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An observational study of clozapine-induced sedation and its pharmacological management

Published online by Cambridge University Press:  23 March 2020

S. Ramos Perdigues*
Nuestra Señora de Jesus, SpainNuestra Señora de Jesus, Spain
A. Mane Santacana
Hospital Del Mar, Psychiatry, Barcelona, Spain
R.B. Sauras Quetcuti
CSMA Horta, Psychiatry, Barcelona, Spain
E. Fernandez-Egea
Behavioural and Clinical Neurosciencie Institute, Psychiatry, Cambridge, United Kingdom
* Corresponding author.
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Clozapine is the only drug approved for resistant schizophrenia, but remains underused because of its side effects. Sedation is common, but its management is unclear.


To analyze factors associated with clozapine-induced sedation and the efficacy of common treatment strategies.


To determine clozapine-induced sedation factors and possible therapeutic strategies.


Using two years’ electronic records of a community cohort of resistant schizophrenia spectrum disorder cases on clozapine, we performed three analyses: a cross-sectional analysis of which factors were associated with number of hours slept (objective proxy of sedation), and two prospective analyses: which factors were associated with changes in hours slept, and the efficacy of the main pharmacological strategies for improving sedation.


One hundred and thirty-three patients were included; 64.7% slept at least 9 hours/daily. Among monotherapy patients (n = 30), only norclozapine levels (r = .367, P = .033) correlated with sleeping hours. Multiple regression analyses confirmed the findings (r = .865, P < .00001). Using the cohort prospectively assessed (n = 107), 42 patients decreased the number of hours slept between two consecutive appointments. Decreasing clozapine (40%) or augmenting with aripiprazole (36%) were the most common factors. In the efficacy analysis, these two strategies were recommended to 22 (20.6%) and 23 (21.5%) subjects, respectively. The majority (81.8% and 73.9%) did not report differences in the hours slept.


Sedationis common and involves pharmacological and non-pharmacological factors. The only correlation was a weak correlation between norclozapine plasma levels and total sleeping hours. Reducing clozapine and aripiprazole augmentation were the most successful strategies to ameliorate sedation, although both strategies were effective only in a limited numbers of subjects.

Disclosure of interest

The authors have not supplied their declaration of competing interest.

Copyright © European Psychiatric Association 2016

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