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Q&A with Dr. Cristina Cusin: What to Know About Esketamine and Ketamine Treatment

In This Article

  • Ketamine is the first of a new type of antidepressant approved by the FDA that uses a mechanism of action predominantly based on glutamate
  • It has been shown to work in patients with treatment-resistant depression who have failed prior trials with antidepressants
  • Intranasal ketamine treatment has fixed doses and scheduled titration. It is also less potent than the intravenous form, generally well tolerated and less expensive, but the personalization of dose and frequency can take much longer

Cristina Cusin, MD, is a psychiatrist who specializes in treatment-resistant depression in the Depression Clinical and Research Program (DCRP) at Massachusetts General Hospital. Much of her research is focused on the use of ketamine as an adjunct to traditional antidepressants for treatment-resistant mood disorders. As a result of this work, she began the Ketamine Clinic for Depression, within the DCRP to offer intravenous and intranasal ketamine treatments and associated clinical services to patients.

Q: How does ketamine differ from traditional treatments for depression?

Cusin: Ketamine is the first of a new type of antidepressant that uses a mechanism of action predominantly based on glutamate. It has been shown to work in patients with treatment-resistant depression who have failed prior trials with antidepressants. It is also the first rapid antidepressant agent to produce improvement hours to days after administration, rather than the usual four to six weeks.

Like any other drug, ketamine's duration of effect is time-limited, so repeated administrations are required for sustained benefits. The interval between administrations varies depending on whether it is given by intranasal or intravenous (IV) application.

Q: How does the esketamine, the nasal ketamine treatment recently approved by the FDA, differ from IV ketamine treatment?

Cusin: The FDA approved the intranasal Spravato, a brand-name esketamine, for patients with treatment-resistant depression. Intranasal ketamine treatment is less potent than the IV form, generally well tolerated and less expensive. However, the personalization of dose and frequency of administration is much more cumbersome and slow. It may take over a month to find the right dose.

IV ketamine treatment, in contrast, is more potent and takes effect much more rapidly. However, it is also more expensive.

At present, no ketamine treatment is covered by insurers and we don't have any information about coverage of Spravato yet.

Q: What type of patients are best suited for ketamine treatments?

Cusin: There is a lot of hype around ketamine right now and the expectations are huge, but it's not a miracle drug. It's a drug like any other, and many patients will not respond. That can be heartbreaking if it is perceived as their last hope and it's not working. This is why we do a lot of preparatory work. We need to have a plan in place, whether ketamine works or doesn't work, because that can lead to serious problems.

Every patient has a long consultation with a member of our team before beginning treatment, and we work with the patient's treating psychiatrist to make sure each patient is a good fit. Patients with a history of depression who have not responded to or not tolerated antidepressants are well suited for ketamine treatment, as are patients with chronic thoughts of suicide. However, patients with major contraindications, including a history of psychosis and recent substance use disorder, are not a good fit.

Q: How is ketamine treatment being utilized at Mass General?

Cusin: We have had an intranasal ketamine clinic at Mass General since 2015. More recently we opened an IV clinic, the Ketamine Clinic for Depression, which offers consultation and treatment services to patients with severe depression or chronic suicidal ideation and conducts ongoing research focused on ketamine treatment.

Our clinic works collaboratively with the outpatient psychiatry treatment team to develop an appropriate treatment plan tailored to each patient.

Q: How do you determine that a patient might be a good fit for ketamine?

Cusin: Potential patients have an in-depth consultation with one of our ketamine clinicians who review their psychiatric and medical history, any previous antidepressant treatments and all possible indications and contraindications. If the patient is deemed a good fit for ketamine treatment, they go through an extensive process for informed consent before starting the treatment.

Learn more about the Ketamine Clinic for Depression

Learn more about the Depression Clinical and Research Program


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Unlike traditional antidepressants, ketamine may be similarly effective in both anxious and nonanxious patients with treatment-resistant depression, according to a secondary analysis of a randomized, controlled clinical trial.