Non-evidence-based antipsychotic drug prescribing in the treatment of adult schizophrenia [PhD Thesis].

Introduction. The extent of combination antipsychotic prescribing (CAP), or polypharmacy, in the treatment of schizophrenia is high, with evidence of prevalence exceeding 40% nationally and 30% across Greater Manchester. CAP increases the incidence of adverse drug events and inadvertent high dosage, whilst elevating treatment costs. Guidance against CAP is contained in both local and national evidence-based treatment guidelines. Few previous studies have attempted to alter this antipsychotic prescribing practice.The aims of the studies described here were to develop and evaluate an intervention to reduce rates of CAP in a mental health services catchment area in Greater Manchester, alongside an investigation of the main aspects of CAP: whether rates of CAP are as high as those recorded previously across the city; whether CAP is associated with other non-evidence-based antipsychotic prescribing; whether some patients are more likely to be treated with CAP than others; and what it is like, from the patient’s perspective, to take antipsychotic drugs, including those taken in combination. Methods. A series of studies was performed to inform the development of the intervention to reduce CAP rates. A systematic review of previous intervention studies to change prescribing habits was undertaken. A survey of current rates of CAP across Greater Manchester was also performed and CAP’s relationship to other non-evidence-based prescribing was assessed. Qualitative patient interviews and the measurement of clinicians’ prescribing attitudes were carried out. The database from a large clinical trial was also analysed to identify predictors of CAP. The resulting multifaceted intervention package comprised audit and feedback, the use of an opinion leader, individual educational visits and a reminder system. Its effectiveness in reducing rates of CAP was assessed in comparison to a parallel catchment area without the intervention. Results. The systematic review and meta-analysis suggested that interventions could change prescribing, with an overall reduction in the probability of CAP of 10% resulting from pooling data. Rates of CAP recorded across treatment settings in Manchester (between 14% and 22%) were lower than those recorded in national prescribing surveys. Most cases of high dose prescribing were secondary to CAP. High rates of CAP predicted low rates of clozapine prescribing but this association failed to reach statistical significance. Demographic and clinical characteristics (older age, longer illness duration, lower global functioning score and higher adherence rating) were associated with receipt of CAP. The intervention failed to reduce rates of CAP post-intervention, compared with pre-intervention, and with rates seen in a site where the intervention did not take place. Conclusions. The systematic literature review showed that behavioural and educational interventions can have modest effects on reducing CAP. The package developed here failed to reduce rates of CAP using a multifaceted prescribing intervention. Reasons for this may include lower than anticipated rates of CAP at baseline. More research is required to explore the role played by patient preference in the continuance of CAP and in clinicians’ prescribing behaviour.