TIME-DEPENDENT AND DOSE-DEPENDENT ANTIDEPRESSANT EFFECT OF FLUOXETINE IN SWISS MICE: A SYSTEMATIC REVIEW AND METAANALYSIS

Resumo

Introduction: Fluoxetine has been to shown be safe and effective in treating of
adult depression [1]. In Swiss mice, different doses and treatment schedules
produced controversial results in the forced swim test (FST). Therefore, the aim of
the present study was to evaluate the antidepressant effect of fluoxetine in the FST
in Swiss mice performing a systematic review and meta-analysis. Material and
Methods: The PRISMA’s 2009 workflow diagram was used to perform the present
analysis. Relevant studies, collected by searching in PubMed database up to August,
2017, were included accordingly to the following criteria: Swiss mice tested in the
FST after treatment with any dose or treatment schedule with fluoxetine. Exclusions
occurred following the criteria “no Swiss mice” or “no adults” or “females” or
“reviews” and “articles without access”.. Data on drug and vehicle treatment, mice,
experimental design and immobility time were extracted to meta-analysis. Results:
21 out of 373 relevant studies obtained through systematic review were included in
the meta-analysis. The antidepressant effect of fluoxetine ranged from less than 5%
to 60% according to the treatment schedule. The standard mean difference (SMD)
with random effect was -1.73[-2.17;-1.29], 95% CI, for all studies. But the
heterogeneity in this studies was high (i2=99%). The effect size (Z) was 7.70 with
p<0.00001. The acute treatment too shown results to favours of fluoxetine SMD
-1.26[-1.75;-0.77]95% CI, RE, as well as subacute (SMD -2.37[-3.43;-1.32] 95% CI)
and chronic (SMD -2.86[-4.13;-1.60] 95% CI, RE). Treatment was favours to
fluoxetine in meta-analysis with doses of 5mg/kg (SMD -0.25[-0.37;-0.12] 95% CI,
RE,) 10mg/kg (SMD -2.59[-3.42;-1.75] 95% CI, RE) and 20mg/kg (SMD -2.31[-2.98;-
1.65] 95% CI, RE). Discussion and Conclusion: Fluoxetine appears to reduce
immobility time in the FST compared to the control group, an index of
antidepressant effect, in Swiss male mice. This systematic review provided
reference to future preclinical studies.
Acknowlegments
Capes, CNPq.