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Ketamine

Does Ketamine Cure Depression?

For some, yes. But there are many limitations.

Key points

  • Ketamine's antidepressant effects fade rather quickly necessitating ongoing treatment.
  • Thirty percent of patients do not respond to ketamine.
  • A new study suggests there may be ways of sustaining ketamine's antidepressant effects through psychological tools.

Ketamine is an amazing medicine being used off label for treatment resistant depression. For many patients with resistant depression, bipolar depression, and suicidal ideation, ketamine can be a miracle. Ketamine works much faster than regular antidepressants, and the results can often be dramatic. However, ketamine does not work for everyone, and it is not without its drawbacks. In the discussion that follows, I will focus on some of the limitations of ketamine.

Ketamine's antidepressant effects fade

Ketamine can rapidly improve depression in about 70% of patients who haven’t responded to other antidepressants. Although this is a stunning statistic, it’s important for patients to understand that the antidepressant effects of ketamine usually wear off, and rather quickly.

If a patient receives one ketamine infusion, the antidepressant effect typically lasts about a week, and sometimes only a few days. If a patient receives an initial group of six ketamine treatments, the antidepressant effect lasts longer, but only about a month. Therefore, as someone is preparing to undergo ketamine treatment, it is important to keep in mind that even if ketamine works, it will likely wear off after a month, and one may need monthly ketamine treatments to sustain the antidepressant effects.

This happens in the majority of patients who respond to ketamine. I believe it is unethical for providers not to communicate this clearly to patients. I’ve come across patients who think they have failed ketamine treatment because the effects wore off a month later. Actually, it is just the opposite, as these patients would be considered ketamine responders who now need monthly boosters.

Ongoing treatments can be costly

With monthly boosters being an ongoing cost, often not covered by insurance, it is clearly unethical for clinicians not to review these expenses with patients before signing them up for ketamine treatments. (Of course, for many people who respond to ketamine, the cost is a small price to pay for the alleviation of depression and being able to function again.)

Thirty percent of patients do not respond to ketamine

Another important caveat which every practitioner should review with their patients is that 30% of people do not respond to ketamine. Ketamine does not work for everyone. Therefore, it is important for practitioners to discuss with their patients what the next steps in treatment will be if ketamine does not lift depression. Patients are often thinking of ketamine as a last resort, and we need to educate patients that there are other options for treating resistant depression.

Ketamine is not a magic bullet

And finally, when depression is linked to past trauma, toxic relationships, unhealthy habits, poor social supports, and other real world stressors, which it very often is (although not always), it seems intuitive that any molecule by itself, whether it be an SSRI, ketamine, or another novel agent, will not be a miraculous cure. There are usually many other treatment components that need to be in place to help treat depression, such as making sure a patient has a solid social support network.

Might there be methods of enhancing ketamine's antidepressant effects?

To end on an optimistic note, there is evidence emerging that there may be ways to sustain and enhance the antidepressant effects of ketamine by combining ketamine treatments with various forms of new learning.

An article recently posted online in the respected American Journal of Psychiatry describes an elegant study combining ketamine with computer program learning. The results demonstrated that "after priming the brain with ketamine, training positive self-association" was able to enhance and sustain ketamine's antidepressant effects. Stay tuned for my next blog post on different approaches to ketamine, focusing on the potential for enhancing ketamine's antidepressant effect through psychotherapy and other forms of new learning.

References

Price et al. (2022). A Novel, Brief, Fully Automated Intervention to Extend the Antidepressant Effect of a Single Ketamine Infusion: A Randomized Clinical Trial. Am J Psychiatry.

Singh et al. (2016). A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression. Am J Psychiatr

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