title: Efficacy and tolerability of flexibly-dosed adjunct TC-5214 (dexmecamylamine) in patients with major depressive disorder and inadequate response to prior antidepressant.
abstract: This paper reports the efficacy and tolerability of the nicotinic channel modulator TC-5214 (dexmecamylamine) as adjunct therapy for patients with major depressive disorder who have an inadequate response to initial antidepressant treatment in 2 Phase III studies. These double-blind, placebo-controlled studies (NCT01157078, D4130C00002 [Study 002] conducted in the US and India; NCT01180400, D4130C00003 [Study 003] conducted in Europe) comprised 8 weeks of open-label antidepressant treatment followed by 8 weeks of active treatment during which patients were randomized to flexibly-dosed TC-5214 1-4 mg twice daily (BID) or placebo as an adjunct to ongoing therapy with SSRI/SNRI. The primary efficacy endpoint in both studies was change in Montgomery Åsberg Depression Rating Scale (MADRS) total score from randomization (week 8) to treatment end (week 16). Secondary endpoints included change in Sheehan Disability Scale and Hamilton Depression Rating Scale 17-item scores. Study 002 randomized 319 patients and Study 003 randomized 295 patients to TC-5214 or placebo. At treatment end, no significant differences were seen for change in MADRS total score with TC-5214 versus placebo. Furthermore, there were no significant differences in any of the secondary endpoints. The most commonly reported (≥ 10%) adverse events with TC-5214 in these studies were constipation and headache. In these 2 flexibly-dosed studies, no specific therapeutic effects were observed for TC-5214 (1-4 mg BID) adjunct to antidepressant in the primary endpoint or any secondary endpoint; however, TC-5214 was generally well tolerated. In conclusion, no antidepressant effect of TC-5214 was observed in these studies.
authors: Department of Psychiatry, Clinical Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Villarroel 170/Rossello 140, 08036 Barcelona, Catalonia, Spain. Electronic address: evieta@clinic.ub.es.
authors: Eduard
authors: E
authors: Vieta
authors: Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors: Michael E
authors: ME
authors: Thase
authors: Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Dieter
authors: D
authors: Naber
authors: Midwest Clinical Research Center, Dayton, OH, USA.
authors: Bernadette
authors: B
authors: D'Souza
authors: Department of Psychiatry and Narcology, Riga Stradins University, Riga, Latvia.
authors: Elmars
authors: E
authors: Rancans
authors: Kuopio Psychiatric Research Clinic, Kuopio, Finland.
authors: Ulla
authors: U
authors: Lepola
authors: AstraZeneca R&D, Södertälje, Sweden.
authors: Bengt
authors: B
authors: Olausson
authors: AstraZeneca R&D, Södertälje, Sweden.
authors: Johan
authors: J
authors: Szamosi
authors: AstraZeneca Pharmaceuticals, Wilmington, NC, USA.
authors: Ellis
authors: E
authors: Wilson
authors: Targacept Inc., Winston-Salem, NC, USA.
authors: David
authors: D
authors: Hosford
authors: Targacept Inc., Winston-Salem, NC, USA.
authors: Geoffrey
authors: G
authors: Dunbar
authors: AstraZeneca Pharmaceuticals, Wilmington, NC, USA.
authors: Raj
authors: R
authors: Tummala
authors: AstraZeneca R&D, Södertälje, Sweden.
authors: Hans
authors: H
authors: Eriksson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000188:drug therapy*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D016903:Drug Monitoring; D004351:Drug Resistance; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D059012:Lost to Follow-Up; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D018733:Nicotinic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D008464:Mecamylamine; D018733:Nicotinic Antagonists; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Adjunct therapy; Major depressive disorder; Nicotinic channel modulator; TC-5214