Clinical trial NCT00321152: A Study of 6(S)-5-MTHF Among Serotonin Reuptake Inhibitor(SSRI)-Resistant Outpatients With Major Depressive Disorder (MDD)
Official title: A Double-Blind, Placebo Controlled Study of 6(S)-5-MTHF Among SSRI-Resistant Outpatients With Major Depressive Disorder (MDD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Major Depressive Disorder
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Pamlab, L.L.C.
First posted: 2006-05-03
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to test whether oral 6(S)-5-MTHF (Deplin®) is safe and effective in relieving depression when it is added to standard kinds of antidepressants called serotonin reuptake inhibitors (SSRIs).

Detailed description: The study consists of two sequential phases, each lasting a total of four weeks (8 weeks total), with visits every 10 days. Once patients agree to participate in the study by signing the informed consent document, a full medical and psychiatric history will be taken and a physical examination and blood draw will be performed. Screen rating scales will be performed. Screened and eligible patients will be asked to return two weeks later for a baseline visit when they will be randomized to double-blind treatment with placebo or Deplin (6(S)-5-MTHF). The double-blind treatment will last 60 days, during which patients will be seen every 10 days. Subjects will be randomized to one of three treatment groups: a)Deplin/Deplin, b) placebo/Deplin, c) placebo/placebo. Patients will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study

* For patients randomly assigned to the Deplin/Deplin sequence, the dose of 6(S)-5-MTHF will be 7.5 mg/day during the first phase of the study, and 15 mg/d during the second phase of the study.
* For patients randomly assigned to the placebo/Deplin sequence, the dose of 6(S)-5-MTHF will be 7.5 mg/day during the second phase of the study.
* For patients randomly assigned to the placebo/placebo sequence, both tablets of study medication will be placebo during both phases of the study.

All patients will be asked to take two tablets of blinded study medication in the morning, in addition to their stable dose of ongoing SSRI treatment. Each study medication tablet will be either 7.5 mg of 6(S)-5-MTHF or matching placebo.

Eligibility criteria: Inclusion Criteria:

* 18-65 years old
* Meet criteria for current Major Depressive Disorder
* Currently taking an SSRI

Exclusion Criteria:

* Pregnant women
* Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
* Prior course of MTHF augmentation, or intolerance to MTHF at any dose
* substance use disorders active within the last six months, any bipolar disorder (current or past), or any psychotic disorder (current or past).
* Have failed more than 2 adequate antidepressant trials during the current Major Depressive Episode.

Primary outcomes:
measure: HAM-D
timeFrame: every visit
Secondary outcomes:
measure: QIDS-SR
timeFrame: every visit
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego School of Medicine
state: California
city: Chicago
country: United States
facility: Rush University Medical Center, Psychiatric Medicine Associates, LLC
state: Illinois
city: New Orleans
country: United States
facility: Lousiana State University Health Sciences Center
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Burlington Medical Associates
state: Massachusetts
city: Waltham
country: United States
facility: Waltham Family Practice
state: Massachusetts
city: Westborough
country: United States
facility: Charles River Medical Associates
state: Massachusetts
city: Cincinnati
country: United States
facility: Univeristy of Cincinnati, College of Medicine
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Southeast Health Consultants, LLC
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Massachusetts General Hospital
name: George I Papakostas, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zajecka JM, Fava M, Shelton RC, Barrentine LW, Young P, Papakostas GI. Long-term efficacy, safety, and tolerability of L-methylfolate calcium 15 mg as adjunctive therapy with selective serotonin reuptake inhibitors: a 12-month, open-label study following a placebo-controlled acute study. J Clin Psychiatry. 2016 May;77(5):654-60. doi: 10.4088/JCP.15m10181.
citation: Papakostas GI, Shelton RC, Zajecka JM, Etemad B, Rickels K, Clain A, Baer L, Dalton ED, Sacco GR, Schoenfeld D, Pencina M, Meisner A, Bottiglieri T, Nelson E, Mischoulon D, Alpert JE, Barbee JG, Zisook S, Fava M. L-methylfolate as adjunctive therapy for SSRI-resistant major depression: results of two randomized, double-blind, parallel-sequential trials. Am J Psychiatry. 2012 Dec;169(12):1267-74. doi: 10.1176/appi.ajp.2012.11071114.