Title: Aripiprazole treatment for antipsychotic induced hyperprolactinaemia in young patients with severe mental illness and learning disabilities
Funder: Department of Health (England)

Abstract: Background Antipsychotic medicines (APs) are used routinely in young people with severe mental illness or learning disability, prescription rates increasing up to six fold in a decade. APs often induce hyperprolactinaemia (high PRL) and in almost all women, and some men, it causes hypogonadism often with osteoporosis, partly explaining SMI patients’ high fracture risk. AP side effects in youth are well documented. High PRL inhibits normal pubertal and skeletal development. Reducing PRL by changing AP or adding a dopamine agonist often worsens psychosis. Adding aripiprazole to current AP normalizes PRL in adult schizophrenic patients, without serious side effects. We thus propose a study of add-on aripiprazole in young people with AP induced hyperprolactinaemia. Aims 1) Normalization of PRL (? 600 mU/l in female and a decrease in PRL sufficient to induce puberty or normalize testosterone in male patients) in 30 young people with severe mental illness or learning disabilities, aged 14 to 25 years 2) Initiation or progression of normal pubertal development in patients with delayed puberty 3) Normalization of plasma oestradiol or testosterone to post-pubertal levels in the patients who had reached full pubertal development before the onset of hyperprolactinaemia 4) To achieve > 2.8% improvement in bone mineral density (BMD)measured in g/cm2 and assessed by Dual Energy X-ray Absorptiometry (DXA) after 1 year and stabilization or continued improvement after 2 years aripiprazole therapy in patients with low BMD (T Score Plan of Investigation Interventional, open label, treat-to-target pilot study in 30 patients aged 14-25 years with AP induced hyperprolactinaemia (PRL > 600mU/l in female and a PRL level causing delayed puberty or low testosterone in male patients). At baseline, a full clinical and laboratory evaluation, including pubertal staging by Tanner method will be peformed. Aripiprazole will be started as single or add-on therapy to current AP at a 5 mg dose and increased if tolerated until PRL normalization. The dose will be increased after one and 3 weeks and then 4 weekly after treatment initiation. Mean effective dose is expected to be 15 mg (maximum 45 mg). Baseline tests will be repeated at each dose increase. In patients with delayed puberty, pubertal stage will be reassessed at 3, 6, 12, 18 and 24 months. Potential Impact A) Immediate impact Successful management of hyperprolactinaemia will confer substantial and immediate health benefit to study patients, allowing normal pubertal development, normalization of sex hormones secretion, normal sexual function and accrual of a normal bone mass B) Long term impact 1) A section on management of AP induced hyperprolactinaemia in adolescents and young people will be added to the current Psychotropic Monitoring Guidelines of the Oxfordshire and Buckinghamshire Mental Health Partnership. These guidelines could be extended to other NHS Trusts 2) This study, or an improved version including a formal cost-benefit analysis, would complement similar studies in AP treated adult women, currently being carried out by our research group Patients with severe mental illness


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: MENTAL HEALTH