ANTIDEPRESSANT EFFECT OF KETAMINE IN SWISS MICE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Resumo

Introduction: Ketamine has been tested to the treatment of Major Depressive Disorder [1]. In Swiss
mice, an organism frequently used in antidepressant basic research, 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 ketamine 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 (keywords: “mice” and “forced swim test” and “ketamine”), were included
accordingly to the following criteria: Swiss mice tested in the FST after treatment with any dose or
treatment schedule with ketamine. Exclusions occurred following the criteria “no Swiss mice” or “no
adults” or “females” or “reviews”. Titles and abstracts were screened in a first round and when needed
a second round on the full text was performed by one person. Data on drug and vehicle treatment,
mice, experimental design and immobility time were extracted to meta-analysis. The quality of studies
was assessed using SYRCLE’s risk bias tool. Results: Eight out of 83 relevant studies obtained through
systematic review were included in the meta-analysis. Additional two studies were excluded because
they presented chronic treatment schedule, a post hoc criterion. The antidepressant effect of ketamine
ranged from less than 5% to 94% according to the doses. The standard mean difference (SMD) with
random effect was -2.66[-3.93;-1.39], 95% CI, for all studies. But the heterogeneity in this studies was
high (i2=100%). The effect size (Z) was 4.10 with p<0.0001. Discussion and Conclusion: Ketamine
appears to reduce immobility time in the FST compared to the control group, an index of antidepressant
effect, in Swiss male mice. Only one study favored the control treatment (ket 100mg, 0.78[0.62;0.95]).
This systematic review provided reference to future preclinical studies.
Acknowlegments
Capes, CNPq.