Skip to main content
KBS_Icon_questionmark link-ico


Ketamine Research

Synpatic ImaGing and Network Activity in Treatment Resistant dEpression study (SIGNATuRE)

What is the study about?
Ketamine is a drug which is commonly used as an anaesthetic. Recent research has shown that at lower doses ketamine can have rapid acting antidepressant effects, including in people who have treatment-resistant depression, that is they have previously not responded to two or more treatments for their symptoms. This study will investigate why ketamine is effective in treating treatment resistant depression in people with major depressive disorder or bipolar disorder.

Using brain imaging techniques, we will observe the effects of ketamine treatment on brain activity patterns and how this relates to any changes in the symptoms of treatment resistant depression.

What does participation in the study involve?
Participation involves 11 visits to the Centre for Neuroimaging Sciences,  King’s College London at Denmark Hill, spread over the course of 2-3 months.

Transport will be provided for you to and from the testing centre for visits 2-11 with support and information being provided throughout the study. If you wish to be accompanied by a friend or relative on any visit, we can also provide transport or cover their transport costs.

The visits are made up of:

  • Visit 1: A screening visit to assess if you are suitable for the study
  • Visits 2, 6 & 10: 3 x study days where you will have an MRI scan and an EEG scan to assess brain function and activity as well as completing tasks and questionnaires assessing your memory, concentration, and mood. Each study day will last up to 7 hours with breakfast and lunch being provided.
  • Visits 3-5 and 7-9: 6 x infusion days where you will receive 3 x intravenous infusion of active placebo and 3 x intravenous infusions of ketamine interspersed with a study day. The order that the 2 sets of infusions are given could be ketamine followed by active placebo; the order is randomly assigned to you. Each infusion day will last up to 5 hours with breakfast or lunch being provided.
  • Visits 11: A follow up visit with some short questionnaires and health checks.

Note: We will also ask you to practice some tasks on your smartphone or home computer for 8 days between visits 6 and 7 and for another 8 days between visits 10 and 11. You will be shown how these short tests work when you visit our research facility.

During the study period there will always be a qualified clinician present and you will be monitored during and after the infusions.

Ketamine is commonly used as an anaesthetic but will be given in much lower doses in this study. The doses we will use have been reported to cause strange experiences and sensations in some people, including feeling disconnected from your body or other distortions of senses. If you experience these effects and you find them unpleasant or frightening, the infusion will be immediately stopped, and these experiences should rapidly fade. Some people report feeling nauseous, slightly clumsy or drunk for up to an hour after the infusion has stopped.

Active Placebo
The placebo effect is a phenomenon where people will experience a positive effect from a treatment even if they have been given a medication that is inactive and cannot have treated their condition. A placebo is something that looks like the medication such as a sugar pill or saline (salt water) infusion but has no active ingredients in it. By giving a placebo and medication allows the two to be compared, gaining an accurate understanding of the medication. In a double-blind study neither the participant or the research team know which order the treatment or the placebo is given.

As ketamine can produce strange experiences, it can be obvious to the participant and research team what they have received. As an active placebo we will use a medication called midazolam which is normally used as a sedative. Midazolam produces similar effects to ketamine but without known antidepressant effects.

What could make you ineligible for the study?
We are looking to recruit adults aged 18-55 with major depressive disorder or bipolar disorder, however the following reasons may mean you can’t take part in the study:

  • If you have, or have had, any serious medical or neurological conditions (including high blood pressure or heart problems), or severe head injury.
  • If you, or an immediate family member, have a current or previously diagnosed major psychiatric disorder other than bipolar disorder or major depressive disorder. We can discuss this with you before or at the screening visit.
  • If you are currently taking other medicines (not for depression or bipolar disorder), or regularly use recreational drugs. We will go through these with you to see if you are eligible.
  • If you consume alcohol in excess of 28 units per week, or consume more than 6 caffeinated drinks per day, or smoke more than 5 cigarettes a day.
  • If you do not speak English fluently (this is due to the instructions you need to follow and the consent you provide).
  • If you already have a good knowledge of the Cantonese or Mandarin language (this is due to one of the learning tasks we will ask you to do).
  • If you weigh more than 126kg (19 stone 12 pounds) (this is due to the capacity of the MRI machine).

Because of the powerful magnetic field in the MRI scanner, you must not have a scan if you:

  • Have had any metal inserted into your body during an operation
  • Had metal injuries to your eyes
  • Have a tattoo on your head/neck
  • Have a heart pacemaker
  • Experience claustrophobia in narrow spaces

We will go through a list of possible risks with you at your first visit.

You will be paid £500 if you complete the study. You will also have the opportunity to win up to £20 in the tasks completed at each of your imaging visits. A pro-rata payment will be made if you do not complete all the study visits.

For attending a full screening visit you will be paid £25. You will receive this compensation regardless of whether you are suitable to take part or not.

We will arrange a taxi to pick you up and take you home for study visits 2-11 and will reimburse any reasonable travel expenses for you and your carer or relative if they are accompanying you, on production of receipts for the screening visit (visit 1).

Group lead

Mitul Mehta

Mitul Mehta

Director, Centre for Innovative Therapeutics

Contact us

If you are interested in taking part or would like more information, please email the Signature study team.

Once you have got in touch with the team, we will go through the study requirements and your suitability in detail with you, first over the phone and then during the in-person screening visit

Please see the participant information sheet for more details.