Trial reportPsychopharmacology2014
Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia.
Trial report in Psychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Exploring the Relationship between Cognitive Performance, Performance-Based Functioning, and Everyday Functioning in People with Schizophrenia: a Systematic Literature Review.Schizophrenia bulletin · 2026Pooled it
- Pharmacological interventions for social cognitive impairments in schizophrenia: A systematic review and network meta-analysis of randomized controlled trials.European psychiatry : the journal of the Association of European Psychiatrists · 2026Pooled it
- Pregnenolone reduces provoked craving and cocaine use in men and women with cocaine use disorder: A pilot trial.Drug and alcohol dependence · 2025Trial
- Effect of Pregnenolone vs Placebo on Self-reported Chronic Low Back Pain Among US Military Veterans: A Randomized Clinical Trial.JAMA network open · 2020Trial
- Neuroactive steroid levels and cocaine use chronicity in men and women with cocaine use disorder receiving progesterone or placebo.The American journal on addictions · 2019Trial
- UPSA-M: Feasibility and initial validity of a mobile application of the UCSD Performance-Based Skills Assessment.Schizophrenia research · 2015Trial
- Schizophrenia: from mechanism to therapy.Science China. Life sciences · 2026Review
- Reproduction under Siege: How Chronic Stress Hijacks the HPG Axis?Neuroendocrinology · 2026Review
- Pharmacological and Mechanistic Interventions for Cognitive Impairment Associated With Schizophrenia: A Review of Registered Clinical Trials.Acta psychiatrica Scandinavica · 2026Review
- Stability and Reliability of Repeated Plasma Pregnenolone Levels After Oral Pregnenolone Dosing in Individuals with Cocaine Use Disorder: Pilot Findings.Life (Basel, Switzerland) · 2024Article
- CLICK-chemoproteomics and molecular dynamics simulation reveals pregnenolone targets and their binding conformations in Th2 cells.Frontiers in immunology · 2023Article
- Article
- A narrative review of treatment interventions to improve cognitive performance in schizophrenia, with an emphasis on at-risk and early course stages.Psychiatry research · 2022Review
- Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia.CNS drugs · 2022Review
- More than a marker: potential pathogenic functions of MAP2.Frontiers in molecular neuroscience · 2022Article
- Inhibition of human macrophage activationFrontiers in immunology · 2022Article
- Multimodal electrophysiological analyses reveal that reduced synaptic excitatory neurotransmission underlies seizures in a model of NMDAR antibody-mediated encephalitis.Communications biology · 2021Article
- Cognitive Deficit in Schizophrenia: From Etiology to Novel Treatments.International journal of molecular sciences · 2021Review
- Pitfalls of NMDA Receptor Modulation by Neuroactive Steroids. The Effect of Positive and Negative Modulation of NMDA Receptors in an Animal Model of Schizophrenia.Biomolecules · 2021Article
- Cognitive Subtyping in Schizophrenia: A Latent Profile Analysis.Schizophrenia bulletin · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationalePreclinical and clinical data suggest that pregnenolone may be a promising therapeutic in schizophrenia. Pregnenolone is neuroprotective and enhances learning and memory, myelination, and microtubule polymerization. Treatment with pregnenolone elevates allopregnanolone (a neurosteroid that enhances GABAA receptor responses) and pregnenolone sulfate (a positive NMDA receptor modulator). Pregnenolone could thus potentially mitigate GABA dysregulation and/or NMDA receptor hypofunction in schizophrenia via metabolism to other neurosteroids.
objectiveThe objective of this study is to conduct a randomized controlled trial of adjunctive pregnenolone in schizophrenia.
methodsFollowing a placebo lead-in, 120 participants were randomized to pregnenolone or placebo for 8 weeks (Institute for Mental Health, Singapore). Primary endpoints were changes in MATRICS Consensus Cognitive Battery (MCCB) composite scores (cognitive symptoms), UCSD Performance-based Skills Assessment-Brief (UPSA-B) composite scores (functional capacity), and Scale for Assessment of Negative Symptoms (SANS) total scores (negative symptoms). A modified intent-to-treat analysis approach was utilized.
resultsNo significant changes compared to placebo were demonstrated in composite MCCB scores. In contrast, participants randomized to pregnenolone (n = 56) demonstrated greater improvements in functional capacity (UPSA-B composite changes) compared to placebo (n = 55), p = 0.03. Pregnenolone was also superior to placebo in the communication subscale of the UPSA-B (p < 0.001). Serum pregnenolone changes post-treatment were correlated with UPSA-B composite score changes in females (r s = 0.497, p < 0.042, n = 17) but not in males. Mean total SANS scores were very low at baseline and did not improve further post-treatment. Pregnenolone was well-tolerated.
conclusionsPregnenolone improved functional capacity in participants with schizophrenia, but did not improve cognitive symptoms over an 8-week treatment period. Neurosteroid changes correlated with functional improvements in female participants. Neurosteroid interventions may exhibit promise as new therapeutic leads for schizophrenia.
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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.