Neuroprotective Properties of Quetiapine versus Lithium in a First Episode Mania Cohort: 12-month Neuroanatomical, Neurochemical and Neuro-cognitive Effects and Preliminary Data of Prophylactic Properties

Evidence shows that many people with bipolar disorder may have problems with concentration and memory after an acute episode of the illness. It was believed that this was caused by the medication used to treat bipolar disorder, however there is increasing evidence that it may be the disorder itself that leads to memory and cognitive impairments. In particular, new technology in psychiatry has allowed researchers to look at images of the brain of patients with bipolar disorder and compare these to people with no psychiatric illness. The results of these studies show that there are a range of changes in the brain that may account for memory and cognitive problems following episodes. These findings raise a number of questions about the response of the brain in bipolar disorder. The first of these is if there are significant changes in the brain over the year following the first acute episode of bipolar disorder. This has implications for how assertively clinicians treat the disorder and the cognitive problems associated with this phase of the illness. Secondly, some findings from new research on lithium’s effects on the brain suggest that lithium can prevent this neuronal damage and hence these cognitive and memory problems. While some evidence for lithium’s role in this neuro-protection has been established, no groups have yet demonstrated similar protective properties of other medications commonly used for the treatment of bipolar disorder. Neuroprotective effects of antipsychotic medicines are shown in schizophrenia, and are suggested in bipolar disorder by laboratory studies. One such drug is quetiapine, an atypical antipsychotic which has become increasingly used for the treatment of bipolar disorder, particularly when psychotic features dominate the clinical picture. The aim of this study is to; 1.) Investigate if cognitive and memory performance changes over the year following a first episode of bipolar disorder. 2.) Investigate whether quetiapine is more or less effective at preventing this deterioration than lithium. 3.) Investigate whether time to and quality of symptomatic recovery differs between lithium and quetiapine. 4.) Use neuroimaging technology to discover if there are structural changes in the brain and whether these are associated with cognitive and memory performance. To complete this study 66 patients will be recruited across three sites with the intention of 52 completing the protocol. Patients will be recruited following stabilisation of their first manic episode. At entry to the study, baseline assessments will be conducted on all participants including neuroimaging. Regular symptomatic scales will be used at regular intervals and neuroimaging and neuropsychological measures will be taken again at 3 and 12 months. Symptomatic and neuropsychological measures will be obtained from clinical interview and structured computer tasks. Neuroimaging will involve participants undergoing an MRI that take around 45 minutes on 3 occasions over a 12-month period. Prior to the start of the study all participants will have been stabilised on lithium and quetiapine combination therapy. At the commencement of the study these participants will be placed on either lithium monotherapy or quetiapine monotherapy. If participants suffer relapse or a new episode during the study period they will be considered drop-outs and other routine therapies will be adopted.