Do Patterns of Instability or Severity of Psychopathology During Screening Predict Relapse in Schizophrenic Outpatient Subjects with Moderate to Severe Negative Symptoms Assigned to Placebo?

David G Daniel; Alan Kott; Jay Saoud; Remy Luthringer; Vadym Rud; Andrii Skyrpnikov; Rodica Stan; Veselin Palazov; Xingmei Wang; Michael Davidson

Do Patterns of Instability or Severity of Psychopathology During Screening Predict Relapse in Schizophrenic Outpatient Subjects with Moderate to Severe Negative Symptoms Assigned to Placebo?

Innov Clin Neurosci. 2020 Jan 1;17(1-3):27-29.

Authors

David G Daniel^{1

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6}, Alan Kott^{1

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6}, Jay Saoud^{1

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6}, Remy Luthringer^{1

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6}, Vadym Rud^{1

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6}, Andrii Skyrpnikov^{1

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6}, Rodica Stan^{1

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6}, Veselin Palazov^{1

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6}, Xingmei Wang^{1

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6}, Michael Davidson^{1

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6}

Affiliations

¹ Dr. Daniel is with Signant Health in Mclean, Virginia.
² Dr. Kott is with Signant Health in Prague, the Czech Republic.
³ Drs. Luthringer, Davidson, and Saoud are with Minerva Neurosciences in Waltham, Massachusetts.
⁴ Drs. Rud and Skyrpnikov are with the Department of Psychiatry, Ukranian Medical Academy in Poltava, Ukraine.
⁵ Dr. Stan is with the County Hospital in Piatra Neamt, Romania.
⁶ Dr. Palazov is with the Clinic of Psychiatry Mental Health in Burgas, Bulgaria. Ms. Wang is with Signant Health in Wayne, Pennsylvania.

PMID: 32547844
PMCID: PMC7239560

Abstract

Background: Patients with schizophrenia who, prior to inclusion in placebo-controlled trials, experience the most severe and/or unstable symptoms might be more likely to manifest symptomatic worsening upon antipsychotic discontinuation. Methods: This retrospective analysis included all randomized patients assigned to placebo (n=83) in a 12-week, double-blind, placebo-controlled outpatient trial of MIN-101 (roluperidone) for the treatment of negative symptoms in schizophrenia. The following risk factors were defined for exacerbation: instability between screening and baseline defined operationally as patients with the highest 10 percent of absolute change from the screening visit to baseline in the Positive and Negative Syndrome Scale (PANSS) total or one of the five PANSS Marder factors; screening or baseline severity in PANSS total or one of the five PANSS Marder factors; and gender and age. We used two operational criteria of relapse and the odds ratios of meeting the relapse criteria were calculated for each risk factor. Results: The odds of meeting one of the operational thresholds for relapse after antipsychotic discontinuation were not statistically significantly increased in the subjects who were unstable on the PANSS total or on one of the five PANSS Marder factors before antipsychotic discontinuation. Further, the severity of PANSS total and Marder factor scores at screening and baseline were not statistically significantly associated with odds of relapse. Neither age nor gender had any effect on relapse rates. Conclusion: Mild to moderate symptomatic variations in the severity of symptoms during screening and more severe symptomology at baseline as measured by the PANSS were not predictive of increased risk of subsequent relapse in schizophrenic patients.

Keywords: Antipsychotic medication; Positive and Negative Syndrome Scale; placebo-controlled trial; schizophrenia.