5 Minute Pearls: Ketamine for Treatment Resistant Depression and Suicidal Ideation

by Staff Writer
August 31, 2023 at 9:05 AM UTC

Clinical Relevance: Christina Cusin, MD is a psychiatrist and the director and founder of the Ketamine Clinic at Massachusetts General Hospital in Boston. In this 5 Minute Pearls video, she shares clinically relevant insights about ketamine for treatment resistant depression.

  • Patient suitability, clinic selection, and administration methods should be carefully considered before initiating ketamine treatment for depression.
  • Ketamine can be combined with other treatments like MAOI inhibitors and atypical antipsychotics. Long-term efficacy varies, necessitating individualized maintenance plans.
  • Patients and providers should discuss financial cost, risks, benefits, and potential relapse if treatment is discontinued.

In this episode of 5 Minute Pearls, Christina Cusin, MD will discuss ketamine and when to recommend it, where to get it, other medication considerations, and ketamine treatment duration.

Spoiler alert! Ketamine is not magic and should be treated like any other antidepressant treatment.

In Which Patients is Ketamine Appropriate?

Dr. Cusin notes that research for ketamine exists in a variety of patient populations, including rigorous control studies in adults and adolescents with treatment-resistant depression and many in major depressive disorder and bipolar depression. There are some studies in PTSD in patients with suicidal ideation, but fewer studies in other disorders like OCD or substance use disorder.

Major contraindication for ketamine is the presence of psychosis or history of psychosis in ongoing active substance use disorder. From the medical point of view, contraindications are unstable cardiovascular illnesses such as aneurysm or uncontrolled hypertension.

Ketamine Research from The Journal of Clinical Psychiatry

Clinical Effectiveness of IV Racemic Ketamine Infusions in a Large Community Sample of Patients With Treatment-Resistant Depression, Suicidal Ideation, and Generalized Anxiety Symptoms

Ketamine vs Esketamine for TRD

Combined Ketamine and Monoamine Oxidase Inhibitors

Where to Access Ketamine

Dr. Cusin suggests providers consider reputable clinics. Those where the clinician allows you to coordinate the care of patients with complex conditions, like depression comorbid with PTSD. And consider clinics where you’re allowed to have close monitoring of the patient, especially regarding suicidal ideation.

Insurance Coverage for Ketamine

This is a frequent question in regards to ketamine treatment. Some insurers do cover ketamine, but the vast majority of patients have to pay out of pocket. This treatment can become extremely expensive.

Ketamine Administration Options

Ketamine can be administered as intravenous, intramuscular, sublingual, or intranasal. Dr. Cusin recommends reviewing the modality used by each specific ketamine clinic, and at what interval that delivery is provided.

In general, intravenous (IV) administration of ketamine lasts much longer compared to the other modalities, but some patients are not appropriate for IV ketamine and it’s very important from a clinician point-of-view to have a plan B ready because ketamine does not work for everyone. There are many patients who do not respond to ketamine, and if they have suicidal ideation, they can become extremely despondent and feel worse.

Other Treatment Options

Ketamine works best as an adjunct of other treatments. Most antidepressants when give together with ketamine are safe and actually increase the response to ketamine.

  • MAOI inhibitors are safe to administer with ketamine.
  • Atypical antipsychotics often augment antidepressants and are OK to use with ketamine.
  • Electroconvulsive therapy (ECT) shows no evidence of an increase of the efficacy when administered with ketamine.
  • Transmagnetic stimulation (TMS) does not have solid data regarding a combination with ketamine.
  • Lamotrigine, benzodiazepines, and gabapentin raise questions of potential interference. These drugs, and those like them, should be tapered or the administration schedule adjusted around the time of ketamine administration.

How Long is Ketamine Treatment Indicated

Another question that is very often posed by patients and clinicians alike is, for how long the ketamine treatment is indicated. We don’t have long-term data. We have a few years of maintenance in very select groups of patients.

For each infusion, the duration of the antidepressant effect is quite variable from few a days to a few weeks, and in some patients a month-and-a-half to two months, but it’s fairly rare.

Final Takeaways for Ketamine Treatment

The overall course of ketamine is difficult to describe because every patient is different. For some patients with a single acute episode, ketamine may help in the treatment of the episode, and then there might be longer intervals between episodes in a patient who has a more episodic or milder form of illness.

Most of the patients Dr. Cusin sees at the clinic have a chronic depression; they have been ill for five to 10 years and they usually relapse when ketamine is stopped.

In the informed consent, she advises the need to discuss the risks and benefits as well as the plan for long-term maintenance. If the patient can no longer afford ketamine, very often a rapid decline occurs with return of the depression in suicidal ideation. Both provider and patient need to be prepared for this.


Christina Cusin, MD is an associate professor of psychiatry at Harvard Medical School and the director and founder of the MGH Ketamine Clinic.

This is Five Minute Pearls for The Journal of Clinical Psychiatry, in partnership with the American Society of Clinical Psychopharmacology.

Original Research

Psychological Pain as a Risk Factor for Suicidal Ideation: An Ecological Momentary Assessment Study on Inpatients With Depression With and Without Comorbid Borderline Personality Disorder

In inpatients with depression, psychological pain is a risk factor for suicidal ideation. Those with borderline personality disorder may experience more prominent and temporally unstable psychological pain, likely underlying their vulnerability to suicidal ideation.

Ilya Baryshnikov and others

Case Report

Psychotic Symptoms Following Ayahuasca Use in a Ceremonial Setting

A 43-year-old woman with no psychiatric history developed schizophreniform psychotic symptoms after taking ayahuasca, which resolved after 1 week of risperidone treatment.

Alfonso Martínez Torres and others