A randomised placebo-controlled trial of immunotherapy in patients with psychosis associated with anti-neuronal membrane antibodies (SINAPPS 2)

BACKGROUND Psychosis is, according to the NHS website, "a mental health problem that causes people to perceive or interpret things differently from those around them. This might involve hallucinations or delusions." Psychosis and schizophrenia are common disorders which hinder people from flourishing, just as they are embarking on life as an adult. These disorders also cost the UK £12 billion per annum. Psychosis has many causes. Recently, we discovered that 5-10% of people with psychosis have antibodies in the blood that are capable of targeting receptors on the surface of brain cells. These receptors are either the "NMDA receptor" or "voltage gated potassium channel complex". The binding of antibodies to these receptors stops them from working properly, which in turn upsets normal brain function. OUR IDEA This proposal is based on the idea that the antibodies we find in the blood of people with psychosis are actually causing the problem. This means that we think these people have a basic problem with their immune system, and that the immune system is preventing their brain from working properly. So, in their particular case, psychosis is an "autoimmune disease". OUR PROPOSAL We will test this idea by getting eliminating these antibodies in their blood, and see whether this has a useful effect on psychosis symptoms. THE PLAN There are three stages to our proposal. (1) First of all, we need to find people with psychosis and antibodies in their blood. This involves testing the blood of around 2460 people with psychosis, over 3 years. To do this, we have set up several centres around England in which there are neurologists and psychiatrists interested in answering the question. We will employ research nurses to work from the centres, seeing as many people with psychosis as possible. Assisting them will be mental health nurses, working in the local trust, as well as an independent mental health advocate. This should identify around 160 people with antibody-associated psychosis, of which we estimate half will be interested in taking part in our trial. (2) Secondly, we will do a "randomised controlled trial" in which 80 people with psychosis and antibodies in their blood are randomly allocated to receive placebo or active immune treatment, alongside their antipsychotic drugs. For immune treatment, we propose people have "intravenous immunoglobulin" (IVIG) for four days, followed by two infusions of "rituximab". THE TREATMENTS - Intravenous Immunoglobulin is a blood product. Once the red cells have been removed from blood, the remaining "serum" is collected. Antibodies in the serum are extracted and then pooled together from many hundreds of individuals. - Rituximab is a drug that causes long-lasting reduction in the "B cells" that are part of the immune system. It is used in many autoimmune diseases, like lupus and rheumatoid arthritis. - All people in the trial can take normal antipsychotic drugs.