S238 I?1 Affective disorders andantidepressants [2] Spom J, Sachs G. The Anticonvulsant Lamotrigine in Treatment- Resistant Manic-Depressive Illness. Journal of Clinical Psychophar- macology 1997; 17: 185-189. IP.1.0491 Mood stabilisation with lamotrigine in rapid cycling bipolar disorder: A double-blind placebo-controlled study V Kusumakar, P Greene, N. Earl, J. Ascher, E. Monaghan, T. Smoot, N. Fouche, C. Bowden, J. Calabrese, R. Post, G. Sachs, I? Suppes, L. Gyulai, T. Young, M. Rapaport. Dalhousie Universi& Halifax. Nova Scotia, Canada Objective: Early experience with the established anticonvulsant drug, lamotrigine (LTG) indicates efficacy in depression (Cal- abrese et al., 1999) as well as suggesting that it may have particular utility in treating rapid cycling bipolar disorder (Calabrese et al., 1996; Bowden et al., 1999). Based on these encouraging results, a multicenter placebo-controlled study was undertaken to further examine the potential for mood stabilising properties of LTG. This paper reports the results from the double-blind, placebo-controlled phase of this study in a rapid cycling bipolar disorder population. Methods: Study GW#614 enrolled 326 rapid cycling bipolar patients into an initial open-label stabilisation phase in which LTG titration was added to the current treatment regimen. Patients experiencing clinical response to LTG were discontinued from other medications and if stable (HAMD- 17 score < 14 and Mania Rating Scale score of ~12 for the last two weeks of the 8812-week open phase) were subsequently randomised to monotherapy with LTG or placebo (PBO). Patients were continued on monotherapy treatment for six months or until the investigator determined that additional treatment intervention was warranted. Results: A total of 177 patients entered into the controlled phase of the study. Forty-one percent of patients on LTG vs. 28% of patients on PBO (p < 0.05) completed six months of randomised monotherapy treatment without any additional pharmacotherapy. Survival analysis based on time from randomi- sation to time of intervention indicated a six-week difference in median survival in favor of LTG. Other clinical assessments also showed substantial clinical benefit in favor of LTG treatment. The drug was well-tolerated: adverse events were mild, there were no clinically significant changes in vital signs, body weight or clinical laboratory parameters. Conclusion: This study, the largest of its kind conducted to date, suggests that LTG is a useful alternative to other mood stabilisers in the maintenance treatment of patients with rapid cycling bipolar disorder. The results also provide further guidance for optimization of clinical study designs in this important area of mood disorders research. References [I] Calabrese, J.R., Bowden, C.L., Sachs, G.S., Ascher, LA., Monaghan, E.. Rudd G.D. (for the Lamictal 602 Study Grouo). A Double-Blind Placebo-Control&d Study of Lamotrigine Monothdmpy in Outpatients With Bipolar I Depression. J Clin Psychiatry 60 (2): 79-88, 1999. [2] Bowden, C.L., Calabrese, J.R., McElroy, S.L., Rhodes, L.J., Keck, PE., Cookson, J., Anderson, J., Bolden-Watson, C., Ascher, J., Monaghan, E.. Zhou. J. The Efficacy of Lamotrigine in Ranid Cycling and Non- Rapid Cycling Patients with Bipolar Disorder. Biol. Psych:latry 1999; 45: 953-958. [3] Calabrese J, Fatemi S, Woyshville M. Antidepressant Effects of Lamot- rigine in Rapid Cycling Bipolar Disorder. Am J Psychiatry 1996; 153: 1236. Assessing the validity of a model of cost- effectiveness of fluvoxamine in depression in France using observational data on treatment patterns J. Piercy’, M.J.C. Nuijten 2. ‘Solvay Pharmaceuticals, Hannwer, Germany; ‘MEDTAP International, Amsterdam, The Netherlands The objective of this study was to validate a previous cost- effectiveness analysis of the long-term treatment with fluvoxamine compared to tricyclic antidepressants in patients with major recur- rent depression’. The setting of this study was France. While the efficacy of treatment and probability of relapse/recurrence were based on clinical evidence, a limitation of this study was that resource use and treatment patterns were mainly derived from clinical opinion. The validation of the original analysis incorporates the findings of a large-scale observational study of treatment patterns in France, which involved over 100 GPs and psychiatrists and more than 1000 patients with a primary diagnosis of depression. This study gives the modelling exercise a higher external validity as it based on real life data by incorporating more accurate and representative information on treatment switches between drug groups, changes in dose and augmentation. It was also possible to more accurately estimate the associated resource utilisation. The results of the initial analysis showed that the use of fluvox- amine in the maintenance treatment of depressive disorders was less costly than that of TCAs with total costs (direct and indirect costs) FF 40,232 versus FF 52,257 respectively. In addition, due to the prevention of relapse and recurrence, effectiveness favoured fluvoxamine as it was associated with a longer period of time without depression, when compared to therapy with TCAs: 79% of the study period compared to 71% for TCAs. The incorporation of the observational data in new model over- comes the main methodological weakness in decision analysis, namely the reliance on expert opinion. Preliminary results indicate that conclusions of the previous study are valid. Hence this study increases the robustness of the conclusion of the original study that fluvoxamine is cost-effective in the maintenance treatment of depression compared to TCA therapy. References [l] Nuijten M, Habjadjeba L, Evans C, van der Berg J. Cost-effectiveness of Fluvoxamine in the Treatment of Recurrent Depression in France. Pharmacoeconomics 1998; 14 (4); 433445 -1 CYPZD6 phenotype and genotype analysis in polymedicated depressed inpatients E. Haffen’, G. Paintaud4, I! Vandel’, E Broly5, S. Vandelz, S. Nezelof’ , B. Benin’ , J.P. Kantelip2, P. Bizouard’ , P.R. Bechte13, D. Sechter’ ‘Department of Clinical Psychiatry; 2Department of Pharmacology; ‘Professor of Clinical Pharmacologv, University Hospital of Besangon; 4Department of Clinical Pharmacology and Toxicology, University Hospital of Tours; ‘Laboratory of Biochemistry and Molecular Biology, University Hospital of Lille. France Background: One of the major cause of interindividual variability of drug effects -therapeutic response and toxicity - is genetic vari- ation of drug metabolizing enzymes. Among the P450 isozymes