P.2.c.012 Adjunctive tianeptine for partial or nonresponders to selective serotonin reuptake inhibitor treatment in major depressive disorder

P.2.c. Affective disorders and antidepressants − Antidepressants (clinical) pion 250.8±42.4 vs. 250.4±42.7×109 /L. There was no thrombocytopenia in every group. Conclusions: As results, platelet counts were reduced with statistical significance in the escitalopram group and there was a platelet decreasing tendency in the venlafaxine group which had been prescribed in common therapeutic doses. There were no significant changes in the bupropion groups. It is possible that the degree of serotonergic property and the change of platelet count is correlated. In this study, there was no clinically meaningful event by reduced platelet counts. It can be owing to wide normal ranges of platelet counts in clinical situation. But it has been reported that combination with nonsteroidal antirheumatic drugs (NSAID) increases the risk of bleeding, particularly in the gastrointestinal tract. Given the widespread use of SSRI, antiplatelet drugs and NSAID, psychiatrist should turn their attention to bleeding as adverse effect and interaction. More studies using various platelet indicators are needed in the future. P.2.c.011 Is pharmacogenetic testing ready for antidepressant treatment? A costeffectiveness simulation P. Olgiati1 ° , A. Serretti1 , M. Bigelli2 , D. De Ronchi1 , E. Bajo2 . 1 University of Bologna, Psychiatry, Bologna, Italy; 2 University of Bologna, Management, Bologna, Italy Purpose: Major depressive disorder (MDD) is a prevalent psychiatric disorder worldwide, weighted by hundreds fold increased mortality from suicide and an impressive burden for society in terms of work disability and health expenditure. Moreover healthrelated quality of life (HRQoL) in major depression is inferior to the general population and comparable with the burden in severe physical disorders. Although novel antidepressant drugs have proven to be effective in reducing symptoms and improving HRQoL, approximately one third of patients with MDD fail to respond to a correctly delivered antidepressant treatment and only 20%-30% achieve remission. Antidepressant response is in part under genetic control as seen in randomized trials and, to a lesser extent, in naturalistic studies. Thus an emerging field of psychiatric research is pharmacogenetics. This approach holds promise to improve the outcome of major depression treatment by tailoring drug choice to individual’s genetic makeup. In other words, if drug ‘X’ was delivered to individuals with a favorable genetic profile, the number of responders would be increased. This hypothesis, although intriguing, is not supported by empirical data. However it is possible to simulate the use of a genetic test to select antidepressant treatment and to forecast outcome based on literature findings. We implemented a similar theoretical model to ascertain the cost-effectiveness of incorporating genetic information in MDD treatment. Methods: A hypothetical cohort of Italian patients with mild to severe major depressive disorder (MDD) are treated with antidepressant monotherapy for 12 weeks. Two algorithms are alternatively used to select antidepressant treatment: A. citalopram monotherapy (10−40 mg/daily) (SSRIs are currently used as first-line treatment for MDD); B. administration of citalopram or bupropion (150–300 mg) based on the results of 5-HTTLPR genetic testing: patients with the 5-HTTLPR long allele, who are more likely to respond to SSRI treatment, are treated with citalopram whereas short-allele homozygous patients, more often nonresponder, are given bupropion. The effect size of 5-HTTLPR impact on SSRI response is estimated from a meta-analysis of pharmacogenetic trials and it serves to calculate theoretical benefit

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under genetic testing strategy The model is based on Italian Mental Health setting; managed care is conducted according to APA guidelines. Cost data are drawn from WHO_CHOICE project (World Health Organization) and Italian official sources. All costs are inflated to 2010 and expressed in international dollars. Results: The use of genetic test increases remitters by 5%, with an estimated gain of 0.07 Quality-Adjusted Life Weeks. This projects incremetal cost effectiveness ratio (ICER) to $3,269 (largely above cost-effectiveness threshold), but only for the worse case scenario, while the distribution was largely below threshold. Sensitivity analysis demonstrates the strongest impact of genetic test cost on ICER. Quality of life (HRQL) assigned to untreated depression and 5-HTTLPR effect size are less important contributors. Modeling variations in these parameters, pharmacogenetic approach becomes cost-effective. Under base-case conditions genetic test should cost $75 or less to drop below cost-effectiveness threshold. In severe depression with low HRQL the cost of genetic test could raise to $270. Conclusions: To date performing a pharmacogenetic test before starting antidepressant treatment may be moderately cost-effective in selected groups of patients with severe and disabling MDD. A widespread use of pharmacogenetics may become cost-effective and therefore recommendable to clinicians if prediction power of tests is improved and costs drop to $50−100.

P.2.c.012 Adjunctive tianeptine for partial or nonresponders to selective serotonin reuptake inhibitor treatment in major depressive disorder W.M. Bahk1 ° , Y.S. Woo1 , J.H. Jeong1 , W. Kim2 , H.M. Sung3 , B.H. Koo4 , S.H. Lee2 , D.I. Jon5 , K.J. Min6 , B.H. Yoon7 . 1 College of Medicine The Catholic University of Korea, Department of Psychiatry, Seoul, South-Korea; 2 College of Medicine Inje University, Department of Psychiatry, Seoul, South-Korea; 3 Pochon Cha University, Department of Psychiatry, Gumi, South-Korea; 4 College of Medicine Yeungnam University, Department of Psychiatry, Daegu, South-Korea; 5 of Medicine Hallym University, Department of Psychiatry, Anyang, SouthKorea; 6 College of Medicine Chung-Ang University, Department of Psychiatry, Seoul, South-Korea; 7 Naju National Hospital, Department of Psychiatry, Naju, South-Korea Introduction: To investigate the effectiveness and safety of the adjunctive tianeptine treatment in treatment-resistant major depression patients. Methods: In this prospective, 6-week, open-label study, we assessed the effectiveness of the addition of tianeptine to 135 patients with major depressive disorder who had previously showed nonrespondse or partial response to selective serotonin reuptake inhibitor (SSRI) monotherapy. Partial or non-response was defined as decrease in the score on the Hamilton Depression Rating Scale (17-item, HDRS) <50% over a period of 6 weeks of treatment. The dose of tianeptine as an adjunct ranged from 25 to 37.5 mg/day. During the study period, the initial SSRI dose remained constant. Patients were not allowed to take other antidepressants, mood stabilizers or antipsychotics during the study. Benzodiazepines and hypnotics were permitted based on the investigator’s clinical decision. Evaluation of antidepressant efficacy was carried out through the application of the Montgomery-Asberg Depression Rating Scale (MADRS), HDRS and the Clinical Global Impression (CGI) in week 1, 2, 4 and 6.

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Results: The mean dose of tianeptine during the study period was 29.7±7.8 mg/day. Combined SSRIs were escitalopram (n = 64, 47.4%, 16.5±5.2 mg/day), paroxetine CR (n = 59, 43.7%, 26.5±9.6 mg/day), fluoxetine (n = 7, 5.2%, 28.3±10.4 mg/day) and sertraline (n = 4, 3.0%, 100 mg/day). Total score of MADRS was decreased from 27.1±7.2 at baseline to 13.1±7.7 at the endpoint (p < 0.0001). HDRS total score was also decreased from 22.4±5.1 at baseline to 10.6±5.9 at the endpoint (p < 0.0001). There was significant decrease in MADRS and HDRS total score from week 1. Responders defined as patients decrease in HDRS or MADRS total score 50% were 66.7% (MADRS) and 63.0% (HAMD). Remission defined as MADRS<10 and HAMD  7 were 39.3% (MADRS) and 34.1% (HDRS). All subscale scores of MADRS and HDRS were significantly decreased from baseline to endpoint. (p < 0.0001) In subgroup analysis, 36 patients treated with high dose tianeptine (37.5 mg/day) showed significantly higher response rate than low dose (<37.5 mg/day) group at week 2 (HDRS), week 4 and week 6 (MADRS). The remission rate at week 6 (HDRS) was also significantly higher in high dose group than low dose group. However, there was no significant group difference in MADRS (p = 0.571) and HDRS (p = 0.446) between high dose group and low dose group based on repeated measure ANOVA. There were 23 patients (17.0%) who discontinued the study: ten patients for lost to follow-up, 4 for ineffectiveness, 1 for adverse event (headache) and 8 for other reason. The 80 cases of adverse events in 27 patients (20.0%) were reported during the study period. Most cases of adverse events (80.0%) were occurred before week 2. Most common adverse events were sedation (n = 8), headache (n = 8), nausea/vomiting (n = 6), dry mouth (n = 5), palpitation (n = 3), and dizziness (n = 3). The combination of tianeptine and SSRI was well tolerated and adverse events were mostly mild. Conclusion: Our findings suggest that the adjunctive tianeptine with SSRI was an effective and safe treatment for the SSRI resistant patients with major depressive disorder

doses of Lu AA21004 were tested separately versus placebo at a 0.025 level of significance, in a pre-specified order. Secondary efficacy outcomes included change from baseline on the MADRS, the 24-item Hamilton Depression (HAM-D24 ), the Hamilton Anxiety (HAM-A), and the Clinical Global Impression − Severity and Improvement (CGI-S and CGI-I) scales. Results: This double-blind, placebo-controlled, duloxetinereferenced fixed-dose study included 776 randomized patients from 100 psychiatric in- and out-patient settings in 20 countries. There were 766 patients treated with either placebo (n = 148), Lu AA21004 2.5 mg (n = 155), Lu AA21004 5 mg (n = 157), Lu AA21004 10 mg (n = 151) or duloxetine (n = 155). On the predefined primary efficacy endpoint, no active treatment group separated from placebo. Most secondary outcome measures of depression (MADRS and HAM-D24 ), anxiety (HAM-A), and global scales (CGI-s and CGI-I) at Week 8 were supportive of likely efficacy for Lu AA21004 5 mg and 10 mg and duloxetine, using observed cases ANCOVA and mixed model repeated measures (MMRM). Treatment-emergent adverse events led to the withdrawal of 72 patients: 8% in the placebo group, 6%, 11% and 9% in the Lu AA21004 2.5 mg, 5 mg and 10 mg groups, and 12% in the duloxetine group. The most common adverse events in the placebo, Lu AA21004 2.5 mg, 5 mg, 10 mg and duloxetine groups were nausea (9%, 17%, 17%, 22%, 34%), headache (16%, 14%, 10%, 13%, 14%), dizziness (7%, 5%, 3%, 4%, 16%) and dry mouth (7%, 4%, 6%, 4%, 8%), respectively. No clinically relevant changes were seen in vital signs, weight, ECG, or clinical laboratory results. Conclusions: None of the active treatment groups separated from placebo on the primary endpoint in this 8-week MDD study. Findings on the secondary outcome measures were supportive of likely efficacy for Lu AA21004 5 mg and 10 mg and duloxetine. Lu AA21004 (2.5, 5 and 10 mg) was well tolerated. Trial Registration: This study has the ClinicalTrials.gov identifier: NCT00635219. Disclosure statement: This study was funded by H.Lundbeck A/S and Takeda Pharmaceutical Company Ltd

P.2.c.013 A randomised, double-blind, placebo controlled, duloxetine-referenced, fixed-dose study of three dosages of Lu AA21004 in MDD treatment

P.2.c.014 Rates and risk factors to readmission before one year after discharge in unipolar depressive patients

D. Baldwin1 ° , H. Loft2 , M. Dragheim2 . 1 University of Southampton Faculty of Medicine, University Department of Psychiatry, Southampton, United Kingdom; 2 H.Lundbeck A/S, Research and Development, Copenhagen, Denmark

M. Guitart Colomer1 ° , E. Nieto Rodr´ıguez1 , A. P´erez Guitart1 , M. Malo L´opez1 , J. Rodr´ıguez Casadevall1 , P. Bonet Dalmau1 . 1 Althaia Xarxa Assistencial, Salut Mental, Manresa, Spain

Objective: Lu AA21004 is a novel multimodal antidepressant that is a 5-HT3 and 5-HT7 receptor antagonist, 5-HT1A receptor agonist, 5-HT1B receptor partial agonist and inhibitor of the 5-HT transporter in recombinant cell lines. Lu AA21004 is in clinical development for the treatment of major depressive disorder (MDD). The goal of this study was to evaluate the efficacy, safety, and tolerability of Lu AA21004 versus placebo using duloxetine as active reference in patients with major depressive disorder (MDD) diagnosed according to DSM-IV-TR. Method: In this 8-week multicentre trial, 766 adult patients ˚ with a baseline Montgomery-Asberg Depression Rating Scale (MADRS) total score 26 were randomly assigned (1:1:1:1:1) to fixed doses of 2.5, 5 or 10 mg Lu AA21004, placebo or 60 mg duloxetine. The primary efficacy endpoint was the change from baseline in MADRS total score at Week 8 (full analysis set, last observation carried forward, ANCOVA). The 5 mg and 10 mg

Introduction: Psychiatric hospitalization in unipolar depressed patients is less frequent than in bipolar patients or schizophrenic patients. It’s very interesting to know the frequency and the risk factors that have influenced on the readmission in hospital within the first year after discharge unipolar depressive inpatients. Comorbidity with personality disorders or alcohol abuse, and the number of previous hospitalizations are found to be predictors of a shorter time of stability [1]. By contrast the treatment with ECT or not [2], or the subtype of antidepressant treatment [3] did not appear to influence the need for readmission in depressed patients Purpose: The purpose of the present study was to investigate the rate and the risk factors that involve in the need of readmission unipolar depressive inpatients before one year after discharge. Method: – Subjects: We selected all the patients that were hospitalized in our psychiatric unit between January 1st 2009 and December