title: Lamotrigine as add-on therapy in schizophrenia: results of 2 placebo-controlled trials.
abstract: OBJECTIVE
  : Lamotrigine previously was found to attenuate ketamine-induced behavioral changes and, in 2 placebo-controlled trials, to improve psychosis when added to antipsychotic medication. We sought to evaluate the potential role of lamotrigine augmentation in schizophrenia patients resistant to atypical antipsychotic medication.
  
  
  METHODS
  : Two multicenter, randomized, double-blind, 12-week, parallel-group trials were conducted to compare flexibly dosed lamotrigine (100-400 mg/d) with placebo as add-on treatment in schizophrenia patients with stable, residual psychotic symptoms. The primary end point was changed in Positive and Negative Syndrome Scale total score at week 12.
  
  
  RESULTS
  : Two hundred seventeen patients were enrolled in study 1 and 212 in study 2; completion rates in the intent-to-treat samples were 71% and 74%, respectively, and did not differ between treatment groups. Overall, mean Positive and Negative Syndrome Scale total scores improved in both studies and did not differ between treatment groups. In study 1, the Scale for Assessment of Negative Symptoms total score and Clinical Global Impression improved more with placebo than with lamotrigine; in study 2, the cognitive composite score improved more with lamotrigine than with placebo.
  
  
  CONCLUSIONS
  : Results from these 2 studies do not support the use of lamotrigine as an adjunct to atypical antipsychotics in patients with refractory psychosis. It is unclear why positive results from previous lamotrigine trials were not replicated. The positive effect of lamotrigine on cognition in one trial, while of uncertain significance, may merit further study.
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, 25 Staniford Street, Boston, MA 02114, USA. goff@psych.mgh.harvard.edu
authors.forename: Donald C
authors.initials: DC
authors.lastname: Goff
authors.forename: Richard
authors.initials: R
authors.lastname: Keefe
authors.forename: Leslie
authors.initials: L
authors.lastname: Citrome
authors.forename: Katherine
authors.initials: K
authors.lastname: Davy
authors.forename: John H
authors.initials: JH
authors.lastname: Krystal
authors.forename: Charles
authors.initials: C
authors.lastname: Large
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Thompson
authors.forename: Jan
authors.initials: J
authors.lastname: Volavka
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Webster
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D003024:Clozapine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance / Q000706:statistics & numerical data; D010352:Patient Dropouts / Q000706:statistics & numerical data; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*; D012720:Severity of Illness Index; D013406:Suicide, Attempted / Q000706:statistics & numerical data; D016896:Treatment Outcome; D014227:Triazines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*
chemical_list: D000927:Anticonvulsants; D014150:Antipsychotic Agents; D014227:Triazines; D003024:Clozapine; D000077213:Lamotrigine