懷孕期間停用情緒穩定劑會使雙極性情感疾病復發風險加倍


  January 3, 2008 — 一篇對89位雙極性情感疾病(bipolar disorder)孕婦的前溯觀察研究中,71%在懷孕期間至少發生1次的情緒發作;相較於繼續服用情緒穩定劑的婦女,停止治療者的復發風險高達2倍,復發間隔縮短 4倍,懷孕期間花費於此病症的時間多達5倍。
  
  克里夫蘭臨床神經研究中心的Adele C. Viguera醫師和同事於12月的美國精神病學期刊(American Journal of Psychiatry)發表上述研究發現。
  
  研究團隊指出,發表的研究發現挑戰了在懷孕期間停止精神異常疾病維持治療的慣例,因為停用情緒穩定藥劑會有較高的發病率,對於胎兒的發展衝擊則不確定,他們建議更均衡地考量雙極性情感疾病孕婦的臨床治療風險與利益。
  
  【知識代溝】
  研究團隊指出,雙極性情感疾病婦女懷孕會面對許多需要關心的問題,包括有關懷孕期間疾病療程、復發之預測、情緒穩定劑對生產的安全性等等的"特別的知識代溝"。
  
  他們目標為檢驗雙極性情感疾病病史婦女於懷孕期間繼續或停止服用情緒穩定劑的復發風險。
  
  他們以前溯方式納入89位雙極性情感疾病孕婦(69%第一型躁鬱症,31%第二型躁鬱症),這些人在專科醫院接受精神諮商,平均年紀為32.7歲,大部分是白人、教育良好、已婚、於職場就業;大部分的婦女 (n=55)服用鋰鹽(lithium),32人服用抗痙攣劑作為主要的情緒穩定劑;46人同時服用抗憂鬱藥,24人同時服用抗精神病藥物。
  
  89人之中共有62人在懷孕期間停止服用精神穩定劑。
  
  【母親發病率高風險】
  懷孕期間,70.8%的婦女發生至少1次的雙極性情感異常,相較於繼續服用精神穩定劑的婦女,停止治療者的復發風險是2倍,復發之間隔縮短 4倍。
  
  懷孕期間發病率:持續使用與停止使用情緒穩定劑

發病率

持續治療, n=27

停止治療, n=62

全部個案, n=89

至少復發 1 次雙極性異常,%

37.0

85.5

70.8

懷孕期間發生雙極性異常的周數百分比, %

8.8

43.3

32.8

第 1 次復發的時間,週數

9.0

>40


  大部份新發作的情緒問題是在懷孕早期;在懷孕第1、2、3期的風險分別是47.2%、31.9%以及18.8%;大部分的發作(74%)是憂鬱或者輕躁狂(hypomania)或躁症之混合。
  
  停用情緒穩定劑的婦女突然 (1–14天內,n=35) 發生情緒復發之風險有50%;漸漸停用者之中,約22週才到達此一風險水平;意外懷孕者更可能越快停用藥物。
  
  作者指出,此研究不代表更廣泛族群的復發風險。
  
  他們寫道,主要的臨床衝擊是,對於嚴重或經常復發雙極性情感異常之婦女,懷孕期間繼續使用情緒穩定劑是最謹慎的策略,就像其他嚴重和慢性疾病,如癲癇建議孕婦維持治療一樣。
  
  【精神科醫師和病患間的害怕與恐懼】
  德州大學西北醫學中心的Marlene P. Freeman醫師在一篇編輯評論中指出,這項對於懷孕期間的雙極性情感異常療程的前溯研究,是一項劃時代的研究。
  
  她表示,精神科醫師和病患在雙極性情感異常婦女懷孕時經常過度恐懼與害怕,有些情緒穩定劑已知的懷孕第1期致畸胎風險包括,valproate和carbamazepine造成的神經管缺損,以及鋰鹽造成的心血管發育不全,如三尖瓣膜異常(艾勃氏異常/Ebstein's, anomaly),抗痙攣劑對於神經管缺損的最大影響期間是在懷孕最初期-在婦女發現自己懷孕之前的時候。
  
  她寫道,萬一是意外懷孕,醫師對於這些藥物的風險的資訊、以及評估停止治療雙極性情感異常的風險,都將幫助避免這種情況下出現因為恐慌或害怕造成的決定。
  
  她結論表示,作者即將提出的產後資料,可望對此論點有更有價值的觀點,也可更了解精神科未被研究的領域。
  
  Viguera醫師是Berlex、阿斯特捷利康、Eli Lilly、Forest、輝瑞、格蘭素史克、諾華、Sepracor、哈佛醫學院醫學研究員獎學金(Harvard Medical School's Scholars in Medicine Fellowship)、anssen、國家心智健康研究中心(National Institute of Mental Health)、國家精神分裂症與沮喪研究聯盟(National Alliance for Research on Schizophrenia and Depression),以及Eli Lilly、格蘭素史克、 諾華和惠氏提供的Wyeth-Ayerst 講課酬勞等之諮詢顧問或接受其研究資助,其他作者的財經宣告列於文中。
  
  Freeman醫師接受亞利桑那心智健康研究中心(Arizona's Institute for Mental Health Research)、Eli Lilly、Forest、國家心智健康研究中心(National Institute of Mental Health)、 Reliant以及美國食品藥物管理局(US Food and Drug Administration)的研究資助。
  
  

Stopping Mood Stabilizers Duri

By Marlene Busko
Medscape Medical News

January 3, 2008 — In a prospective observational study of 89 pregnant women with bipolar disorder, 71% had at least 1 mood episode recurrence during pregnancy. Compared with the women who continued taking mood stabilizers, those who stopped this treatment had a 2-fold higher risk for mood relapse, a 4-fold shorter time to relapse, and a 5-fold greater amount of time spent ill during pregnancy.

These findings by Adele C. Viguera, MD, from the Cleveland Clinic Neurological Institute, in Ohio, and colleagues are published in the December issue of the American Journal of Psychiatry.

"The present findings challenge the evidently common practice of abruptly stopping maintenance treatment for psychiatric disorders during pregnancy," the group writes, adding that given the high morbidity associated with discontinuation of mood stabilizing treatment and its uncertain impact on fetal development, they recommend a more balanced consideration of risks and benefits in the clinical management of pregnant women with bipolar disorder.

Knowledge Gaps

Women with bipolar disorder who become pregnant encounter several obstacles to care, including "extraordinary knowledge gaps" about the course of the illness during pregnancy, predictors of recurrence, and reproductive safety data for mood stabilizers, the group writes.

They aimed to examine the risk for recurrence of mood episodes among women with a history of bipolar disorder who continued or discontinued taking mood stabilizers when they became pregnant.

They prospectively enrolled 89 pregnant women diagnosed with bipolar disorder (69% bipolar 1 disorder and 31% bipolar 2 disorder) who were seeking psychiatric consultation in a specialized center. The women had a mean age of 32.7 years, and most were white, well educated, married, and working outside the home. Most women (n=55) were taking lithium and 32 were taking an anticonvulsant as their primary mood stabilizer; 46 women were also taking an antidepressant and 24 women were also taking an antipsychotic agent.

A total of 62 of the 89 women discontinued treatment with a mood stabilizer.

High Risk for Maternal Morbidity

During pregnancy, 70.8% of the women experienced at least 1 episode of bipolar disorder. Compared with the women who continued taking a mood stabilizer, those who discontinued this treatment had a 2-fold greater risk for recurrence and a more than 4-fold shorter time to a new episode of bipolar disorder.

Morbidity During Pregnancy: Continuing vs Stopping Mood Stabilizers
Morbidity Continued Treatment, n=27 Discontinued Treatment, n=62 All Subjects, n=89
At least 1 recurrence of bipolar episode, % 37.0 85.5 70.8
% of pregnancy weeks spent ill with a mood disorder 8.8 43.3 32.8
Median time to first recurrence, weeks 9.0 >40

Most new mood episodes emerged early in pregnancy; risk in the first, second, and third trimester was 47.2%, 31.9%, and 18.8%, respectively. Most episodes (74%) were depression or a mixed state rather than hypomania or mania.

Women who discontinued their mood stabilizers abruptly (1–14 days, n=35) had a 50% risk for recurrence of mood episodes within 2 weeks; among women who discontinued more gradually, it took 22 weeks to attain this risk level. Rapid discontinuation of medication was more likely with unplanned pregnancy.

The authors note that this study might underrepresent the relapse risk in a broader population.

A major clinical implication is that "for women with severe and frequent recurrences of bipolar disorder, maintenance treatment with a mood stabilizer during pregnancy may be the most prudent strategy, much as maintenance treatment is recommended for pregnant women with other serious and chronic conditions, such as epilepsy," they write.

Fear and Panic Among Psychiatrists, Patients

This is a "groundbreaking" study in that it is the largest known prospective study of the course of bipolar disorder during pregnancy, and it provides a greater understanding of the serious risk for relapse during pregnancy, writes Marlene P. Freeman, MD, from the University of Texas Southwestern Medical Center at Dallas, in an accompanying editorial.

"Psychiatrists and patients alike are frequently overwhelmed with fear and panic when a woman with bipolar disorder discovers she is pregnant," she writes. Known teratogenic risks in the first trimester from treatment with some commonly used mood stabilizers include neural tube defects with valproate and carbamazepine and cardiovascular malformations such as Ebstein's anomaly with lithium, she adds, noting that the time of greatest concern for neural tube defects from anticonvulsants is very early in pregnancy, often before a woman discovers that she is pregnant.

"In the case of an unplanned pregnancy, information from the treating physician about the risks of the medication as well as the risks of untreated bipolar disorder would help avoid the panicked and fear-based decision that often occurs in this situation," she writes.

The authors' postpartum data in a forthcoming report is expected to add valuable insights into this important and understudied area of psychiatry, she concludes.

Dr. Viguera has served as a consultant to or received research support from Berlex, AstraZeneca, Eli Lilly, Forest, Pfizer, GlaxoSmithKline, Novartis, Sepracor, Harvard Medical School's Scholars in Medicine Fellowship, Janssen, National Institute of Mental Health, the National Alliance for Research on Schizophrenia and Depression, and Wyeth-Ayerst and lecturer's honoraria from Eli Lilly , GlaxoSmithKline, Novartis and Wyeth. The financial disclosures of the other authors are listed in the article.

Dr. Freeman has received research support from Arizona's Institute for Mental Health Research, Eli Lilly, Forest, National Institute of Mental Health, Reliant, and the US Food and Drug Administration.

Am J Psychiatry. 2007; 164:1817-1824, 1771-1773.

    
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