Thursday April 3 2014
High doses of ketamine can damage the bladder
“The illegal party drug ketamine is an ‘exciting’ and ‘dramatic’ new treatment for depression,” BBC News reports. A small study found that some people with severe depression responded well to the drug.
The study involved people with severe depression (including people with depression as part of bipolar disorder) who had failed to respond to conventional treatments.
They were treated with intravenous infusions of ketamine either once or twice a week for three weeks.
Some people responded well to treatment; eight people (almost a third) experienced a significant improvement in depression symptoms.
Though another seven people withdrew from the study – two because of side effects during the infusion; and five because they were getting no benefit and were becoming more anxious.
This may suggest ketamine may only be effective and tolerable for a minority of patients.
Researchers were concerned that ketamine may have a detrimental effect on memory (as has been reported among heavy recreational users) but this does not seem to have been the case.
This was an early stage study and not a randomised controlled trial, which is the most reliable way to measure a drug’s effectiveness. Much more research is needed into its safety and effectiveness before it is known whether it could one day be licensed for treatment of depression. And if it is, it is likely to be for very specific groups of people receiving hospital care for their condition who have not responded to all other treatment options.
Where did the story come from?
The study was carried out by researchers from Oxford Health NHS Foundation Trust and the University of Oxford. It was funded by the National Institute for Health Research.
The study was published in the peer-reviewed Journal of Psychopharmacology.
It was widely covered in the media, sometimes misleadingly. For example, BBC News reported that depression is common, affecting one in 10 people at some point in their lives (which is correct). However, in this study ketamine was only used for people with severe depression that had not responded to other treatments. This type of depression only affects a small number of people with the condition.
Even for this group of people, this is early stage research into the use of ketamine, carried out in highly controlled conditions.
What kind of research was this?
This was an open label study which investigated the use of two different doses of ketamine in a group of people with depression that had not responded to previous antidepressant treatment (this included people with resistant depression as part of bipolar disorder).
The study took place in a hospital clinic where electroconvulsive therapy (ECT) is normally performed. ECT is a treatment sometimes used in people with severe depression that has not responded to previous treatment. Although it can be effective, the benefits of ECT have to be balanced against the risk of memory loss, a side effect of ECT. Other side effects include short-term headaches, nausea and muscle aches. So there is a need for further treatment options for such people with treatment-resistant depression.
In this open label study two groups of people were treated with one of the two different dose schedules. It was not a randomised controlled trial (RCT), which would randomise people to either the treatment being investigated or a comparison treatment. And being open label meant that both researchers and participants knew the treatment that was being given.
A study such as this is an early stage study, which primarily aims to give an indication of the possible safety and effectiveness of a treatment, and so see whether further testing in an RCT would be indicated as the next stage.
The researchers say that several RCTs have shown that a single dose of ketamine can have a rapid antidepressant effect in some people with treatment resistant depression, who have been taken off other treatments.
The response, they say, has been seen in both people with resistant depression and people with resistant depression as part of bipolar disorder.
However these patients have relapsed within a short time – typically a week.
In this study the researchers aimed to explore the safety and effectiveness of giving repeated ketamine infusions to people who continued using other antidepressant medication.
In particular they wanted to find out of ketamine had any adverse effects on memory and cognitive function.
What did the research involve?
Researchers recruited 28 patients with diagnosed, treatment-resistant depression or bipolar disorder. They identified people who had been referred to psychiatry, or those who self-referred to advertisements for the study. All potential participants had their diagnosis confirmed by a specialist using standard diagnostic criteria. Treatment resistant was defined as a failure to respond to two separate ‘trials’ of antidepressant treatment.
The participants were injected intravenously with ketamine over three weeks, in the ECT clinic of a local hospital. One group of 15 people had one infusion a week, while a second of 13 people had two infusions a week. Each infusion lasted 40 minutes. The dose administered was 0.5mg per kg of body weight. (This is a much lower dosage that people typically take for recreational use – some heavy users can take several grams at a time).
Before each infusion researchers measured the participants’ mood, using a number of established psychological scales. Vital signs such as blood pressure and heart rate were monitored before and during each infusion, and participants were monitored for any immediate side effects.
The main outcome the researchers were interested in was response at the end of the three weeks of treatment which was defined as a 50% or more reduction in depression score on a widely used depression scale (the Beck Depression Inventory). Participants completed other established mood and depression scales over the three weeks, and also took a number of established tests to measure their memory function.
Participants were followed up for six months where possible, with the severity of depression and possible side effects monitored throughout.
What were the basic results?
Below are the study’s main findings:
- Eight people (29%) responded to the treatment.
- Of those who responded, only three (11%) had responded within six hours after a single infusion. However, all of those who responded did so before the third infusion.
- How long the response lasted varied – from 25 days to 24 weeks.
- Eight people (29%) did not complete their infusions, two because of acute adverse reactions during the infusion and five because of failure to benefit and increasing anxiety.
- Common side effects experienced by most people included nausea, anxiety, confusion and altered perception. Participants commonly reported short lived “dissociative” effects – such as feeling disconnected from their body – but they did not feel any euphoria with the treatment.
- Ketamine was not associated with memory impairment.
How did the researchers interpret the results?
The researchers say their study suggests that repeated ketamine infusions for treatment resistant depression can be safely given to patients while still taking their usual medication, although they can occasionally cause problems such as anxiety and vomiting. There were no problems with cognitive function.
“Intravenous ketamine is an inexpensive drug which has a dramatic, but often short-term, effect in some patients whose lives are blighted by chronic severe depression”, says principal investigator Dr Rupert McShane, a consultant psychiatrist at Oxford Health and a researcher in Oxford University's Department of Psychiatry.
He adds: “We now need to build up clinical experience with ketamine in a small number of carefully monitored patients. By trying different infusion regimes and adding other licensed drugs, we hope to find simple ways to prolong its dramatic effect”.
This small open label trial aimed to further investigate the safety and possible effectiveness of giving repeated ketamine infusions over a three week period to a small group of people with depression that had not responded to previous treatments. Almost a third responded to treatment. The treatment also had no detrimental effect on participants in terms of memory, though there were some side effects and seven people withdrew from the study. Two because of side effects during the infusion; and five because they were getting no benefit and were becoming more anxious.
This was an early stage study and not a randomised controlled trial, which is the most reliable way to measure a drug’s effectiveness and reduce the possibility of bias. The study cannot show definitively that ketamine is safe and effective for treatment resistant depression. Taken with previous research it suggests that repeated injections of ketamine can be given safely under carefully controlled conditions in the hospital setting, and could be of some benefit to specific groups of people with treatment resistant depression.
However, much further research in larger randomised controlled trials will now be needed to look further into the safety of ketamine and see how it compares to other treatments for this group of people.
It is not currently licensed for use in depression, and it is not yet known whether it could one day be licensed for use in depression. Though if it is, it is likely to be for very specific groups of people receiving hospital care of their condition who have not responded to all other treatment options (much in the same way as ECT services are currently provided).
It is highly unlikely that ketamine will ever be prescribed in the same way as antidepressants.
Using ketamine without medical supervision is both illegal and dangerous. Regular users often develop what is known as ‘ketamine bladder’, caused by the drug’s inflammatory effects.
Symptoms of ketamine bladder include:
- a sudden intense need to urinate which can result in urinary incontinence (wetting yourself)
- urinating more frequently
- severe pain when passing urine
- blood in the urine
If you think you have developed a dependency on ketamine contact your GP for advice. You can also use the NHS Choices service finder to find your nearest NHS drug misuse service.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.