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C.03.01 Depression is more than just low mood
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C.03. Defining remission in depression: is MADRS enough?
clinical studies. Poster presented at the 53rd ACNP Congress. Phoenix, Arizona, USA. 7−11 December. Disclosure statement: This abstract is financially supported by an educational grant from Otsuka Pharmaceutical Development & Commercialization, Inc. and H. Lundbeck A/S
C.03. Defining remission in depression: is MADRS enough? C.03.01 Depression is more than just low mood K. Demyttenaere1 ° Belgium
1 KU
Leuven, Faculty of Medicine, Leuven,
Major depressive disorder is frequently diagnosed based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), which emphasises depressed mood and anhedonia as key symptoms. It is, therefore, remarkable that in the most frequently used questionnaires, anhedonia is not mentioned. Furthermore, the reliability of the DSM-5 as a diagnostic instrument has often been doubted. Recent field trials have indicated that the test reliability of the DSM-5 for major depressive disorder is ‘questionable’ [1], ie the degree to which two clinicians could independently agree on the presence or absence of selected DSM-5 diagnoses in the same patient. Furthermore, patients and clinicians regard different symptoms as a priority when considering cure [2]. While patients consider positive affect items as most important (the experience of positive emotions), clinicians generally perceive depressive symptoms as the more important. This is of relevance because poor physicianpatient agreement regarding the relative importance of these symptoms is associated with a worse clinical outcome for three variables: anxiety, positive affect and social relationships [3]. In addition to drugs that broadly affect depressive symptoms, a range of antidepressants are now available with different pharmacological actions, developed to target specific symptoms in depression beyond low mood. These symptoms include positive affect (eg agomelatine), cognitive symptoms (eg vortioxetine) [4], physical symptoms (eg duloxetine) and anxiety symptoms (eg selective serotonin reuptake inhibitors). Exploring the historical use of antidepressants highlights how depression is a disease with multiple dimensions and may help further our understanding of this complex disorder. References [1] Regier, D.A., Narrow, W.E., Clarke, D.E., Kraemer, H.C., Kuramoto, S.J., Kuhl, E.A., Kupfer, D.J., 2013. DSM-5 Field Trials in the United States and Canada, Part II: test-retest reliability of selected categorical diagnoses. Am J Psychiatry 170, 59−70. [2] Demyttenaere, K., Donneau, A.F., Albert, A., Ansseau, M., Constant, E., van Heeringen, K., 2015. What is important in being cured from depression? Discordance between physicians and patients (1). J Affect Disord 174, 390–396. [3] Demyttenaere, K., Donneau, A.F., Albert, A., Ansseau, M., Constant, E., van Heeringen, K., 2015. What is important in being cured from depression? Does discordance between physicians and patients matter? (2). J Affect Disord 174, 372–377. [4] McIntyre, R.S., Lophaven, S., Olsen, C.K., 2014. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol 17, 1557– 1567. Disclosure statement: Advisory boards/speaker bureaus: AstraZeneca, Eli Lilly, Lundbeck, Servier, Aurex.
C.03.02 Capturing patient relevant outcomes in depression objectively C. Harmer1 ° 1 University of Oxford, Department of Psychiatry, Oxford, United Kingdom Cognitive dysfunction in depression can include biases towards negative emotional information and deficits in memory, attention and executive function. In depression, experimental models have revealed early effects of antidepressants on emotional biases [1]. One week of selective serotonin reuptake inhibitor (SSRI) treatment reduced the recognition of negative versus positive affective facial expressions, accompanied by reduced amygdala response to fearful faces. These early changes in emotional processing predict a reduction in symptoms after 6−8 weeks of treatment and have led to the hypothesis that early reduction in affective bias is a key mechanism of antidepressant drug effects [1]. The effects of SSRIs on other cognitive deficits in depression are less consistent; improvements can often be accounted for by mood effects. The multimodal antidepressant vortioxetine improved executive function in depressed patients and these effects may be direct rather than via symptom improvement [2,3]. In support of these clinical observations, we found an early effect of vortioxetine in individuals remitted from depression and healthy volunteers. Compared to placebo, vortioxetine facilitated subjective and objective measures of cognitive function while reducing activation in the dorsolateral prefrontal cortex and hippocampus during the n-back working memory task. This suggests that vortioxetine modulates neural responses across a circuit subserving working memory conversely to the changes described in depression. Compared to clinical rating scores, objective measurement of cognitive function with behavioural assessment and neuroimaging may provide more information about the early effects of antidepressants. These early effects may be fundamental to later effects on patient functioning in depression. References [1] Harmer, C.J., Cowen, P.J., 2013. ‘It’s the way that you look at it’— a cognitive neuropsychological account of SSRI action in depression. Philos Trans R Soc Lond B Biol Sci 368, 20120407. [2] Mahableshwarkar, A.R., Zajecka, J., Jacobson, W., Chen, Y., Keefe, R.S.E., 2015. A randomized, placebo-controlled, activereference, double-blind, flexible-dose study of the efficacy of vortioxetine on cognitive function in major depressive disorder. Neuropsychopharmacology 17 Feb, [Epub ahead of print]. [3] McIntyre, R.S., Lophaven, S., Olsen, C.K., 2014. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol 17, 1557– 1567. Disclosure statement: Catherine Harmer has consulting roles at P1vital, Servier and Lundbeck and receives research funding from Servier, Lundbeck, UCB, Janssen and AstraZeneca. Catherine is a company director and shareholder of Oxford Psychologists Ltd.
C.03.03 Pathways to improve cognitive dysfunction in depression J. Jaeger1 ° 1 CognitionMetrics, President and Principal Scientist, Wilmington, USA Cognitive dysfunction has been recognised as an important feature of major depression since its earliest historical descriptions. The prominence of mood symptoms led to the belief that cognitive
C.03. Defining remission in depression: is MADRS enough?
clinical studies. Poster presented at the 53rd ACNP Congress. Phoenix, Arizona, USA. 7−11 December. Disclosure statement: This abstract is financially supported by an educational grant from Otsuka Pharmaceutical Development & Commercialization, Inc. and H. Lundbeck A/S
C.03. Defining remission in depression: is MADRS enough? C.03.01 Depression is more than just low mood K. Demyttenaere1 ° Belgium
1 KU
Leuven, Faculty of Medicine, Leuven,
Major depressive disorder is frequently diagnosed based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), which emphasises depressed mood and anhedonia as key symptoms. It is, therefore, remarkable that in the most frequently used questionnaires, anhedonia is not mentioned. Furthermore, the reliability of the DSM-5 as a diagnostic instrument has often been doubted. Recent field trials have indicated that the test reliability of the DSM-5 for major depressive disorder is ‘questionable’ [1], ie the degree to which two clinicians could independently agree on the presence or absence of selected DSM-5 diagnoses in the same patient. Furthermore, patients and clinicians regard different symptoms as a priority when considering cure [2]. While patients consider positive affect items as most important (the experience of positive emotions), clinicians generally perceive depressive symptoms as the more important. This is of relevance because poor physicianpatient agreement regarding the relative importance of these symptoms is associated with a worse clinical outcome for three variables: anxiety, positive affect and social relationships [3]. In addition to drugs that broadly affect depressive symptoms, a range of antidepressants are now available with different pharmacological actions, developed to target specific symptoms in depression beyond low mood. These symptoms include positive affect (eg agomelatine), cognitive symptoms (eg vortioxetine) [4], physical symptoms (eg duloxetine) and anxiety symptoms (eg selective serotonin reuptake inhibitors). Exploring the historical use of antidepressants highlights how depression is a disease with multiple dimensions and may help further our understanding of this complex disorder. References [1] Regier, D.A., Narrow, W.E., Clarke, D.E., Kraemer, H.C., Kuramoto, S.J., Kuhl, E.A., Kupfer, D.J., 2013. DSM-5 Field Trials in the United States and Canada, Part II: test-retest reliability of selected categorical diagnoses. Am J Psychiatry 170, 59−70. [2] Demyttenaere, K., Donneau, A.F., Albert, A., Ansseau, M., Constant, E., van Heeringen, K., 2015. What is important in being cured from depression? Discordance between physicians and patients (1). J Affect Disord 174, 390–396. [3] Demyttenaere, K., Donneau, A.F., Albert, A., Ansseau, M., Constant, E., van Heeringen, K., 2015. What is important in being cured from depression? Does discordance between physicians and patients matter? (2). J Affect Disord 174, 372–377. [4] McIntyre, R.S., Lophaven, S., Olsen, C.K., 2014. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol 17, 1557– 1567. Disclosure statement: Advisory boards/speaker bureaus: AstraZeneca, Eli Lilly, Lundbeck, Servier, Aurex.
C.03.02 Capturing patient relevant outcomes in depression objectively C. Harmer1 ° 1 University of Oxford, Department of Psychiatry, Oxford, United Kingdom Cognitive dysfunction in depression can include biases towards negative emotional information and deficits in memory, attention and executive function. In depression, experimental models have revealed early effects of antidepressants on emotional biases [1]. One week of selective serotonin reuptake inhibitor (SSRI) treatment reduced the recognition of negative versus positive affective facial expressions, accompanied by reduced amygdala response to fearful faces. These early changes in emotional processing predict a reduction in symptoms after 6−8 weeks of treatment and have led to the hypothesis that early reduction in affective bias is a key mechanism of antidepressant drug effects [1]. The effects of SSRIs on other cognitive deficits in depression are less consistent; improvements can often be accounted for by mood effects. The multimodal antidepressant vortioxetine improved executive function in depressed patients and these effects may be direct rather than via symptom improvement [2,3]. In support of these clinical observations, we found an early effect of vortioxetine in individuals remitted from depression and healthy volunteers. Compared to placebo, vortioxetine facilitated subjective and objective measures of cognitive function while reducing activation in the dorsolateral prefrontal cortex and hippocampus during the n-back working memory task. This suggests that vortioxetine modulates neural responses across a circuit subserving working memory conversely to the changes described in depression. Compared to clinical rating scores, objective measurement of cognitive function with behavioural assessment and neuroimaging may provide more information about the early effects of antidepressants. These early effects may be fundamental to later effects on patient functioning in depression. References [1] Harmer, C.J., Cowen, P.J., 2013. ‘It’s the way that you look at it’— a cognitive neuropsychological account of SSRI action in depression. Philos Trans R Soc Lond B Biol Sci 368, 20120407. [2] Mahableshwarkar, A.R., Zajecka, J., Jacobson, W., Chen, Y., Keefe, R.S.E., 2015. A randomized, placebo-controlled, activereference, double-blind, flexible-dose study of the efficacy of vortioxetine on cognitive function in major depressive disorder. Neuropsychopharmacology 17 Feb, [Epub ahead of print]. [3] McIntyre, R.S., Lophaven, S., Olsen, C.K., 2014. A randomized, double-blind, placebo-controlled study of vortioxetine on cognitive function in depressed adults. Int J Neuropsychopharmacol 17, 1557– 1567. Disclosure statement: Catherine Harmer has consulting roles at P1vital, Servier and Lundbeck and receives research funding from Servier, Lundbeck, UCB, Janssen and AstraZeneca. Catherine is a company director and shareholder of Oxford Psychologists Ltd.
C.03.03 Pathways to improve cognitive dysfunction in depression J. Jaeger1 ° 1 CognitionMetrics, President and Principal Scientist, Wilmington, USA Cognitive dysfunction has been recognised as an important feature of major depression since its earliest historical descriptions. The prominence of mood symptoms led to the belief that cognitive