| dc.description.abstract | Background: Awareness of severe clozapine side-effects
is an important factor for good therapeutic alliance and
for prevention of treatment discontinuation. Professionals
worry the most about agranulocytosis and routine blood
screening, while patients are mainly concerned about physical symptoms, such as hypersalivation and sleepiness [1,2].
While the life-threatening side effects are dose independent and typically occur during the initial phase, the more
common, non-lethal side effects,can occur at all times
during clozapine treatment.
The Glasgow antipsychotic side-effects scale for clozapine (GASS-C), developed for measurement of subjective
side-effects has been validated in clozapine-treated in- and
outpatients [3].
The aim of our study was to investigate whether subjectively perceived clozapine side-effects are dose-dependent.
Methods: A demographic questionnaire and GASS-C
were given to 95 participants who fulfilled the diagnostic
inclusion criteria (age>18, diagnosis of schizophrenia,
schizoaffective disorder or unspecified nonorganic psychosis according to ICD-10, and an ongoing treatment with
clozapine for at least 7 days). The GASS-C version used in
this study contained 16 questions and for each side effect
of clozapine, patients noted how often hey had experienced it in the past week (0-never, 1-once, 2-a few times,
3-everyday). Total scores were separated as: 0-16 absent
or mild side effects, 17-32 moderate, and 33-48 severe side
effects. The participants were instructed to tick a box if
they felt a symptom was particularly distressing, no matter
how often it occurred. Dosage of clozapine was assessed
through patient medical charts. Partial correlation was used
to determine how much clozapine doses correlated with
the intensity of side effects, controlling for gender and age.
Results: Sample consisted of 53.7% male subjects, mean
age 46.11±11.61, diagnosed as: F20 (76.8%), F29 (14.7%),
F25 (8.4%). Clozapine doses ranged from 25-425mg/day
(M=158.16±98.47). Fourty-five patients (47.4%) received
another antipsychotic together with clozapine. There was a
weak correlation between mean clozapine dose and sexual
issues (r=.23, p<0.05), hypersalivation (r=.25, p<0.05), as
well as total GASS-C scores (r=.22, p<0.05), and moderate
correlation between mean clozapine dose and obstipation
(r=.30, p<0.05).
Conclusion: We found a significant correlation between
several distressful side effects and mean clozapine dose.
Other studies have shown conflicting reports on this correlation – Yusufi et al. [4] found a reduction of side effectsS106 Abstracts
when reducing doses of clozapine, but the study of Hynes
et al. [3] did not find any correlation between these two
variables. Although they are not life-threatening, the importance of these side effects should not be underestimated
as they can lead to treatment cessation. A limitation of our
study is that no therapeutic drug monitoring took place, so
therapy (in-)compliance could be a potential explanation
for the weak to moderate correlation coefficients we found.
Also, antipsychotic polypharmacy was not corrected for,
which should be rectified in future studies. Furthermore,
additional research is needed to explore the link between
patients’ reported adverse effects, mean clozapine doses
and clozapine serum concentrations. | en_US |
