title: Long-term outcome of bipolar depressed patients receiving lamotrigine as add-on to lithium with the possibility of the addition of paroxetine in nonresponders: a randomized, placebo-controlled trial with a novel design.
abstract: OBJECTIVE
  In two previous manuscripts, we described the efficacy of lamotrigine versus placebo as add-on to lithium (followed by the addition of paroxetine in nonresponders) in the short-term treatment of bipolar depression. In this paper we describe the long-term (68 weeks) outcome of that study.
  
  
  METHODS
  A total of 124 bipolar depressed patients receiving lithium were randomized to addition of lamotrigine or placebo. After eight weeks, paroxetine was added to nonresponders for another eight weeks. Responders continued medication and were followed for up to 68 weeks or until a relapse or recurrence of a depressive or manic episode.
  
  
  RESULTS
  After eight weeks, the addition of lamotrigine to lithium was significantly more efficacious than addition of placebo, while after addition of paroxetine in nonresponders both groups further improved with no significant difference between groups at week 16. During follow-up the efficacy of lamotrigine was maintained: time to relapse or recurrence was longer for the lamotrigine group [median time 10.0 months (confidence interval: 1.1-18.8)] versus the placebo group [3.5 months (confidence interval: 0.7-7.0)].
  
  
  CONCLUSIONS
  In patients with bipolar depression, despite continued use of lithium, addition of lamotrigine revealed a continued benefit compared to placebo throughout the entire study.
authors.affiliation: Department of Psychiatry, Isala Klinieken Location Sophia, Zwolle, The Netherlands. m.l.m.van.der.loos@isala.nl
authors.forename: Marc L M
authors.initials: ML
authors.lastname: van der Loos
authors.forename: Paul
authors.initials: P
authors.lastname: Mulder
authors.forename: Erwin G Th M
authors.initials: EG
authors.lastname: Hartong
authors.forename: Marc B J
authors.initials: MB
authors.lastname: Blom
authors.forename: Anton C
authors.initials: AC
authors.lastname: Vergouwen
authors.forename: Martijn S
authors.initials: MS
authors.lastname: van Noorden
authors.forename: Manuela A
authors.initials: MA
authors.lastname: Timmermans
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use*; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077213:Lamotrigine; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000627:therapeutic use*; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D018687:Antidepressive Agents, Second-Generation; D018692:Antimanic Agents; D018020:Lithium Compounds; D014227:Triazines; D017374:Paroxetine; D000077213:Lamotrigine