Selected publication milestones through 9 October 2026. These dates identify source publication years, not priority claims or a comprehensive history.
2001 — Antidepressant prophylaxis during prolonged interferon exposure tests clinically diagnosed depression. PMID 11274622.
2013 — Overall infliximab trial null with exploratory inflammation-related findings. PMID 22945416.
2021 — MINDEP overall null and exploratory higher-CRP subgroup. PMID 33504955.
2022 — Multicentre MinoTRD trial retains a null primary clinical result. PMID 36103181.
2024 — Prospectively stratified PREDDICT report challenges automatic CRP-subtype benefit. PMID 37635396.
2025 — Acute challenge tests anhedonia and time-dependent mood response. PMID 40264292.
2025 — Older-insomnia challenge tests transient mood effects, excluding recent MDD. PMID 40668551.
CRP concentration is neither a specific immune pathway nor a validated causal-subtype definition.
Exploratory threshold effects need prospective independent replication.
Acute anhedonia and sickness require separate assessment from sustained MDD and function.
Immune, metabolic, sleep and medication pathways need selective controls.
Named prospective trials require current registry/result verification; old estimated completion dates are not completed evidence.
Prospectively registered marker-stratified MDD trial with a fixed assay/cut-off, powered treatment-by-marker interaction, selective immune-pathway engagement, matched clinical attention and blinded sustained clinical/function outcomes; compare a mechanistically distinct intervention and replicate independently. INSTA-MD addresses part of this design, but drug pleiotropy and target engagement still require examination.
INSTA-MD: NCT05644301. The retrieved registry still lists recruiting, last verified October 2024, with an estimated September 2026 primary completion date. This is stale administrative status, not an outcome or proof of completion. The investigator recruitment page displays an update of 12-08-2026. The protocol is PMID 39350954, auxiliary and outside the primary-outcome count.