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
The University of Melbourne
66 participants
Aug 1, 2007
Interventional
Conditions
Summary
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.
Eligibility
Inclusion Criteria1
- Meet Diagnostic and Statistical Manual IV Text Revised (DSM-IV TR) diagnosis for mania as part of bipolar I disorder or schizoaffective disorder. Have a Young Mania Rating Scale at baseline of at least 20. Not have had a previous treated manic episode. Have the capacity to provide informed consent to the study and comply with study procedures. Be utilising effective contraception if female, sexually active and of childbearing age. Patients will need to have been on quetiapine and lithium as standard therapy for at least 1 month prior to randomisation.
Exclusion Criteria22
- Exclusion from the trial includes:
- Patients with a known or suspected clinically relevant systemic medical disorder.
- Individuals who are pregnant or lactating.
- Patients who have had a prior sensitivity or allergy to quetiapine, lithium or their components.
- Inability to comply with either the requirements of informed consent or the treatment protocol.
- Non-fluency in English.
- History of epilepsy.
- Clinically relevant biochemical or haematological abnormalities at baseline.
- Patients at immediate risk of self harm or risk to others.
- Organic mental disease, including mental retardation (Full scale IQ<70).
- Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir
- Use of any of the following cytochrome P450 inducers in the 14 days preceding enrollment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John’s Wort, and glucocorticoids
- A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:
- Unstable DM defined as enrollment glycosylated hemoglobin (HbA1c) >8.5%.
- Admitted to hospital for treatment of DM or DM related illness in past 12 weeks.
- Not under physician care for DM
- Physician responsible for patient’s DM care has not indicated that patient’s DM is controlled.
- Physician responsible for patient’s DM care has not approved patient’s participation in the study
- Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomization. For thiazolidinediones (glitazones) this period should not be less than 8 Weeks.
- Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks
- Note: If a diabetic patient meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study.
- An absolute neutrophil count (ANC) of 1.5 x 109 per liter
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Interventions
This study investigates the outcomes of using the medication quetiapine versus lithium for long term treatment following a manic episode. Patients will be stabilised on a combination of these treatments and then randomly removed from one medication if they consent to the study procedures. The dose of both medications are prescribed as clinically indicated so the patient and their treating physician will be able to tailor their treatment including the use of other medications as necessary to their own needs. Both quetiapine and lithium are taken daily in oral form and regular blood tests may be required to monitor the concentrations of these medications. The trial will last for 12 months and over this period, after which patients may choose to remain on their current medication or switch to another.
Locations(1)
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ACTRN12607000639426