Ketamine clinics vary widely in pregnancy-related safeguards, study finds
With use growing for treatment-resistant depression and other mental health conditions, more use of tests and contraception by patients who could become pregnant is needed, authors say
Michigan Medicine - University of Michigan
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A patient receives a ketamine infusion for depression at the University of Michigan Health clinic, which requires pregnancy testing before treatment begins and weekly testing during treatment, as well as specifically recommending the use of highly reliable forms of contraception during the course of ketamine therapy, for all patients who could become pregnant.
view moreCredit: University of Michigan/Leisa Thompson
More hospitals and clinics now offer patients ketamine therapy for severe depression, post-traumatic stress disorder and other mental health conditions that haven’t responded to other treatments.
While ketamine is a safe medication when used with medical supervision, it does have a little-known complication: it may be very harmful to a developing fetus. It should not be used during pregnancy.
But a new study suggests that ketamine prescribers aren’t paying enough attention to this risk and should do more to make sure that patients receiving ketamine aren’t pregnant and are aware of the need to use contraception while undergoing a course of treatment over multiple months.
The new article in the Journal of Clinical Psychiatry was written by researchers from the University of Michigan’s academic medical center, Michigan Medicine. It reports the results of a survey and document review conducted of ketamine clinics nationwide, and a review of records from the ketamine clinic for depression at U-M Health.
In all, they found a wide variation in policies, practices and warnings about ketamine use related to pregnancy and reproduction. This is despite the fact that the 119 clinics that answered the survey report treating a total of more than 7,000 patients with ketamine per month, and estimate that a third of patients they serve are female and pre-menopausal.
Key findings
More than 75% of responding clinics said they have a formal pregnancy screening process, but only 20% actually require a pregnancy test at least once prior to or during treatment.
More than 90% of clinics said they note that pregnancy is a contraindication to ketamine treatment in their informed consent documents and/or conversations. But less than half of clinics reported discussing specific potential risks with patients.
The researchers also looked at informed consent documents on the websites of 70 other ketamine clinics. In all, 39% did not include language about pregnancy in their documents, and those that did were generally vague.
When it came to contraception counseling, only 26% of the clinics that answered the survey said they discuss the potential need for contraception with ketamine patients. Less than 15% of the clinics specifically recommend or require contraception use during treatment.
This is especially striking, the authors say, because more than 80% of clinics reported prescribing long-term maintenance ketamine, with nearly 70% of these saying their patients receive care for more than six months and many saying patients receive ketamine for a year or more.
The review of records from 24 patients treated with ketamine at U-M’s clinic in the past showed all had taken a pregnancy test before beginning treatment and weekly during treatment, and but only half had documentation in their records that they were using contraception.
Inspiration for the study
Lead author Rachel Pacilio, M.D., a psychiatrist who recently joined Michigan Medicine as a clinical assistant professor after completing her residency at U-M Health, said the idea for the study came to her during a rotation in the perinatal psychiatry clinic.
Patients who were pregnant or had recently given birth asked her about ketamine as an option for their treatment-resistant depression. They had heard of the potential positive impact of the drug when given intravenously as an off-label use of a common anesthetic, or as an intranasal spray of esketamine that’s marketed as Spravato and approved by the U.S. Food and Drug Administration.
“There was little guidance available to prescribers other than the general recommendation to avoid ketamine in patients who are pregnant, because of the unknown potential impact on a fetus or a breastfeeding newborn,” says Pacilio. “That sparked our interest in surveying clinics to see how they were handling this during their intake processes, initial treatment courses, and during the maintenance therapy phase. As far as we know, this is the first time this has been looked into.”
Variation in oversight
Clinics offering intravenous ketamine require specialized staff and post-administration monitoring for each session. And the FDA specifically requires least two hours of in-person observation after dosing of intranasal Spravato to ensure safety and monitor for complications.
By contrast, other formulations of ketamine can be administered outside the clinical setting with minimal oversight. Some clinics surveyed reported prescribing sublingual ketamine for at-home use.
The new study did not include online, direct-to-consumer ketamine providers that offer treatment exclusively via telehealth consultations. It is unknown how these companies address reproductive and other safety concerns despite their growing popularity among patients.
“These data suggest that a large population of patients could be pregnant, or could become pregnant, while receiving ketamine treatment via multiple routes of administration. This risk increases with the duration of therapy which can last weeks for the initial course and a year or more for maintenance,” said Pacilio. “Many patients do not know that they’re pregnant in the first weeks, and animal studies of ketamine are very concerning for potential harm to the fetus during this time.”
She noted that while many psychotropic medications have been studied extensively and found to be safe for use in pregnancy, including a variety of antidepressants, antipsychotics and other psychiatric drugs, there is no data to support the use of ketamine for psychiatric illness in pregnancy.
Pacilio pointed out that the FDA’s risk mitigation program for Spravato, the nasal form of ketamine, does not include any provisions about pregnancy. A warning issued by the FDA last fall about the risks of compounded forms of ketamine available online also does not mention precautions about pregnancy.
“The variability in practice that we see among clinics in the community in this study is stark,” said Pacilio. “The field is really in need of standardization around reproductive counseling, pregnancy testing and the recommendation for contraception during ketamine treatment.”
If someone becomes pregnant while undergoing ketamine treatment, and has to stop receiving the drug for the remainder of the pregnancy, they are at risk for a depression relapse that could continue after the baby is born. Perinatal and postpartum depression are major risk factors for a range of issues in both the birthing parent and the infant.
Need for standard guidance
After sharing their findings about U-M patients in the new study with leaders of the U-M Health ketamine clinic, Pacilio said that the clinic began recommending the use of highly-reliable forms of contraception to patients who could become pregnant while receiving ketamine treatment.
Small standalone community clinics offering ketamine therapy may not have the same resources that a large clinic like U-M’s does, so standard guidance could especially benefit them.
Interventions including improved patient education with an emphasis on the requirement for pregnancy prevention for the duration ketamine treatment during the informed consent process, routine pregnancy testing before and during treatment for appropriate patients, and effective contraceptive counseling are needed. Many of these could be easily implemented and have the potential to positively impact public health.
“Ketamine is a really effective, potentially lifesaving, treatment for the right patients, but not everyone is a good candidate for it,” she said. “As psychiatrists, we need to ensure this treatment is being delivered in a way that benefits patients while preventing harm.”
In a commentary in the journal about the U-M team’s findings, psychiatrist and journal editor Marlene Freeman, M.D., wrote that based on the new findings, “It is imperative that best practices for women of reproductive age for the use of ketamine and esketamine are determined and utilized.” She added that this is especially important in light of the changing landscape of abortion-related laws.
Freeman also noted that those who have used ketamine in any form during pregnancy, as well as other psychotropic medications, can join the National Pregnancy Registry for Psychiatric Medications during pregnancy and help provide much-needed information on the impacts of these medications.
In addition to Pacilio, the study’s authors include Jamarie Geller, M.D., M.A., a psychiatry fellow at U-M, and faculty members Juan F. Lopez, M.D.; Sagar V. Parikh, M.D. and Paresh D. Patel, M.D., Ph.D.
The study was funded by U-M Department of Psychiatry.
Safe ketamine use and pregnancy: a nationwide survey and retrospective review of informed consent, counseling, and testing practices. J Clin Psychiatry, DOI:10.4088/JCP.24m15293.
Journal
Journal of Clinical Psychiatry
Method of Research
Survey
Subject of Research
People
Article Title
Safe ketamine use and pregnancy: a nationwide survey and retrospective review of informed consent, counseling, and testing practices
Pregnancy-related heart failure is under-detected; AI-enabled stethoscope helped doctors diagnose twice as many cases
Mayo Clinic
ROCHESTER, Minn. — Heart failure during pregnancy is a dangerous and often under-detected condition because common symptoms – shortness of breath, extreme fatigue and trouble breathing while lying down – are easily mistaken for typical pregnancy discomforts. Late-breaking research presented at the European Society of Cardiology Congress on a Mayo Clinic study showed an artificial intelligence (AI)-enabled digital stethoscope helped doctors identify twice as many cases of heart failure compared to a control group that received usual obstetric care and screening. Full study findings are published in Nature Medicine.
The trial was conducted in Nigeria, where more women experience pregnancy-related heart failure than anywhere in the world. The results also indicate that screening including the AI-enabled digital stethoscope were 12-times more likely than traditional screening to flag heart pump weakness when evaluated at a ejection fraction threshold lower than 45%, which is the cutoff indicating a specific type of heart failure called peripartum cardiomyopathy.
"Recognizing this type of heart failure early is important to the mother's health and well-being," says Demilade Adedinsewo, M.D., a cardiologist at Mayo Clinic and lead investigator of the study. "The symptoms of peripartum cardiomyopathy can get progressively worse as pregnancy advances, or more commonly following childbirth, and can endanger the mother's life if her heart becomes too weak. Medicines can help when the condition is identified but severe cases may require intensive care, a mechanical heart pump, or sometimes a heart transplant, if not controlled with medical therapy."
The randomized, controlled, open-label clinical trial included nearly 1,200 participants who were screened for heart conditions through typical obstetric care or AI-enhanced solutions. Mayo Clinic researchers previously developed a foundational 12-lead AI-electrocardiogram (ECG) algorithm to predict a weak heart pump, clinically known as low ejection fraction. A version of this algorithm was further enhanced by Eko Health for its point-of-care digital stethoscope which is U.S. Food and Drug Administration (FDA)-cleared to detect heart failure with low ejection fraction.
The researchers found that doctors using AI-based screening with the digital stethoscope and 12-lead ECG detected weak heart function with high accuracy. Within the study cohort, the digital stethoscope helped flag twice as many cases of low ejection fraction <50% and doctors using it were 12-times more likely to identify an ejection fraction <45% as compared to usual care.
The AI-supported tools were evaluated at three different levels of ejection fraction used in clinical diagnosis. Less than 45% is the cut point for diagnosing peripartum cardiomyopathy. Less than 40% indicates heart failure with reduced ejection fraction and has strong evidence in favor of specific medications to reduce symptoms and the risk of death. An ejection fraction of less than 35% signals severely low heart pump function that often requires more intense management, including advanced heart failure therapies and an implantable defibrillator if pump function does not recover. Patients in the intervention group each had an echocardiogram at study entry to provide confirmation of the AI-predictions.
"This study provides evidence that we can better detect peripartum cardiomyopathy among women in Nigeria. However, there are more questions to be answered," says Dr. Adedinsewo. "Our next steps would be to evaluate usability and adoption of this tool by Nigerian healthcare providers (including doctors and nurses) and importantly, its impact on patient care. Peripartum cardiomyopathy affects approximately 1 in 2,000 women within the U.S. and as many as 1 in 700 African American women. Evaluating this AI tool in the U.S. will further test its abilities in varied populations and healthcare settings."
Funding for this clinical trial includes Mayo Clinic (Centers for Digital Health and Community Health and Engagement Research), the Mayo Clinic Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) Program funded by the National Institutes of Health (NIH), and Mayo Clinic’s Center for Clinical and Translational Sciences (CCATS) funded by the NIH.
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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.
Journal
Nature Medicine
Article Title
Artificial intelligence guided screening for cardiomyopathies in an obstetric population: a pragmatic randomized clinical trial
Article Publication Date
3-Sep-2024
Eating fish but not omega-3 supplements during pregnancy associated with lower likelihood of autism diagnosis, NIH-funded study finds
Environmental influences on Child Health Outcomes
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For more information, visit echochildren.org.
view moreCredit: NIH Environmental influences on Child Health Outcomes (ECHO) Program
Eating any amount of fish during pregnancy was associated with about a 20% lower likelihood of autism spectrum disorder (ASD) diagnosis, particularly in females, and a slight reduction in autism-related traits in offspring, according to a new study funded by the Environmental influences on Child Health Outcomes (ECHO) Program at the National Institutes of Health.
However, researchers did not find the same association with supplements containing omega-3 fatty acids.
Fish is an important source of omega-3 fatty acids, an essential nutrient during pregnancy for supporting maternal health and child neurodevelopment. A recent analysis of ECHO Cohort data revealed that about 25% of the pregnant participants reported never eating fish or consuming it less than once a month during their pregnancy. Even fewer participants reported taking omega-3 fish oil supplements.
ECHO Cohort researchers wanted to see whether low fish consumption and omega-3 supplement use during pregnancy might be associated with the occurrence of an autism diagnosis or parent-reported autism-related traits.
“Our study contributes to a growing body of evidence that demonstrates the role that prenatal diet can play in autism-related outcomes in offspring,” said ECHO Cohort researcher Emily Oken, MD, MPH, of Harvard Medical School.
Dr. Oken said the findings underscored the need for better public health messaging about guidelines for fish consumption for pregnant people, considering the low fish intake in the U.S. and the rising diagnoses of autism.
What happened during the study?
Researchers analyzed data from about 4,000 participants, examining the relationships among fish intake, supplement use, and neurodevelopmental outcomes related to autism.
Fish consumption and omega-3 supplement use were measured with dietary information reported by participants. Participants’ fish consumption was categorized as less than once a month, more than once a month but less than weekly, weekly, and two or more servings per week. About 20% of adult participants reported no fish intake, and most reported not using omega-3 or fish oil supplements.
The researchers then looked at the relationship between maternal fish intake and omega-3 fish oil supplement use during pregnancy and the occurrence of clinician-diagnosed autism and parent-reported autism-related traits. These traits were measured using the Social Responsiveness Scale (SRS), a widely used survey completed by parents or caregivers. Higher scores on the SRS indicate the presence of more autism-related behaviors.
Consuming fish during pregnancy was associated with a lower likelihood of offspring being diagnosed with autism and a slight decrease in total SRS scores compared to not eating fish. These results were consistent across all levels of fish consumption, from "any" amount or "less than once per week" to "more than twice per week." No significant associations were found between omega-3 fish oil supplements and autism diagnosis compared to no use.
Experts recommend that people consume additional omega-3 fatty acids during pregnancy. Prenatal fish intake is a key source of omega-3 fatty acids that are critical for fetal brain development. However, fish and omega-3 fatty acid supplementation in the U.S. is low.
“This study provides yet more evidence for the safety and benefit of regular fish consumption during pregnancy,” said Dr. Oken. “Other proven benefits include lower risk for preterm birth and improved cognitive development.”
Dr. Oken led this collaborative research published in the American Journal of Clinical Nutrition.
Oken, E. & Lyall, K. (2024) Association of maternal fish consumption and ω-3 supplement use during pregnancy with child autism-related outcomes: results from a cohort consortium analysis. American Journal of Clinical Nutrition. 10.1016/j.ajcnut.2024.06.013
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About ECHO: Launched in 2016, the Environmental influences on Child Health Outcomes (ECHO) Program is a research program in the Office of the Director at the NIH with the mission to enhance the health of children for generations to come. ECHO investigators study the effects of a broad range of early environmental influences on child health and development. For more information, visit echochildren.org.
About the NIH: NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information, visit www.nih.gov.
Journal
American Journal of Clinical Nutrition
Method of Research
Observational study
Subject of Research
People
Article Title
Association of maternal fish consumption and ω-3 supplement use during pregnancy with child autism-related outcomes: results from a cohort consortium analysis
