Prospective Validation of a Nomogram for Determining the Optimal Dose of Lamotrigine for Augmentation Therapy in Patients With Treatment-Resistant Depression.

Background: Previous research has shown that a plasma lamotrigine concentration of 12.7 µmol/L may be a threshold for a good therapeutic response to lamotrigine augmentation therapy in Japanese patients with treatment-resistant depression. The optimal dose of lamotrigine can be predicted using a previously established nomogram based on the plasma lamotrigine concentration at week 2. The aim of the present study was to prospectively evaluate the validity of this nomogram.

Methods: Participants included 59 patients with depression who showed insufficient therapeutic responses to psychotropics, including antidepressants, antipsychotics, and mood stabilizers. The patients were diagnosed with major depressive disorder (n = 26), bipolar II disorder (n = 25), or bipolar I disorder (n = 8). Lamotrigine was administered to all the patients. The initial dose of lamotrigine was 25 mg/d for 32 patients not taking valproate and 25 mg/d every other day for 27 patients taking valproate. Blood samples were collected at week 2 and at least 2 weeks after the final daily dose, which was estimated by a nomogram based on the plasma lamotrigine concentration at week 2. The plasma concentrations of lamotrigine were measured by liquid chromatography-mass spectrometry.

Results: In 30 of the 32 patients (93.8%) who were not taking valproate and 23 of the 27 patients (85.2%) who were taking valproate, a plasma lamotrigine concentration of 12.7 mcg/mL or higher was achieved at the final daily administration of lamotrigine.

Conclusions: The results of the present study suggest that the previously established nomogram is valid for determining the optimal dose of lamotrigine for Japanese patients with treatment-resistant depression in clinical settings.