The PRIME North America randomized double-blind clinical trial of olanzapine versus placebo in patients at risk of being prodromally symptomatic for psychosis
Abstract
The first double-blind placebo-controlled clinical trial of an atypical neuroleptic medication is being conducted in symptomatic treatment-seeking patients meeting new diagnostic criteria for a putative prodromal syndrome. This identifies them as being at high risk for developing psychosis in the near future. The study aims include prevention of psychosis onset and disability, as well as palliation of ongoing symptomatology. The purpose of this report is to describe the study's "prodromally symptomatic" sample at baseline, i.e., at intake immediately prior to randomization and prior to receiving study medication. Sixty treatment-seeking patients meeting prodromal inclusion criteria were recruited across four sites: New Haven, CT (n=39), Toronto, Ontario (n=9), Calgary, Alberta (n=6), and Chapel Hill, NC (n=6). The sample was young (median age 16), largely male (65%), and came from families with high titers of serious mental illness (44%). Most patients (93%) met criteria for the Attenuated Positive Symptom (APS) prodromal syndrome and presented with significant but nonpsychotic suspiciousness, perceptual aberrations, unusual thought content, and conceptual disorganization. They presented with minimal to mild affective symptoms and substance use/abuse, but they were quite functionally compromised (mean Global Assessment of Functioning (GAF) score=42). The prodromal sample was compared with other clinical-trial samples of adolescent depression, adolescent mania, and first episode schizophrenia. Prodromal patients proved not to be depressed or manic. They were less severely ill than untreated first episode schizophrenia but more severely ill than treated first episode schizophrenia. While not psychotically disabled, these patients nevertheless present with a clinical syndrome. Subsequent reports will detail the effects of drug versus placebo on prodromal symptoms, neuropsychological profile, and the rate of conversion to psychosis.
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Sleep disturbance is common among individuals at risk of psychosis.
“Sleep disturbance is common among individuals at risk of psychosis, yet few studies have investigated the relationship between sleep disturbance and clinical trajectory.”
From Sleep duration and psychotic experiences in patients at risk of psychosis: a secondary analysis of the EDIE-2 trial (2019) · cites this paper as Miller et al., 2003
Between 37% and 78% of individuals at risk of psychosis report sleep disturbance, as assessed on the Scale of Assessment of Positive Symptoms (SAPS).
“Between 37% and 78% of this population have been found to report sleep disturbance, as assessed on the Scale of Assessment of Positive Symptoms (SAPS) across several studies (Miller et al., 2003; Poe et al., 2017).”
From Sleep duration and psychotic experiences in patients at risk of psychosis: a secondary analysis of the EDIE-2 trial (2019) · cites this paper as Miller et al., 2003
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Self-citation
- Authors
- Miller, T. J., Zipursky, R. B., Perkins, D., Addington, J., Woods, S. W., Hawkins, K. A., Hoffman, R., Preda, A., Epstein, I., Addington, D., Lindborg, S., Marquez, E., Tohen, M., Breier, A., & McGlashan, T. H.
- Affiliations
- Yale University (US)
- University of Toronto (CA)
- University of North Carolina at Chapel Hill (US)
- Eli Lilly (United States) (US)
- Corresponding author
- McGlashan, T.H.
- ORCID
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 61
- Issue
- 1
- Pages
- 19-30
- ISSN
- 0920-9964 (ISSN-L)
- OpenAlex
- W2587918810
- Cited by
- 150
- References
- 23
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 4 · 2022: 3 · 2021: 1 · 2020: 4 · 2019: 1 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 15 · 2012: 11
- FWCI
- 7.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH01654, K05MH001654)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- olanzapine, prodromal psychosis
- MeSH terms
- Olanzapine, Adolescent, Adult, Benzodiazepines, Bipolar Disorder, Depressive Disorder, Major, Major Depressive Disorder, Double-Blind Method, Female, Humans, Male, Pirenzepine, Psychomotor Disorders, Psychotic Disorders, Risk Factors, Schizophrenia, Schizophrenic Psychology, Sleep Wake Disorders, Speech Disorders, Antipsychotic Agents, Comorbidity, Mood Disorders
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