Risks and benefits
Potential side effects
Ketamine is not a licensed treatment for depression and the effects of taking it long term are unknown. There may also be unusual side-effects which occur acutely which have not yet been reported.
About 10% of people who have a ketamine infusion have an experience that is very challenging. If you find any of the side effects too unpleasant then these will almost always resolve within 15 minutes of stopping the infusion. Occasionally people experience a worsening in their depressive symptoms and suicidality which persists for up to two weeks after taking ketamine. Sometimes this is sufficiently unpleasant that they do not want to take further ketamine. Those who do persist with further treatment often find that it starts to help after 1-2 more infusions.
Of the remaining 90%, about half have a very pleasant experience and in the remainder it is neither unpleasant nor pleasant.
Brief side effects
Ketamine commonly causes brief side effects. These are more common at higher doses, but the relationship between dose and side-effects is variable, even within the same patient.
Side-effects which occur during or shortly after treatment include:
Feeling dissociated (mind and body feel separate). Occasionally, this extends to the point of an ‘out of body’ experience. ‘My feet didn’t seem as if they belonged to me’. A floating sensation.
‘Ego dissolution’. The feeling of ‘oneness with everything’, as if you are a drop of water being dropped into a river. A feeling of being very tiny, like an electron or atom. Often accompanied by a sense of awe – but can be experienced as frightening.
Feeling a bit drunk or lightheaded.
Feeling tired for the rest of the day after treatment.
Altered perception. Things “look peculiar” or sound different.
Nausea or vomiting. This can be treated with antinausea agents. If you feel sick, we will give you ondansetron with your next and subsequent infusions. Do not have a big meal before treatment.
Anxiety. This can extend to the point of panic. It may be associated with a ‘near death’ experience. This can occur ‘out of blue’ even in people who have had many treatments. The anxiety diminishes rapidly as the drug is broken down in the body, so the infusion can be turned off if necessary. In this case, the anxiety settles within 5-10 minutes.
Headache. Usually responds to paracetamol.
Tinnitus – a ringing in the ears. This can get louder in those who already experience it, or start in people who have never had it. It is probably more likely if you are also taking drugs with tinnitus listed as a known side-effect such as venlafaxine and duloxetine. The tinnitus usually resolves if the ketamine is stopped. If the ketamine is not stopped, it is possible that hearing may be affected so it is important you let us know if you develop tinnitus.
Temporary bruising. The treatment involves a needle being put into the vein on the back of your hand and a low dose of ketamine infused over 40 minutes.
An increase in blood pressure or a fast heart rate. The extent of this comparable to changes that occur naturally in everyday activities. Therefore, we do not monitor this routinely after the first infusion. If you would like us to do so, please say.
Less-common side effects
Hallucinations. Feeling, seeing or hearing something that is not actually there.
Mania. Unusually elevated mood which causes problems. Ketamine should be stopped immediately if you suspect this is happening. The ketamine team and your local team need to be informed promptly.
Rare physical side-effects
Liver damage. Rarely, people taking very regular ketamine experience liver damage. This is sufficiently rare that we do not routinely check this. However, if you feel unwell during ongoing ketamine treatment, please let us know and we will review whether you need a blood test.
Long term theoretical risks
Sometimes people find that if they stop ketamine their depression relapses. This is not the same as addiction. This is reliance.
However, non-clinical ketamine is sometimes taken illegally in large, frequent doses and cause addiction. This has not happened in any of the patients treated with our protocol. For further discussion of addiction see our FAQs
It is not uncommon for patients taking ketamine for depression to find that their depression, which was initially relieved by the ketamine, is no longer controlled despite continuing to have treatment with ketamine. There can be several possible reasons, one of which is that they have developed tolerance to ketamine. This may mean that a treatment break is needed or that it is no longer an effective treatment and therefore will be stopped. Sometimes, the dose can be safely increased. Keeping the interval between doses as long as possible helps to maintain the effect. Adding a regular weekly dose of oral ketamine, taken at home, between monthly infusions, is another common way of managing this. We can also use other medicines successfully to augment the effect of the ketamine.
Rarely, people find that they think a lot about ketamine and crave it. It is important to notice that this is happening and to be open and honest with the clinical team about this.
For comparison, ketamine is much less addictive and dangerous than strong opiates (eg fentanyl, methadone) or nicotine, probably less addictive than benzodiazepines and probably about as addictive as whiskey.
Bladder damage. This is common in people who take illegal ketamine recreationally, usually at nasal doses of over 1g ketamine daily. This dose is much higher than the maximum we use.
The main symptoms of ketamine-induced bladder damage are lower abdominal pain, pain passing urine, and needing to pass urine more often. If you start to experience these symptoms please contact your GP and the ketamine clinic.
This has not been observed over 1 year treatment with esketamine, or in our patients, but has been seen in addicts taken high doses daily. It is associated with evidence of brain shrinking and other brain lesions.
Apathy has been reported in addicts but not in patients receiving medical doses.
Ketamine is a treatment for depression which has not responded to other treatments. A rapid antidepressant effect has been demonstrated in many clinical trials of single intravenous infusions over the last 20 years in patients with depression which has not responded to at least 2 or 3 antidepressants.
The response lasts at least a day for about 70% of patients and up to three days for 30% of patients. The majority of patients relapse within two weeks after treatment.
In our clinic 50% of people who try ketamine have enough of a benefit that they think it is worth continuing with it.
It is important to recognise that ketamine is not licensed as an antidepressant. It has not been evaluated in large, or long term, clinical trials. This means that the long-term success rates have not been fully documented.
Large trials of the closely related drug esketamine, which is a component of ketamine, have shown broadly similar effects. A safety study of over 800 patients who took intranasal esketamine and a newly initiated antidepressant showed a 43% remission rate after 12 months of treatment. Remission is when there are no longer any significant symptoms of depression. For comparison, a large randomised study of people with depression found that those whose depression had not responded adequately to two previous antidepressants had a 5% chance of being in remission 12 months later if they tried a third antidepressant.
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Page last reviewed: 28 November, 2022