Efficacy of Lithium versus Lamotrigine for the treatment of bipolar II disorder

The study is a randomised controlled trial which will compare Lithium or Lamotrigine open-label monotherapy for patients newly diagnosed with bipolar II disorder and who have not previously been treated with either medication. Patients will be randomised 1:1 to receive either Lithium or Lamotrigine and assessed over a 28-week period, with the study expected to be conducted over a three-year period. Eligible participants will be recruited principally through the Black Dog Institute clinics, following initial diagnosis of that condition and meeting other study inclusion/exclusion criteria. Potential participants will be informed about the trial by a research assistant and that it seeks to compare two effective bipolar II medications in terms of their comparative cost/benefits in terms of stabilising their mood swings. Following provision of consent, participants will be randomised to one of the two treatment conditions detailed below. All patients will be informed about which treatment group they are allocated, and have the possible risks and side-effects associated with their particular medication(s) detailed. Patients will be managed and assessed by a psychiatrist at the Black Dog Institute three times in the first six weeks and then once every four weeks for 28 weeks as part of the trial – and on a needs basis if any clinical problems arise. During such visits they will be assessed in terms of their mood state over the preceding interval by a research assistant blind to their actual drug treatment. Details of Treatment Groups Group 1: Will receive Lamotrigine as a monotherapy (Trade name, Lamictal) and titrated over 8 weeks in the following manner: 25 mg/day for the first week, increasing 25 mg each week to reach 200 mg at week 8 and allowed to be increased at a similar rate to a maximum dose of 300 mg/day as judged by treating clinician (Further increases or decreases will be dictated by consideration of clinical symptoms, maximum dosing, and tolerability). As noted below, the serum Lamotrigine level will be assessed on two occasions. Group 2: Will receive Lithium (Trade name, Quilonum SR) which will be titrated starting at 450 mg/day for a week then its serum Lithium concentration will be obtained and dose adjusted until the Lithium concentration reaches 0.8 mEq/L. Lithium has linear kinetics so if 450 mg Lithium gives a serum level of 0.4, then the Lithium dose of 450 mg will be doubled to seek a 0.8 level. If level 0.6 then Lithium dose increased from 450 mg to 625 mg. At the next scheduled visit the serum level will be checked to confirm serum level of 0.8 and, if not, any further adjustments will be made. Once a 0.8 serum level has been obtained then serum levels will be checked every 3 months including at the last visit, along with the creatinine level and thyroid function tests, Lithium dosing will be dictated by clinical response, tolerability, and blood levels (minimum 0.8 to maximum 1.2 mEq/L). For all participants the managing psychiatrist will assess clinical progress and side-effects at each individual consultation for the first six weeks, and then monthly until week 28. Both Lamotrigine and Lithium will be administered orally. Medication adherence will be monitered by checking serum Lithium levels at intervals noted above and for Lamotrigine, levels tested at 12 weeks and at trial end