Bipolar Depression Before and After Lamotrigine Treatment
Condition: Bipolar Depression
MeSH terms: Depression; Depressive Disorder; Bipolar Disorder
Intervention: Lamotrigine; 1H-MR
Intervention description: 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).
Intervention MeSH terms: Lamotrigine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 72.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bipolar; depression

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).
    

Eligibility criteria:

        Bipolar Group Inclusion Criteria:

          -  Diagnosis of Bipolar Type I or II disorder depress phase (SCID confirmed)

          -  Moderate depression as confirmed by Montgomery Asberg Depression Rating Scale greater
             than or equal to 20

          -  Negative urine toxicology screen

          -  Negative urine pregnancy test

          -  No clinically significant lab abnormalities for complete blood count (CBC), Thyroid
             stimulating hormone (TSH), Sodium (Na+), Potassium (K+), Chlorine (Cl-), Carbon
             dioxide (CO2), creatinine (CREA), blood urea nitrogen (BUN), Glucose, hepatic panel.

        Bipolar Group Exclusion Criteria:

          -  Inability to provide informed consent

          -  Any current Axis I diagnosis other than anxiety disorders needing concurrent
             antidepressant therapy

          -  History of active substance abuse/dependence within the last 3 months

          -  History of claustrophobia

          -  History of adverse reaction to Lamotrigine

          -  Fluoxetine and decanoate antipsychotic therapy

          -  Unwilling or unable to taper current sub-optimal psychotropic medications other than a
             stable dosage of Lithium, Depakote, or an Atypical Antipsychotic approved by study
             personnel

          -  Unstable active medical illness

          -  Pregnancy or breast-feeding

          -  Male/ Female not practicing a reliable form of birth control (condom, Intrauterine
             Device (IUD), depo injection)

          -  Female wishing to commence oral contraceptive therapy within 3 months of enrollment
             date (stable oral contraceptive therapy exception)

          -  Active suicidal ideation with plan

          -  History of major head trauma with loss of consciousness > 5 minutes or skull fracture

          -  History of previous neurological event (epilepsy, stroke, transient ischemic attack)

          -  Implanted metal objects (i.e., pacemakers, aneurysm clips, metal prostheses, joints,
             rods)

          -  Inability to speak English

          -  Prominent Axis II disorder [This will be assessed by the principal investigator, who
             has >10 years clinical experience with this population. Hospital discharge summaries
             and outpatient medical records will be reviewed for evidence that Axis II pathology is
             the primary psychiatric disturbance (i.e., adequate trials of mood stabilizing
             treatments with minimal to no response, prominent self injurious behavior in the
             absence of significant mood symptomatology, or atypical cycle patterns)].

        Healthy Control Group Inclusion Criteria:

          -  Negative urine toxicology screen

          -  Negative urine pregnancy test

          -  Normal blood values for thyroid stimulating hormone (TSH)

        Healthy Control Group Exclusion Criteria:

          -  Inability to provide informed consent

          -  Any current Axis I or II diagnosis

          -  Known history of claustrophobia

          -  Lifetime personal or family history (first-degree relative) of dementia,
             substance-related disorder (nicotine abuse or dependence exception), psychotic
             disorder, mood disorder (history of bereavement exception), anxiety disorder (specific
             phobia exception)

          -  Unstable active medical illness

          -  Pregnancy or breast-feeding

          -  Male /Female not practicing a reliable form of birth control (condom, IUD, depo
             injection)

          -  History of major head trauma with loss of consciousness > 5 minutes or skull fracture

          -  History of previous neurological event (epilepsy, stroke, transient ischemic attack)

          -  Implanted metal objects (i.e., pacemakers, aneurysm clips, metal prostheses, joints)

          -  Inability to speak English

          -  On current medications known to affect glutamate (i.e., Riluzole).

          -  Any medically remarkable impairment due to a medical condition or brain injury
             resulting in significant impairment in cognitive functioning based on
             neuropsychological test battery and/or MRS scan results.