Evidence map›Paper›PMID 40908273›Full record

ReviewActa psychiatrica Scandinavica2026

Pharmacological and Mechanistic Interventions for Cognitive Impairment Associated With Schizophrenia: A Review of Registered Clinical Trials.

Bahareh Peyrovian, Lena Palaniyappan, Theodore T Kolivakis, Howard C Margolese

Abstract readReview
In one paragraph

Review in Acta psychiatrica Scandinavica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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.

Bahareh PeyrovianDepartment of Psychiatry, McGill University Health Centre, Allan Memorial Institute, Quebec, Canada.ORCID https://orcid.org/0009-0005-8024-6792
Lena PalaniyappanDepartment of Psychiatry, Douglas Research Centre, McGill University, Quebec, Canada.
Theodore T KolivakisDepartment of Psychiatry, McGill University Health Centre, Allan Memorial Institute, Quebec, Canada.
Howard C MargoleseDepartment of Psychiatry, McGill University Health Centre, Allan Memorial Institute, Quebec, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSchizophrenia is characterized by positive, negative, and cognitive symptoms. Current pharmacological treatments often fail to address cognitive deficits. In this review of clinical trials, we aim to identify studies that explore neurobiological (non-psychological) strategies to address Cognitive Impairment Associated with Schizophrenia (CIAS).

methodsA search of clinical trial databases was conducted through US National Institutes of Health's ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform (ICTRP) on August 2, 2024, with complementary searches performed on July 4 and 10, 2025, for each respective database to update the results.

resultsWe identified 510 relevant interventional studies that objectively measured cognitive performance. Most trials were conducted in the United States (36.4%) and focused on treatment (79%), with randomized designs (88%), investigating drugs (56%), devices (33%), and dietary supplements (10%). Of these trials, 17% reported positive pro-cognitive evidence. Glutamate modulators were the most studied drug category (63 trials), with positive results for sarcosine, BI425809 (Iclepertin), d-serine, d-cycloserine, and minocycline in small-scale trials, although the results were not replicated in larger studies. Nicotinic receptor modulators like ABT-126 and encenicline also showed some cognitive benefits. Device-based interventions, particularly rTMS and iTBS, demonstrated improvements in global cognition, working memory, attention, and processing speed in a subset of trials.

conclusionIn this comprehensive overview of clinical trials on pro-cognitive agents in schizophrenia, we identify emerging opportunities but also acknowledge a lack of replicated evidence. Despite extensive attempts to address CIAS, it remains an undertreated domain, and future trials should explore better ways to treat this important condition.

Indexed as

Antipsychotic AgentsClinical Trials as TopicCognitive DysfunctionSchizophreniaHumansAntipsychotic Agentsclinical trialscognitionneuromodulationpsychopharmacologyschizophreniatreatment

Identifiers

PMID40908273
PMCPMC13050601

What OpenQuestion holds

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Registered trials

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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.