Ketamine Infusions for Depression, Anxiety, and other Mood and Pain Conditions: Does the Route of Administration Matter?

Intravenous (IV) ketamine infusions are very successful in treating patients suffering from depression, bipolar depression, postpartum depression, obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), generalized anxiety, fibromyalgia, and chronic pain syndromes like complex regional pain syndrome.  At Ketamine Treatment Centers, we perform IV (intravenous) ketamine infusions, but does the route of administration matter?

Route of administration simply describes the particular biological barrier(s) that a given drug or medicine must cross to become absorbed into the bloodstream. Some common routes of administration include oral, transdermal, sublingual, intranasal, rectal, subcutaneous, inhalational, intramuscular, and intravenous (IV). (See table below for various ketamine routes of administration.) The most common route of administration for most medications, used every day worldwide, is oral or using the gastrointestinal tract after swallowing a pill.

Route of Ketamine Administration Ketamine Bioavailability Source
Intravenous  100%
Intramuscular ~93% Clements et al., 1982
Intranasal ~45% Yanagihara et al., 2003
Sublingual 19–50% Chong et al., 2009

Yanagihara et al., 2003

Oral 17–27% Chong et al., 2009

Clements et al., 1982

Rectal ~30% Yanagihara et al., 2003

A very common route of administration in the hospital is IV and there are multiple reasons why. One such reason has to do with speed of absorption and another has to do with obtaining an accurate dose per a given body weight. IV drugs are frequently given to adult patients in urgent situations where time passed may mean life or death. IV medications are frequently administered to infants when dose accuracy matters to prevent toxicity or accidental overdose. Accuracy is just as important for maintaining efficacy as too little and too much medication can prevent an efficient mechanism of action.

So how do IV medications achieve increased accuracy and speed as compared to other routes of administration? This primarily has to do with a concept called bioavailability and by definition IV medications have 100% bioavailability. This simply means 100% of the medication administered will enter into the patient’s bloodstream. Generally speaking all other routes of administration have less than 100% bioavailability and this has to do with barriers that the medication must cross to enter into the bloodstream. The more barriers a medication must cross, the more variable the absorption. Additionally, certain barriers are more problematic than others and some even modify the chemical composition of drugs in an attempt to eliminate the drug via metabolism.

For example, if we take a swallowed oral pill, it must first travel down the gastrointestinal (GI) tract, transport across the mucosa or lining of the GI tract, then become filtered through the liver before entering the bloodstream. It is the bloodstream which will finally deliver the medication to a targeted organ, such as the brain. The first barrier, being the the GI tract, varies from person to person based on health of the GI tract, gut bacteria, and co-nutrients that may help or preclude absorption. Once the medication makes it across the GI mucosa, it makes its way to the liver. Liver metabolism varies widely from patient to patient and is usually dependent on genetics and liver health. Sometimes the liver can metabolize medications into inactive chemical compositions before they even enter the arterial bloodstream thereby negating any beneficial effects. Furthermore, enzymes in the liver determine how fast any given drug is eliminated if not eliminated directly via the kidney – this is why patients with liver and kidney disease have to take certain drugs at lower doses.

The process described above hopefully makes it more apparent why IV medications have fewer variables that can affect absorption. Understanding this process also allows for appreciation of IV medications in research protocols wherein variables that alter dose can sometimes mean everything. In fact, the most robust studies of ketamine for treatment of depression use intravenous ketamine.

Ketamine dose becomes very important as we start to understand how the medication affects a large number of different receptors in the brain (and in different anatomical locations) relative to the dose. We know that too little of any given dose may result in zero efficacy, but along the same lines, too much of a dose could cause toxicity and also lower efficacy! Most research studies have used 0.5 mg/kg of ketamine over 40-45 minutes for treatment of depression. If we increase ketamine dose, we know that it starts to affect some parts of the brain relatively more than those parts of the brain that we think may be causing the antidepressant effects (e.g. prefrontal cortex). In addition, although ketamine has a very good safety profile, all drugs have some side effects. We are fortunate that most of ketamine’s side effects are not troublesome at the lower doses; however, if intravenous ketamine causes any negative side effects, an infusion can be disconnected and the side effects will go away within about 15 minutes. If the ketamine was not given intravenously it may take much longer for any negative side effects to subside.

In conclusion, IV is currently the most common route of administration used for ketamine in adult patients. This is because the IV route of administration takes away barriers that can impede the mechanism of ketamine in the brain, and thus creates better standardization. At Ketamine Treatment Centers, safety is of utmost importance and the intravenous route of administration helps achieve this goal.

Ketamine Treatment Centers is proudly combatting major depression, bipolar depression, postpartum depression, PTSD, OCD, anxiety, fibromyalgia, CRPS, and chronic pain one patient at a time! If you or your loved one is suffering, give us a call at 888-566-8774 or email us at to learn more about how ketamine can help.

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Comments (7)

  • John Reply

    It’s good to know that ketamine has positive effects on dealing with depression but still has relatively low-side effects at smaller doses. I think this could be really good for people similar to my sister-in-law who suffer from depression but are generally sensitive to the side-affects associated with other depression treatment medicines. It’s also nice that ketamine can easily be administered in a safe and effective dose based off the body wight of the individual receiving treatment.

    May 22, 2017 at 4:37 pm
  • Sandra N. Spencer Reply

    I suffer from severe anxiety and depression and my doctor has tried almost every medication possible. I have been taking Adepsique (only available in Mexico) for many years but now due to the psychotic element that is in the tablet I have developed askasia (?), not being able to walk properly. He has now put me on Ritalin (generic) 10mg and slowly weaning me off of the Adepsique.

    I saw him last Friday and that was when he put me on the Ritalin…no improvement yet.

    Then he mentioned the use of Katamine IV. He said if I could afford it he was quite sure that it would alleviate the anxiety and depression. Yes, he is a psychiatrist.

    Any feed back about side effects, the success rate in using this medication would be greatly appreciated.

    Thank you.

    July 9, 2017 at 5:37 pm
  • Lori B Reply

    Ketamine is fantastic! After several years of severe depression and anxiety I had my first infusion on Sept 15. I felt like a million bucks! I feel like a giant smile overflowing with love and can do anything! Haven’t finished my treatments yet but its made a huge difference so far. Don’t think about it just do it. It’s that good. If you are suffering from depression and anxiety, imagine a day feeling fantastic and happy and can take on the world! I have so much love and smiles inside, I want to hug and kiss people in my life who have caused me pain even two weeks ago. LB

    September 24, 2017 at 10:32 am
  • Melinda Reply

    I’ve just completed 3 ketamine treatments. The short version…it hasn’t helped with my chronic pain and I can’t tell if it’s helped with my depression. I first found out about Ketamine this year when I qualified for a depression study at UT Southwestern in Dallas, TX. I have treatment resistant depression. I’ve been taking antidepressants for years. In the last couple of years my depression has gotten worse and my psychiatrist has tried me on about 6 different antidepressants without success. She’s heard great things about Ketamine infusions for depression but didn’t know where I could get it done (I decided not to do the study b/c it was a double blind study…I wouldn’t know if I was getting the Ketamine or a placebo). The more I read about Ketamine the more I thought it was for me b/c I suffer from chronic back pain and Ketamine infusions are supposed to relieve chronic pain. I believe part of my depression is caused from living in chronic pain. I found a neurologist in Dallas that is currently giving me the Ketamine infusions for chronic pain. I’m scheduled for 1 more treatment (my 4th) and if I don’t feel any benefits, they said there is no reason for me to continue. I am trying to remain OPTIMISTIC. I’m HOPING AND PRAYING it will work. The neurologist is treating me for chronic pain….not depression. So, I don’t know if the Ketamine protocol would be different if a psychiatrist was administering it. My current protocol is 50mg Ketamine on an every other day basis. My very first Ketamine infusion was THE BEST. I had VERY POSITIVE EUPHORIC thoughts…even about the things I’m depressed about (i.e., my dad being diagnosed with Alzheimers, etc). It was a WONDERFUL experience! I left there very happy!!!! But, at my 2nd treatment, I told the nurse about my “euphoric dreams” and she said that they DID NOT want me having thoughts like this b/c my thoughts could also go the other direction (frightening feelings, thoughts). She said adjustments could be made so I won’t have any thoughts/dreams. I’m really not sure if they changed anything but on my 2nd and 3rd treatment the thoughts were gone. Now, on this ktcpartership website, I’ve just read that having these positive, euphoric thoughts are the outcome DESIRED from Ketamine infusion treatments for depression. I’m so confused b/c the goals are different for different physicians.
    Whether this ends up helping me or not, I’m hoping some day insurance will pay for Ketamine treatments so that every one of you at least gets the opportunity to see if Ketamine treatments will work for you. I know SO WELL how just a little bit of HOPE is often the only thing we (those w/major depression) have to get us through each day.

    October 3, 2017 at 3:56 pm
    • Ryan Wetter Reply

      Hi Melinda, we appreciate hearing your story! If you’re looking for answers as to what may be considered expected in regards to the ketamine infusion experience, you could start by calling us at 888-566-8774.

      October 23, 2017 at 2:51 pm
  • Leslie Crosby Reply

    I had series of Ketamine infusions for depression over 5 years ago. It was done in a surgical center. The ketamine dose was .5mg/kg of the patients weight given over 40 minutes. It was given by an anesthesiologist. I was continuously monitored, heart rate, blood pressure and given oxygen through a nasal cannula. A nurse was in the room for the entire infusion. I had to stay for about 2 hours after the infusion was completed and could not drive for 24 hours. My question is do you follow this protocol of dose, monitoring, etc. ? The cost was 400 dollars per infusion. Thanks

    October 18, 2017 at 7:30 pm
  • Ryan Wetter Reply

    Hi Leslie, the particulars of treatment are best answered by our clinical team. If you’d like, call us at 888-566-8774 to start the process of getting your answers.

    October 23, 2017 at 2:55 pm

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