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. 2025 Oct 1;47(5):648-652.
doi: 10.1097/FTD.0000000000001316. Epub 2025 Feb 25.

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

Takeshi Suzuki  1 , Goyo Nagai  2 , Kazuo Mihara  2   3 , Yoko Tomori  2 , Shoko Kagawa  2 , Akifumi Nakamura  2 , Kenji Nemoto  2 , Tsuyoshi Kondo  2
Affiliations

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

Takeshi Suzuki et al. Ther Drug Monit. .

Abstract

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.

Keywords: lamotrigine; nomogram; therapeutic concentration; treatment-resistant depression.

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Conflict of interest statement

K. Mihara received honoraria from GlaxoSmithKline and Otsuka. A. Nakamura received honoraria from Dainippon Sumitomo Pharma, Otsuka, and Pfizer. T. Kondo received honoraria from Eli Lilly, GlaxoSmithKline, and Otsuka. The remaining authors declare no conflict of interest.

References

    1. Geddes JR, Calabrese JR, Goodwin GM. Lamotrigine for treatment of bipolar depression: independent meta-analysis and meta-regression of individual patient data from five randomised trials. Br J Psychiatry. 2009;194:4–9.
    1. Kagawa S, Nemoto K, Suzuki T, et al. Lamotrigine augmentation for the treatment-resistant mood disorder. Clin Neuropsychopharmacol Ther. 2010;1:35–42.
    1. Kagawa S, Mihara K, Nakamura A, et al. Relationship between plasma concentrations of lamotrigine and its early therapeutic effect of lamotrigine augmentation therapy in treatment-resistant depressive disorder. Ther Drug Monit. 2014;36:730–733.
    1. Ruberto VL, Jha MK, Murrough JW. Pharmacological treatments for patients with treatment-resistant depression. Pharmaceuticals. 2020;13:116.
    1. Solmi M, Veronese N, Zaninotto L, et al. Lamotrigine compared to placebo and other agents with antidepressant activity in patients with unipolar and bipolar depression: a comprehensive meta-analysis of efficacy and safety outcomes in short-term trials. CNS Spectr. 2016;21:403–418.

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