It is estimated that up to 95% of women experience some type of sleep disturbance during pregnancy. While for many women the insomnia is relatively benign and may respond to simple interventions, other women experience more severe insomnia which has a significant impact on their quality of life and ability to function. While zolpidem (Ambien), a sedative-hypnotic agent used for the short-term treatment of insomnia, is commonly prescribed in pregnant women, the information regarding its reproductive safety has been sparse.
Up until very recently only animal studies, case reports, and two very small cohort studies were available regarding zolpidem use and pregnancy. The first study included 18 women and did not find any association between zolpidem use and risk of congenital anomalies. The second study included 45 pregnant women with psychiatric illness treated with zolpidem and found that in the zolpidem-exposed group, as compared to unexposed controls, there was an increased risk of preterm delivery (26.7% vs. 15.6%) and low birth weight (13.3% vs. 4.4%).
A recent study, published in Clinical Pharmacology & Therapeutics, adds to the limited data available regarding the use of zolpidem (Ambien) during pregnancy. In this study, Wang and colleagues conducted a population-based study in Taiwan comparing rates of adverse pregnancy outcomes between mothers who received zolpidem during pregnancy and those who did not. They linked two large data sets: the Taiwan National Health Insurance Program and the national birth certificate registry for a one year period in 2005.
During this period there were 218,776 singleton births to mothers utilizing prenatal care. Of these, 10,343 women were prescribed zolpidem during pregnancy, but they defined women who had been prescribed zolpidem for at least 30 days during pregnancy as those who had received zolpidem treatment (n=2984). Thus the percentage of pregnant women treated with zolpidem was calculated to be 4.72%, which is slightly lower than the reported prevalence in the general adult female population in Taiwan (5.24%). Women were excluded from the analysis if they had a mental health disorder (n=446), or hypertension, diabetes or coronary heart disease prior to conceiving (n=41). Data from a total of 2,497 mothers who had received zolpidem treatment were analyzed. An age-matched comparison group of 12,485 was extracted from the remaining women in the database using the same exclusion criteria.
Of the total sample the mean age was 29.7 years old, and on average the mothers who received zolpidem had lower educational levels, higher rates of gestational hypertension and anemia, and greater parity. After adjusting for these factors, the authors observed that zolpidem-exposed women had higher rates of adverse pregnancy outcomes including lower birth weight (adjusted odds ratio (OR) =1.39), preterm delivery (OR=1.49), small for gestational age babies (OR=1.34), and were more likely to have a caesarean section (OR=1.74). There was no observed increase in congenital anomalies in the exposed group. The risk of adverse pregnancy outcomes was the highest in women who took zolpidem for more than 90 days.
The authors hypothesize, drawing from findings from animal studies, that zolpidem and other GABAergic agonists may cause the pituitary to release higher levels of vasopressin and oxytocin which may result in uterine vasoconstriction in the mother. Also, GABAergic agonists that penetrate the CNS may cause respiratory depression by depressing the central ventilatory drive. Both of these mechanisms might result in decreased blood flow to the uterus and may thus influence fetal growth.
While this report suggests an increased risk of certain adverse outcomes, the results are difficult to interpret. The study excludes women with a formal psychiatric diagnosis; however, they do not assess symptoms of depression or anxiety during pregnancy. It is likely that many of the women who require a sleeping aid during pregnancy experience insomnia as a symptom of an underlying mood or anxiety disorder. Multiple studies have shown that certain adverse outcomes– preterm delivery, low birth weight, and small for gestational age babies– occur at higher rates in women with depression and anxiety in the absence of medication exposure. Thus, do these results reflect the adverse effects of exposure to zolpidem? Or are they related to an underlying mood or anxiety disorder?
Furthermore, the authors were not unable to account for the effect of insomnia severity, which may directly affect the pregnancy, nor were they able to assess the degree of adherence to the prescription medication. Data regarding other variables which may affect pregnancy outcomes, including alcohol use, smoking status, and use of non-prescription medications were not collected.
Despite the prevalence of sleep problems in pregnancy, there are few guidelines to help clinician choose appropriate interventions. Improving sleep hygiene and cognitive-behavioral interventions may be helpful in many cases, but some women may require pharmacologic treatment. In light of these findings, the authors suggest the prescription of zolpidem be avoided for pregnant women when possible. All women who present with insomnia should be screened for underlying mood or anxiety disorders. By addressing these symptoms first, sleep problems may diminish or resolve. Other pharmacologic options for the treatment of insomnia during pregnancy include benzodiazepines and tricyclic antidepressants.
April Hirschberg, MD
Wang LH, Lin HC, Lin CC , Chen YH & Lin HC. Increased Risk of Adverse Pregnancy Outcomes in Women Receiving Zolpidem During Pregnancy. Clin Pharm Ther 88:3, 369-374 (2010).
Wilton LV, Pearce GL, Martin RM, Mackay FJ & Mann RD. The outcomes of pregnancy in women exposed to newly marketed drugs in general practice in England. Br J Obstet Gynaecol. 105, 882-889 (1998).
Juric S, Newport DJ, Ritchie JC, Galanti M & Stowe ZN. Zolpidem (Ambien) in pregnancy: placental passage and outcome. Arch Womens Ment Health 12, 441-446 (2009).
Interesting article. I was on ambien during 2 pregnancies (I am bipolar) was very closely monitored, in fact, had consult at Mass General for second pregnancy, and ambien had no effect on either birth.
Thank you for examining this issue. I formerly worked as an antepartum nurse and had concerns about the routine prescription of Ambien for pregnant in-patients.
Thank you for a very useful summary! As a pharmacist I have been asked many times about the safety profile of zolpidem in pregnancy. The recent 2010 study definately provides more information regarding the medications saftey profile.
Most queries I receive in the pharmacy are from women who took zolpidem during their first trimester (not knowing they were pregnant).
Are there any studies or information which examines the use of zolpidem usage recently before and during the first trimester?
I found the article useful, however, at the end of the article it is suggested that other options for insomnia during pregnancy are benzodiazepians and anti-depressents. That I would not agree with. Benzodiazepians are generally a class D medication for pregnancy and have been known to cause birth defects. I would like to see that part of the article taken out.
@Rachel, Thanks for bringing up this point. The data regarding the benzodiazepines is not so straightforward. While the FDA lists most benzodiazepines as Category D (positive evidence of fetal risk), this designation may not accurately reflect the risks associated with exposure. We have previously discussed the limitations of the FDA system of pregnancy category labeling and the need for a more clinically useful system of classification of risk.
In the 1970s, several case control studies linked exposure to benzodiazepines (primarily diazepam) to an increased risk of oral clefts. However, pooled data from cohort studies have shown no association between fetal exposure to benzodiazepines and a risk of major malformations or oral clefts. It is important to note that, if we are to assume that an association between oral clefts and benzodiazepine exposure does exist, the absolute risk of this malformation is relatively low, about 0.6%.
Hi I am an overseas reader and by chance I found this articile. I really appreciate your opinion, but there is still sth concerning me a lot: will prenatal exposure to Ambien cause any long term effect on IQ, behavioral problems etc? Although I know such regarding information has been sparse, can you give me a bit suggestion? I am planning for pregnance and in the past 10 years insomnia has been a problem to me occasionally, so I expect I will have to be on Ambien like before once in a while say several times per month to keep me emotional smooth and avoid anxiety. Will that be a problem for long term baby’s development? I am quite anxious.
Beyond benzo’s there is also busparone which is labeled a Cat. B in the FDA scheme. My wife has an anxiety disorder and she when she got pregnant switched to busparone. Watching her get off benzodiazepines, I wondered why these drugs are still used so much. Busparone worked so well she was able to stop taking it. And now, since the anxiety only manifests itself as insomnia, she takes only Ambien. Although our OB has greenlighted her use, we are trying not to take it more than two nights in a row to avoid dependency issues (but this is still a major concern of mine).
While this blog was very well written and these studies are very useful, I believe there are possible adverse effects caused by these drugs that are not easy (read impossible today) to study, so we try to be as conservative as possible with her use.
I too have chronic insomnia and it started after my son was born and he is now twelve and I am pregnant with twins. Prior to getting pregnant the longest I had gone without Ambien QHS was close to two weeks and I was a zombie. I spoke to my physician, she too said she’d rather I continue the medication and get the rest I need. Again I tried to go off of it and today it’s been a week and I fold. I picked up my refill today and cannot wait for a good nights rest. I was taking Unisom and dye free Benadryl and they do not work whatsoever for me. I can manage anxiety and slight depression on my own without meds for anxiety or depression however only if I take Ambien. I do take 10 mg, I am still not completely comfortable taking it because of course I want my babies to be round happy healthy babies and anything that could so much as work against that, even a diet mt dew, no problem, gone. Ambien, my only vice. I will be 10 weeks soon and any advice other than the “do as you physician says” would help me in my decision. I am 33 years old and of course twins is considered high risk. How much of this drug is passed on to baby? Is it more harmful taken in the second or third trimester as opposed in the first?
I found this article very helpful and sets my mind at ease about using sedative/anxiety relief during a pregnancy which I am planning. Thanks again
This article was very helpful for me. I’ve been weaning off of klonopin, and it has been excruciating. The insomnia has gotten so severe that I began contemplating suicide after going 3 days with no sleep. At this point, the risks associated with Ambien are lower than the risks associated with not getting any sleep. I just hope the Ambien works, because nothing else has so far.
I agree the article was very helpful; however, the comments more so. I believe I may be pregnant although very early. I have stopped taking my prescribed Xanax as I read it is not healthy before pregnancy for those trying to conceive and during pregnancy. I was prescribed Ambien and felt quite groggy in the mornings, that is when my doctor gave me low dose Xanax instead. As of now, I have been taking Melatonin, trying to keep my body cleaner for pregnancy yet it just isn’t doing the job lately. I think perhaps I have become immune to the dose I have been taking. I have begun to consider taking my Ambien again, leading me to research if this would cause a problem with a possible pregnancy.
Hey people who left this comment few years ago. It would be great to have any updated from you. Greatfull for any comments. Did you end up using ambient? How did it go? Everything was fine or not, thanks.
I am a light sleeper and have battled with insomnia a few times in my life. However, at the end of both of my pregnancies, it was physical discomfort that was/is keeping me from sleeping. I had very minimal use and for a short period of time, but getting 6 or 7 hours of sleep versus 2 or 3 went a long way for not only my general well-being, but my family’s as well. I carried to term with no issues with my Singleton the first time. I am carrying twins this time and expect no issues there either.
I am up late. Cant sleep. I found this article. So I am 48 , and I had a tubal ligation at age 42. I went to dr today to refill my temazepam for sleep. Nurse asked LMP , not exactly sure. Two positive tests later I had stat ultrasound. No ectopic. Must wait till tommorrow for blood test results. Meanwhile I have been lying awake all night wondering. Not sure what tommorrow will bring. I am an RN (21) yrs. This article was very informative. Thank you.
Would love to have an update from the posts from a few Years ago .. how are your babies? Everything turn out ok?