title: Two Phase III randomised double-blind studies of fixed-dose TC-5214 (dexmecamylamine) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to prior antidepressant therapy.
abstract: OBJECTIVE
  To evaluate the neuronal nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy in patients with major depressive disorder (MDD) and inadequate response to prior antidepressant treatment.
  
  
  METHODS
  Study 004 (D4130C00004) and Study 005 (D4130C00005) comprised an 8-week open-label antidepressant (SSRI/SNRI) treatment period followed by an 8-week randomised, active treatment with twice-daily TC-5214 (0.5, 2 or 4 mg in Study 004; 0.1, 1 or 4 mg in Study 005) or placebo, adjunct to ongoing SSRI/SNRI. Primary efficacy endpoint was change in MADRS total score from randomisation (Week 8) to treatment end (Week 16). Secondary endpoints included MADRS response and remission, and changes in SDS and HAM-D-17-item scores. Safety and tolerability were monitored throughout.
  
  
  RESULTS
  Studies 004 and 005 randomised 640 and 696 patients, respectively, to TC-5214 or placebo. No statistically significant improvements in MADRS total score or any secondary endpoints were seen with TC-5214 versus placebo in either study at treatment end. The most commonly reported adverse events (> 10%) with TC-5214 were constipation, dizziness and dry mouth.
  
  
  CONCLUSIONS
  TC-5214 adjunct to antidepressant was generally well tolerated. However, the studies were not supportive of an antidepressant effect for TC-5214 in patients with MDD and inadequate response to prior antidepressant therapy.
authors.affiliation: a Department of Psychiatry , Ludwig-Maximilians University , Munich , Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Möller
authors.affiliation: b Department of Psychiatry , University Hospital Gasthuisberg , Leuven , Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Demyttenaere
authors.affiliation: c Formerly AstraZeneca R&D, Södertälje , Sweden.
authors.forename: Bengt
authors.initials: B
authors.lastname: Olausson
authors.affiliation: c Formerly AstraZeneca R&D, Södertälje , Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Szamosi
authors.affiliation: d Formerly AstraZeneca Pharmaceuticals , Wilmington , DE , USA.
authors.forename: Ellis
authors.initials: E
authors.lastname: Wilson
authors.affiliation: e Targacept, Inc. , Winston-Salem , NC , USA.
authors.forename: David
authors.initials: D
authors.lastname: Hosford
authors.affiliation: f Formerly Targacept, Inc. , Winston-Salem , NC , USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Dunbar
authors.affiliation: g AstraZeneca Pharmaceuticals , Wilmington , DE , USA.
authors.forename: Raj
authors.initials: R
authors.lastname: Tummala
authors.affiliation: c Formerly AstraZeneca R&D, Södertälje , Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Eriksson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015283:Citalopram / Q000008:administration & dosage; D003865:Major Depressive Disorder / Q000188:drug therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D020280:Sertraline / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D015283:Citalopram; D008464:Mecamylamine; D020280:Sertraline
keywords: Adjunct therapy; TC-5214; antidepressant; major depressive disorder; nicotinic channel modulator