A team of researchers looking to assess the feasibility of using racemic ketamine as an alternative to electroconvulsive therapy (ECT) have published their findings in the International Journal of Neuropsychopharmacology.
Ketamine was first synthesised in 1956 by chemists from the USA, and was subsequently introduced into clinical practice in the 1960s. It was championed as an exceptionally safe and effective anaesthetic for a broad range of patient populations. Ketamine has many other uses within medicine, including being effective in the treatment of unipolar depression.
ECT is widely regarded as the most effective therapy for unipolar depression, and some cases of bipolar depression. The ECT machine was developed in 1938 and was first used on a patient of the inventors, Italian neurologist Ugo Cerletti and colleague Lucio Bini. The intention was to treat the patient’s delusions, hallucinations and confusion caused by schizophrenia.
ECT works by administering a brief electrical stimulation of the brain while the patient is sedated. A psychiatrist, an anesthesiologist, and a nurse or physician assistant are usually part of a team of qualified medical professionals that administer it.
To determine whether ketamine could be a suitable substitute for ECT, researchers studied 186 participants who were hospitalised for unipolar depression; all participants were current inpatients at the time of the study. Participants were randomly selected to receive ECT or ketamine infusions three times a week. Observations of different outcomes were recorded; remission which was measured on the Montgomery Åsberg Depression Rating Scale, adverse events and time to remission and/or relapse. Treatment sessions were continued (up to a maximum of 12), until remission or ‘maximal effect’ was achieved.
The results of the study show that 63% of participants receiving ECT entered into remission, compared to 46% who received the ketamine infusions. Both treatments took an average of six sessions for remission to be achieved.
Distinct adverse events (AE) were recorded with each treatment; ECT produced more serious and long-lasting cases of AE such as amnesia, whereas ‘treatment-emergent’ AEs were more closely associated with those who received ketamine infusion.
Among those who relapsed after having spent time in remission, (an average of 57 days in remission (ketamine group), and 61 days in remission (ECT group)), 70% and 63% respectively relapsed within 12 months.
In their conclusion, the researchers recognise the inferiority of ketamine infusion therapy in comparison to ECT, however they agree that ketamine, due to the remission and cumulative symptom reduction results seen in the study, can be a safe and effective tool in treating unipolar depression in severely ill patients aged 18-85.
“We believe that ketamine infusion can be offered as an alternative treatment option perhaps for younger patients in some cases or patients who have experienced severe side effects from ECT. It is important to realize that remission can be achieved after multiple infusions even in the absence of rapidly appearing antidepressant effects and to not stop after only a single or a few infusions,” researchers said.
“Preparations prior to and psychological support during infusions might encourage patients not to discontinue prematurely because of side-effects such as anxiety and dissociation. Individual patients may prefer ketamine. Nevertheless, given the high remission rate, in particular for patients who are older or present with psychotic symptoms, the superior efficacy of ECT must be emphasized.”
Ketamine therapy clinics have now started to open up in the UK, with companies including Awakn LIfe Sciences, Saveminds and Pasithea clinics opening clinics in Bristol and London and other locations.
Ketamine is not currently licensed in the UK for depression treatment, however, because of the supporting evidence around its safety, it is possible for the drug to be prescribed ‘off-label’ for use in clinical settings.
