16-week Comparative Effectiveness Trial of Lamotrigine vs. Fluoxetine for Bipolar Depression
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Intervention: Lamotrigine; Fluoxetine
Intervention description: Lamotrigine dosing: 25 mg daily x 2 weeks, 50 mg daily x 2 weeks, 100 mg daily x 2 weeks, 200 mg (100 mg bid)) x 4 weeks. If patient still has at least mild depressive symptoms, the dose can be increased to 300 mg daily for 2 weeks and 400 mg for 4 weeks. Dose will be held for treatment response and can be reduced for side effects.; Fluoxetine dosing: 20mg for month 1, 40mg for month 2, and if still depressed (CGI ≥ 3) 60mg for month 3 and 4. Lower doses of fluoxetine will be prescribed for those with side effects. For known Cytochrome P450 2D6 poor metabolizers, fluoxetine will not be dosed > 40mg.
Intervention MeSH terms: Lamotrigine; Fluoxetine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Bipolar Disorder; Mayo Clinic

Summary:

      The FLAME Study is a 16-week clinical trial to study treatment with lamotrigine or fluoxetine
      in bipolar I, II and bipolar schizoaffective depressed adults. The purpose of the trial is to
      have a better understanding of whether individuals with a particular gene type and other
      inherited biological markers will have a good response to fluoxetine or lamotrigine, or
      alternatively, would be more likely to have side effects to this medication.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult participants, age 18-65.

          -  Outpatients or inpatients with a diagnosis of bipolar I, II or schizoaffective bipolar
             disorder, depressed phase, non-psychotic, (DSM-5 criteria, Structured Clinical
             Interview for the Diagnostic and Statistical Manual for Mental Disorders Module D
             confirmed)

          -  At least mild symptom severity of depression as defined by the Clinical Global
             Impression for Bipolar Disorder (CGI-BP, Spearing et al. 1997) >2.

          -  Bipolar I participants must be on conventional mood stabilizing treatment [lithium,
             divalproex or valproate, or an atypical antipsychotic]. Participants with a bipolar II
             disorder may pursue the FLAME Study as monotherapy.

          -  Negative urine pregnancy test.

          -  Participants not planning pregnancy in the near future (6 months).

          -  Negative urine toxicology screen (except cannabis).

          -  No evidence of clinically significant laboratory screening tests (complete blood count
             (CBC); electrolytes; thyroid stimulating hormone (TSH); creatinine/blood urea
             nitrogen, Aspartate Aminotransferase (AST)/ALT). Clinical laboratory evaluation within
             the last three months is acceptable.

        Exclusion Criteria:

          -  Inability or unwilling to provide informed consent.

          -  Inability to understand English.

          -  Actively suicidal participants at screening or enrollment visit as defined by a
             response of 3 or 4 on question 4 of the Bipolar Inventory of Symptoms Scale (BISS).

          -  Active delusions or hallucinations defined as a score of 3 or 4 on the BISS question
             40 (persecutory ideas) or 41 (delusions or hallucinations).

          -  Impaired insight as defined as a score of 3 or 4 on BISS question 42 (insight).

          -  Hypomania defined by a BISS manic subscore of ≥15.

          -  Axis I or II comorbidity that by referring mental health professional and/or study
             psychiatrist is primary need of treatment. (This will be assessed by the site
             principal investigator, who has >10 years clinical experience with this population.
             Hospital discharge summaries and outpatient medical records may be reviewed (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) to make this decision.

          -  Pregnant participants

          -  Unwilling or unable to taper any current antidepressant therapy

          -  Participants currently breastfeeding

          -  Female not practicing a reliable form of birth control (condom, intrauterine device
             (IUD), Depo-Provera injection)

          -  Due to lamotrigine pharmacokinetics, female subjects wishing to commence oral
             contraceptive therapy (OCT) within 3 months of enrollment date or anticipate
             discontinuing OCT during study (stable oral contraceptive therapy exception).

          -  History of active substance abuse disorder within the last 3 months (other than
             caffeine or cannabis)

          -  Participants with medical contraindications that preclude lamotrigine or fluoxetine
             treatment

          -  History of severe adverse reaction to lamotrigine and/or fluoxetine

          -  Current carbamazepine or oxcarbazepine treatment

          -  Unstable active medical illness