A Study of 6(S)-5-MTHF Among Serotonin Reuptake Inhibitor(SSRI)-Resistant Outpatients With Major Depressive Disorder (MDD)

A Double-Blind, Placebo Controlled Study of 6(S)-5-MTHF Among SSRI-Resistant Outpatients With Major Depressive Disorder (MDD)

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).

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Other: 6(S)-5-MTHF (a Medical Food)

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.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92161
      • University of California San Diego School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center, Psychiatric Medicine Associates, LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Lousiana State University Health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Burlington, Massachusetts, United States, 01803
      • Burlington Medical Associates
    • Waltham, Massachusetts, United States, 02453
      • Waltham Family Practice
    • Westborough, Massachusetts, United States, 01581
      • Charles River Medical Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Univeristy of Cincinnati, College of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Southeast Health Consultants, LLC
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Deplin/Deplin = participants will receive 7.5 mg/day of Deplin (6(S)-5-MTHF)for the first 4 weeks, and then 15 mg/day of Deplin for the next 4 weeks.	Other: 6(S)-5-MTHF (a Medical Food); The study consists of 8 visits over a period of 8 weeks or 60 days. Eligible participants will be randomized to double-blind treatment with placebo or Deplin (6(S)-5-MTHF). Participants will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study. At the end of the double-blind phase, both responders and non-responders who have completed the 8 week study will have the option of receiving free, open-label adjunctive treatment with either 7.5 mg or 15 mg of 6(S)-5-MTHF for 12 months. Subjects who agree to receive open-label treatment with 6(S)-5-MTHF for 12 months will be assessed every three (3) months until the end of the follow-up phase.
Experimental: 2; placebo/Deplin = participants will receive placebo for the first 4 weeks, and then 7.5 mg/day of Deplin (6(S)-5-MTHF) for the next 4 weeks.	Other: 6(S)-5-MTHF (a Medical Food); The study consists of 8 visits over a period of 8 weeks or 60 days. Eligible participants will be randomized to double-blind treatment with placebo or Deplin (6(S)-5-MTHF). Participants will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study. At the end of the double-blind phase, both responders and non-responders who have completed the 8 week study will have the option of receiving free, open-label adjunctive treatment with either 7.5 mg or 15 mg of 6(S)-5-MTHF for 12 months. Subjects who agree to receive open-label treatment with 6(S)-5-MTHF for 12 months will be assessed every three (3) months until the end of the follow-up phase.
Placebo Comparator: 3; placebo/placebo = both tablets of study medication will be placebo during both phases of the study.	Other: 6(S)-5-MTHF (a Medical Food); The study consists of 8 visits over a period of 8 weeks or 60 days. Eligible participants will be randomized to double-blind treatment with placebo or Deplin (6(S)-5-MTHF). Participants will have a greater than 50% chance of receiving active medication (Deplin) at some point in the 8 week study. At the end of the double-blind phase, both responders and non-responders who have completed the 8 week study will have the option of receiving free, open-label adjunctive treatment with either 7.5 mg or 15 mg of 6(S)-5-MTHF for 12 months. Subjects who agree to receive open-label treatment with 6(S)-5-MTHF for 12 months will be assessed every three (3) months until the end of the follow-up phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
HAM-D	every visit

Secondary Outcome Measures

Outcome Measure	Time Frame
QIDS-SR	every visit

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Pamlab, L.L.C.
• Investigators: Principal Investigator: George I Papakostas, M.D, Massachusetts General Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: May 1, 2006
• First Submitted That Met QC Criteria: May 1, 2006
• First Posted (Estimate): May 3, 2006

Study Record Updates

• Last Update Posted (Estimate): June 8, 2010
• Last Update Submitted That Met QC Criteria: June 7, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: 2006P000604