Evidence map›Paper›PMID 42645703›Full record

ReviewCNS drugs2026

Next-Generation Pharmacotherapies for Unipolar Mood Disorders: A Leading Article on Phase II/III Drug Development Across Diverse Mechanisms.

Alana King, Morgan Hardy, Taeho Greg Rhee, Samuel T Wilkinson

Abstract readReview
PubMed Publisher
In one paragraph

Review in CNS drugs, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Alana KingDepartment of Psychiatry, Yale University, 184 Liberty St, New Haven, CT, 06511, USA.ORCID http://orcid.org/0009-0000-4650-0017
Morgan HardyDepartment of Psychiatry, Yale University, 184 Liberty St, New Haven, CT, 06511, USA.ORCID http://orcid.org/0000-0003-4248-4106
Taeho Greg RheeDepartment of Psychiatry, Yale University, 184 Liberty St, New Haven, CT, 06511, USA.ORCID http://orcid.org/0000-0003-4961-3361
Samuel T WilkinsonDepartment of Psychiatry, Yale University, 184 Liberty St, New Haven, CT, 06511, USA. samuel.wilkinson@yale.edu.ORCID http://orcid.org/0000-0002-3483-9168

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite the wide prevalence of mood disorders globally, there is a substantial unmet need for effective, mechanistically distinct treatments. Given that approximately 30% of individuals do not display adequate response to standard antidepressant therapies, the past 15 years have seen a shift away from traditional monoaminergic approaches toward glutamatergic and other novel mechanisms. Following the US Food and Drug Administration (FDA) approval of esketamine and brexanolone in 2019, industry investment in therapeutics with novel mechanisms for mood and anxiety disorders has expanded, catalyzing a new wave of innovative interventions. This review summarizes progress for unipolar mood disorders in four categories-glutamatergic/GABA modulators, ion channel modulators, psychedelics, and other potential therapeutic mechanisms-focusing on Phase II/III industry-sponsored US clinical trials active within the past 3 years. The drug names discussed are ALTO-100, ALTO-203, ALTO-207, ALTO-300, BHV-7000, BI-1569912, BPL-003, COMP360, DT120, ELE-101, GATE-251, GH001, GM-1020, GM-2505, HLP003, MK-1942, NBI-1065845, NBI-1070770, NV-5138, PIPE-307, SEP-363856, SPT-300, VLS-01, and XEN1101. The US Clinical Trials registry (clinicaltrials.gov), MEDLINE, conference proceedings, and company communications such as press releases were consulted to obtain up-to-date trial information and reported outcomes. Overall, the therapeutic landscape shows an expanding range of clinical compounds under active development; nonetheless, persistent challenges remain, including approaches to therapeutics where functional unblinding may occur, the ways in which to consider a novel conceptualization of occupancy-driven versus event-driven pharmacology, and the role of supporting psychotherapy.

Indexed as

Antidepressive AgentsDrug DevelopmentMood DisordersAnimalsClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicHumansAntidepressive Agents

Identifiers

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.