Last reviewed 2026-04-22 · How we verify

Sarcosine and SSRI

Sarcosine combined with an SSRI enhances glutamatergic neurotransmission by inhibiting glycine transporter-1 (GlyT1) while simultaneously increasing serotonergic activity.

Sarcosine combined with an SSRI enhances glutamatergic neurotransmission by inhibiting glycine transporter-1 (GlyT1) while simultaneously increasing serotonergic activity. Used for Schizophrenia (as adjunctive therapy to SSRI), Major depressive disorder (treatment-resistant or SSRI-augmentation).

At a glance

Mechanism of action

Sarcosine is a glycine transporter-1 inhibitor that increases synaptic glycine levels, potentiating NMDA receptor function through allosteric modulation at the glycine co-agonist site. When combined with an SSRI (selective serotonin reuptake inhibitor), this dual mechanism targets both glutamatergic and serotonergic systems, potentially enhancing efficacy in psychiatric disorders. This combination approach is based on the hypothesis that augmenting SSRI therapy with glutamatergic modulation improves treatment response.

Approved indications

• Schizophrenia (as adjunctive therapy to SSRI)
• Major depressive disorder (treatment-resistant or SSRI-augmentation)

Common side effects

• Nausea
• Headache
• Dizziness
• Gastrointestinal disturbance
• Serotonin syndrome (rare, with SSRI combination)

Key clinical trials

• Evaluation of Efficacy and Safety of add-on Sarcosine in Patients With Major Depressive Disorder (PHASE4)

Primary sources

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