Study of immunotherapy in antibody positive psychosis: feasibility and acceptability (SINAPPS1)

Antibodies against N-methyl D-aspartate receptor (NMDAR) and other neuronal cell surface targets are recognised associations of immunotherapy-responsive autoimmune encephalitis. Initially, patients present with symptoms of behavioural change and psychosis, often subsequently developing seizures and cognitive impairment, rapidly progressing over a few weeks to develop a life-threatening combination of autonomic instability and loss of consciousness.1 There is in vitro and in vivo evidence that these antibodies are pathogenic and directly cause encephalitis. Although never formally demonstrated in a controlled trial, open label clinical studies show that patients receiving immunotherapy, such as intravenous immunoglobulins (IVIG) or plasma exchange (PLEX) with or without corticosteroids, have better recovery and reduced relapse rates. Therefore, clinical consensus guidelines recommend that immunotherapy should be given as soon as possible after diagnosis.2 Several studies have assessed the prevalence of these antibodies in purely psychiatric presentations. NMDAR antibodies are the most commonly identified; in some studies, these are twice as prevalent in patients with early psychosis than in healthy controls, being seen at rates of between 4% and 12% of cases (OR 2.70, 95% CI 1.11 to 6.56).3 We have seen a number of such cases which respond to immunotherapy in an uncontrolled study.4 We have therefore proposed a randomised, placebo-controlled trial of immunotherapy in psychosis associated with antineuronal antibodies, to inform clinical practice and to advance understanding of the …