Ketamine clinics vary widely in pregnancy-related precautions, study finds

More and more hospitals and clinics are offering patients ketamine therapy for severe depression, post-traumatic stress disorder, and other mental health conditions that do not respond to other treatments.

Although ketamine is a safe drug when used under medical supervision, it has a little-known complication: it can be very harmful to a developing fetus. It should not be used during pregnancy.

However, a new study shows that ketamine prescribers are not paying enough attention to this risk and need to do more to ensure that patients receiving ketamine are not pregnant and are aware of the need to use contraception during multi-month treatment.

The new article in the Journal of Clinical Psychiatry was written by researchers at the University of Michigan’s academic medical center, Michigan Medicine. It reports the results of a survey and document review conducted at ketamine clinics across the country, and a review of records from the ketamine clinic for depression at UM Health.

Overall, the team found wide variation in policies, practices, and warnings about ketamine use in relation to pregnancy and reproduction. This is despite the fact that the 119 clinics that responded to the survey reported treating more than 7,000 patients with ketamine per month in total, and estimated that a third of the patients they treat were women and premenopausal.

Key Findings

More than 75% of clinics responding to the survey reported having formal pregnancy screening, but only 20% actually require a pregnancy test at least once before or during treatment.

More than 90% of clinics reported that they note in their informed consent documents and/or interviews that pregnancy is a contraindication for ketamine treatment. However, 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. Overall, 39% did not include language about pregnancy in their documents, and those that did were generally vague.

When it came to contraceptive counseling, only 26% of clinics that responded to the survey said they discuss the potential need for contraception with ketamine patients. Less than 15% of clinics specifically recommend or require the use of contraception during treatment.

This is particularly striking, the authors say, because more than 80% of clinics reported prescribing ketamine as a long-term maintenance treatment. Nearly 70% of these clinics reported that their patients receive care for more than six months, and many reported that their patients receive ketamine for a year or longer.

An analysis of the records of 24 patients who had previously been treated with ketamine at the UM clinic showed that all had taken a pregnancy test before starting treatment and weekly during treatment. However, only half had recorded in their records that they were using contraception.

Inspiration for the study

Lead author Rachel Pacilio, MD, a psychiatrist who recently joined Michigan Medicine as a clinical assistant professor after completing her residency at U-M Health, said she got the idea for the study during an internship 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 about the drug’s potential positive impact when administered intravenously, as an off-label use of a commonly used anesthetic, or as an intranasal spray of esketamine marketed as Spravato, which is 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 pregnant patients, due to the unknown potential impact on a fetus or a breastfeeding newborn,” Pacilio said. “That sparked our interest in surveying clinics to see how they were addressing this during their intake processes, initial treatment pathways, and during the maintenance therapy phase. To our knowledge, this is the first time this has been looked at.”

Variation in supervision

Clinics that offer intravenous ketamine require specialized staffing and post-administration monitoring for each session. And the FDA specifically requires at least two hours of in-person observation after intranasal Spravato administration to ensure safety and monitor for complications.

In contrast, other formulations of ketamine can be administered outside of the clinical setting with minimal supervision. Some clinics surveyed reported prescribing sublingual ketamine for home use.

The new study did not include online, direct-to-consumer ketamine providers who offer treatment exclusively via teleconsultations. It is unknown how these companies are addressing reproductive and other safety concerns, despite their growing popularity among patients.

“These data suggest that a significant number of patients could be pregnant, or become pregnant, while receiving ketamine treatment via multiple routes of administration. This risk increases with the duration of therapy, which can be weeks for the initial course and a year or more for maintenance,” Pacilio said. “Many patients are unaware they are pregnant in the first few weeks, and animal studies of ketamine are particularly concerning because of the potential for fetal harm during this time.”

She noted that many psychotropic medications have been extensively studied and found to be safe for use during pregnancy, including several antidepressants, antipsychotics, and other psychiatric medications. However, there are no data to support the use of ketamine for psychiatric conditions during 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. An FDA warning from last fall about the risks of compounded forms of ketamine available online also does not include any precautions about pregnancy.

“The variation in practice that we see across community clinics in this study is striking,” Pacilio said. “The field really needs standardization around reproductive counseling, pregnancy testing, and contraceptive recommendations during ketamine treatment.”

If a person becomes pregnant while on ketamine and has to stop taking the drug for the rest of the pregnancy, they are at risk for a relapse of depression that can persist after the baby is born. Perinatal and postnatal depression are major risk factors for a range of problems in both the birthing parent and the baby.

Need for standard guidance

After sharing their findings about UM patients in the new study with leaders at UM Health’s ketamine clinic, Pacilio said the clinic began recommending the use of high-reliability forms of contraception for patients who could become pregnant during ketamine treatment.

Small, independent clinics in the community that offer ketamine therapy may not have the same resources as a large clinic like UM, so standard guidelines could be a solution for them.

Interventions including improved patient education emphasizing the requirement for pregnancy prevention for the duration of ketamine treatment during the informed consent process, routine pregnancy testing before and during treatment for eligible patients, and effective contraceptive counseling are needed. Many of these can be easily implemented and have the potential to positively impact public health.

“Ketamine is a very effective, potentially life-saving treatment for the right patients, but not everyone is a good candidate for it,” she said. “As psychiatrists, we need to make sure that this treatment is delivered in a way that benefits patients and prevents harm.”

In a commentary In the journal article about the UM team’s findings, psychiatrist and journal editor Marlene Freeman, MD, wrote that based on the new findings, “it is critical that best practices for women of childbearing age for the use of ketamine and esketamine be 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 drugs, should be aware of the National Pregnancy Registry for Psychiatric Drugs during pregnancy and to provide much needed information about the effects of these medications.

In addition to Pacilio, the study authors are Jamarie Geller, MD, MA, a psychiatry fellow at U-M, and faculty members Juan F. Lopez, MD; Sagar V. Parikh, MD, and Paresh D. Patel, MD, Ph.D.