus slow discontinuation of mood stabilizers is not surprising and is consistent with the literature in this area, including Viguera et al.’s previous retrospective study of relapse rates in pregnancy and the postpartum (1). However, this finding is profoundly relevant to clinical practice and invites us to consider a paradigm shift in the treatment of women with bipolar disorder of reproductive age. A large number of women suffer from bipolar disorders, as bipolar I disorder generally affects women and men with equal prevalence and bipolar II disorder disproportionately affects women. The onset of bipolar disorder is frequently in childhood and adolescence. When considering the chronic and recurrent course of bipolar disorder, optimal treatment for most women with this illness includes mood stabilizing medications for most, if not all, of their reproductive years.

Viguera et al. also found that rapid discontinuation of medication was associated with unplanned pregnancies, a scenario often seen in clinical practice. The authors take the well supported position that the practice of rapid discontinuation of psychotropic medication needs to be reassessed. The implications of this study affect most practicing psychiatrists. Assuming that women with bipolar disorder are similar to the general population, the great majority of patients with bipolar disorder of reproductive age will experience pregnancy and childbirth and will be faced with decisions about treatment during pregnancy. Psychiatrists should anticipate that unplanned pregnancies will occur during the course of treatment of women with chronic disorders such as bipolar disorder.

Pregnancies, including those that are not planned, need to be conceptualized as expected events that intersect with treatment course. Unfortunately, most health care providers are not trained to consider pregnancy as an expected event that is likely to occur during the course of treatment of a chronic and/or recurrent illness. Instead, psychiatrists and patients alike are frequently overwhelmed with fear and panic when a woman with bipolar disorder discovers she is pregnant. Concern about medication exposure for the fetus often precipitates abrupt discontinuation of mood stabilizers, with or without physician input. There are known teratogenic risks from treatment with some commonly utilized mood stabilizers in the first trimester, such as neural tube defects with valproate and carbamazepine and cardiovascular malformations such as Ebstein’s anomaly with lithium (4). Especially in the case of neural tube defects with the use of anticonvulsants, the window of greatest concern is very early in pregnancy; by the time a woman discovers she is pregnant, the most serious period of risk for the fetus has frequently already passed. Therefore, by abruptly discontinuing medication in an attempt to protect her baby, a woman or her physician may unwittingly increase the risk of relapse for mood episodes, while having little impact on the teratogenic effects of medication exposure.

Routine treatment planning for female patients should systematically include a discussion regarding the scenario of unplanned pregnancy. In the case of an unplanned pregnancy, information from the treating physician about the risks of medication, as well as the risks of untreated bipolar disorder, would help avoid the panicked and fear-based decision making that typically occurs in this situation. This strategy may decrease the number of women who are subject to abrupt discontinuation of mood stabilizers during pregnancy.

As Viguera and colleagues acknowledge, their findings may not generalize to other clinical populations. This study was conducted in a specialty research program by leaders in the field. As it was a specialty program, patients either were referred by obstetricians or were self-referred. An overwhelming majority were Caucasian, educated, married, and employed outside the home. As noted by the investigators, despite these demographic characteristics, which may be associated with greater access to care and resources, patients still experienced a high relapse rate. Therefore, the reported risk of recurrence during pregnancy in this study may actually underrepresent the risk in the broader population. In other clinical and more diverse populations of pregnant women with bipolar disorder, rates of relapse may indeed be much higher.

This study represents an excellent step forward in the understanding of bipolar disorder in women. This observational prospective study provides a greater understanding of the serious risk of relapse during pregnancy. As the authors state, they will present the postpartum data from the study population in a forthcoming report, which is expected to add further valuable insights into this important and understudied area of psychiatry.


   

  Footnotes
 
Address correspondence and reprint requests to Dr. Freeman, University of Texas Southwestern Medical Center at Dallas, Exchange Park/American General Building, 6363 Forest Park, Suite 800, Dallas, TX 75235-9086; marlene.freeman@utsouthwestern.edu (e-mail). Editorial accepted for publication September 2007 (doi: 10.1176/appi.ajp.2007.07091408).

Dr. Freeman has received research support from Arizona’s Institute for Mental Health Research, Eli Lilly, Forest, NIMH, Reliant, and the U.S. Food and Drug Administration. Dr. Freedman has reviewed this editorial and found no evidence of influence from these relationships.


  References
 

   1. Viguera AC, Nonacs R, Cohen LS, Tondo L, Murray A, Baldessarini RJ: Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance. Am J Psychiatry 2000; 157:179–184[Abstract/Free Full Text]
   2. Freeman MP, Smith KW, Freeman SA, McElroy SL, Kmetz GE, Wright R, Keck PE Jr: The impact of reproductive events on the course of bipolar disorder in women. J Clin Psychiatry 2002; 63:284–287[Medline]
   3. Cohen LS, Sichel DA, Robertson LM, Heckscher E, Rosenbaum JF: Postpartum prophylaxis for women with bipolar disorder. Am J Psychiatry 1995; 152:1641–1645[Abstract/Free Full Text]
   4. Yonkers KA, Wisner KL, Stowe Z, Leibenluft E, Cohen L, Miller L, Manber R, Viguera A, Suppes T, Altshuler L: Management of bipolar disorder during pregnancy and the postpartum period. Am J Psychiatry 2004; 161:608–620[Abstract/Free Full Text]
   5. Wisner KL, Zarin DA, Holmboe ES, Appelbaum PS, Gelenberg AJ, Leonard HL, Frank E: Risk-benefit decision making for treatment of depression during pregnancy. Am J Psychiatry 2000; 157:1933–1940[Abstract/Free Full Text]


Related Articles:

Risk of Recurrence in Women With Bipolar Disorder During Pregnancy: Prospective Study of Mood Stabilizer Discontinuation
    Adele C. Viguera, Theodore Whitfield, Ross J. Baldessarini, D. Jeffrey Newport, Zachary Stowe, Alison Reminick, Amanda Zurick, and Lee S. Cohen
    Am J Psychiatry 2007 164: 1817-1824. [Abstract] [Full Text]


Risk of Recurrence in Women With Bipolar Disorder During Pregnancy: Prospective Study of Mood Stabilizer Discontinuation
Adele C. Viguera, M.D., Theodore Whitfield, Sc.D., Ross J. Baldessarini, M.D., D. Jeffrey Newport, M.D., Zachary Stowe, M.D., Alison Reminick, B.A., Amanda Zurick, B.A., and Lee S. Cohen, M.D.

OBJECTIVE: This study estimated the risk of recurrence of mood episodes among women with a history of bipolar disorder who continued or discontinued treatment with mood stabilizers during pregnancy. METHOD: In a prospective observational clinical cohort study, the authors determined recurrence risk and survival-analysis-based time to recurrence of a new episode in 89 pregnant women with DSM-IV bipolar disorder. Eligible subjects were euthymic at conception and continued mood stabilizer treatment or discontinued treatment proximate to conception. RESULTS: The overall risk of at least one recurrence in pregnancy was 71%. Among women who discontinued versus continued mood stabilizer treatment, recurrence risk was twofold greater, median time to first recurrence was more than fourfold shorter, and the proportion of weeks ill during pregnancy was five times greater. Median recurrence latency was 11 times shorter after abrupt/rapid versus gradual discontinuation of mood stabilizer. Most recurrences were depressive or mixed (74%), and 47% occurred during the first trimester. Predictors of recurrence included bipolar II disorder diagnosis, earlier onset, more recurrences/year, recent illness, use of antidepressants, and use of anticonvulsants versus lithium. CONCLUSIONS: Discontinuation of mood stabilizer, particularly abruptly, during pregnancy carries a high risk for new morbidity in women with bipolar disorder, especially for early depressive and dysphoric states. However, this risk is reduced markedly by continued mood stabilizer treatment. Treatment planning for pregnant women with bipolar disorder should consider not only the relative risks of fetal exposure to mood stabilizers but also the high risk of recurrence and morbidity associated with stopping maintenance mood stabilizer treatment.


Related Articles:

Bipolar Disorder and Pregnancy: Risks Revealed
    Marlene P. Freeman
    Am J Psychiatry 2007 164: 1771-1773.




questions   élements de réponse  conférence de consensus  références

 

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11/05/2013
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