Why are we doing this research?
Schizophrenia is a severe mental illness that affects 1 in 100 people. It is one of the top causes of adult disease burden globally, and the top reason for NHS bed occupancy. Healthcare and other costs for schizophrenia amount to ~100 billion Euros/ year across Europe. The main treatment is with antipsychotic drugs. However, for many patients, these drugs are ineffective at improving their symptoms. This is a major cause of the extra NHS admissions and healthcare costs. We estimate this affects 1 in 3 patients with schizophrenia
In people whose illness is treatment resistant, the only alternative licensed medication is called clozapine. However, clozapine’s use is restricted because of safety concerns and requires careful physical health monitoring and frequent blood tests. These factors mean it is not suitable for, or acceptable to, many patients, leaving them with no treatment option. Patients and carers identify the need for treatment options for patients where clozapine is not suitable or acceptable as a priority. We aim to investigate a potential treatment for these patients. This is a drug called valproate, which is taken in addition to antipsychotic treatment. Valproate is not licensed for this purpose, but we conducted a survey across UK NHS trusts, and found that in nearly 20% of patients it is used in this way, costing ~£60 million per year to the NHS. There is some evidence to support this practice, but the evidence is inconclusive. Thus, whilst adding valproate to antipsychotic treatment is widely used, it is unknown if it helps reduce symptoms, improves quality of life or is cost-effective. Therefore, we aim to conduct a study that will answer these questions.
What are we doing?
To address this, we will conduct a pragmatic 12-month, parallel group, placebo-controlled double-blind randomized controlled trial of augmenting existing antipsychotic treatment with valproate in patients (men and women, aged 18 and above) who fulfil DSM-5 criteria for schizophrenia and schizoaffective disorder and have persistent psychotic symptoms despite adequate (non-clozapine) antipsychotic treatment. The primary outcome will be psychotic symptom severity after 12 months, measured using the PANSS positive subscale. Our secondary outcome measures will be discontinuation rates, change in clinical global impression scale (CGI), cost-effectiveness and quality of life measures. Cost-effectiveness will be assessed using the PANSS positive subscale, quality-adjusted life years (QALYS) and Client Service Receipt Inventory (CSRI), which covers services and support. There will be an extension beyond 12 months to determine longer-term outcomes using electronic healthcare records. Our planned recruitment period is from 01/11/2021 to 01/10/2024.