16-week Comparative Effectiveness Trial of Lamotrigine vs. Fluoxetine for Bipolar Depression

• Status: Terminated
• Trial end date: 2018-05-23
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mayo Clinic
• Collaborators: J Willard and Alice S. Marriott Foundation; Marriott Family and Foundation
• Treatments: Anticonvulsants; Fluoxetine; Lamotrigine

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