Supplementary Table S1- Novel neurotherapeutic agents for treatment-resistant depression
(TRD).
Agent
Ketamine
Route of administration
Intravenous
Notes
NMDA receptor antagonist; one RCT supports efficacy
for TRD [21]; antidepressant effects last 1 week; there is
an ongoing study with intranasal ketamine for TRD
(ClinicalTrials.gov identifier: NCT01304147)
CP-101,606
Intravenous
NR2-subunit specific NMDA receptor antagonist. One
RCT supports efficacy for TRD [119]. Antidepressant
effects last 1 week.
AZD6765
Intravenous
Low–trapping NMDA channel blocker. One RCT
supports antidepressant effects [120]. Effects are
transient.
Riluzole
Oral administration
Blocks voltage-gated sodium channels, thereby blocking
glutamate release and enhancing astrocytic uptake of
glutamate. Approved for the treatment of amyotrophic
lateral sclerosis. One small open-label trial supports
riluzole augmentation as an effective strategy for TRD
[121].
D-cycloserine
Oral administration
NMDA partial agonist. Clinical trial has been completed
(ClinicalTrials.gov identifier: NCT00408031)
EVT 101
Oral administration
Orallly active NR2B subtype-selective NMDA receptor
antagonist.
Clinical
trial
has
been
completed.
(ClinicalTrials.gov identifier: NCT01128452). No results
are available.
GLYX-13
Intravenous
NMDA receptor glycine-site functional partial agonist.
Clnical
trial
for
TRD
has
been
completed.
(ClinicalTrials.gov identifier: NCT01234558).
Scopolamine
Intravenous
A selective antagonist of muscarinic acetylcholine
receptors. Two RCTs support efficacy for TRD [22,123].
Table S1 - Cont.
Agent
Mecamylamine
Route of administration
Oral administration
Notes
Acts as an antagonist to nicotinic acetylcholine receptors.
At least two small RCTs support its efficacy as an
augmenting agent for TRD [125,126].
LY2456302
Not disclosed
A specific kappa-opioid receptor antagonist. A registered
clinical protocol for TRD is available (ClinicalTrials.gov
identifier: NCT01913535)
Buprenorphine
Oral administration
Act as a Partial agonist at delta and kappa opioid
receptors and as an antagonist at delta receptors. Ongoing
trial
for
TRD
(ClinicalTrials.gov
identifier:
NCT01407575)
Infliximab
Intravenous administration
Act as a TNF-α antagonist. A small proof-of-concept
RCT tested the efficacy of IV infliximab (5 mg/Kg) or
placebo administered at baseline and at weeks 2, 4 and 6
of 12-week trial in a sample of 60 participants with TRD.
By the end of the trial there was no difference between
groups in the primary outcome (17-item HDRS) [136].
Oxytocine
adjuncts
and
tibolone Oxytocine intranasal
Tibolone
has
a
complex
mechanism
of
action.
Oxytocine intranasal plus
Characterized as a selective oestrogen acitivity regulator.
placebo (oral)
This three arm trial is under way (ClinicalTrials.gov
Oxytocine intranasal plus
identifier: NCT01239888)
tibolone (oral)
Cysteamine
Oral administration
Cysteamine
is
FDA
approved
for
nephropathic
cystinosis. It increases BDNF in the brain and promotes
neuronal growth. Clinical trial for TRD has been
terminated (ClinicalTrials,giv identifier: NCT00715559).
No results are available.
Creatine
Oral administration
Brain creatine reserves shift creatine kinase activity,
thereby enhancing ATP production. May have effects on
CNS bioenergetics. There is an ongoing augmentation
trial
for
TRD
NCT01175616)
(ClinicalTrials.gov
identifier: