D-serine Supplementation for Depression

A Randomized add-on Trial of D-serine for Depression

The glutamate system is emerging as target for the development of novel antidepressant medication, in particular compounds modulating the NMDA receptor. While the NMDA receptor antagonist ketamine is an effective option for many treatment-restistant patients, it is also accompanied by dissociative and cognitive effects and also bears the risk to develop addiction, side effects that are significantly restricting its clinical utility. There is now compelling evidence of the antidepressant potential of D-serine, a NMDAR co-agonist. Compared to ketamine, D-serine goes along without any psychotomimetic effects or other side effects and thus might be a prom-ising novel antidepressant.

This study represents the first randomized control trial to test the efficacy of D-serine as an adjuvant therapy in patients with depression and thereby adds to re-cent efforts to establish novel glutamatergic antidepressants. Besides clinical measures, this study also explores the biological mechanisms underlying D-serine's clinical effect.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Dietary supplement: D-serine; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Baselstadt
    • Basel, Baselstadt, Switzerland, 4002
      • University of Basel, Department of Psychiatry (UPK)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18-60
• Inpatients with a diagnosis of MDD with a current moderate-to-severe episode (HAM-D score > 16) (7)
• Treatment as usual (TAU) for depression. TAU for depression may include no treatment at all or standard pharmacotherapy (antidepressants and antipsychotics such as aripiprazole, risperidone or quetiapine) and / or psychotherapy.
• Able to read and understand study procedures and participant's information

Exclusion Criteria:

• Other primary psychiatric diagnoses than MDD such as substance use and psychotic disorders
• Serious suicide attempts
• Contradiction for MRI (no pacemaker, MRI incompatible metal implants or splinters in the body, past heart/head surgery, past stroke/brain injury, claustrophobia)
• Pregnant or lactating women (pregnancy test)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: Placebo; Patients in the placebo group will receive four placebo capsules each day (two after breakfast and two after dinner). The placebo capsules will contain Mannotol / Mannitol-Silica (99.5/0.5, respectively) and will be indistinguishable from D-serine by matching colour, shape, size and packaging.
Active Comparator: Verum	Dietary supplement: D-serine; Patients will receive four 500mg capsules of D-serine each day over a course of six weeks (two after breakfast and two after dinner).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depression Severity	measured with the Hamilton Depression Rating Scale (HAM-D)	Change from baseline HAM-D score at 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety	measured with the State-and Trait-Anxiety Inventory (STAI)	Change from baseline STAI score at 6 weeks
Anhedonia	measured with the Snaith-Hamilton-Pleasure Scale (SHAPS)	Change from baseline SHAPS score at 6 weeks
Neurocognition	measured with the Verbal Learning and Memory Test (VLMT)	Change from baseline VLMT score at 6 weeks
Prefrontal glutamate concentration	measured with magnetic resonance spectroscopy (MRS)	Change from baseline glutamate level at 6 weeks
Stress level	measured with Cortisol awakening responses	Change from baseline cortisol level at 6 weeks
Inflammation	measured with the blood levels of interleukin 1 and 6	Change from baseline interleukin 1 and 6 level at 6 weeks

Collaborators and Investigators

• Sponsor: André Schmidt
• Investigators: Principal Investigator: André Schmidt, PD Dr, University of Basel, Department of Psychiatry (UPK)

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2021
• Primary Completion (Actual): October 30, 2023
• Study Completion (Actual): January 30, 2024

Study Registration Dates

• First Submitted: January 15, 2021
• First Submitted That Met QC Criteria: January 20, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 10, 2024
• Last Update Submitted That Met QC Criteria: May 9, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: AS-2124

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No