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.

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.

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.