- Email: [email protected]
E.05.01 The unmet needs in the treatment of schizophrenia
S150
E.05. EPA session: the true unmet needs in the therapeutic armamentarium seen from a clinical perspective
The evidence shows that acute and long term treatment, including both pharmacological and psychological methods can significantly decrease the risk of completed and attempted suicide in this high risk populations.
E.03.03 Methodological design and limitations of current studies on psychotropic medication in pregnancy
References
M. Galbally1 ° , A.J. Lewis2 1 Mercy Hospital for Women, Perinatal Mental Health, Heidelberg, Australia; 2 Deakin University, Department of Psychology, Burwood, Australia
[1] Wasserman, D., Rihmer, Z., Rujescu, D., Sarchiapone, M., Sokolowski, M., Titelman, D., Zalsman, G., Zemishlany, Z., Carli, V., 2012. The European Psychiatric Association (EPA) guidance on suicide treatment and prevention. Eur. Psych. 27(2), 129−41.
E.03. Clinical pharmacology and research during pregnancy E.03.02 Review presentation of available safety data on major psychotropic categories S. Gentile1 ° 1 Mental Health Center Cava de’ Tirreni, Department of Mental Health, Cava de’ Tirreni, Italy Background: During the last few years, several researches, often showing contradictory findings, have investigated the safety of psychotropic medications used for treating mental disorders in pregnancy. Hence, the necessity exists to revise constantly this information in order to ensure the safest option for the mother– infant pair. Updated findings: The risk of fetal anomalies associated with early pregnancy exposure to antidepressants seems to be increased after paroxetine and chlorimipramine exposure, while late pregnancy exposure to nearly all antidepressants is linked to the potential onset of the Prenatal Antidepressant Exposure Syndrome [1]. As regards classic mood stabilizers, the risk of cardiac malformations historically reported with lithium should probably be softened. In contrast, an increased incidence of neural tube defects and perinatal complications associated with prenatal lithium exposure has recently been assessed [2]. However, valproate and carbamazepine are the medications which show the strongest association with birth defects. An increased risk of autism-spectrum disorders and infant neurodevelopmental delay is also associated with valproate exposure through the placenta. No significant reproductive safety data are available on atypical antipsychotics, although such medications may directly increase the risk of perinatal complications and indirectly increase the rate of fetal malformation by inducing gestational diabetes [3]. Conclusions: Since no classes of psychotropics are devoid of risks for the fetus and the newborn, the decision to start or continue pharmacological treatment during pregnancy should be weighed on a case-by-case basis. However, avoiding the use of chlorimipramine, paroxetine, valproate, carbamazepine, and atypical antipsychotics is highly advisable. References [1] Gentile, S. 2010 On categorizing gestational, birth, and neonatal complications following late in utero exposure to antidepressants. The prenatal antidepressant exposure syndrome. CNS Spectr 15, 67–185. [2] Gentile, S. In press. Lithium in pregnancy: the need to treat, the duty to ensure safety. Exp Opin Drug Saf. [3] Gentile, S. 2010 Antipsychotic therapy during early and late pregnancy. A systematic review. Schizophr Bull 36, 518–544.
For all psychotropic medications, including antidepressants, antipsychotics and lithium carbonate, there are methodological limitations in existing studies examining the risks these treatments pose in pregnancy [1]. Since ethical considerations limit the capacity to conduct blinded placebo randomized controlled trials the majority of studies either use a case–control prospective cohort design or examination of large population-based datasets. Case–control prospective cohort studies often have small numbers and in the area of psychotropic medication in pregnancy most have follow-up of less than 1 year. Therefore, these studies often suffer from lack of power, may have recruitment bias and many cannot assess longer term developmental outcomes. While the examination of large population-based datasets is useful for prescription rates in pregnancy and for broad screening for major developmental deficits, they tend to lack detail regarding the amount and timing of prenatal exposures, compliance and also tend to utilize brief survey instruments as primary outcome measures. These limitations, including the number of confounding variables, lack of clarity around compliance and exposure and the predictive validity of outcomes measures all make it difficult to establish clearly the risks for either pregnancy related or neonatal complications or the long term safety of psychotropic medications for offspring. This lack of clarity for women about risks and benefits for pharmacological treatment of mental illness in pregnancy can increase the anxiety and burden that they face [2]. But by understanding the strengths and limitations of the studies available clinicians can more accurately interpret these findings for women and their families. References [1] Galbally, M., Lewis, A. J., Snellen, M., 2011 A review of the use of psychotropic medication in pregnancy. Current Opinion in Obstetrics and Gynaecology 23, 408–414. [2] Mulder, E., Davis, A., Gawley, L., Bowen, A., Einerson, A., 2012 Negative impact of non-evidence based information received by women taking antidepressants during pregnancy from health care providers and other. JOGC 34, 66−71. Disclosure statement: I have received research funding in the past from Wyeth, Lundbeck and Pfizer.
E.05. EPA session: the true unmet needs in the therapeutic armamentarium seen from a clinical perspective E.05.01 The unmet needs in the treatment of schizophrenia I. Bitter1 ° , S. Galderisi2 1 Semmelweis University, Dept. of Psychiatry and Psychotherapy, Budapest, Hungary; 2 University of Naples SUN, Dept. of Psychiatry, Naples, Italy Recent treatment options in schizophrenia are associated in a large proportion of patients with unsatisfactory outcomes which are
E.05. EPA session: the true unmet needs in the therapeutic armamentarium seen from a clinical perspective mainly related to their limited efficacy but also partly to their side effect burden and high discontinuation rates [1,2]. Cognitive impairment, primary negative symptoms/deficit schizophrenia, depression, suicidality, functional outcomes and high mortality are the areas where the need for improved treatment is major. Recent focus on recovery has emphasized that outcome should be measured not only by remission of symptoms, but also by improvement in cognitive and psychosocial functioning. Declining investment into psychiatric research by private industry, governments and EU funding agencies decreases the likelihood of breakthrough drug discovery for the treatment of schizophrenia. High discontinuation rates of available antipsychotic drugs are associated with worse outcomes. While discontinuation rates are related to the insight/cooperation of patients, the large differences in discontinuation rates between different regions of the world [3] call attention to the differences between health care systems; between different formulation of the same drug stress the need for considering higher utilization of depot injections and for the development of longer acting tablets. To our knowledge the development of once a week tablets for schizophrenia has been hindered by recent reimbursement policies. There is a need for better development and integration of community psychosocial and health care services in many areas of the world, including Europe, which could improve the continuous delivery of already available effective treatments to more patients suffering from schizophrenia.
S151
illness (untreated depression: DUP) may result in a damage, like reduced volume size of the hippocampus for depression. It is well established that with currently available treatment options up to 20% of the patients with major depression fail to respond to standard interventions and remission may not be achieved in over 60% of treated patients. Up to now the decision for a specific treatment option in clinical routine is only based on the clinician’s expertise and experience. No additional results, such as neuroimaging findings or laboratory parameters are available to provide a tailored individual treatment plan. In the last years, the knowledge about key targets of antidepressant treatment as revealed by neuroimaging techniques, magnetic resonance imaging (MRI) and positron emission tomography (PET) have substantially contributed to a broader understanding about the neurobiological mechanisms implicated in treatment response. Besides individual knowledge of the patient’s psychosocial situation a more thorough characterisation of the underlying pathophysiology of depression including brain imaging results as well as molecular biological variables are necessary to be studied in research protocols. This will hopefully result in further insight into the understanding of the illness and therefore at least partly resolve unmet needs in the treatment of depression. Disclosure statement: Dr. Kasper has received grant/research support from Bristol Myers-Squibb, Eli Lilly, GlaxoSmithKline, Lundbeck, Organon, Sepracor and Servier has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, Merck Sharp and Dome (MSD), Novartis, Organon, Pfizer, Schwabe, Sepracor, and Servier and has served on speakers’ bureaus for Angelini, AstraZeneca, Bristol Myers-Squibb, Eli Lilly, Janssen, Lundbeck, Pfizer, Pierre Fabre, Schwabe, Sepracor, and Servier.
References [1] Lieberman, JA, Stroup, TS, McEvoy, JP, Swartz, MS, Rosenheck, RA, Perkins, DO, Keefe, RS, Davis, Clarence E. Davis, CE, Lebowitz, BD, Severe, J, Hsiao, JK for the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators, 2005. Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia. N Engl J Med 353, 1209–1223. [2] Kahn, RS, Fleischhacker, WW, Boter, H, Davidson, M, Vergouwe Y, Keet, IP, Gheorghe, MD, Rybakowski, JK, Galderisi, S, Libiger, J, Hummer, M, Dollfus, S, L´opez-Ibor, JJ, Hranov, LG, Gaebel, W, Peuskens J, Lindefors, N, Riecher-R¨ossler, A, Grobbee, DE, 2008. EUFEST study group. Effectiveness of antipsychotic drugs in firstepisode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet. 29; 371(9618): 1085−97. [3] Bitter, I, Treuer, T, Dyachkova, Y, Martenyi, F, McBride, M, Ungvari, GS, 2008. Antipsychotic prescription patterns in outpatient settings: 24-month results from the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study. Eur Neuropsychopharmacology 18, 170–180. Disclosure statement: Istvan Bitter has been in the last 5 years an advisory board member/consultant/lecturer for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, EGIS, Janssen, Lundbeck, Novartis, Pfizer and Richter. Silvana Galderisi received fees for educational programmes or advisory boards from AstraZeneca, Innova-Pharma, Bristol-Myers Squibb, Janssen-Cilag.
E.05.02 The unmet needs in the treatment of unipolar depression S. Kasper1 ° 1 Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna, Austria Like in other medical conditions, early treatment should be achieved and watchful waiting, which is for instance also not done in the treatment of high blood pressure, has not been proven to be a sophisticated approach based on neurobiological considerations in depression. It is apparent that days of untreated
E.05.03 The unmet needs in the treatment of alcohol dependence P. Gorwood1 ° France
1 Hˆ opital
de Sainte Anne, CMME, Paris cedex 14,
Alcohol dependence concerns 14.6 millions of Europeans and was the most disabling male condition (according to DALYs) in 2010 [1]. As only one out of 10 patients with alcohol dependence perceives a need for treatment, large progresses are needed to facilitate early recognition, reduce the delay in obtaining adequate treatment, and increase the quality of proposed care. Alcohol dependence is considered as a homogenous syndrome, but in fact has many facettes which constitute different treatment targets including early abuse, binging, craving, withdrawal symptoms, relapse avoidance and severe physical dependence. Reducing harmful consumption of alcohol, rather than curing the dependence per se, is an example for early intervention that might have a larger impact. This increase the interest of Nalmefene (and opioid receptors antagonist) and Lyoresal (a GABA-B antagonist). Nevertheless, demonstrating the long term benefits of this exciting new approach raises questions for long term impact, quality of live and delayed risk of the lethal complications observed in alcohol dependence. Deep brain stimulations might be more interesting for very severe dependence, with preliminary interesting findings [2]. Focusing on brain loops that are specifically involved in the addictive processes, such as the prefrontal-striatum loop recently put to the forth [3], is a logical next step. Finally, combining the pharmacological approach with different types of psychotherapy, and using the genetic profile of the patient
E.05. EPA session: the true unmet needs in the therapeutic armamentarium seen from a clinical perspective
The evidence shows that acute and long term treatment, including both pharmacological and psychological methods can significantly decrease the risk of completed and attempted suicide in this high risk populations.
E.03.03 Methodological design and limitations of current studies on psychotropic medication in pregnancy
References
M. Galbally1 ° , A.J. Lewis2 1 Mercy Hospital for Women, Perinatal Mental Health, Heidelberg, Australia; 2 Deakin University, Department of Psychology, Burwood, Australia
[1] Wasserman, D., Rihmer, Z., Rujescu, D., Sarchiapone, M., Sokolowski, M., Titelman, D., Zalsman, G., Zemishlany, Z., Carli, V., 2012. The European Psychiatric Association (EPA) guidance on suicide treatment and prevention. Eur. Psych. 27(2), 129−41.
E.03. Clinical pharmacology and research during pregnancy E.03.02 Review presentation of available safety data on major psychotropic categories S. Gentile1 ° 1 Mental Health Center Cava de’ Tirreni, Department of Mental Health, Cava de’ Tirreni, Italy Background: During the last few years, several researches, often showing contradictory findings, have investigated the safety of psychotropic medications used for treating mental disorders in pregnancy. Hence, the necessity exists to revise constantly this information in order to ensure the safest option for the mother– infant pair. Updated findings: The risk of fetal anomalies associated with early pregnancy exposure to antidepressants seems to be increased after paroxetine and chlorimipramine exposure, while late pregnancy exposure to nearly all antidepressants is linked to the potential onset of the Prenatal Antidepressant Exposure Syndrome [1]. As regards classic mood stabilizers, the risk of cardiac malformations historically reported with lithium should probably be softened. In contrast, an increased incidence of neural tube defects and perinatal complications associated with prenatal lithium exposure has recently been assessed [2]. However, valproate and carbamazepine are the medications which show the strongest association with birth defects. An increased risk of autism-spectrum disorders and infant neurodevelopmental delay is also associated with valproate exposure through the placenta. No significant reproductive safety data are available on atypical antipsychotics, although such medications may directly increase the risk of perinatal complications and indirectly increase the rate of fetal malformation by inducing gestational diabetes [3]. Conclusions: Since no classes of psychotropics are devoid of risks for the fetus and the newborn, the decision to start or continue pharmacological treatment during pregnancy should be weighed on a case-by-case basis. However, avoiding the use of chlorimipramine, paroxetine, valproate, carbamazepine, and atypical antipsychotics is highly advisable. References [1] Gentile, S. 2010 On categorizing gestational, birth, and neonatal complications following late in utero exposure to antidepressants. The prenatal antidepressant exposure syndrome. CNS Spectr 15, 67–185. [2] Gentile, S. In press. Lithium in pregnancy: the need to treat, the duty to ensure safety. Exp Opin Drug Saf. [3] Gentile, S. 2010 Antipsychotic therapy during early and late pregnancy. A systematic review. Schizophr Bull 36, 518–544.
For all psychotropic medications, including antidepressants, antipsychotics and lithium carbonate, there are methodological limitations in existing studies examining the risks these treatments pose in pregnancy [1]. Since ethical considerations limit the capacity to conduct blinded placebo randomized controlled trials the majority of studies either use a case–control prospective cohort design or examination of large population-based datasets. Case–control prospective cohort studies often have small numbers and in the area of psychotropic medication in pregnancy most have follow-up of less than 1 year. Therefore, these studies often suffer from lack of power, may have recruitment bias and many cannot assess longer term developmental outcomes. While the examination of large population-based datasets is useful for prescription rates in pregnancy and for broad screening for major developmental deficits, they tend to lack detail regarding the amount and timing of prenatal exposures, compliance and also tend to utilize brief survey instruments as primary outcome measures. These limitations, including the number of confounding variables, lack of clarity around compliance and exposure and the predictive validity of outcomes measures all make it difficult to establish clearly the risks for either pregnancy related or neonatal complications or the long term safety of psychotropic medications for offspring. This lack of clarity for women about risks and benefits for pharmacological treatment of mental illness in pregnancy can increase the anxiety and burden that they face [2]. But by understanding the strengths and limitations of the studies available clinicians can more accurately interpret these findings for women and their families. References [1] Galbally, M., Lewis, A. J., Snellen, M., 2011 A review of the use of psychotropic medication in pregnancy. Current Opinion in Obstetrics and Gynaecology 23, 408–414. [2] Mulder, E., Davis, A., Gawley, L., Bowen, A., Einerson, A., 2012 Negative impact of non-evidence based information received by women taking antidepressants during pregnancy from health care providers and other. JOGC 34, 66−71. Disclosure statement: I have received research funding in the past from Wyeth, Lundbeck and Pfizer.
E.05. EPA session: the true unmet needs in the therapeutic armamentarium seen from a clinical perspective E.05.01 The unmet needs in the treatment of schizophrenia I. Bitter1 ° , S. Galderisi2 1 Semmelweis University, Dept. of Psychiatry and Psychotherapy, Budapest, Hungary; 2 University of Naples SUN, Dept. of Psychiatry, Naples, Italy Recent treatment options in schizophrenia are associated in a large proportion of patients with unsatisfactory outcomes which are
E.05. EPA session: the true unmet needs in the therapeutic armamentarium seen from a clinical perspective mainly related to their limited efficacy but also partly to their side effect burden and high discontinuation rates [1,2]. Cognitive impairment, primary negative symptoms/deficit schizophrenia, depression, suicidality, functional outcomes and high mortality are the areas where the need for improved treatment is major. Recent focus on recovery has emphasized that outcome should be measured not only by remission of symptoms, but also by improvement in cognitive and psychosocial functioning. Declining investment into psychiatric research by private industry, governments and EU funding agencies decreases the likelihood of breakthrough drug discovery for the treatment of schizophrenia. High discontinuation rates of available antipsychotic drugs are associated with worse outcomes. While discontinuation rates are related to the insight/cooperation of patients, the large differences in discontinuation rates between different regions of the world [3] call attention to the differences between health care systems; between different formulation of the same drug stress the need for considering higher utilization of depot injections and for the development of longer acting tablets. To our knowledge the development of once a week tablets for schizophrenia has been hindered by recent reimbursement policies. There is a need for better development and integration of community psychosocial and health care services in many areas of the world, including Europe, which could improve the continuous delivery of already available effective treatments to more patients suffering from schizophrenia.
S151
illness (untreated depression: DUP) may result in a damage, like reduced volume size of the hippocampus for depression. It is well established that with currently available treatment options up to 20% of the patients with major depression fail to respond to standard interventions and remission may not be achieved in over 60% of treated patients. Up to now the decision for a specific treatment option in clinical routine is only based on the clinician’s expertise and experience. No additional results, such as neuroimaging findings or laboratory parameters are available to provide a tailored individual treatment plan. In the last years, the knowledge about key targets of antidepressant treatment as revealed by neuroimaging techniques, magnetic resonance imaging (MRI) and positron emission tomography (PET) have substantially contributed to a broader understanding about the neurobiological mechanisms implicated in treatment response. Besides individual knowledge of the patient’s psychosocial situation a more thorough characterisation of the underlying pathophysiology of depression including brain imaging results as well as molecular biological variables are necessary to be studied in research protocols. This will hopefully result in further insight into the understanding of the illness and therefore at least partly resolve unmet needs in the treatment of depression. Disclosure statement: Dr. Kasper has received grant/research support from Bristol Myers-Squibb, Eli Lilly, GlaxoSmithKline, Lundbeck, Organon, Sepracor and Servier has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, Merck Sharp and Dome (MSD), Novartis, Organon, Pfizer, Schwabe, Sepracor, and Servier and has served on speakers’ bureaus for Angelini, AstraZeneca, Bristol Myers-Squibb, Eli Lilly, Janssen, Lundbeck, Pfizer, Pierre Fabre, Schwabe, Sepracor, and Servier.
References [1] Lieberman, JA, Stroup, TS, McEvoy, JP, Swartz, MS, Rosenheck, RA, Perkins, DO, Keefe, RS, Davis, Clarence E. Davis, CE, Lebowitz, BD, Severe, J, Hsiao, JK for the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators, 2005. Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia. N Engl J Med 353, 1209–1223. [2] Kahn, RS, Fleischhacker, WW, Boter, H, Davidson, M, Vergouwe Y, Keet, IP, Gheorghe, MD, Rybakowski, JK, Galderisi, S, Libiger, J, Hummer, M, Dollfus, S, L´opez-Ibor, JJ, Hranov, LG, Gaebel, W, Peuskens J, Lindefors, N, Riecher-R¨ossler, A, Grobbee, DE, 2008. EUFEST study group. Effectiveness of antipsychotic drugs in firstepisode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet. 29; 371(9618): 1085−97. [3] Bitter, I, Treuer, T, Dyachkova, Y, Martenyi, F, McBride, M, Ungvari, GS, 2008. Antipsychotic prescription patterns in outpatient settings: 24-month results from the Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study. Eur Neuropsychopharmacology 18, 170–180. Disclosure statement: Istvan Bitter has been in the last 5 years an advisory board member/consultant/lecturer for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, EGIS, Janssen, Lundbeck, Novartis, Pfizer and Richter. Silvana Galderisi received fees for educational programmes or advisory boards from AstraZeneca, Innova-Pharma, Bristol-Myers Squibb, Janssen-Cilag.
E.05.02 The unmet needs in the treatment of unipolar depression S. Kasper1 ° 1 Medical University of Vienna, Department of Psychiatry and Psychotherapy, Vienna, Austria Like in other medical conditions, early treatment should be achieved and watchful waiting, which is for instance also not done in the treatment of high blood pressure, has not been proven to be a sophisticated approach based on neurobiological considerations in depression. It is apparent that days of untreated
E.05.03 The unmet needs in the treatment of alcohol dependence P. Gorwood1 ° France
1 Hˆ opital
de Sainte Anne, CMME, Paris cedex 14,
Alcohol dependence concerns 14.6 millions of Europeans and was the most disabling male condition (according to DALYs) in 2010 [1]. As only one out of 10 patients with alcohol dependence perceives a need for treatment, large progresses are needed to facilitate early recognition, reduce the delay in obtaining adequate treatment, and increase the quality of proposed care. Alcohol dependence is considered as a homogenous syndrome, but in fact has many facettes which constitute different treatment targets including early abuse, binging, craving, withdrawal symptoms, relapse avoidance and severe physical dependence. Reducing harmful consumption of alcohol, rather than curing the dependence per se, is an example for early intervention that might have a larger impact. This increase the interest of Nalmefene (and opioid receptors antagonist) and Lyoresal (a GABA-B antagonist). Nevertheless, demonstrating the long term benefits of this exciting new approach raises questions for long term impact, quality of live and delayed risk of the lethal complications observed in alcohol dependence. Deep brain stimulations might be more interesting for very severe dependence, with preliminary interesting findings [2]. Focusing on brain loops that are specifically involved in the addictive processes, such as the prefrontal-striatum loop recently put to the forth [3], is a logical next step. Finally, combining the pharmacological approach with different types of psychotherapy, and using the genetic profile of the patient