New treatment available for refractory major depressive disorder

By Francie Williamson, Communications Coordinator, Department of Psychiatry

Heather Sloma-Weber, RN, takes a patient’s blood pressure and checks the patient’s oxygen level at the Behavioral Health Clinic at UI Hospitals & Clinics. This late summer day marks the seventh time she’s seeing the patient, she remarks, for this treatment.

That treatment is esketamine, which the FDA approved in 2019 for refractory major depressive disorder (MDD). The FDA approved a second use for intranasal esketamine in 2020 – MDD with acute suicidal ideation and behavior.

Sloma-Weber has been administering Spravato, the brand name for esketamine, at UI Hospitals & Clinics since June. It is delivered intranasally, and is derived from the parent drug ketamine, which has been used as an anesthetic since the 1970s. 

“I think esketamine is cutting edge,” Sloma-Weber says. “It’s another modality to help people that’s not invasive.”

The UI Department of Psychiatry originally had intended to begin an esketamine service a couple of years ago, but the COVID-19 pandemic delayed its startup.

Going about treatment

Mark Niciu, MD, PhD, who came to the UI Department of Psychiatry in 2018, has been interested in the effectiveness of ketamine in combatting depression for over 10 years. He says Yale University, where he did his psychiatry residency and additional neuroscience fellowship training, was the first institution to systematically study the antidepressant effects of subanesthetic (low dose) ketamine in major depression.

According to Niciu, unlike traditional antidepressants that work on serotonin or norepinephrine, ketamine works primarily on glutamate. And, unlike traditional antidepressants, which often take weeks-to-months for maximal response, ketamine works rapidly, in hours-to-days. A hastening of antidepressant response can be lifesaving for actively suicidal depressed patients.

“Most, if not, all academic institutions are doing ketamine infusions for some condition,” Niciu says, “whether it be treatment-resistant depression, chronic pain, or another neuropsychiatric disorder.”

Although IV ketamine is not FDA approved for depression, it has been available at UI for more than 5 years now. However, most insurances, including Medicare and Medicaid, will not cover IV ketamine for major depression. The typical market rate in Iowa is $500 per infusion, Niciu says, which is prohibitive for depressed patients with limited financial resources, like those on disability.

Before a patient can be considered for IV ketamine or intranasal esketamine treatment at UI Hospitals & Clinics, they must have a referral placed by their provider to the Interventional Psychiatry Service. Even though the patient may be specifically interested in ketamine, according to Niciu, the providers at the clinic consider whether something else may be more effective for their target symptoms. Such treatments include medication adjustments, or evidence-based psychotherapies like dialectical behavior therapy, transcranial magnetic stimulation (TMS), or electroconvulsive therapy (ECT).

If IV ketamine or intranasal esketamine is determined to be the best course of action, a physical examination, labs and EKG are required, Niciu says, to minimize the likelihood of undesirable side effects.

Administering the drug

When a patient arrives for an IV ketamine or intranasal esketamine session, they cannot have previously ingested any food or drink for at least 4 hours, mostly to mitigate the risk of nausea and/or vomiting, a possible side effect of ketamine. Patients are monitored throughout for other side effects including vital sign changes, dissociation and sedation. According to Niciu, the patient typically is back at their pre-treatment baseline within 60 minutes after the infusion and may be able leave the clinic shortly thereafter, but must have someone else drive them home.

Niciu says patients who have a positive experience during the ketamine infusion, including feeling elated or a “mystical experience,” like obtaining increased clarity or a deeper sense of purpose or meaning in their lives during the ketamine session, often have a better antidepressant response.

For intranasal esketamine, the patient will blow their nose then self-administer the drug into the nasal cavity. Sloma-Weber says the process reminds her of the administration of Flonase, an antihistamine used to combat allergies.

“I’ve had people say they are surprised the patient does it themself,” Sloma-Weber says.

After the first administration, the patient waits five minutes before taking a second dose. Sloma-Weber then checks the patient’s vital signs and assesses for side effects every 15 minutes for 45 minutes. While she takes vitals, Sloma-Weber asks the patient if they have any feelings of dissociation or sedation. She says its normal to see an increase in blood pressure and pulse with guidelines on when to alert the physician on the Interventional Psychiatry Service if the blood pressure or pulse change is significant.

Two hours after the first dose, the patient can be discharged from the clinic. After treatment, Sloma-Weber says many patients have told her they will go home and eat or rest or take a nap, and that helps them return to how they were feeling prior to treatment. Niciu stressed that a good night’s sleep correlates with antidepressant and antisuicidal efficacy of ketamine.

“One thing about this being a small service is that I appreciate being able to provide continuity of care,” Sloma-Weber says.

Future of Ketamine

Niciu says there is potential for IV ketamine and intranasal esketamine to be used in the emergency settings, for example in acutely suicidal patients in the emergency department. He believes that the administration of ketamine where suicidal patients are first encountered and in greatest crisis may “jump start depression treatment for emergency psychiatrists” to prevent hospitalization or shorten lengths of stay on the inpatient psychiatric units.

Wednesday, October 5, 2022