Subcutaneous vs. IV Ketamine: What the Research Shows

The difference is where the medicine goes in. An intravenous (IV) dose goes directly into a vein, usually as a slow infusion. A subcutaneous dose is injected into the fatty layer just beneath the skin, and an intramuscular dose goes into a muscle.

Only the subcutaneous route. Every dose is a small injection under the skin, given at our Tampa clinic while a clinician monitors you, and the supervising clinician calculates the dose for you individually.

We do not offer IV infusions, tablets or lozenges, or any ketamine to take at home.

On current evidence, nobody can say one route is better, because the routes have only been compared in small studies. The most direct comparison is a 2016 pilot trial by Colleen Loo and colleagues in 15 adults with treatment-resistant depression: four received ketamine by IV, five by intramuscular injection, and six by subcutaneous injection, with one control session using midazolam inserted at random.

Doses started low and rose step by step across sessions at least a week apart. Twelve of the 15 participants met response and remission criteria, some at the lowest dose tested. All three routes produced comparable antidepressant effects, the subcutaneous route caused the fewest side effects, and both benefit and side effects increased with dose. The authors described the results as preliminary.

A 2021 systematic review of subcutaneous ketamine found only 12 relevant studies, just two of them randomized trials, and called for future research to compare the subcutaneous route directly with IV.

It found that subcutaneous ketamine at an adequate dose did better than an active control drug over four weeks, while a lower fixed dose did not. KADS was a double-blind trial at seven mood disorder centers in Australia and New Zealand, published in the British Journal of Psychiatry in 2023. Adults with treatment-resistant depression received injections under the skin twice a week for four weeks, or the comparison drug midazolam.

Practicality is a large part of the reason. The KADS authors noted that a 40-minute IV infusion involves medical complexity and cost, and concluded that the subcutaneous route is practical and feasible. The 2021 review described subcutaneous injection as a convenient and cost-effective route.

In these studies, dose mattered a great deal. In KADS, the fixed dose did not separate from the control while the adjustable range did, and in the 2016 pilot both benefit and side effects rose with dose. The pilot's authors described stepwise dose adjustment as a practical way to balance benefit against side effects for each person, and the authors of a small trial in adults aged 60 and older recommended the same approach.

Monitoring, regulation, and the core short-term effects. By any route, ketamine can cause dissociation, sleepiness, and short-lived increases in blood pressure and pulse. According to the FDA, compounded ketamine used without a provider watching for those effects may put patients at risk.

Route does not change the regulatory picture either. Ketamine is not FDA-approved for any psychiatric disorder. The ketamine we use is compounded by a licensed outsourcing facility. Compounded drugs are not FDA-approved, and the FDA notes that they therefore have no FDA-approved uses or routes of administration, by injection under the skin or any other way.

It is a small injection under the skin, given at our clinic at 3971 Moran Rd Ste 101-2, Tampa, FL 33618, with monitoring from start to finish. Set aside about 90 minutes to two hours for each visit, which covers preparation, the treatment, and monitored recovery.

A responsible adult will need to drive you home, and you should not drive again until the next day. Your consultation, treatment planning, and follow-up conversations can take place by telehealth while you are located in Florida.