Lamotrigine Augmentation in Resistant Depression
Condition: Unipolar Depression
MeSH terms: Depression; Depressive Disorder
Study type: Interventional

Summary: 
      This study is intended to evaluate the efficacy and safety of lamotrigine as an
      antidepressant augmentation agent in a sample of individuals with major depression and a
      history of both prior non-response and prospective failure to respond to at least one
      adequate trial of an antidepressant (for a total of two failed trials).
    

Detailed description: 
      The study will consist of four phases: screening, open-label, double-blind and
      discontinuation phases. After screening to ensure that subjects meet the study criteria,
      individuals will enter an open-label (flexible-dose) trial of paroxetine-CR given in dosages
      up to 62.5 mg for a period of eight weeks. Paroxetine may be substituted for paroxetine-CR in
      dosages up to 50 mg. Subjects may be switched from paroxetine-CR to the bioequivalent dose of
      paroxetine due to drug supply disruption but should not be switched back to paroxetine-CR.
      Subjects are not allowed to switch from paroxetine to paroxetine-CR. Subjects who start on
      paroxetine at the first visit must remain on paroxetine for the duration of the study. At the
      discretion of the investigator, additional monitoring or interim visits may be needed for
      subjects who require a switch from paroxetine-CR to paroxetine. Those individuals who fail to
      respond adequately will then continue into the second phase (double-blind portion) of the
      study, in which participants will continue on either paroxetine-CR or paroxetine, and will be
      randomized to either placebo or lamotrigine in a flexible-dose design up to 400mg for a
      10-week period. Subjects will remain on the same dose of paroxetine-CR or paroxetine that
      they were taking at the final visit in the first phase of the study (Visit 5/Week 8). The
      study medications will be discontinued following the final study visit (Visit 11/Week 18 or
      the early termination visit). Paroxetine-CR or paroxetine may be continued in the dosages
      used during the study after completion of the protocol if, in the judgment of the
      investigator, the subject has shown a partial response to treatment with the drug. The
      lamotrigine (or placebo) dose will be decreased by half for one week and then discontinued.
      Subjects will return two weeks post-study and four weeks post study for follow up visits
      consisting of safety evaluations. In addition, a MADRS and CGI should be performed at the
      two-week post study follow up visit. The visit at four weeks post study may be omitted if the
      3rd and 4th week of taper are not needed. The decision to restart lamotrigine at that time
      would also be up to the investigator, but the dosage of lamotrigine would have to be titrated
      in the first month per the manufacturer's clinical trial program. This is necessary since all
      subjects will be discontinuing from the drug following Visit 11/Week 18 or the early
      termination visit in order to maintain the blind at the conclusion of each subject's
      participation in the study. Subjects who are discontinued from paroxetine-CR at dosages of 25
      mg/day or higher should undergo a gradual dose reduction of 12.5 mg per week rather than
      abrupt cessation. Subjects who are discontinued from paroxetine at dosages of 20 mg/day or
      higher should undergo a gradual dose reduction of 10 mg per week rather than abrupt
      cessation.
    

Intervention name(s): lamotrigine; placebo; paroxetine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): lamotrigine augmentation 25 to 100 mg tablets, 25 to 200 mg bid,10 weeks; placebo: 1-2 tablets bid; 10 weeks; open label paroxetine 10 to 50 mg, at bedtime for 18 weeks (8 weeks prior to randomization and 10 weeks after)
Other intervention name(s): Lamictal; paxil
Intervention MeSH terms: Lamotrigine; Paroxetine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: augmentation; depression; resistance