title: Relationship between plasma concentrations of lamotrigine and its early therapeutic effect of lamotrigine augmentation therapy in treatment-resistant depressive disorder.
abstract: BACKGROUND
  The relationship between plasma concentrations of lamotrigine and its therapeutic effects was prospectively studied on 34 (9 men and 25 women) inpatients with treatment-resistant depressive disorder during an 8-week treatment of lamotrigine augmentation using an open-study design.
  
  
  METHODS
  The subjects were depressed patients who had already shown insufficient response to at least 3 psychotropics, including antidepressants, mood stabilizers, and atypical antipsychotics. The diagnoses were major depressive disorder (n = 12), bipolar I disorder (n = 7), and bipolar II disorder (n = 15). The final doses of lamotrigine were 100 mg/d for 18 subjects who were not taking valproate and 75 mg/d for 16 subjects taking valproate. Depressive symptoms were evaluated by the Montgomery Åsberg Depression Rating Scale (MADRS) before and after the 8-week treatment. Blood sampling was performed at week 8. Plasma concentrations of lamotrigine were measured by high-performance liquid chromatography.
  
  
  RESULTS
  There was a significant linear relationship between the plasma concentrations of lamotrigine and percentage improvements at week 8 (r = 0.418, P < 0.05). A stepwise multiple regression analysis showed that plasma lamotrigine concentrations alone had a significant effect on the percentage improvements at week 8 (standardized partial correlation coefficients = 0.454, P < 0.001). The receiver operating characteristics analysis indicated that a plasma lamotrigine concentration of 12.7 μmol/L or greater was significantly (P < 0.001) predictive of response (50% or more reduction in the MADRS score). The proportion of the responders was significantly higher in the groups with a lamotrigine concentration >12.7 μmol/L (11/15 versus 4/19, P < 0.01).
  
  
  CONCLUSIONS
  The present study suggests that an early therapeutic response to lamotrigine is dependent on its plasma concentration and that a plasma lamotrigine concentration of 12.7 μmol/L may be a threshold for a good therapeutic response in treatment-resistant depressive disorder.
authors.affiliation: Departments of *Neuropsychiatry, and †Pharmacy, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Kagawa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Mihara
authors.forename: Akifumi
authors.initials: A
authors.lastname: Nakamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Nemoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Goyo
authors.initials: G
authors.lastname: Nagai
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage*; D061218:Depressive Disorder, Treatment-Resistant / Q000097:blood* / Q000188:drug therapy* / Q000523:psychology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014227:Triazines / Q000008:administration & dosage* / Q000097:blood*
chemical_list: D000928:Antidepressive Agents; D014227:Triazines; D000077213:Lamotrigine