title: Prediction of an Optimal Dose of Lamotrigine for Augmentation Therapy in Treatment-Resistant Depressive Disorder From Plasma Lamotrigine Concentration at Week 2.
abstract: The authors have previously shown that an early therapeutic response to lamotrigine augmentation therapy 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. The present study investigated whether or not an optimal dose of lamotrigine could be predicted from plasma lamotrigine concentration at week 2.
  
  
  
  The subjects were 37 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 = 15), bipolar I disorder (n = 6), and bipolar II disorder (n = 16). They received augmentation therapy with lamotrigine for 8 weeks. The final doses of lamotrigine were 100 mg/d for 16 subjects who were not taking valproate and 75 mg/d for 21 subjects taking valproate, respectively. Blood sampling was performed at weeks 2 and 8. Plasma concentrations of lamotrigine were measured by high-performance liquid chromatography.
  
  
  
  There were significant linear relationships between the plasma lamotrigine concentrations at week 2 (x) and those at week 8 (y) for subjects who were not taking valproate (P < 0.01) and those taking valproate (P < 0.01). Regression equations were y = 2.032x + 2.549 for the former and y = 3.599x + 5.752 for the latter, respectively. Based on the equations, a nomogram to estimate an optimal dose of lamotrigine could be calculated.
  
  
  
  The present study suggests that an optimal dose of lamotrigine for augmentation therapy in treatment-resistant depressive disorder can be predicted from a plasma lamotrigine concentration at week 2.
authors.affiliation: Departments of *Neuropsychiatry and †Pharmacy, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Nakamura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Mihara
authors.forename: Goyo
authors.initials: G
authors.lastname: Nagai
authors.forename: Shoko
authors.initials: S
authors.lastname: Kagawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kenji
authors.initials: K
authors.lastname: Nemoto
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kondo
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D018692:Antimanic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D061218:Depressive Disorder, Treatment-Resistant / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014227:Triazines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014635:Valproic Acid / Q000008:administration & dosage
chemical_list: D000928:Antidepressive Agents; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D014227:Triazines; D014635:Valproic Acid; D000077213:Lamotrigine