Lamotrigine for the Treatment of Mania in Youth Ages 6-17 With Bipolar Disorder
Condition: Bipolar Disorder; Mania
MeSH terms: Mania; Bipolar Disorder
Intervention: lamotrigine
Intervention description: Open-label, flexible-dose, BID treatment of lamotrigine (Lamictal). For children <12 years, dosing began at 0.35 mg/kg/day, divided in 2 doses, rounded down to nearest 5mg, to be increased weekly depending on response and tolerability to maintenance dose of 5-15 mg/kg/day (maximum 400 mg/day in 2 divided doses). For children ≥12 years, dose began at 25 mg/day in 1 dose, to be increased weekly depending on response and tolerability to maintenance dose of 300-500 mg/day in 2 divided doses.
Intervention MeSH terms: Lamotrigine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: bipolar disorder; lamotrigine; children; mania

Summary:

      The main objective of this study is to assess the effectiveness and safety of lamotrigine in
      the treatment of youth with bipolar and bipolar spectrum disorder. This is an exploratory,
      12-week, open-label treatment period, pilot study, of youth ages 6-17, who meet the DSM-IV
      diagnostic criteria for bipolar I, bipolar II, or bipolar spectrum disorder. The study
      results will be used to generate hypotheses for a larger randomized controlled clinical
      trial. Based on the available literature in adults with bipolar disorder, we hypothesized
      that lamotrigine will be efficacious and well tolerated in youth with pediatric bipolar and
      bipolar spectrum disorders.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female subjects, 6-17 years of age.

          2. Subjects must have a DSM-IV diagnosis of bipolar I, bipolar II disorder or bipolar
             spectrum disorder and currently displaying manic, hypomanic, or mixed symptoms (with
             or without psychotic features) according to the DSM-IV based on clinical assessment
             and confirmed by structured diagnostic interview (Kiddie Schedule of Affective
             Disorders and Schizophrenia Epidemiological Version. Bipolar Spectrum Disorder (or
             sub-threshold bipolar disorder) is operationalized as having severe mood disturbance,
             which meets DSM-IV Criteria A for bipolar disorder but meet fewer elements in criteria
             B (only require 2 items for elation category and 3 for irritability).

          3. Subjects and their legal representative must have a level of understanding sufficient
             to communicate intelligently with the investigator and study coordinator, and to
             cooperate with all tests and examinations required by the protocol.

          4. Subjects and their legal representative must be considered reliable.

          5. Each subject and his/her authorized legal representative must understand the nature of
             the study. The subject's authorized legal representative must sign an informed consent
             document and the subject must sign an informed assent document.

          6. Subjects must have an initial score on the Y-MRS total score of at least 20.

          7. Subject must be able to participate in mandatory blood draws.

          8. Subject must be able to swallow pills.

          9. Subjects with comorbid ADHD, ODD, CD, anxiety and depressive disorders will be allowed
             to participate in the study provided they do not meet for any of the exclusionary
             criteria.

         10. For concomitant stimulant therapy used to treat ADHD, subjects must have been on a
             stable dose of the medication for 1 month prior to study enrollment. The dose of the
             stimulant therapy will not change throughout the duration of the study.

        Exclusion Criteria:

          1. Investigator and his/her immediate family; defined as the investigator's spouse,
             parent, child, grandparent, or grandchild.

          2. Subjects unable to swallow pills.

          3. Serious, unstable illness including hepatic, renal, gastroenterological, respiratory,
             cardiovascular (including ischemic heart disease), endocrinologic, neurologic,
             immunologic, or hematologic disease.

          4. History of sensitivity to lamotrigine or known, severe allergies or multiple adverse
             drug reactions.

          5. History of previous bone marrow depression.

          6. History of serious rashes.

          7. DSM-IV substance (except nicotine or caffeine) dependence within past 3 months.

          8. Judged clinically to be at serious suicidal risk.

          9. Any other concomitant medication with primarily central nervous system activity other
             than specified in Concomitant Medication portion of the protocol.

         10. A non-responder or a history of intolerance to lamotrigine in an adequate trial (2
             months or more at an adequate dose) as determined by the clinician.

         11. Current diagnosis of schizophrenia.

         12. Pregnant or nursing females.