Electroconvulsive therapy (ECT) is the most effective treatment for depression (see recent news regarding this). However, it can be associated with a number of side effects, particularly memory problems.
Ketamine is a drug that has been used for many years as an anaesthetic. In the last few years, there have been a number of studies suggesting that, at low doses, an injection of ketamine can lead to a very rapid improvement in mood (within hours) in some patients with depression.
The way ketamine works has led researchers to suggest that it may protect against memory problems from ECT, if given either as the only anaesthetic or with another standard anaesthetic when a person has treatment. This suggestion was tested in the ‘Ketamine ECT’ study.
The study was led from Manchester by Prof Ian Anderson, with Dr Hamish McAllister-Williams from the Northern Centre for Mood Disorders (NCMD) and Newcastle University, and Dr Tim Oakley from Northumberland Tyne and Wear NHS Trust, as collaborators. Funding for the study (over £1million) came from the “Efficacy and Mechanism Evaluation” (EME) Board of the National Institute for Health research and Medial Research Council. The findings from the study have recently been published in the journal 'Lancet Psychiatry'.
Patients who had consented and been prescribed ECT by their regular psychiatrists were asked if they would be prepared to take part in the study. Those who agreed were either given an injection of ketamine or plain salt solution along with their anaesthetic when they had each ECT treatment in their course. Which injection they had was determined randomly and neither they nor their psychiatrist knew which was given. Researchers met with the patients regularly during the course of their ECT treatment to assess their mood and memory.
79 patients took part in the study (23 from the North East of England), making this the largest study related to ECT for over 40 years. The findings from the study showed that ketamine made no difference to the beneficial effect of ECT on mood nor reduced the side effects (which were generally mild and short lived). The conclusion from the study is therefore that ketamine should not routinely be given together with ECT.
It is disappointing that the study did not show a benefit of giving ketamine with ECT. While side effects from ECT are usually (though not always) mild and short lived, they can lead both doctors and patients to be reluctant to use the treatment. This is a shame since it remains the most effective treatment we have for severe depression.
There seems to be reluctance to fund research into ECT (as shown by the Ketamine ECT being the largest study for many years, despite being relatively modest in size). While there are possible ways in which its effectiveness and safety may be further improved, research into this is unlikely soon.
Research, however, does continue into the use of ketamine for the treatment of depression. Two big issues however remain to be solved before it is likely to be used widely. The first is that the beneficial effects of ketamine on depression tend to be short lived, usually only lasting for 2-3 days. The second is that currently, ketamine treatment requires the medication to be injected over 30-60 minutes and patients require close monitoring during the process. A possibly exciting development is giving the ketamine by a nasal spray. This is safer and easier. This also makes repeat treatments more possible. Studies are currently ongoing looking at how long the benefits of this form of ketamine last after a short course of treatment.
A possible alternative to ECT for some patients is an alternative treatment called ‘transcranial magnetic stimulation’ (TMS). TMS has the advantage that it does not require a patient to have an anaesthetic when having the treatment, and it does not cause memory problems. However, currently it does not appear to be quite as effective as ECT. There are interesting developments taking place trying to make TMS more effective and the NCMD is hoping to be working on a study soon looking at one of these.