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

TITLE=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

JOURNAL=Frontiers in Psychiatry

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2021.693788

DOI=10.3389/fpsyt.2021.693788

ISSN=1664-0640

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), 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 to 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 to 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.