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Combining Ketamine With Psychotherapy to Treat Depression

August 24, 2020
Lynne McInnes, MD

A session being presented at Psych Congress 2020 will educate attendees on the practice of combining ketamine treatment with psychotherapy for patients with treatment-resistant depression (TRD). In this Q&A, Lynne McInnes, MD, discusses the benefits of this treatment approach, the best candidates for it, and possible side effects and risks.

Dr. McInnes, a private practice adult psychiatrist in California, founded and directed a program to provide ketamine therapy to TRD patients at Kaiser Permanente San Francisco. She will present the session, titled Ketamine-Assisted Psychotherapy: A Practical Guide for Medical Providers, with Jessica Yu, NP, a psychiatric and family nurse practitioner at Kaiser Permanente.

Psych Congress is being held virtually Sept. 10-13, 2020, with a preconference on Sept. 9, 2020.

Q: What are the benefits of combining psychotherapy with ketamine treatment?

A: Ketamine promotes the rapid growth of neuronal processes and the formation of synapses, a process that constitutes the cellular basis of learning. People with treatment-resistant depression may have stopped benefiting from therapy because their capacity to learn is impaired by stress-induced neuronal atrophy.  A group at Yale University has published preliminary data suggesting that cognitive behavioral therapy can act synergistically with ketamine to prolong the antidepressant effects of ketamine infusions. Anecdotally, many of us know that ketamine enhances the psychotherapeutic process by accelerating the transference, enhancing openness, and fostering empathy between the patient and provider. It also tends to reduce inhibitions, making it easier to talk about difficult subjects.

Q: Which patients are best suited for ketamine-assisted psychotherapy, and which patients are not candidates for the treatment?

A: Patients with active substance abuse problems or certain types of medical conditions including uncontrolled hypertension are not candidates for this therapy. We also do not know if ketamine therapy is safe during pregnancy. Otherwise, adult candidates with treatment-resistant depression are welcome.

Q: Do you recommend any particular types of therapy to combine with ketamine treatment?

A: As mentioned, there is already evidence that cognitive behavioral therapy pairs well with ketamine. Gregor Hasler wrote a brief theoretical review of psychotherapies appropriate for ketamine treatment in 2019.1 For instance, as increased energy and initiative are hallmarks of the ketamine response, behavioral activation is a good fit. Ketamine may disrupt fear memory consolidation and strengthen the formation of extinction memory which could help explain its usefulness in exposure-based therapies. Humanistic psychotherapy and interpersonal psychotherapy are also sound methodologies. Ultimately, providers are best served by cultivating an attitude of open-ended inquiry. “Follow the patient” is a good maxim.

Q: What are the most common side effects and risks associated with ketamine treatment?

A: A transient hypertensive response to ketamine is common, as is dissociation, mood elevation or anxiety, nausea, vomiting, dizziness, sedation, blurred vision, and numbness.

Q: Does combining it with psychotherapy add any risks or possible side effects?

A: Blood pressure needs to be monitored before dosing and at the close of the session. If the patient’s baseline BP is somewhat elevated, the provider in some cases may want to assess it 20-30 minutes after dosing. Blood pressure checks should be done routinely at the initiation of therapy and after dosage increases.

Q: What steps do you recommend for clinicians who want to begin treating patients with ketamine-assisted psychotherapy?

A: Listen to our talk. Many practices offer experiential training courses. Understanding the diverse array of experiences encompassed in the term dissociation is really essential as providers will need to understand this concept to accurately determine the target dose of ketamine, which will vary among individuals.

"Ketamine-Assisted Psychotherapy: A Practical Guide for Medical Providers" will be presented at 4 p.m. Sept. 12, 2020.


1. Hasler G. Toward specific ways to combine ketamine and psychotherapy in treating depression. CNS Spectrums. 2020;25(3):445-447.

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