憂鬱與懷孕:評估治療選項的新報告


  August 21, 2009 — 美國精神醫學會(APA)與美國婦產科學院(ACOG)的一篇聯合報告,提供醫師有關照護發生重度憂鬱異常之風險或已有此疾病之孕婦的新資訊。
  
  由紐哈芬耶魯醫學院、生殖科學系、婦產科、精神科的Kimberly A. Yonkers醫師等人提出的此一報告,目標在提供醫師與病患衡量各種治療選項的風險與利益。
  
  此報告中也深入探討了現有的研究與治療建議。
  
  Yonkers醫師在Medscape Psychiatry的訪問中指出,我們希望提供一篇有全盤論述的文獻,避免以偏概全,讓醫師得窺全貌。
  
  Yonkers醫師指出,就生產方面的結果,文獻認為,憂鬱症和抗憂鬱治療皆有風險,且與不佳的生產結果有關。不過,這兩者的整體資料看來,目前的證據尚不充分。
  
  該報告線上登載於9/10月合刊的General Hospital Psychiatry以及9月的婦產科(Obstetrics & Gynecology)期刊。
  
  此外,作者們寫道,現有的研究並未適當控制其他影響生產結果的風險因素,包括母親的疾病或者有問題的健康行為。懷孕期間使用多種藥物也會導致難以評估單一藥物(如抗憂鬱藥)對於母親和胎兒的影響。
  
  根據該報告,有14%至23%的孕婦發生過憂鬱症狀,在2003年,有將近13%的婦女在懷孕時服用過一種抗憂鬱劑。作者們寫道,因此,醫師和病患需要更新資訊,以幫助懷孕期間的憂鬱治療決策。
  
  作者們試圖藉此報告表達出憂鬱症和抗憂鬱藥物對於母親和胎兒的風險,且發展出在受孕前後以及產前的一套管理規則。來自APA與ACOG的代表以及一名諮商發展小兒科醫師,一起回顧Medline搜尋的文獻與書目。
  
  回顧結束時,研究者發現,雖然憂鬱症狀以及抗憂鬱藥物都與胎兒生長改變及縮短妊娠期間有關,研究中有多數都是評估抗憂鬱劑的風險,而未能控制憂鬱異常本身的可能影響。
  
  研究者也發現:
  * 相較於沒有憂鬱之母親所生的新生兒,憂鬱異常母親所生的新生兒,易怒的風險增加、活動力與注意力較差、臉部表情較少。
  * 許多研究報告指出,胎兒畸形與懷孕第一期使用抗憂鬱藥物有關,但是沒有單一藥物或某類藥物的特定影響模式。
  * Paroxetine與心臟缺陷之間的關係,比較常在包括所有畸形的研究中發現,而不是臨床顯著的畸形。
  * 懷孕晚期使用選擇性血清素再吸收抑制劑類抗憂鬱藥物,與暫時性新生兒徵兆有關,且會增加新生兒持續性肺高壓的風險。
  * 多數研究未顯示懷孕期間使用三環抗憂鬱劑和構造畸形之間的關係,但是三環抗憂鬱劑與增加出生前後併發症,如新生兒悸動、易怒、抽搐等有關。
  
  該報告也建議多種治療規則。概略簡介如下。
  
  【考慮懷孕的婦女】
  * 對於那些輕微或者已經有6個月以上沒有憂鬱症狀者,調整與停用藥物。
  * 對於嚴重或復發憂鬱症者(或者有精神病、躁鬱症、其他需藥物治療的精神疾病、曾試圖自殺者),則不適合停用藥物。
  
  【目前正使用憂鬱藥物的孕婦】
  * 和精神科醫師與婦產科醫師諮商討論有關風險之後,精神穩定之婦女應繼續使用可讓她達到穩定的藥物。
  * 對於想要停藥以及沒有症狀者,可以嘗試調整與停用藥物。不過,有復發憂鬱症之病史者,可能會有復發的高風險。
  * 對於那些復發憂鬱或症狀者,除了藥物之外,可能可以從心理治療著手,以取代或輔助藥物治療。
  * 嚴重憂鬱的婦女應繼續使用藥物。如果病患拒絕,在停藥之前,應採用替代療法與監控。
  
  【目前未使用憂鬱藥物的孕婦】
  * 對於那些想避免使用抗憂鬱藥物者,可以使用心理治療。
  * 對於那些願意服用藥物者,應評估和討論治療選項的風險與利益。
  
  此外,不論任何狀況,任何有自殺或精神症狀的孕婦,都應立即尋求精神科醫師的諮商,以便治療。
  
  ACOG總裁Gerald F. Joseph, Jr.醫師在聲明中表示,以前,生殖健康執業醫師認為沒有能力治療這些病患,因為缺乏懷孕婦女之憂鬱處置的可用指引。許多人— 包括醫師和婦女—將樂於瞭解他們的選擇,不論是藥物或者其他。
  
  此報告的限制是,只有包括母親精神疾病的少數研究被納入回顧。有關診斷和抗憂鬱劑使用之詳細資料的研究一般都比較小型,發現重要關聯的強度有限。
  
  此外,影響生產結果的其他因素,如不佳的產前照護與藥物、酒精、抽菸等,在各研究中列為變項的情形不一。
  
  Yonkers醫師指出,本篇報告希望能幫助精神科醫師以及婦產科醫師。我認為我們發展的論述可以反映事實,也就是在憂鬱孕婦、或準備懷孕之憂鬱婦女的處置上,要考量多種因素而不能單憑直覺。精神病史以及婦女的偏好也都必須納入考量。
  
  她指出,諸如APA和ACOG等團體之間的合作將有助於其他異常之研究。有許多精神疾病在生育年齡時達到高峰,所以我認為,納入其他領域考量將大有幫助。
  
  研究者宣告多種財務關係,載於原始文獻中。
  

Depression and Pregnancy: New Report Weighs Treatment Options

By Deborah Brauser
Medscape Medical News

August 20, 2009 — A joint report from the American Psychiatric Association (APA) and the American College of Obstetricians and Gynecologists (ACOG) aims to provide a new resource for clinicians who care for pregnant women who either have or are at risk of developing major depressive disorder.

The report by Kimberly A. Yonkers, MD, from the Department of Psychiatry, Department of Obstetrics and Gynecology, and Department Reproductive Sciences, Yale School of Medicine, in New Haven, Connecticut, and colleagues, aims to help physicians and patients weigh the risks and benefits of various treatment options.

The report includes an extensive review of existing research and a list of treatment recommendations.

"We wanted to provide a comprehensive story of where the literature stands at this point so that one single study does not trump all the work that's been done, and so clinicians have a full context," said Dr. Yonkers in an interview with Medscape Psychiatry.

"In terms of birth outcomes, the literature suggests that it's likely that both depression as well as antidepressant treatment confer risks and may be associated with adverse birth outcomes. However, the data looking at both of these together are insufficient at this point," Dr. Yonkers added.

The report will be published in both the September/October issue of General Hospital Psychiatry and the September issue of Obstetrics & Gynecology.

In addition, the authors write that available research has not yet adequately controlled for other factors that may influence birth outcomes, including maternal illness or problematic health behaviors. The use of multiple medications during pregnancy also makes it difficult to assess the effect of a single compound, such as an antidepressant, on maternal and fetal outcomes.

According to the report, between 14% and 23% of pregnant women experience depressive symptoms, and approximately 13% of women in 2003 took an antidepressant at some time during pregnancy. "Thus, clinicians and patients need up-to-date information to assist with decisions about depression treatment during pregnancy," the authors write.

For the report, the authors sought "to address the maternal and neonatal risks of both depression and antidepressant exposure and develop algorithms for periconceptional and antenatal management." Representatives from the APA and ACOG and a consulting developmental pediatrician reviewed articles from Medline searches and bibliographies.

At the end of the review, the investigators found that although both depressive symptoms and antidepressant exposure are associated with fetal growth changes and shorter gestation periods, the majority of the studies that evaluated antidepressant risks were unable to control for the possible effects of a depressive disorder.

The researchers also found that:

  • Neonates born to mothers with a depressive disorder have an increased risk for irritability, less activity and attentiveness, and fewer facial expressions compared with those born to mothers without depression.
  • Several studies report fetal malformations in association with first-trimester antidepressant exposure, but there is no specific pattern of defects for individual medications or class of agents.
  • The association between paroxetine and cardiac defects is more often found in studies that included all malformations, rather than clinically significant malformations.
  • Late gestational use of selective serotonin reuptake inhibitor antidepressants is associated with transitory neonatal signs and an increased risk for persistent pulmonary hypertension in the newborn.
  • Most of the studies did not show an association between tricyclic antidepressant use in pregnancy and structural malformations, but tricyclic antidepressants are associated with increased perinatal complications such as jitteriness, irritability, and convulsions in neonates.

The report also recommends several treatment algorithms. These common scenarios include the following.

Women Thinking About Getting Pregnant

  • Tapering and discontinuing medication for those with mild or no depressive symptoms for 6 months or longer.
  • This discontinuation may not be appropriate for women with a history of severe or recurrent depression (or who have psychosis, bipolar disorder, other psychiatric illness requiring medication, or a history of suicide attempts).

Pregnant Women Currently on Medication for Depression

  • After a consultation between their psychiatrist and obstetrician/gynecologist (to discuss risks), psychiatrically stable women who prefer to stay on medication may be able to do so.
  • For those who want to discontinue medication and are not experiencing symptoms, tapering and discontinuation may be attempted. However, women with a history of recurrent depression are at a high risk for relapse.
  • Those with recurrent depression or symptoms despite their medication may benefit from psychotherapy to replace or augment medication.
  • Women with severe depression should remain on medication. If a patient refuses, alternative treatment and monitoring should be in place, preferably before discontinuation.

Pregnant Women Not Currently on Medication for Depression

  • For those who want to avoid antidepressant medication, psychotherapy may be beneficial.
  • For those who prefer taking medication, risks and benefits of treatment choices should be evaluated and discussed.

In addition, regardless of circumstances, any pregnant woman with suicidal or psychotic symptoms should seek an immediate consultation with a psychiatrist for treatment.

"In the past, reproductive health practitioners have felt ill equipped to treat these patients because of the lack of available guidance concerning the management of depressed women during pregnancy. Many people — physicians and women alike — will be glad to know that their choices go beyond medication or nothing," ACOG President Gerald F. Joseph, Jr, MD, said in a statement.

Limitations of this report are that only a minority of the studies reviewed included information on maternal psychiatric illness. Studies with detailed information regarding diagnoses and antidepressant use were usually smaller and had limited power to find important associations.

In addition, confounding factors that influence birth outcomes, such as poor prenatal care and drug, alcohol, and nicotine use, were variably controlled.

"This is a report intended to reach out to psychiatrists as well as obstetrician-gynecologists," said Dr. Yonkers. "We developed algorithms which I think reflect the fact that there are multiple issues to consider and [that] there should be no knee-jerk response in managing a woman who is depressed and pregnant or contemplating pregnancy. Psychiatric history and a woman's preference are among the important features that should be taken into consideration."

She added that collaboration between groups such as the APA and ACOG would be helpful for other disorders as well. "There are many psychiatric illnesses that are at their peak during the reproductive years, so I think there are a number of areas where the combined input would be extremely helpful."<

    
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