PI Affctive disorders andantidepwssants S237 Methods: This study (GW #2014) was a one-year, open- label, flex~We-dose continuation study conducted in 127 bipolar depressed patients who had completed a double-blind, placebo- controlled monotherapy trial (GW #603). All @tients met DSM- IV criteria for Bipolar I or II Disorder and were experiencing a depressed episode at the time of entry into the initial study. Results: Patients previously randomised to either placebo or lamotrigine demonstrated consistent, statistically significant im- provement in HAMD-17 and MADRS scores throughout the one- year study compared to scores rec6rded at study entry. Fitly-seven percent of patients completed one year of treatment. Fifty-four per- cent received lamotrigine as monotherapy. Doses ranged as high as 500 mg/day and were well tolerated, with few patients (15%) discontinuing therapy due to adverse events. The most common adverse event was infection. There were no cases of serious rash. There was no evidence that long-term lamotrigine treatment had any negative effect on clinical laboratory parameters, vital signs, or weight. Conclusion: This open-label study provides evidence that lamotrigine is safe, well-tolerated and effective as a long-term treatment for bipolar depression. References Ill 121 Calabrese, J.R., Bowden, C.L., McElroy, S.L., Cookson, J., Anderson, J., Keck, PE., Rhodes, L.J., Bolden-Watson, C., Zhou, J., Ascher, J. Spectrum of Activity of Lamotrigine in Treatment-Refractory Bipolar Disorder. Am. J. Psychiatry 1999; 156: 1019-1023. Hoopes, S.P Lamotrigiue in the Treatment of Affective Disorders: A Clinical Experience. European Neuropsychophammology 1998; 8 (S2): s1384139. Ip.1.047] A one-year continuation study of lamotrigine treatment in bipolar depression R. Huffman, J. Ascher’, N. Earl, E. Monaghan, G. Womble, P Mitchell, J. Cookson, B. Vanier, T. Dinan, J. Calabrese. G&o Wellcome Research and Development, Research Ttiangle Park, NC, USA Objective: Lamotrigine has previously demonstrated efficacy in a seven-week, placebo-controlled study of bipolar depression (Cal- abrese et al., 1999). The current study was designed to evaluate the continued long-term safety and efficacy of lamotrigine, as monotherapy or adjunctive therapy, in bipolar depressed patients who had completed the initial double-blind study. Methods: This study (GW #604) was a one-year, open-label, flexible-dose continuation study conducted in 124 patients who previously enrolled and completed a seven-week, double-blind placebo-controlled study of lamotrigine (GW #602). All patients met DSM-IV criteria for Bipolar I Disorder, were in a depressed episode at the time of initial study entry and had completed seven weeks of treatment in the initial double-blind, placebo-controlled study. Results: Patients who were previously randomised to placebo, but were subsequently switched to lamotrigine, showed statisti- cally significant improvement on HAMD- 17, MADRS and CGI scales throughout the one year of active treatment. Patients who were previously randomised to lamotrigine continued to show im- provement on continuation therapy, and maintained the statistically significant difference vs. placebo observed during the double- blind study. Lamotrigine was well tolerated at doses of up to 500 mgday, with 15% of patients discontinuing prematurely due to an adverse event. There were no serious rashes. Lamotrigine had no effect on clinical laboratory parameters or body weight. Conclusion: This open-label study provides evidence that lam- otrigine is safe and well-tolerated as a long-term treatment for bipolar depression, and that lamotrigine’s mood stabilising effect, as demonstrated in a placebo-controlled trial, is maintained for at least one year of continuation treatment. References [l] Calabrese, J.R., Bowden, C.L.,‘Sachs, G.S., Ascher, J.A., Monaghau, E., Rudd, G.D. (for the Lam&al 602 Study Group). A Double-Blind Placebo-Conbolled Study of Lamotrigine Monotherapy in Outpatients With Bipolar I Depression. J Clin Psychiatry. 1999; 60 (2): 79-88. Ip.1.0481 Mood stabilisation with lamotrigine in rapid cycling bipolar disorder N. Earl, P Greene, J. Ascher, N. Fouche*, C. Chang, G. Evoniuk, A. Swann, S. Pope, T. Ketter, S. McElroy, R. Post, J. Zajecka, L. Altshuler, J. Apter, S. West, C. Risch, A. Khan. Glaxo Wellcome Research and Development, Greenford, UK Objective: Lamotrigine (LTG), an established anticonvulsant drug, is currently under investigation for the treatment of bipolar disorder. Initial experience with the drug has suggested particular utility in treating depressed and rapid cycling presentations of the illness (Calabrese et al., 1996; Sporn and Sachs, 1997). Based on these encouraging preliminary results, a multicenter, double-blind, placebo-controlled study was initiated to investigate the safety and efficacy of LTG in rapid cycling bipolar disorder. The initial open- label phase of this study examined the efficacy of lamotrigine in stabilising Bipolar I and II patients with a recent history of rapid cycling. Methods: Study GW#614 enrolled 326 rapid cycling bipolar I and II patients into an initial open-label stabilisation phase. Patients could be in any phase of the illness, and initially had LTG added to their current treatment regimen via gradual titration over an eight-week period. Subjects achieving clinical stability were discontinued from all other medications and, if they remained stable (defined as HAMD-17 score < 14 and Mania Rating Scale score of ~12 for the last two weeks of the 8-12-week open phase), were subsequently randomised to monotherapy treatment with LTG or placebo for six months. Results: The majority of patients enrolled were experiencing a depressed episode at screening. For the intent-to-treat sample, the rate of mood stabilisation and randomisation after LTG treatment was 56%. LTG appeared to show comparable efficacy across pa- tients with differing polarities at study entry. There was substantial and significant improvement in several endpoints including CGI and GAF scores. LTG was well-tolerated: there were no cases of serious rash. The rate of simple rash attributed to LTG was 7%, and other adverse events rarely interfered with successful treatment. Conclusion: The open-label data from the initial phase of this study suggest that LTG is useful in the stabilisation of patients with rapid cycling bipolar disorder and may be an useful alternative for these difficult-to-treat patients. References [l] Calabrese J, Fatemi S, Woyshville M. Antidepressant Effects of Lamot- rigine in Rapid Cychng Bipolar Disorder. Am J Psychiatry 1996; 153: 1236.