title: Combining clinical variables to optimize prediction of antidepressant treatment outcomes.
abstract: The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug.
authors.affiliation: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK. Electronic address: raquel.iniesta@kcl.ac.uk.
authors.forename: Raquel
authors.initials: R
authors.lastname: Iniesta
authors.affiliation: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
authors.forename: Karim
authors.initials: K
authors.lastname: Malki
authors.affiliation: Department of Psychiatry, University of Bonn, Regina-Pacis-Weg 3, 53113 Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.affiliation: Central Institute of Mental Health, Division of Genetic Epidemiology in Psychiatry, Square J5, 68159, Mannheim, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Research Department P, Aarhus University Hospital, Norrebrogade 44, Aarhus C, DK-8000, Risskov, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Mors
authors.affiliation: Laboratory of Psychiatric Genetics, Department of Psychiatry, Poznan University of Medical Sciences, Collegium Maius, Fredry 10, 61-701, Poznań, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Hauser
authors.affiliation: Croatian Institute for Brain Research, Medical School, University of Zagreb, Salata 3, 10 000, Zagreb, Croatia.
authors.forename: Neven
authors.initials: N
authors.lastname: Henigsberg
authors.affiliation: University Psychiatric Clinic and the Medical Faculty, University of Ljubljana, Kongresni trg 12, 1000, Ljubljana, Slovenia.
authors.forename: Mojca Zvezdana
authors.initials: MZ
authors.lastname: Dernovsek
authors.affiliation: Laboratoire de Psychologie Médicale, Université Libre de Bruxelles and Psy Pluriel - Centre Européen de Psychologie Médicale, Av Jack Pastur 47a, 1180, Uccle, Belgium.
authors.forename: Daniel
authors.initials: D
authors.lastname: Souery
authors.affiliation: Institute of Psychiatry, Psychology and Neuroscience, Kings College London, 16 De Crespigny Park, London, SE5 8AF, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stahl
authors.affiliation: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Dobson
authors.affiliation: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK; Department of Psychiatry and Medical Genetics, University of Alberta, 116 St and 85 Ave, Edmonton, AB, T6G 2R3, Canada.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Aitchison
authors.affiliation: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Farmer
authors.affiliation: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
authors.forename: Cathryn M
authors.initials: CM
authors.lastname: Lewis
authors.affiliation: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.affiliation: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK; Dalhousie University Department of Psychiatry, 5909 Veterans' Memorial Drive, Halifax, B3H 2E2, Nova Scotia, Canada.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Uher
mesh_terms: D000367:Age Factors; D000928:Antidepressive Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D015992:Body Mass Index; D015283:Citalopram / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D000069550:Machine Learning; D008297:Male; D009661:Nortriptyline / Q000627:therapeutic use*; D010551:Personality; D057285:Precision Medicine; D011379:Prognosis; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D009661:Nortriptyline
keywords: Antidepressant; Depression; Machine learning; Outcome; Prediction; Statistical learning