Zuranolone (Zurzuvae, by Biogen) made medical news headlines when it was approved by the U.S. Food and Drug Administration (FDA) last August as the first oral treatment for postpartum depression. However, some experts have concerns about the drug’s pivotal trials that they feel should give health professionals pause in prescribing it.

“The FDA saw fit to approve zuranolone based on modest efficacy data in trials that compared it with substandard medical care,” wrote Vinay Prasad, M.D., M.P.H., of the University of California, San Francisco, and David Allely, B.S., of the Icahn School of Medicine at Mount Sinai in New York in JAMA.

The authors described two trials that the FDA reviewed when making its decision to approve zuranolone, the ROBIN study and the SKYLARK study, both of which had placebo control arms.

“The use of placebo control is inappropriate. Multiple guidelines endorse treatment of severe postpartum depression with SSRIs and psychotherapy. Yet, in ROBIN and SKYLARK, just 20% and 15% of women, respectively, were using antidepressants at baseline,” they wrote, adding that each participant should have been prescribed an SSRI and psychotherapy based on current standards of care. “The median length of time to response expected with these interventions does not justify withholding treatment from the control group. We are unable to assess whether the improvement in the treatment group would have been observed versus standard of care.”

They added that although the trials assessed the drug’s efficacy in people with severe postpartum depression, the FDA’s approval “does not qualify its indication for individuals with postpartum depression of this severity, instead granting a blanket approval for milder forms of postpartum depression—an indication that lacks evidence.”

The authors also noted that both trials suggested a large placebo effect, accounting for roughly 75% of the effect in both trials.

“Patients with postpartum depression in this study tended to get better, regardless of treatment,” the authors explained.

The authors had several other concerns, as follows:

• Misuse potential
• Impaired psychomotor functioning
• Lack of compatibility with breastfeeding
• Anticipated exorbitant cost, estimated to be $10,000 to $30,000 for the two-week course

“We suggest that the FDA require control groups that reflect standards of care to better inform and equip physicians with medications that might improve the health of patients, and we caution the current use of zuranolone,” Prasad and Allely concluded.