Day 2 :
Jina Pharmaceuticals, Inc., USA
Keynote: The calming down of emotional ferris wheel, Bipolar disease: Demonstration of anti-manic efficacy of endoxifen in Bipolar I disorder patients
Time : 10:00-10:40
Ateeq Ahmad, Ph.D. is vice president for science & technology at Jina pharmaceuticals, Inc., USA. Prior to joining Jina in 2006, Dr. Ahmad worked at Neopharm, Inc., Pharmacia (Searle), Sanofi, J &J, Medarex, Biotherapeutics and National Institutes of Health. He has more than 30 years of experience in drug discovery, drug targeting, therapeutic proteins, immunotoxins, liposomes and clinical pharmacology. Currently, Dr. Ahmad is directing drug development program including safety assessment, efficacy evaluation and pharmacokinetics of drug candidates for cancer therapeutics and neurological disorders. He has authored 61 original articles in peer reviewed scientific journals.
Protein kinase C (PKC) activity is increased in frontal cortex of subjects with bipolar affective disorder. Endoxifen, an active metabolite of tamoxifen, was recently demonstrated to inhibit PKC1. We report for the first time the anti-manic effect of endoxifen in patients with bipolar I disorder (BPD I) with current manic or mixed episode. The efficacy was evidenced by change from baseline on total scores of mania [e.g., Young Mania Rating Scale (YMRS)] measures. In a double-blind, active-controlled study, 84 subjects with BPD I were randomly assigned to receive endoxifen (4 mg/day or 8 mg/day) or divalproex (1000 mg/day) in a 2:1 ratio. Patients orally administered at 4 or 8 mg/day endoxifen showed significant improvement in mania assessed by the YMRS as early as 4 days. The effect remained significant throughout the 21-day period. At study end point, YMRS scores showed the response rates were 44.44% and 64.29% at 4 and 8 mg/day of endoxifen treatment respectively. The Exposure-Response (PK-PD) analysis shows dose proportionality of endoxifen2. Thus, endoxifen has been shown as a promising anti-manic or mood stabilizing agent.
Linkoping University, Sweden
Keynote: Electrodermal hyporeactivity and suicidal propensity – Results from three studies of more than 2500 depressive patients in total
Time : 10:40-11:20
Lars-Hakan Thorell was born in 1943 in Sweden. His academic background is research in psychology, psychiatry, particularly psychophysiology and suicidology. He has also been involved in research in neuropsychology and neurophysiology and in creating an advanced psychophysiological laboratory. He has, since 1974, also developed computer programs for real-time experimental applications and for comprehensive statistical analyses. When he retired from his appointment since 1994, as Associate Professor in and Senior Lecturer in Experimental Psychiatry, particularly Psychophysiology he succeeded to continue his research in the fi eld
through support from the medical technological company Emotra AB in Gothenburg, Sweden, that he founded together with his wife. Today he is the Director of Research at that company. He has a increasing research collaboration with a growing number of psychiatric top clinics in Europe and in other countries. He was
in 2014-2015 the president of the World Suicidology Net, founded by Professor Sergio Perez, and is a member of the Net of Suicide Prevention in the European College of Neuropsyho Pharmacology.
Since 1987, several publications have revealed a strong relationship between electrodermal hyporeactivity and suicidal propensity in depression. A meta-analysis (Thorell, 2009) from ten smaller materials showed a very sensitivity (97 %) and very high negative predictive value (“raw specificity”) (93 %) for suicide from tests of electrodermal hyporeactivity. In a study of 783 depressed patients in the Weissenau hospital in Ravensburg (Thorell et al., 2013) these terms were 83 % and 98 %, respectively. In this study the follow-up period was much longer, several years.
The electrodermal hyporeactivity seems to be unrelated to the depth of depression, to genus and age between 18 – 65 years, to clinical results of antidepressive treatments and to levels of 5-HIAA in liquor. It seems also to remain in remission and be stable in later depressive episodes. The prevalence of hyporeactivity was particularly high in patients with bipolar disorders and the relationship was very high, especially in that group.
A third naturalistic study EUDOR-A of about 1 500 depressed patients tested by the test of Electrodermal Orienting Reactivity (EDOR) is still going on in 10 European countries and 15 psychiatric centers involving more than 50 co-researchers.