Pregnenolone and Dehydroepiandrosterone as an Adjunctive Treatment in Schizophrenia and Schizoaffective Disorder: An 8-Week, Double-Blind, Randomized, Controlled, 2-Center, Parallel-Group Trial
Abstract
OBJECTIVE: Pregnenolone (PREG) and dehydroepiandrosterone (DHEA) are reported to have a modulatory effect on neuronal excitability, synaptic plasticity, and response to stress; they are associated with mood regulation and cognitive performance. We investigated the influence of PREG and DHEA on psychotic symptoms and cognitive functioning as an add-on to ongoing antipsychotic treatment of patients with chronic schizophrenia or schizoaffective disorder. METHOD: This 8-week, double-blind, randomized, placebo-controlled, 2-center study compared 30 mg/d of PREG (PREG-30), 200 mg/d of PREG (PREG-200), 400 mg/d of DHEA, and placebo as an adjunctive treatment of 58 chronic schizophrenia or schizoaffective disorder patients (DSM-IV). The data were collected from February 2005 until June 2007. The outcome measures were symptomatic and neurocognitive changes, functioning, and tolerability as assessed primarily by the Clinical Global Impressions-Severity of Illness scale and the Positive and Negative Syndrome Scale. Analyses are presented for 44 patients who completed 8 weeks of treatment and for 14 noncompleters. RESULTS: Compared with subjects who received placebo, those administered PREG-30 had significant reductions in positive symptom scores and extrapyramidal side effects (EPS) and improvement in attention and working memory performance, whereas subjects treated with PREG-200 did not differ on outcome variable scores for the study period. The general psychopathology severity and general functioning of patients receiving placebo and PREG-30 improved more than that of those subjects treated with DHEA, while EPS improved more in subjects treated with DHEA than in patients receiving placebo. Negative symptoms and akathisia were not significantly benefited by any treatment. The administration of PREG and DHEA was well tolerated. CONCLUSIONS: Low-dose PREG augmentation demonstrated significant amelioration of positive symptoms and EPS and improvement in attention and working memory performance of schizophrenia and schizoaffective disorder patients. Further double-blind controlled studies are needed to investigate the clinical benefit of pregnenolone augmentation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00174889.
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In the Ritsner et al trial, the PREG 30 mg group experienced significant reduction in positive and extrapyramidal symptoms.
“• PREG 30 mg group experienced significant reduction in positive and extrapyramidal symptoms and improvement in attention and working memory performance”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [45]
In the Ritsner et al trial, the PREG 30 mg group experienced improvement in attention and working memory performance.
“• PREG 30 mg group experienced significant reduction in positive and extrapyramidal symptoms and improvement in attention and working memory performance”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [45]
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Effects of Blockade of Cholinesterase on Negative Disorders in Schizophrenia
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- Authors
- Ritsner, M. S., Gibel, A., Shleifer, T., Boguslavsky, I., Zayed, A., Maayan, R., Weizman, A., & Lerner, V.
- Affiliations
- Technion – Israel Institute of Technology (IL)
- Corresponding author
- Ritsner, Michael S.
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2010-06-15
- Volume
- 71
- Issue
- 10
- Pages
- 1351-1362
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2080194097
- Cited by
- 85
- References
- 0
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 6 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 5 · 2014: 17 · 2013: 7 · 2012: 6
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Keywords
- pregnenolone, dehydroepiandrosterone, adjunctive therapy, schizophrenia, schizoaffective disorder, antipsychotic augmentation, positive symptoms, extrapyramidal symptoms, akathisia, attention, working memory, neurocognitive function, negative symptoms
- MeSH terms
- Adolescent, Adult, Attention, Dehydroepiandrosterone, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Dyskinesia, Drug-Induced, Female, Humans, Male, Memory, Short-Term, Middle Aged, Pregnenolone, Psychotic Disorders, Schizophrenia, Severity of Illness Index, Antipsychotic Agents, Neurotransmitter Agents
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