Randomized, Double-Blind Trial of Olanzapine Versus Placebo in Patients Prodromally Symptomatic for Psychosis

Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
American Journal of Psychiatry (Impact Factor: 12.3). 06/2006; 163(5):790-9. DOI: 10.1176/appi.ajp.163.5.790
Source: PubMed


This study assessed the efficacy of olanzapine in delaying or preventing conversion to psychosis and reducing symptoms in people with prodromal symptoms of schizophrenia.
This randomized trial occurred at four North American clinics in the Prevention Through Risk Identification, Management, and Education project. Outpatients received olanzapine (5-15 mg/day, N=31) or placebo (N=29) during a 1-year double-blind treatment period and no treatment during a 1-year follow-up period. Efficacy measures included the conversion-to-psychosis rate and Scale of Prodromal Symptoms scores.
During the treatment year, 16.1% of olanzapine patients and 37.9% of placebo patients experienced a conversion to psychosis, a nearly significant difference. The hazard of conversion among placebo patients was about 2.5 times that among olanzapine-treated patients, which also approached significance. In the follow-up year, the conversion rate did not differ significantly between groups. During treatment, the mean score for prodromal positive symptoms improved more in the olanzapine group than in the placebo group, and the mixed-model repeated-measures least-squares mean score showed significantly greater improvement between weeks 8 and 28 with olanzapine. The olanzapine patients gained significantly more weight (mean=8.79 kg, SD=9.05, versus mean=0.30 kg, SD=4.24).
A significant treatment difference in the conversion-to-psychosis rate was not demonstrated. However, these results may be influenced by low power. The nearly significant differences suggest that olanzapine might reduce the conversion rate and delay onset of psychosis. Olanzapine was efficacious for positive prodromal symptoms but induced weight gain. Further treatment research in this phase of illness is warranted.

Download full-text


Available from: A. Preda,
  • Source
    • "For those at the highest end of the risk spectrum, early commencement of preventive treatments may win time in combatting the pathophysiological processes associated with psychosis onset (de Koning et al. 2009; Pasternak et al. 2012). In contrast, for those in the low-risk group, reliable risk estimation will prevent the potentially stigmatizing consequences of a psychiatric diagnosis and exposure to potentially harmful effects of pharmacological and other interventions (McGlashan et al. 2006). Clinical assessments alone for determination of transition risk to psychosis are problematic due to the fluctuating course of symptoms in high-risk individuals (Ruhrmann et al. 2010a). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The concept of indicated prevention has proliferated in psychiatry, and accumulating evidence suggests that it may indeed be possible to prevent or delay the onset of a first episode of psychosis though adequate interventions in individuals deemed at clinical high risk (CHR) for such an event. One challenge undermining these efforts is the relatively poor predictive accuracy of clinical assessments used in practice for CHR individuals, often leading to diagnostic and therapeutic uncertainty reflected in clinical guidelines promoting a 'watch and wait' approach to CHR patients. Using data from published studies, and employing predictive models based on the odds-ratio form of Bayes' rule, we simulated scenarios where clinical interview, neurocognitive testing, structural magnetic resonance imaging and electrophysiology are part of the initial assessment process of a CHR individual (extended diagnostic approach). Our findings indicate that for most at-risk patients, at least three of these assessments are necessary to arrive at a clinically meaningful differentiation into high- intermediate-, and low-risk groups. In particular, patients with equivocal results in the initial assessments require additional diagnostic testing to produce an accurate risk profile forming part of the comprehensive initial assessment. The findings may inform future research into reliable identification and personalized therapeutic targeting of CHR patients, to prevent transition to full-blown psychosis.
    Journal of Neural Transmission 10/2014; 122(1). DOI:10.1007/s00702-014-1325-9 · 2.40 Impact Factor
  • Source
    • "In North America, the Prevention through Risk Identification Management and Education (PRIME) study compared the transition rates of a 12-month treatment with olanzapine (5–15 mg daily) or placebo.66 At the end of the treatment phase, 16% of the UHR individuals treated with olanzapine and 38% of the placebo group converted to psychosis, but the difference between transition rates did not reach statistical significance.66 "
    [Show abstract] [Hide abstract]
    ABSTRACT: In the last few decades, substantial research has focused on the possibility of early detection and prevention of the first psychotic episode in young individuals at risk of developing this mental disturbance; however, unresolved clinical and ethical issues still call for further investigations. New perspectives and opportunities may come from the identification of selective psychopathological and instrumental markers linking the appearance of subtle psychotic symptoms with the clinical outcome of specific mental pathologies. Furthermore, empirically derived algorithms and risk staging models should facilitate the identification of targeted prevention therapies, possibly improving the efficacy of well-tolerated therapeutic approaches, such as psychological interventions and natural compound supplementations. To date, the collected evidence on the efficacy and tolerability of pharmacological prevention therapies raises more doubts than hopes. A very early detection of risk and appropriate symptomatic pattern classifications may provide a chance to better match prevention strategies with the development of psychosis.
    Therapeutics and Clinical Risk Management 03/2014; 10(1):241-253. DOI:10.2147/TCRM.S55770 · 1.47 Impact Factor
  • Source
    • "Recent controlled studies using antipsychotics have demonstrated a decrease of the conversion rate,3,4) but most researchers and clinicians still hesitate to prescribe drugs for ARMS due to ethical considerations such as the risk of false-positive identification of ARMS and the adverse reactions related to pharmacotherapy. In fact, antipsychotics are often associated with adverse effects that are undesirable for young people, such as pronounced weight gain and sexual dysfunction.3,5) "
    [Show abstract] [Hide abstract]
    ABSTRACT: Interest in the "at-risk mental state" (ARMS) for psychosis has increased because early intervention is expected to delay or prevent the onset of schizophrenia. However, the optimum intervention strategy remains controversial, especially with regard to antipsychotics. Although administration of antipsychotic medications is often associated with adverse effects and raises ethical considerations, recent studies have shown that some novel antipsychotics are safer and more tolerable for young people than conventional antipsychotics. We investigated whether administration of perospirone, a combined serotonin (5-HT)/dopamine antagonist and 5-HT1A receptor agonist, could alleviate prodromal symptoms and be well tolerated by clinical high risk patients. The participants were outpatients seeking help. The Structured Interview for Prodromal Symptoms was performed in patients identified as being at clinical high risk. The Scale of Prodromal Symptoms (SOPS) was also completed and changes of subjective experience were assessed with the Subjective Well-being under Neuroleptics, short version. The incidence of akathisia was recorded by using the Barnes Akathisia Scale. Subjects were monitored for 26 weeks after starting medication. SOPS scores improved significantly after 26 weeks of perospirone therapy, while BAS scores did not show deterioration. No serious adverse events occurred during the study. This trial suggests that perospirone therapy provides a clinical benefit for clinical high risk subjects without causing serious adverse events. Although further placebo-controlled studies are needed for confirmation, perospirone might be one of optimum treatments for individuals at imminent risk of psychosis.
    Clinical Psychopharmacology and Neuroscience 12/2013; 11(3):132-6. DOI:10.9758/cpn.2013.11.3.132
Show more