I would love to answer this question in a very precise scientific manner with extensive research studies to support my conclusion. Unfortunately, the research on this question doesn’t exist. So, I can give you my opinion based on observations and experience as well as from the little bit that we do know based on the existing research in this area. First, keep in mind that ketamine can’t practically be swallowed in a pill form like other medications. It becomes ineffective and very little gets into the bloodstream. Most research on ketamine being used off label for treatment resistant depression (TRD) is on the intravenous (IV) route or through the vein. So, we know the most about how to use ketamine through an IV. Other advantages to IV are that we know exactly how much is getting into your body, and we can slow it down or stop it if there are problems or uncomfortable side effects. Ketamine is so short acting that if you stop the IV, most side effects resolve within a few minutes. We can also add dosing or extend the treatments quite easily if needed as well.
Many clinics are offering ketamine as a shot in the skin or subcutaneous (SQ) or in the muscle (IM). It’s hard to predict how much gets into the bloodstream using these methods but we know that you get a lot of medicine in a very short period of time. My experience has been that when trying to use ketamine as a psychotherapy tool and to trigger a very profound dissociative experience, IM or SQ can be very effective ways of getting the medication. However, I don’t like that I can’t take the medicine away or slow it down if someone does not like how they start feeling. Many clinics offer IM or SQ because they are not set up to administer an IV and it’s a lot easier to give a shot.
There are oral dissolvable ketamine tablets that sit in your cheek or under your tongue for 10 minutes or so and slowly absorb into the bloodstream. Much less of the medication gets into the bloodstream this way than IV, IM, or SQ. Also, it can taste pretty bad. If someone doesn’t like needles or you are receiving ketamine in a non-medical environment such as your home or therapist's office, this may be a good way to take the medication. When used more as a psychotherapy tool (ketamine assisted psychotherapy-KAT) oral ketamine may be fine. For TRD, I like to have more control over the amount you are getting. Also, like IM and SQ, you can’t take it back once it is absorbed into your bloodstream. Intranasal (IN) is another method we use the most after IV. IN has higher rates of absorption and a smoother onset than the SQ or IM. We often will use intranasal if somebody does not want an IV or as a maintenance therapy after improving from a short series of IV treatments.
In short, my preference is for IV when using it as a rapid onset antidepressant or anti-suicidal medication. The other routes are less invasive and may have other benefits, especially when using with psychotherapy.
Pharmaceutical companies are working on other innovative ways to deliver ketamine and it will be interesting to see how those developments change the landscape. At PsychAtlanta, we offer all these methods-IV, IN, IM, SQ, and oral-for our patients based on their clinical presentation and personal preference. If you’re pursuing ketamine as an option for TRD, I would recommend going to a clinic where you have the option for any or all of these routes so you can get the treatment that’s best for you, not simply the one that they offer. Since ketamine is an off-label treatment for depression, make sure your healthcare practitioner explains all the potential risks and benefits and do your own due diligence to see if ketamine is right for you. See our website www.psychatlanta.com for more information on TRD and ketamine.