PS103. Search for biomarkers for ketamine response from changes of cytokines in the patients with treatment resistant depression

s | 35 administered at baseline, weeks 1, 2, 4, and week 8.The dose of desvenlafaxine was fixed (50mg/day) until week 4, after which it was flexible up to 100mg/day, based on response and tolerability. Results: Montgomery Asberg Depression Scale scores significantly decreased from baseline (M=23.61, SD=5.51) to end of treatment (M=12.29, SD=8.41), p<.0001. Severity of illness, as measured by the Clinical Global Impression scale, as well as selfreported depressive symptom scores, significantly decreased from baseline to end of treatment (p<.0001). Improvement in quality of life (p<.0001), levels of perceived stress (p<.0001), coping styles (p<.0001), and work impairment (p<.01) were noted over the course of treatment. Conclusions: Overall results indicate that desvenlafaxine is effective in reducing depressive symptoms and improving functioning in patients with persistent depressive disorder. Further, results provide evidence of good safety and tolerability of desvenlafaxine in this population. These results support the further investigation of desvenlafaxine for this condition using larger, placebo controlled, randomized control trials. PS101 Oral Ketamine for Treatment Resistant Major Depression – A double blind randomized controlled trial Yoav Domany MD, Maya Bleich-Cohen PhD, Nadav Stoppelman PhD, Talma Hendler MD PhD, Ricardo Tarrasch PhD, Shaul Schreiber MD, Roi Meidan MD and Haggai Sharon, MD Tel Aviv Sourasky Medical Center, Israel Abstract Background: Major depression is a devastating common disorder. Current pharmacotherapy relies on the monoaminergic theory, and requires a substantial time for full therapeutic effect. Regrettably, about 40% fail to attain remission, defined as Treatment Resistant Depression (TRD). Recently, intravenous ketamine has been shown to provide rapid, short lived, amelioration of TRD. We aimed to assess the clinical efficacy and safety of oral ketamine for TRD. Methods: In a double-blind, randomized, placebo-controlled trial 27 TRD outpatients received either oral ketamine or placebo for 21 days. Patients were evaluated pre-trial and after 21 days. The main outcome measure was the change in Montgomry Asberg Depression Rating Scale(MADRS) score. Result: 14 subjects were randomized to the ketamine group, and 13 to the placebo group. Of these, 12 and 9 respectably completed the study. No significant differences were obtained at time zero. A significant reduction of 13.4 points of the MADRS score was obtained after 21 days in the ketamine group (p=0.003) while a nonsignificant reduction of 2.9 was observed in the placebo group. Four subjects (33%) attained remission (MADRS ≤10) in the ketamine group compared to none in the placebo group. No serious side effects were reported. Conclusion: In this study, sub-anesthetic oral ketamine produced rapid amelioration of depressive symptoms in ambulatory TRD patients, and was well tolerated. The results of this study suggest that oral ketamine may hold significant promise in the care of TRD.Background: Major depression is a devastating common disorder. Current pharmacotherapy relies on the monoaminergic theory, and requires a substantial time for full therapeutic effect. Regrettably, about 40% fail to attain remission, defined as Treatment Resistant Depression (TRD). Recently, intravenous ketamine has been shown to provide rapid, short lived, amelioration of TRD. We aimed to assess the clinical efficacy and safety of oral ketamine for TRD. Methods: In a double-blind, randomized, placebo-controlled trial 27 TRD outpatients received either oral ketamine or placebo for 21 days. Patients were evaluated pre-trial and after 21 days. The main outcome measure was the change in Montgomry Asberg Depression Rating Scale(MADRS) score. Result: 14 subjects were randomized to the ketamine group, and 13 to the placebo group. Of these, 12 and 9 respectably completed the study. No significant differences were obtained at time zero. A significant reduction of 13.4 points of the MADRS score was obtained after 21 days in the ketamine group (p=0.003) while a nonsignificant reduction of 2.9 was observed in the placebo group. Four subjects (33%) attained remission (MADRS ≤10) in the ketamine group compared to none in the placebo group. No serious side effects were reported. Conclusion: In this study, sub-anesthetic oral ketamine produced rapid amelioration of depressive symptoms in ambulatory TRD patients, and was well tolerated. The results of this study suggest that oral ketamine may hold significant promise in the care of TRD. PS102 Apathy in elderly depression and the antidepressant response Takahisa Shimano, Hajime Baba Junendo University Koshigaya Hospital, Japan Abstract Background: Although apathy is a common symptom in late-life depression, the treatment effect of antidepressant on apathy in those patients is still unclear. The aim of the present study is to reveal the difference of treatment response on apathy among the class of antidepressant. Methods: A total of 128 elderly inpatients (>or=60 years old) with a DSM-IV major depressive disorder were recruited from Juntendo Koshigaya Hospital. Patients showing clinical evidence of dementia or with mini-mental state examination (MMSE) scores <24 were excluded. Finally 92 elderly patients were treated with selective serotonin reuptake inhibitors (SSRI, n=52) and serotonin and norepinephrine reuptake inhibitors (SNRI, n=40). We evaluated depressive symptom using Hamilton Depression Scale (HAM-D) and apathy using the Apathy Evaluation Scale Japanese version (AES-J) before and after 4 weeks treatment. Responder was defined as the patients with 50 percent improvement of each score by treatment. Result: There are no significant differences between SSRI and SNRI on responder rates of HAM-D and AES-J scores. Conclusion: The treatment response on apathy in patients with late-life depression was not different according to the class of antidepressant. The results with a larger dataset will be reported in the congress. PS103 Search for biomarkers for ketamine response from changes of cytokines in the patients with treatment resistant depression Tung-Ping Su1,2,3,4, Mu-Hong Chen2,3, Cheng-Da Li1, 2,3, Ya-Mei Bai1,2,3, Annie Chang2, Hui-Ju Wu, Wei-Chen Lin 2,3, Pei-Chi Tu2,4,5 1 Department of Psychiatry, National Yang-Ming University 2 Department of Psychiatry, Taipei Veterans General Hospital 3 Institute of Brain Science, national Yang-Ming University 4 Department of Medical Research, Taipei Veterans General Hospital 5 Institute of Philosophy of Mind and Cognition Abstract Objective: Increased levels of pro-inflammatory cytokines were reported to be associated with depression. The aim of this study is to search for biomarker for ketamine antidepressant response using levels of cytokines to account for and predict clinical response. Methods: we conducted a randomized, double-blind placebocontrolled study comparing the two single subanesthetic doses of ketamine infusion (0.5mg/kg & 0.2mg/kg) vs. placebo (PBO) to see the primary behavioral outcome and the alterations of cytokines level for the secondary outcome. The levels of cytokines such as CRP, IL2, IL6, TNF α measured at baseline, 240 mins, D2 (48 hrs), and D6 with concommitant mood ratings (HAMD-17 and MADRS) and their changes from baseline were assessed and correlated. Results: RepeatedMeasure ANOVA showed no significant differences of group effect on these four-cytokine levels (p=NS) but with significant time effect on IL2, IL6, TNF α. (p=0.034, 0.001 & 0.004 respectively). In that, we observed minimal decreasing rate from baseline to 40 mins and 240 mins post-infusion in IL2 and IL6 (< 5%) while moderate decreasing in TNF α (10–15%). However, no correlations between decreasing rate of cytokines with mood improvemnt rate nor predictors of baseline or changes of cytokines for responder rate (>=50% reduction of either HAMD-17 and MADRS from D2 to D4) were found. Nevertheless, If we divided the cytokine levels using median No into high and low level group, only baseline IL6 high level group (IL6 > 28953pg/ml) and CRP low level group (CRP< <518ng/ml)Objective: Increased levels of pro-inflammatory cytokines were reported to be associated with depression. The aim of this study is to search for biomarker for ketamine antidepressant response using levels of cytokines to account for and predict clinical response. Methods: we conducted a randomized, double-blind placebocontrolled study comparing the two single subanesthetic doses of ketamine infusion (0.5mg/kg & 0.2mg/kg) vs. placebo (PBO) to see the primary behavioral outcome and the alterations of cytokines level for the secondary outcome. The levels of cytokines such as CRP, IL2, IL6, TNF α measured at baseline, 240 mins, D2 (48 hrs), and D6 with concommitant mood ratings (HAMD-17 and MADRS) and their changes from baseline were assessed and correlated. Results: RepeatedMeasure ANOVA showed no significant differences of group effect on these four-cytokine levels (p=NS) but with significant time effect on IL2, IL6, TNF α. (p=0.034, 0.001 & 0.004 respectively). In that, we observed minimal decreasing rate from baseline to 40 mins and 240 mins post-infusion in IL2 and IL6 (< 5%) while moderate decreasing in TNF α (10–15%). However, no correlations between decreasing rate of cytokines with mood improvemnt rate nor predictors of baseline or changes of cytokines for responder rate (>=50% reduction of either HAMD-17 and MADRS from D2 to D4) were found. Nevertheless, If we divided the cytokine levels using median No into high and low level group, only baseline IL6 high level group (IL6 > 28953pg/ml) and CRP low level group (CRP< <518ng/ml) 36 | International Journal of Neuropsychopharmacology, 2016 showed better response in 0.5mg/kg than PBO groups (OR=8.9, CI1.2–20.2 and OR=10.3, CI 1.3–86.5, ps<0.05, respectively). Conclusion: the results did not find significant biomarkers to predict better respons to 0.5mg/kg ketamine but baseline high IL6 and low CRP level may possible do. Moderate reduction of TNF α level with 0.5mg/kg ketamine might be related to initial antiinflammtory effect. PS104 An attempt to construct a 7-item short version of the Temperament and Character Inventory to predict the treatment response of patients with depression Tetsu Tomito, Masamichi Ishioka, Ayako Kaneda, Kazuhiko Nakamura, Norio Sugawara, Norio Yasui-Furukori Hirosaki University, Japan Abstract Objectives: Previous studies have reported associations between Temperament and Character Inventory (TCI) and the response to treatment in patients with major depressive disorder (MDD). We aimed to determine which TCI items could predict the response to treatment with paroxetine in patients with MDD and to provide cut-off values of the scores from these items. Methods: Seventy-three patients were enrolled in this study. Participants completed the TCI and were treated with paroxetine for six weeks. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate depression. Participants were divided into responders and non-responders. We used a chi-squared test to identify the 10 items with the strongest association with treatment response from among all 240 items on the TCI. We rated the answers to each item associated with treatment response as a “1”, and the answers associated with a non-response were rated as a “0”. We calculated predictive scores using 10 models. Each model consisted of 1–10 scores of the best 1–10 items. We defined cut-off values for predicting treatment responses using a receiver operating characteristic (ROC) curve analysis. Results: Ranked by the strength of the association with treatment response, items 174, 137, 70, 237, 106, 191, 34, 232, 161, and 215 significantly predicted treatment responses. All the models significantly predicted treatment response using a multiple logistic regression analysis. All predictive scores from models 1–10 significantly predicted treatment responses. The predictive score threshold of model 7 was 3/4 with an area under the curve of 0.825, and it showed the highest odds and likelihood ratios (19.3 and 8.86, respectively). Conclusions: Some TCI items showed significant associations with the response to paroxetine treatment in the patients with MDD. We might predict the response using TCI predictive scoring, including items 174, 137, 70, 237, 106, 191, and 34 and a cutoff value of 3/4.Objectives: Previous studies have reported associations between Temperament and Character Inventory (TCI) and the response to treatment in patients with major depressive disorder (MDD). We aimed to determine which TCI items could predict the response to treatment with paroxetine in patients with MDD and to provide cut-off values of the scores from these items. Methods: Seventy-three patients were enrolled in this study. Participants completed the TCI and were treated with paroxetine for six weeks. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to evaluate depression. Participants were divided into responders and non-responders. We used a chi-squared test to identify the 10 items with the strongest association with treatment response from among all 240 items on the TCI. We rated the answers to each item associated with treatment response as a “1”, and the answers associated with a non-response were rated as a “0”. We calculated predictive scores using 10 models. Each model consisted of 1–10 scores of the best 1–10 items. We defined cut-off values for predicting treatment responses using a receiver operating characteristic (ROC) curve analysis. Results: Ranked by the strength of the association with treatment response, items 174, 137, 70, 237, 106, 191, 34, 232, 161, and 215 significantly predicted treatment responses. All the models significantly predicted treatment response using a multiple logistic regression analysis. All predictive scores from models 1–10 significantly predicted treatment responses. The predictive score threshold of model 7 was 3/4 with an area under the curve of 0.825, and it showed the highest odds and likelihood ratios (19.3 and 8.86, respectively). Conclusions: Some TCI items showed significant associations with the response to paroxetine treatment in the patients with MDD. We might predict the response using TCI predictive scoring, including items 174, 137, 70, 237, 106, 191, and 34 and a cutoff value of 3/4. PS105 Effects of CYP2C19 genotype on steady-state plasma concentrations of escitalopram and desmetyl metabolite in Japanese depressed patients Shoko Tsuchimine1, Yoshimasa Inoue1, Shinichiro Ochi2, Yutaro Suzuki3, Misuzu Tajiri3, Norio Yasui-Furukori1 1Hirosaki University, Japan, 2Ehime University, Japan, 3Niigata