Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2008
A placebo-controlled add-on trial of the Ampakine, CX516, for cognitive deficits in schizophrenia.
Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00235352 (A Placebo-Controlled Trial of CX516), which is not on this map. Cited by 73 papers, 4 of them syntheses that pooled 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.
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.
A Placebo-Controlled Trial of CX516 (Ampakine) Added to Clozapine, Olanzapine or Risperidone in Patients With Schizophrenia
Who cites it
73 citing papers in PubMed, 4 syntheses or guidelines pooled it, 179 citations in OpenAlex.
- Antipsychotic combinations for schizophrenia.The Cochrane database of systematic reviews · 2017Pooled it
- Effects of glutamate positive modulators on cognitive deficits in schizophrenia: a systematic review and meta-analysis of double-blind randomized controlled trials.Molecular psychiatry · 2015Pooled it
- Adjunctive pharmacotherapy for cognitive deficits in schizophrenia: meta-analytical investigation of efficacy.The British journal of psychiatry : the journal of mental science · 2013Pooled it
- Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia.CNS drugs · 2011Pooled it
- Evaluation of a plasticity-based cognitive training program in schizophrenia: Results from the eCaesar trial.Schizophrenia research · 2019Trial
- Using neuroplasticity-based auditory training to improve verbal memory in schizophrenia.The American journal of psychiatry · 2009Trial
- Acute Administration of Ampakine CX1739 after Cervical Spinal Cord Injury.Journal of neurotrauma · 2026Article
- Neurovascular and synaptic milieu of brain-resident cells in cognitive dysfunction of myalgic encephalomyelitis/chronic fatigue syndrome.Journal of translational medicine · 2026Review
- Positive AMPA and Kainate Receptor Modulators and Their Therapeutic Potential in CNS Diseases: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Glutamate-Based Therapeutic Strategies for Schizophrenia: Emerging Approaches Beyond Dopamine.International journal of molecular sciences · 2025Review
- Amplification of the therapeutic potential of AMPA receptor potentiators from the nootropic era to today.Pharmacology, biochemistry, and behavior · 2025Review
- Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review.Translational psychiatry · 2025Review
- Pharmacological modulation of respiratory control: Ampakines as a therapeutic strategy.Pharmacology & therapeutics · 2025Review
- Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes.Brain : a journal of neurology · 2024Article
- Novel α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) potentiator LT-102: A promising therapeutic agent for treating cognitive impairment associated with schizophrenia.CNS neuroscience & therapeutics · 2024Article
- A Comprehensive Review of the Current Status of the Cellular Neurobiology of Psychedelics.Biology · 2023Review
- Strategies for Treatment of Disease-Associated Dementia Beyond Alzheimer's Disease: An Update.Current neuropharmacology · 2023Review
- Glutamatergic dysfunction in Schizophrenia.Translational psychiatry · 2022Review
- Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia.CNS drugs · 2022Review
- Beyond antipsychotics: a twenty-first century update for preclinical development of schizophrenia therapeutics.Translational psychiatry · 2022Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 7 institutions in 1 country.
Funding
Abstract
AMPA-receptor-positive modulators (Ampakines) facilitate learning and memory in animal models and in preliminary trials in human subjects. CX516 is the first Ampakine to be studied for cognitive enhancement in schizophrenia. Stable schizophrenia patients treated with clozapine (n=52), olanzapine (n=40), or risperidone (n=13) were randomly assigned to add-on treatment with CX516 900 mg three times daily or placebo for 4 weeks. Subjects were assessed with a cognitive battery at baseline, week 4, and at 4-week follow-up. Clinical scales and safety monitoring were also performed. The primary endpoint was the change from baseline in a composite cognitive score at week 4 for the intent-to-treat sample. Additional analyses examined change in symptom rating scores and examined drug effects on patients treated with clozapine separately from patients treated with either olanzapine or risperidone. A total of 105 patients were randomized and 95 (90%) completed the 4-week trial. Patients treated with CX516 did not differ from placebo in change from baseline on the composite cognitive score, or on any cognitive test at weeks 4 or 8. The between groups effect size at week 4 for the cognitive composite score was -0.19 for clozapine-treated patients and 0.24 for patients treated with olanzapine or risperidone. The placebo group improved more on the PANSS total score than the CX516 group; no other clinical rating differed between treatment groups. CX516 was associated with fatigue, insomnia and epigastric discomfort compared to placebo, but was generally well tolerated. CX516 was not effective for cognition or for symptoms of schizophrenia when added to clozapine, olanzapine, or risperidone.
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What OpenQuestion holds
Registered trials
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.