Nasal spray administration of therapeutic ketamine offers several benefits and raises some concerns. This mode of administration is gaining traction as an alternative to intravenous (IV), IM and sublingual administration.
Benefits:
- Ease of administration: Nasal spray is non-invasive and easy to use, making it convenient for patients and healthcare providers. This may improve patient adherence and reduce treatment-related anxiety (Freeman et al., 2020).
- Rapid onset of action: Ketamine’s bioavailability through nasal administration is relatively high, with a reported range of 45-50% (Yanagihara et al., 2003). It is absorbed quickly through the nasal mucosa, providing a rapid onset of therapeutic effects (Lapidus et al., 2014).
- Lower risk of adverse effects: Nasal spray administration of ketamine may result in lower systemic exposure and a reduced risk of side effects compared to IV administration. Some studies report fewer dissociative and psychotomimetic side effects (Janssen et al., 2018).
Concerns:
- Variability in absorption: The bioavailability of ketamine via nasal spray can be influenced by factors such as nasal congestion, inflammation, or structural anomalies, potentially leading to inconsistent dosing (Illum, 2003).
- Dosing: Optimal dosing for nasal spray ketamine has yet to be established, and more research is needed to determine the most effective and safe dosing regimens. Existing studies suggest doses between 20-84 mg for depression (Lapidus et al., 2014; Janssen et al., 2018).
- Potential for abuse: Ketamine has a known potential for abuse due to its dissociative and hallucinogenic effects. Nasal spray takes effect somewhat more rapidly than sublingual or rectal ROAs; but less rapidly than IV or IM. We conjecture that regulators fear that at-home nasal ketamine might be used with recreational intent which the War on Drugs stigmatizes. Whether this concern is justified is debatable.
- Long-term safety and efficacy: More research is needed to evaluate the long-term safety and effectiveness of ketamine nasal spray, as most studies have focused on short-term outcomes. Understanding the long-term effects and potential complications is crucial to establish the best treatment protocols and patient selection criteria (Daly et al., 2019).
- Self-administration of nasal spray requires developing the appropriate techniques. Tipping the head, administering a couple of sprays in one nostril, then a couple more in the other nostril, repeating until the prescribed dose – measured in sprays – is achieved. Some patients have difficulty with the nasal ROA.
Nasal spray ketamine involves inhaling a ketamine solution sprayed into the nostrils.
Pros of nasal spray:
- Non-invasive, painless, and easy to administer [1]
- Rapid onset within 15-30 minutes [2]
- Bypasses first-pass metabolism for good bioavailability [3]
- Lower abuse potential than IV route [4]
Cons of nasal vs other routes:
- Shorter effects than IV infusion (around 2 hours) [5]
- Can cause nasal irritation or congestion [1]
- Less precise dosing control than injections/IV [3]
- Lower peak plasma levels than IM/IV [4]
- Less evidence on long-term efficacy than IV [6]
Overall, nasal ketamine provides a convenient option, but may require frequent re-dosing. More comparative effectiveness research needed, especially on sustained benefits with chronic use.
A point of frequent confusion. There are two forms of commercial ketamine: racemic ketamine, and, esketamine, which is sold under the trade name Spravato.
Spravato is only administered in a doctor’s office via a nasal spray, due to an FDA REMS regulation. Spravato is discussed in detail elsewhere on this site. The point of mentioning Spravato here is to point out that it is not the only form of nasal ketamine.
All other commercial ketamine – apart from Spravato – is racemic ketamine. And racemic ketamine is compounded into nasal spray formulations (as well as injectable, sublingual and rectal formulations). If you get a prescription for at-home ketamine nasal spray it will always be racemic ketamine.
Providers seem somewhat reluctant to prescribe at-home racemic ketamine nasal sprays. It is not clear why they are reluctant. Expect difficulty finding a provider willing to prescribe at-home nasal ketamine.
Nevertheless, a Mucosal Atomization Device syringe can spray liquid drugs into the nostrils. It seems feasible to dissolve an RDT in 2 ml of a sterile saline solution (available in pharmacies for nasal rinsing). The liquified ketamine can then be atomized using this MOD device. We urge you to discuss this ROA with your provider if it interests you.
(The manufacturer sells the product in 25-unit boxes for $250. The manufacturer ships only to providers such as hospitals in boxes of 25.) This vendor will sell one or a few for about $10 each: https://www.vitalitymedical.com/lma-mad-nasal-intranasal-mucosal-atomization-device-with-syringe.html
which makes it practical to try it. It seems feasible for patients to reuse one of these devices by thoroughly rinsing it after each use.)
In summary, nasal spray administration of therapeutic ketamine offers benefits such as ease of administration, rapid onset of action, and potentially lower adverse side effects. However, concerns include variability in absorption, the need for further research on optimal dosing, the potential for abuse, and long-term safety and efficacy data.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048904/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6143064/
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020109/
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6139733/
[5] https://www.psychiatrist.com/JCP/ketamine/
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6048904/