Lamotrigine Monotherapy in Pediatric Bipolar Disorder
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Interventional
Phase: Phase 2

Summary: 
      There are two purposes for this project. Study 1 is intended to study the safety and efficacy
      of Lamotrigine in stabilizing the mood in all phases of pediatric bipolar disorder (Phases:
      mixed, manic, hypomanic, or depressed episodes) in 8-17 year old children. These children and
      adolescents must be treatment resistant (who failed on two adequate trials of mood
      stabilizing medications) to qualify for this study. Study 2 is aimed at examining brain
      activity and/or dysfunction before lamotrigine treatment, and to look for any alteration
      after lamotrigine treatment. Brain systems associated with attention and emotional processing
      will targeted.
    

Detailed description: 
      Procedure Study 1 This study is planned to be conducted over 18 months, with an average
      recruitment of 2 subjects per month. Each subject is involved in the study for 18 to 26
      weeks. While the study medication is dosed over 8 weeks and treated with full dose over 6
      weeks, withdrawal of medications that are on board prior to the study drug administration and
      drug free period post washout required additional time line that is up to 12 weeks over and
      above the 14 weeks of administering the study drug. Conversely, the range of time is
      necessary to account for factors such as the child's age, sex, weight, reactions to the
      medications and side effects. Based on these factors, the time it takes to titrate the
      medication dose to the optimal amount will vary. Maintaining this flexibility in the protocol
      is part of good clinical practice where medication is involved. Only children whose
      medication is not currently improving their symptoms will be recruited. Therefore no children
      who have been stabilized on a drug will be taken off of it. The initial 2 week screening
      period includes a diagnostic interview and collection of demographic information. Previous
      medication will be tapered slowly over 2-12-week period and is based on tolerability and need
      to keep subjects in drug free state prior to start of study medication. It is an open trial
      where subjects are aware of the type of medication and the strength (For example, one pill=25
      mg strength) of the pill. Research assessment of mood symptoms and side effects will be
      carried out 5 times over the course of the active trial period. Blood will be collected 3
      times: once the subject is washed-out (baseline), once optimal medication dose has been
      reached, and finally at the end of the 6-week period on full dose.

      The dose of lamotrigine will be 12.5 mg per day beginning the first day. It is increased in
      12.5 mg increments every week until it reaches 50 mg and 25 mg per week of increment
      thereafter until maximum dose of 150 mg in those below 50 kg and 200-400 mg depending on
      clinical response in those above 50 kg. Increasing the medication to final dose will take 8
      weeks and the response on full and tolerable dose is further monitored for response over 6
      weeks. Therefore, this is a 18-26 week trial (2 to 12 weeks=screening and wash out; 8
      weeks=dosing; 6 weeks=acute trial period on full dose).

      Study 2 involves adolescent subjects (>10years of age) recruited from the Study 1 sample.
      This part of the study is a fMRI treatment study to examine how the brain functions before
      and after receiving lamotrigine medication for bipolar disorder. The goal of study 2 is to
      understand how and where lamotrigine works in the brain. In order to do this, we will view
      brain images in a fMRI scanner pre- and post-treatment. This will be done once before
      subjects begin taking lamotrigine (subjects who require a "wash-out" period, described in
      study 1, this will occur after the "wash-out.") The second scan will take place after the
      medication trial (after the 6-week active treatment period). While in the scanner, subjects
      will complete tasks related to thinking and emotion. Subjects will be shown pictures of faces
      with varying expressions including happy, neutral and angry and will be asked to identify the
      emotions of the faces, remember and identify previously seen faces, and determine the age
      group of various faces (i.e., above or below 30 years). Subjects will also complete tasks
      that involve processing words that express different emotions (e.g., happy, angry), and
      respond to different "go" and "no-go" images that flash on a screen. Brain activity will be
      recorded during these tasks. Each task will take around 5 minutes. Before the actual fMRI
      scan, subjects practice lying in a simulator, a machine that looks and sounds like a scanner.
    

Intervention name(s): Lamotrigine
Intervention type(s): Drug
Intervention description(s): It is a mood stabilizer that is clinically the first choice if patients present with depression and is effective in adults for mania in maintenance phase. So it is administered to see how effective it is in children and adolescents.
The dose of lamotrigine will be 12.5 mg per day beginning the first day. It is increased in 12.5 mg increments every week until it reaches 50 mg and 25 mg per week of increment thereafter until maximum dose of 150 mg in those below 50 kg and 200-400 mg depending on clinical response in those above 50 kg.
Other intervention name(s): Lamictal
Intervention MeSH terms: Lamotrigine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment