IV vs Intranasal Ketamine: Which is Best?

Intravenous ketamine and intranasal esketamine are both equally effective in improving symptoms of treatment-resistant depression (TRD) in adults, but “speed and cost” appear to favor IV ketamine in clinical practice, results of an observational, single-center study show.

Because of insurance restrictions on esketamine nasal spray, treatment initiation can take several weeks longer than IV ketamine. In addition, the cost of achieving the same clinical benefit is about six times higher for esketamine vs ketamine, study investigator Thomas Scott, MD, with Scott Integrated Pain Management, Philadelphia, Pennsylvania, told Medscape Medical News.

Scott and co-investigator Blake Gilbert-Bono, BA, MS2, University of Pennsylvania Perelman School of Medicine, Philadelphia, presented the study at the American Psychiatric Association (APA) 2023 Annual Meeting.

Let Patients Decide?

Both ketamine and esketamine have been shown to have rapid antidepressant effects in adults with TRD.

Using patient-level data, the investigators compared the efficacy and cost of the two drugs in a real-world setting.

Among 89 patients with TRD treated at their clinic, 19 were treated with intranasal esketamine at a starting dose of 56 mg, up to a maximum dose of 84 mg, and 70 were treated with IV ketamine at a starting dose of 0.5 mg/kg adjusted for body weight, up to 1 mg/kg. All patients also received an oral antidepressant.

At each treatment, patient mood was evaluated using the Quick Inventory of Depressive Symptomatology – Self Reported (QIDS-SR) scale. Suicidality was also assessed at each treatment on a binary scale.

Scott said comparisons across all efficacy endpoints revealed “no reliable or statistically significant” differences between nasal esketamine and IV ketamine.

Based on the analysis, patients “should expect a relatively fast reduction of 5.57 points on the QIDS scale in the first 6 treatments (3 weeks) of using either drug,” the researchers note.

In addition, among the 44 patients who initially presented with suicidal ideation, no differences were found between the two drugs in terms of reducing suicidality. There was also no significant difference in the side-effect profile between the two drugs.

However, the researchers calculate that the cost of intranasal esketamine is roughly sixfold higher than IV ketamine. Furthermore, because of insurance restrictions for esketamine, time to treatment initiation can take “several weeks” longer than ketamine, Scott said.

“In my practice, I give patients the choice” of intranasal esketamine or IV ketamine, he said.

“An advantage of IV ketamine is I can usually start the treatment quicker and usually patients are eager to start. Sometimes it takes longer to start esketamine because we have to get them registered in the REMS program,” Scott added.

Supportive Data, Large RCT Needed

Commenting on the study for Medscape Medical News, Gerard Sanacora, MD, PhD, professor of psychiatry, Yale School of Medicine, and director of the Yale Depression Research Program, New Haven, Connecticut, said the results of this study are “interesting” and similar to a recent publication by his team.

In the Yale study of 210 patients with TRD, IV ketamine and intranasal esketamine were both shown to help alleviate symptoms of depression.

However, there are “a few major issues with this report, as there were with our report,” said Sanacora.

The study was not randomized, “so it is likely that patients were receiving one treatment or another due to some other factor” such as insurance coverage or personal preference.

“This means there is likely to be some form of bias in the sampling of the two groups. We just don’t know how strong of an effect this bias has on outcome.”

“This is my major concern, and really argues that a true randomized controlled study needs to be done,” Sanacora said.

The study had no specific funding. Scott and Gilbert-Bono report no relevant financial relationships .

American Psychiatric Association (APA) 2023 Annual Meeting: Poster P12-007. Presented May 23, 2023.

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