title: Combining escitalopram and cognitive-behavioural therapy for social anxiety disorder: randomised controlled fMRI trial.
abstract: Selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioural therapy (CBT) are often used concomitantly to treat social anxiety disorder (SAD), but few studies have examined the effect of this combination.
  
  
  
  To evaluate whether adding escitalopram to internet-delivered CBT (ICBT) improves clinical outcome and alters brain reactivity and connectivity in SAD.
  
  
  
  Double-blind, randomised, placebo-controlled neuroimaging trial of ICBT combined either with escitalopram (n = 24) or placebo (n = 24), including a 15-month clinical follow-up (trial registration: ISRCTN24929928).
  
  
  
  Escitalopram+ICBT, relative to placebo+ICBT, resulted in significantly more clinical responders, larger reductions in anticipatory speech state anxiety at post-treatment and larger reductions in social anxiety symptom severity at 15-month follow-up and at a trend-level (P = 0.09) at post-treatment. Right amygdala reactivity to emotional faces also decreased more in the escitalopram+ICBT combination relative to placebo+ICBT, and in treatment responders relative to non-responders.
  
  
  
  Adding escitalopram improves the outcome of ICBT for SAD and decreased amygdala reactivity is important for anxiolytic treatment response.
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden malin.gingnell@psyk.uu.se.
authors.forename: Malin
authors.initials: M
authors.lastname: Gingnell
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Frick
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Engman
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Iman
authors.initials: I
authors.lastname: Alaie
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Johannes
authors.initials: J
authors.lastname: Björkstrand
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Vanda
authors.initials: V
authors.lastname: Faria
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Carlbring
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Andersson
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Margareta
authors.initials: M
authors.lastname: Reis
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Elna-Marie
authors.initials: EM
authors.lastname: Larsson
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Kurt
authors.initials: K
authors.lastname: Wahlstedt
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Fredrikson
authors.affiliation: Malin Gingnell, MD, PhD, Andreas Frick, PhD, Jonas Engman, MSc, Iman Alaie, MSc, Johannes Björkstrand, MSc, Department of Psychology, Uppsala University, Uppsala, Sweden; Vanda Faria, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden, and Center for Pain and the Brain, Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Per Carlbring, PhD, Department of Psychology, Stockholm University, Stockholm, Sweden; Gerhard Andersson, PhD, Department of Behavioural Sciences and Learning, Psychology, Linköping University, Linköping, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Margareta Reis, PhD, Division of Drug Research/Clinical Pharmacology, Department of Health Sciences, Linköping University, Linköping, Sweden; Elna-Marie Larsson, MD, PhD, Department of Surgical Sciences/Radiology, Uppsala University, Uppsala, Sweden; Kurt Wahlstedt, MD, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden; Mats Fredrikson, DMSc, PhD, Department of Psychology, Uppsala University, Uppsala, and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Tomas Furmark, PhD, Department of Psychology, Uppsala University, Uppsala, Sweden.
authors.forename: Tomas
authors.initials: T
authors.lastname: Furmark
mesh_terms: D000328:Adult; D000679:Amygdala / Q000502:physiology*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology* / Q000628:therapy*; D015283:Citalopram / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D000066499:Facial Recognition / Q000502:physiology; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D020407:Internet; D008279:Magnetic Resonance Imaging; D008297:Male; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013813:Therapy, Computer-Assisted; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015283:Citalopram; D017367:Selective Serotonin Reuptake Inhibitors