Association of Optimal Lamotrigine Serum Levels and Therapeutic Efficacy in Mood Disorders: A Systematic Review

Rakesh Kumar, Nicolas A. Nuñez, Larry J. Prokop, Marin Veldic, Hannah Betcher, Balwinder Singh

Research output: Contribution to journalArticlepeer-review


Purpose The aim of the study was to appraise the current evidence on the optimal serum level for lamotrigine (LAM) in the treatment of mood disorders (major depressive disorder, bipolar disorder). Methods Major databases were searched for randomized controlled trials, open-label trials, and observational studies reporting serum LAM levels in adult patients treated with LAM for mood disorders. Results A total of 814 abstracts were screened and 24 articles were selected for full-text review. Seven studies (226 bipolar disorder and 17 major depressive disorder patients) including 1 randomized controlled trial (n = 43), 3 prospective (n = 53), and 3 retrospective (n = 147) studies met the study criteria with a study duration range from 6 to 96 weeks. Lamotrigine daily dosage varied from 25 to 425 mg/d among the studies. Studies reported inconsistent findings between LAM concentration and efficacy. Three studies did not identify a relationship between LAM levels and a significant improvement in mood symptoms. Two studies (n = 99) reported higher response rates with LAM serum levels of greater than 3.25 μg/mL and 1 study (n = 25) reported a wide therapeutic window of 5 to 11 μg/mL. Overall, LAM was well tolerated with no major significant adverse effects. Conclusions Most studies showed a minimum LAM threshold level of 3 μg/mL in patients with mood disorders; however, the data are inconsistent regarding the therapeutic range for LAM. Based on the pooled data, there is inconsistent evidence to make conclusive recommendations on therapeutic LAM serum levels for mood improvement. Further studies including larger sample sizes are required to address this relevant clinical question.

Original languageEnglish (US)
Pages (from-to)681-686
Number of pages6
JournalJournal of Clinical Psychopharmacology
Issue number6
StatePublished - Nov 1 2021


  • bipolar disorder
  • lamotrigine
  • mood disorders

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)


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