Bipolar Depression Before and After Lamotrigine Treatment
Condition: Bipolar Depression
MeSH terms: Depression; Depressive Disorder; Bipolar Disorder
Study type: Interventional
Phase: Phase 3

Summary: 
      This study compared glutamate and other neurometabolites measured by proton magnetic
      resonance spectroscopy (1H-MRS) in bipolar I and II patients currently depressed with
      age-matched healthy controls. The study will also compare 1H-MRS of bipolar I and II patients
      before and after taking a 12-week course of lamotrigine.

      The goal of this study was to better understand the neurobiology of bipolar depression and
      how lamotrigine may therapeutically impact brain function and mood response.

      The hypothesis was that in comparison to non-remission participants, bipolar participants who
      achieve remission (defined as a Montgomery Asberg Depression Rating Scale (MADRS) score <12
      at week 12) associated with lamotrigine monotherapy will exhibit a greater decrease in
      glutamate (Glu) and an increase in N-acetyl aspartate (NAA), reported as a cerebrospinal
      fluid (CSF)-corrected absolute concentration percent change from baseline to endpoint in
      anterior cingulate (AC) and dorsolateral prefrontal cortex (DLPFC).
    

Detailed description: 
      Depression is the predominant prevailing mood state in bipolar disorder and bipolar
      depression is associated with substantial morbidity and mortality. However, in comparison to
      acute mania, bipolar depression is understudied both from the standpoint of its
      pathophysiology as well as clinical trials which include FDA-approved treatments. Given this
      lack of evidence to base guidelines, clinicians and patients are limited as to how best to
      treat the depressive phase of the illness.

      Proton magnetic resonance spectroscopy (1H-MRS) is a valuable, non-invasive method to study
      in-vivo brain biochemistry. Of the novel imaging paradigms, MRS is uniquely positioned to
      investigate biochemical mechanism of drug action that is objectively measurable and
      clinically relevant. As there is increasing interest in glutamatergic dysregulation in mood
      disorders, this project will utilize 1H-MRS to study glutamate and glutamine levels in brain
      regions implicated in bipolar disorder (anterior cingulate and dorsolateral prefrontal
      cortex).

      This was a 5-year single-site study of bipolar depression utilizing 1H-MR spectroscopy before
      and after treatment with lamotrigine. At baseline bipolar depressed subjects and age-matched
      controls underwent a 1H-MRS at Mayo Clinic in Rochester, Minnesota. The bipolar depressed
      subjects were then be placed on 12-week, open evaluation of lamotrigine monotherapy. After 12
      weeks, the bipolar subjects underwent a second 1H-MRS scan.

      Two different MRS sequences were used to measure the brain chemicals in a single 2 x 2 x 2 cm
      cube located in the center of anterior cingulate cortex: an intermediate echo-time PRESS
      sequence and a 2D J-resolved averaged PRESS sequence. Spectroscopic data were inspected for
      quality; subjects whose data were contaminated by artifact were excluded from the study.
      Spectra were then processed using LCModel to quantify brain chemical levels. Regular brain
      MRI images were segmented, yielding a map of the amount of CSF in the head. The MRS cube was
      overlaid onto the CSF map and the fraction of CSF within the cube measured. This measurement
      was used to "remove" the CSF from the MRS cube giving brain chemical concentrations. The
      concentrations were then used for statistical analysis.

      Note: All of the spectroscopy data are expressed in Institutional Units (IU).
    

Intervention name(s): Lamotrigine; 1H-MR
Intervention type(s): Drug; Procedure
Intervention description(s): 12 week open trial: 25mg/day for 2 weeks, 50mg/day for 2 weeks, 100mg/day for 2 weeks, 200mg/day for 6 weeks. Flexible titration for early response and/or side effects.; Proton magnetic resonance spectroscopy (1H-MR) evaluation of medial anterior cingulate cortex (MACC) and left dorsal lateral prefrontal cortex (LDLPC).
Other intervention name(s): Lamictal®
Intervention MeSH terms: Lamotrigine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Bipolar; depression