Clinical trial NCT00977353: N-methylglycine (Sarcosine) Treatment for Depression
Official title: N-methylglycine (Sarcosine) for Treatment of Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Major Depressive Disorder
Depression
Major Depression
Keywords: Major depressive disorder
Depression
Sarcosine
N-methylglycine
NMDA
Lead sponsor: China Medical University Hospital
Sponsor class: OTHER
Collaborators: name: National Science and Technology Council, Taiwan
First posted: 2009-09-15
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 17-item Hamilton Depression Rating Scale
timeFrame: week 0, 2, 4, 6
measure: Remission rate
timeFrame: week 0, 2,4, 6
measure: GAF(Global Assessment of Function)
timeFrame: Week 0, 2, 4, 6
Secondary outcomes:
measure: dropout rate
timeFrame: week 0, 2, 4, 6
measure: CGI(clinical global impression)
timeFrame: week 0, 2, 4,6
measure: Response Rate
timeFrame: Week 0, 2, 4, 6
measure: Factors of 17-item Hamilton Depression Rating Scale
timeFrame: Week 0, 2, 4, 6
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: Department of Psychiatry, China Medical University Hospital
Study officials:
affiliation: Department of Psychiatry, China Medical University Hospital, Taichung, Taiwan
name: Hsien-Yuan Lane, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Psychiatry, China Medical University Hospital,Taichung,Taiwan
name: Chieh-Liang Huang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.