title: Analgesic effect of perioperative escitalopram in high pain catastrophizing patients after total knee arthroplasty: a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Sufficient pain treatment remains a challenge after total knee arthroplasty (TKA), especially in high pain catastrophizing patients. Serotonergic signaling may be involved in pain processing, but the effect of selective serotonin reuptake inhibitors on well-defined postoperative pain has not previously been investigated. The authors hypothesized that perioperative escitalopram would reduce pain after TKA in high pain catastrophizing patients.
  
  
  METHODS
  A total of 120 pain catastrophizing patients (selected using the pain catastrophizing scale as preoperative screening tool) scheduled for TKA were randomized in a double-blind manner to either 10 mg escitalopram or placebo daily from preanesthesia to postoperative day 6 in addition to a standardized analgesic regime. The primary outcome was pain upon ambulation 24 h after surgery. Secondary outcomes were overall pain during well-defined mobilizations and at rest from 2 to 48 h and from days 2 to 6, morphine equivalents, anxiety, depression, and side effects.
  
  
  RESULTS
  Pain upon ambulation (mean [95% CI]) 24 h after surgery in the escitalopram versus placebo group was 58 (53 to 64) versus 64 (58 to 69), the mean difference being -5 (-13 to 3), P = 0.20. Overall pain upon ambulation and at rest from days 2 to 6 was lower in the escitalopram versus placebo group, as was depression score at day 6 (all P ≤ 0.01 in analyses uncorrected for multiple tests). Side effects were nonsignificant except for reduced tendency to sweat and prolonged sleep in the escitalopram group. No other between-group differences were observed.
  
  
  CONCLUSIONS
  Escitalopram did not reduce pain upon ambulation 24 h after TKA in high pain catastrophizing patients. Future studies on optimal timing, dose, and duration of selective serotonin reuptake inhibitor treatment might be warranted.
authors.affiliation: From the Department of Anesthesiology, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark (T.H.L.); The Lundbeck Centre for Fast-track Hip and Knee Arthroplasty, Copenhagen, Denmark (T.H.L., T.B.H., P.W.K., T.L., H.K.); Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (V.G.F.); University Clinic for Hand, Hip and Knee Surgery, Holstebro Hospital, Aarhus University, Aarhus, Denmark (T.B.H.); Department of Orthopedic Surgery, Section for Hip and Knee Replacement, Vejle Hospital, Vejle, Denmark (P.W.K.); Department of Orthopedic Surgery, Copenhagen University Hospital, Gentofte, Denmark (T.L.); and Section of Surgical Pathophysiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark (H.K.).
authors.forename: Troels H
authors.initials: TH
authors.lastname: Lunn
authors.forename: Vibe G
authors.initials: VG
authors.lastname: Frokjaer
authors.forename: Torben B
authors.initials: TB
authors.lastname: Hansen
authors.forename: Per W
authors.initials: PW
authors.lastname: Kristensen
authors.forename: Thomas
authors.initials: T
authors.lastname: Lind
authors.forename: Henrik
authors.initials: H
authors.lastname: Kehlet
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000698:Analgesia / Q000379:methods*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D058443:Catastrophization / Q000188:drug therapy* / Q000209:etiology; D015283:Citalopram / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010149:Postoperative Pain / Q000188:drug therapy* / Q000209:etiology; D019990:Perioperative Care / Q000379:methods*; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D015283:Citalopram