Bipolar Depression Before and After Lamotrigine Treatment

• Status: Completed
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This study compared glutamate and other neurometabolites measured by proton magnetic resonance spectroscopy (1H-MRS) in bipolar I and II patients currently depressed with age-matched healthy controls. The study will also compare 1H-MRS of bipolar I and II patients before and after taking a 12-week course of lamotrigine.

The goal of this study was to better understand the neurobiology of bipolar depression and how lamotrigine may therapeutically impact brain function and mood response.

The hypothesis was that in comparison to non-remission participants, bipolar participants who achieve remission (defined as a Montgomery Asberg Depression Rating Scale (MADRS) score <12 at week 12) associated with lamotrigine monotherapy will exhibit a greater decrease in glutamate (Glu) and an increase in N-acetyl aspartate (NAA), reported as a cerebrospinal fluid (CSF)-corrected absolute concentration percent change from baseline to endpoint in anterior cingulate (AC) and dorsolateral prefrontal cortex (DLPFC).

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Mayo Clinic
• Collaborator: National Institute of Mental Health (NIMH)
• Treatments: Anticonvulsants; Lamotrigine

Criteria

Bipolar Group Inclusion Criteria:

• Diagnosis of Bipolar Type I or II disorder depress phase (SCID confirmed)

• Moderate depression as confirmed by Montgomery Asberg Depression Rating Scale greater than or equal to 20

• Negative urine toxicology screen

• Negative urine pregnancy test

• No clinically significant lab abnormalities for complete blood count (CBC), Thyroid stimulating hormone (TSH), Sodium (Na+), Potassium (K+), Chlorine (Cl-), Carbon dioxide (CO2), creatinine (CREA), blood urea nitrogen (BUN), Glucose, hepatic panel.

Bipolar Group Exclusion Criteria:

• Inability to provide informed consent

• Any current Axis I diagnosis other than anxiety disorders needing concurrent antidepressant therapy

• History of active substance abuse/dependence within the last 3 months

• History of claustrophobia

• History of adverse reaction to Lamotrigine

• Fluoxetine and decanoate antipsychotic therapy

• Unwilling or unable to taper current sub-optimal psychotropic medications other than a stable dosage of Lithium, Depakote, or an Atypical Antipsychotic approved by study personnel

• Unstable active medical illness

• Pregnancy or breast-feeding

• Male/ Female not practicing a reliable form of birth control (condom, Intrauterine Device (IUD), depo injection)

• Female wishing to commence oral contraceptive therapy within 3 months of enrollment date (stable oral contraceptive therapy exception)

• Active suicidal ideation with plan

• History of major head trauma with loss of consciousness > 5 minutes or skull fracture

• History of previous neurological event (epilepsy, stroke, transient ischemic attack)

• Implanted metal objects (i.e., pacemakers, aneurysm clips, metal prostheses, joints, rods)

• Inability to speak English

• Prominent Axis II disorder [This will be assessed by the principal investigator, who has >10 years clinical experience with this population. Hospital discharge summaries and outpatient medical records will be reviewed for evidence that Axis II pathology is the primary psychiatric disturbance (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)].

Healthy Control Group Inclusion Criteria:

• Negative urine toxicology screen

• Negative urine pregnancy test

• Normal blood values for thyroid stimulating hormone (TSH)

Healthy Control Group Exclusion Criteria:

• Inability to provide informed consent

• Any current Axis I or II diagnosis

• Known history of claustrophobia

• Lifetime personal or family history (first-degree relative) of dementia, substance-related disorder (nicotine abuse or dependence exception), psychotic disorder, mood disorder (history of bereavement exception), anxiety disorder (specific phobia exception)

• Unstable active medical illness

• Pregnancy or breast-feeding

• Male /Female not practicing a reliable form of birth control (condom, IUD, depo injection)

• History of major head trauma with loss of consciousness > 5 minutes or skull fracture

• History of previous neurological event (epilepsy, stroke, transient ischemic attack)

• Implanted metal objects (i.e., pacemakers, aneurysm clips, metal prostheses, joints)

• Inability to speak English

• On current medications known to affect glutamate (i.e., Riluzole).

• Any medically remarkable impairment due to a medical condition or brain injury resulting in significant impairment in cognitive functioning based on neuropsychological test battery and/or MRS scan results.