N-methylglycine (Sarcosine) Treatment for Depression

N-methylglycine (Sarcosine) for Treatment of Major Depressive Disorder

Major depressive disorder is a complex disease and most currently available antidepressants aiming at monoamine neurotransmission exhibit limited efficacy and cognitive effects. N-methyl-D-aspartate (NMDA), one subtype of glutamate receptors, plays an important role in learning and memory. N-methyl-D-aspartic acid (NMDA) enhancing agents, such as sarcosine (N-methylglycine), have been used as adjunctive therapy of schizophrenia. Sarcosine improved not only psychotic but also depressive symptoms in patients with schizophrenia. To confirm its antidepressant effect, the purpose of this study is to compare citalopram and sarcosine in efficacy for major depressive patients.

Study Overview

• Status: Completed
• Conditions: Depression; Major Depression; Major Depressive Disorder
• Intervention / Treatment: Drug: sarcosine; Drug: citalopram

Detailed Description

Major depressive disorder is a complex disease and most currently available antidepressants aiming at monoamine neurotransmission exhibit limited efficacy and cognitive effects. Novel therapies via manipulating other neurotransmission (e.g. glutamate receptor) are being developed.

NMDA enhancing agents, such as sarcosine have been demonstrated to improve negative symptoms and depressive symptoms of schizophrenic patients. The purpose of this study is to compare citalopram and sarcosine in aspects of efficacy, safety in major depressive patients.

In the study, 40 major depressive patients are recruited into the 6-week trial and randomly assigned into the two groups (20-60 mg/d citalopram, or 500 - 1500 mg/d sarcosine) with a double-blind manner. Hamilton Depression Rating Scale(17-item), CGI(Clinical Global Impression), GAF(Global Assessment of Function)and side effects are evaluated every two weeks during the trial. The efficacies of two groups are compared.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan
    • Department of Psychiatry, China Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18-55 years
• Fulfilled the DSM-IV criteria of major depressive disorder
• Had a 17-item Hamilton Rating Scale for Depression (HAMD-17)>or= 18
• No DSM-IV diagnosis of substance abuse or dependence (including alcohol) within the past 6 months
• Had been drug free for > 3 months
• Physically healthy and had all laboratory parameters within normal limits.
• Agree to participate in the study and provide informed consent

Exclusion Criteria:

• Had history of epilepsy, head trauma or other major neurological or medical diseases
• Had psychotic depression, bipolar I/II disorder, schizophrenia or any other psychotic disorder
• Moderate-severe suicidal risks
• Severe cognitive impairment
• Female subjects who were pregnant, or at risk of pregnancy or lactation
• Initiating or stopping formal psychotherapy within six weeks prior to enrollment
• Had a history of poor response to SSRIs or previously received electroconvulsive therapy
• Had a history of severe adverse reaction to SSRIs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sarcosine	Drug: sarcosine; 500-1500 mg/day, oral, for 6 weeks
Active Comparator: citalopram	Drug: citalopram; 20-60 mg/day, oral, for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
17-item Hamilton Depression Rating Scale	score change	week 0, 2, 4, 6
Remission rate		week 0, 2,4, 6
GAF(Global Assessment of Function)	score changes	Week 0, 2, 4, 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
dropout rate		week 0, 2, 4, 6
CGI(clinical global impression)	score changes	week 0, 2, 4,6
Response Rate		Week 0, 2, 4, 6
Factors of 17-item Hamilton Depression Rating Scale		Week 0, 2, 4, 6

Collaborators and Investigators

• Sponsor: China Medical University Hospital
• Collaborators: National Science Council, Taiwan
• Investigators: Principal Investigator: Hsien-Yuan Lane, M.D., Ph.D, Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan; Principal Investigator: Chieh-Liang Huang, MD, Department of Psychiatry, China Medical University Hospital,Taichung,Taiwan

Publications and helpful links

General Publications

• Dean RL, Hurducas C, Hawton K, Spyridi S, Cowen PJ, Hollingsworth S, Marquardt T, Barnes A, Smith R, McShane R, Turner EH, Cipriani A. Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder. Cochrane Database Syst Rev. 2021 Sep 12;9(9):CD011612. doi: 10.1002/14651858.CD011612.pub3.
• Huang CC, Wei IH, Huang CL, Chen KT, Tsai MH, Tsai P, Tun R, Huang KH, Chang YC, Lane HY, Tsai GE. Inhibition of glycine transporter-I as a novel mechanism for the treatment of depression. Biol Psychiatry. 2013 Nov 15;74(10):734-41. doi: 10.1016/j.biopsych.2013.02.020. Epub 2013 Apr 3.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: September 11, 2009
• First Submitted That Met QC Criteria: September 14, 2009
• First Posted (Estimate): September 15, 2009

Study Record Updates

• Last Update Posted (Estimate): July 12, 2011
• Last Update Submitted That Met QC Criteria: July 10, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Depression; Major depressive disorder; NMDA; Sarcosine; N-methylglycine
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: DOH95-TD-B-111-TM002