Retrospective Observational Study of Daytime Add-On Administration of Zopiclone to Difficult-to-Treat Psychiatric Inpatients With Unpredictable Aggressive Behavior, With or Without EEG Dysrhythmia

Alfonso Ceccherini-Nelli; Elena Bucuci; Lisa Burback; Daniel Li; Maryam Alikouzehgaran; Zahid Latif; Kevin Morin; Karthikeyan Ganapathy; Manhaz Salsali; Ubaid Abdullah; Wanda Westwood; Janice Orris; Patrick J White

doi:10.3389/fpsyt.2021.693788

Retrospective Observational Study of Daytime Add-On Administration of Zopiclone to Difficult-to-Treat Psychiatric Inpatients With Unpredictable Aggressive Behavior, With or Without EEG Dysrhythmia

Front Psychiatry. 2021 Aug 17:12:693788. doi: 10.3389/fpsyt.2021.693788. eCollection 2021.

Authors

Alfonso Ceccherini-Nelli^{1

2}, Elena Bucuci^{1

2}, Lisa Burback^{1

2}, Daniel Li^{1

2}, Maryam Alikouzehgaran^{1

2}, Zahid Latif^{1

2}, Kevin Morin^{1

2}, Karthikeyan Ganapathy^{1

2}, Manhaz Salsali^{1

2}, Ubaid Abdullah^{1

2}, Wanda Westwood², Janice Orris², Patrick J White^{1

2}

Affiliations

¹ Department of Psychiatry, University of Alberta, Edmonton, AB, Canada.
² Alberta Health Care Services, Edmonton, AB, Canada.

Abstract

Managing violent behavior is a particularly challenging aspect of hospital psychiatric care. Available pharmacological interventions are often unsatisfactory. Aim: To assess the effectiveness and safety of daytime zopiclone add-on administration in violent and difficult-to-treat psychiatric inpatients. Methods: Chart review of inpatients treated with daytime zopiclone, between 2014 and 2018, with up to 12 weeks follow-up. Effectiveness was retrospectively assessed with the Clinical Global Impression rating scale (CGI) and the frequency and severity of aggressive incidents recorded with the Staff Observation Aggression Scale-Revised (SOAS-R). Results: Forty-five (30 male, 15 female) cases, 18-69 years age range, average (SD) baseline CGI-S score of 5.4 (1.0), and a variety of diagnoses. Sixty-nine percent showed CGI-S improvement of any degree. For patients with at least one aggressive incident within 7 days prior to initiation of zopiclone (N = 22), average (SD) SOAS-R-Severity LOCF to baseline change was -3.5 (2.7) P < 0.0001. Most patients reported no side effects; 24% reported one or more side effects, and 11% discontinued zopiclone due to sedation (4), insomnia (1) or slurred speech (1). No SAEs were recorded. Zopiclone maximum daily dose correlated with CGI-S baseline-to-LOCF change (rho = -0.5, P = 0.0003). The ROC AUC of zopiclone maximum daily dose and improvement on CGI-S was 0.84 (95% CI 0.70-0.93, P < 0.0001). The ROC AUC of zopiclone maximum daily dose and SOAS-R-N improvement was 0.80 (95% CI 0.58-0.92; P = 0.0008) and maximum Youden's index value was achieved at a dose of >30 mg. Conclusions: Zopiclone doses >30 mg daily achieved the best anti-aggressive effect.

Keywords: GABA; difficult-to-treat; inpatients; neurocognitive disorders; neurodevelopmental disorders; schizophrenia; violence; zopiclone.