Optimal Routes of Administration for Ketamine

The bioavailability of ketamine administered via IM injection is only slightly lower (93%) than IV infusion (100%) and may be much more comfortable for many people to experience as there is no need for an IV line during the experience. Intranasal administration (such as in the ketamine-related medication Esketamine) is unpredictable ranging between 8%–45% making it less than ideal for treatment. Sublingual administration offers a more consistent though low bioavailability with a 24%–30% range.

We tend to utilize sublingual ketamine for psychelytic therapy rather than psychedelic therapy. With the lower bioavailability of sublingual ketamine, the experience is milder; most people experience a loosening of defenses and an ability to engage on a deeper level in the work of therapy. This is especially helpful for people who have a desire to engage in deeper work in therapy and yet struggle to let go of resistance due to a history of trauma or a very strong defense system.

Esketamie vs Ketamine

Esketamine is a recently FDA-approved (2019) treatment for depression that is closely related to ketamine. We have decided to work with Ketamine rather than Esketamine for reasons relating to efficacy, access, and treatment philosophy

Esketamine (Spravato) is an intranasal spray of S-Ketamine (a compound related to Ketamine but different enough to allow for a patent). The bioavailability of intranasal administration is unpredictable (8-45% range) making the effects of Esketamine somewhat unpredictable person to person. We prefer the consistency and predictability of IV, IM and sublingual administrations which offer 100%, 97% and 25-30% bioavailability respectively.

The evidence for the efficacy of ketamine appears stronger than the efficacy of Esketamine. The efficacy study used for Esketamine’s FDA approval did not show remission in depressive symptoms at 4 weeks post-treatment and of the five-phase 3 trials of intranasal administration of (S)‐ketamine in treatment‐resistant patients Janssen presented to the FDA, only two trials demonstrated positive results. In contrast, over 70% of patients with treatment-resistant depression responded to ketamine infusions in multiple clinical trials.

S-Ketamine is designed to remove the psychedelic “side effects” of Ketamine, our opinion based on the research with other promising psychedelics (psilocybin and MDMA) and the foundational research on using Ketamine for mental health treatment is that the psychedelic experience may be a core component of long-term remission from major depressive disorder.

Finally, the medication cost to the client is much higher for Esketamine than ketamine due to the financial interests of Janssen, the pharmaceutical company that owns the patent on Esketamine. Ketamine has been FDA approved since 1970 and thus is now available generically, making it a much more accessible option.

The Good New about FDA Approval and Ketamine

With the 2019 FDA approval of Esketamine, FDA approval for the use of ketamine to treat major depressive disorder is made more promising. The evidence for the efficacy of ketamine for the treatment of depression is arguably much stronger than the evidence presented to the FDA for the approval of Esketamine. The challenge to FDA approval is financial rather than clinical. Since ketamine is generically available, there are no financial incentives for pharmaceutical research into the mental health application of this medication. The research on the use of ketamine for depression and other mental health conditions relies solely on academic and clinical researchers who do not have the funding of big pharma behind them. At present, Ketamine for the treatment of mental health conditions remains in off-label application with strong efficacy evidence related to the treatment of major depressive disorder.

ketamine significantly reduces suicidal ideation in patients with depression

At the Catalyst Center we offer a comprehensive ketamine treatment plan designed to maximize the efficacy of this cutting edge treatment

Further Reading about Ketamine and Esketamine (Spravato)

See also our overview of Ketamine Research

The following three articles outline the efficacy of and guidelines for using Ketamine for major depressive disorder:

Singh I, Morgan C, Curran V, Nutt D, Schlag A, McShane R. Ketamine treatment for depression: Opportunities for clinical innovation and ethical foresight. Lancet Psychiatry 2017; 4: 419–426.

Wilkinson ST, Toprak M, Turner MS, Levine SP, Katz RB, Sanacora G. A survey of the clinical, off‐label use of ketamine as a treatment for psychiatric disorders. Am. J. Psychiatry 2017; 174: 695–696.

Short B, Fong J, Galvez V, Shelker W, Loo CK. Side‐effects associated with ketamine use in depression: A systematic review. Lancet Psychiatry 2018; 5: 65–78.

Article about the study of Esketamine (did not show improvement at 4 week follow up, still was FDA approved)

Canuso CM, Singh JB, Fedgchin M et al Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: Results of a double‐blind, randomized, placebo‐controlled study. Am. J. Psychiatry 2018; 175: 620–630

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