Comparative Efficacy of Animal Depression Models and Antidepressant Treatment: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Inclusion/Exclusion Criteria
- P: Animal studies: Studies involving rats (Rattus norvegicus) and investigating depression-like behaviour (various animal models of depression). Both adult and juvenile male rats were valid.
- I: Interventions: Only studies investigating the effects of sertraline, citalopram, escitalopram, fluoxetine, and paroxetine on depression-like behaviour of rats were included. The dose of the interventions has not been taken into account.
- C: Control group: Studies with a control group received either a vehicle, CMC, or NaCl and naïve were included.
- O: Outcomes: Only studies using the standard 5 min (300 s) observation of the forced swim test (FST) with the IT factor to measure depression-like behaviour were included.
- Language: Only English-written papers were included.
2.3. Search/Screening/Data Extraction
2.4. Data Availability Statement vs. Reality
2.5. SYRCLE
2.6. Certainty of the Evidence—ARRIVE Instead of GRADE
2.6.1. GRADE
- When conducting a GRADE assessment, it must be assumed that all the studies we analysed were non-randomised (classified as other studies), and therefore, these studies start with a score of 2 out of 4, which can be further upgraded or downgraded.
- Based on the SYRCLE analysis, it was determined that most of the analysed studies had a high Risk of Bias in terms of Blinding (Performance Bias), Blinding (Detection Bias), and Random outcome assessment (Detection Bias), which indeed translates to a significant downgrade based on those factors through the GRADE assessment.
- Conducted meta-analyses present high inconsistency due to the high heterogeneity of included studies (Higgins I2), another factor for downgrading these results.
- The overall meta-analysis results were consistent; however, subgroup data for citalopram and a few models (Immobilisation, Maternal Deprivation, Myocardial Infarction, Prenatal Stress, Social Defeat, Thermoregulation) were inconsistent and should be downgraded.
2.6.2. ARRIVE
2.7. Meta-Analysis Methodology
2.8. Sensitivity Analysis
- Various types of ADMs were used in the included studies, leading to inherent heterogeneity that sensitivity analysis could not adequately address.
- Differences in study design include variations in drug dosages, duration of treatment, and experimental conditions.
- Differences in the methodologies used for the forced swimming test across the included studies.
2.9. Publication Bias
3. Results
3.1. Literature Search Result
3.2. Data Availability
3.3. Included Studies
3.4. Models and Strains’ Popularity
3.5. Quality Assessment
ARRIVE Table
3.6. Risk of Bias Assessment
3.7. Receptor Affinity of the Tested Drugs
3.8. Meta-Analysis
SSRI Efficacy
- and sertraline (1 study [37], IV-MD −74.22 [−107.05, −41.39] p < 0.00001 (95% CI)).
3.9. Animal Depression Model Comparison
3.10. RoB Assessment
4. Discussion
4.1. The Efficacy of SSRIs
4.2. Animal Depression Models
4.3. Animal Strains
4.4. Data Availability
4.5. Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Authors and Year | Arrive Item | Total | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | |||
Alam et al. (2018) [25] | 2 | 1 | 1 | 0 | 0 | 2 | 2 | 2 | 2 | 2 | 0 | 1 | 2 | 2 | 1 | 0 | 1 | 1 | 0 | 0 | 2 | 24 | |
Alshammari et al. (2019) [43] | 2 | 1 | 1 | 0 | 0 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 2 | 2 | 0 | 1 | 1 | 0 | 2 | 2 | 29 | |
Ampuero et al. (2015) [29] | 2 | 1 | 1 | 0 | 1 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 2 | 1 | 1 | 1 | 1 | 0 | 0 | 2 | 28 | |
Bah et al. (2011) [31] | 2 | 1 | 1 | 0 | 2 | 2 | 2 | 2 | 2 | 0 | 1 | 2 | 2 | 2 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 25 | |
Berton et al. (1999) [47] | 2 | 1 | 1 | 0 | 1 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 1 | 2 | 1 | 1 | 1 | 0 | 0 | 0 | 26 | |
Dashti et al. (2022) [27] | 2 | 1 | 1 | 0 | 0 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 2 | 1 | 1 | 1 | 2 | 0 | 2 | 2 | 30 | |
Desbonet et al. (2010) [44] | 2 | 1 | 1 | 0 | 1 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 2 | 2 | 1 | 1 | 1 | 0 | 2 | 0 | 29 | |
Evans et al. (2012) [26] | 2 | 1 | 1 | 0 | 1 | 2 | 2 | 2 | 2 | 1 | 1 | 2 | 1 | 2 | 2 | 1 | 1 | 1 | 0 | 2 | 2 | 29 | |
Guo et al. (2009) [28] | 2 | 1 | 1 | 0 | 2 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 1 | 2 | 0 | 1 | 1 | 0 | 0 | 0 | 26 | |
Hale et al. (2017) [32] | 2 | 1 | 1 | 0 | 1 | 2 | 2 | 2 | 2 | 0 | 2 | 2 | 2 | 2 | 2 | 1 | 1 | 1 | 0 | 0 | 2 | 28 | |
Jagadeesan et al. (2019) [41] | 2 | 1 | 1 | 0 | 0 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 1 | 1 | 1 | 0 | 2 | 2 | 31 | |
Khedr et al. (2015) [35] | 2 | 1 | 1 | 0 | 0 | 2 | 0 | 2 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 0 | 1 | 1 | 0 | 0 | 2 | 25 | |
Khedr et al. (2018) [30] | 2 | 1 | 1 | 0 | 0 | 2 | 2 | 2 | 2 | 2 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 2 | 2 | 24 | |
Lin et al. (2014) [33] | 2 | 1 | 1 | 0 | 0 | 2 | 2 | 2 | 2 | 0 | 1 | 2 | 2 | 2 | 1 | 0 | 1 | 1 | 0 | 1 | 2 | 25 | |
Marchetti et al. (2020) [34] | 2 | 1 | 1 | 0 | 1 | 2 | 1 | 2 | 2 | 0 | 1 | 2 | 2 | 1 | 1 | 0 | 1 | 1 | 0 | 2 | 2 | 25 | |
Qi et al. (2018) [36] | 2 | 1 | 1 | 0 | 0 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 1 | 2 | 0 | 1 | 1 | 0 | 0 | 2 | 26 | |
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Solak et al. (2022) [37] | 2 | 1 | 1 | 0 | 0 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 1 | 1 | 1 | 0 | 2 | 2 | 31 | |
Steyn et al. (2018) [48] | 1 | 1 | 1 | 0 | 1 | 2 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 1 | 1 | 1 | 1 | 0 | 0 | 2 | 27 | |
Szymańska et al. (2009) [45] | 2 | 1 | 1 | 1 | 0 | 2 | 1 | 2 | 2 | 2 | 1 | 2 | 2 | 1 | 2 | 0 | 1 | 1 | 0 | 0 | 2 | 26 | |
Zavvari et al. (2020) [39] | 2 | 0 | 1 | 0 | 0 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 2 | 1 | 1 | 1 | 1 | 0 | 0 | 2 | 26 | |
Zaavari et al. (2020) [38] | 2 | 1 | 1 | 0 | 0 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 2 | 1 | 0 | 1 | 1 | 0 | 0 | 2 | 26 | |
Zangen et al. (2001) [49] | 1 | 1 | 1 | 0 | 0 | 2 | 1 | 2 | 2 | 2 | 1 | 2 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 20 | |
Zhao et al. (2008) [42] | 2 | 0 | 1 | 1 | 1 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 1 | 2 | 0 | 1 | 1 | 0 | 0 | 0 | 25 | |
Zhou et al. (2021) [40] | 2 | 1 | 1 | 0 | 1 | 2 | 2 | 2 | 2 | 2 | 1 | 2 | 2 | 1 | 1 | 1 | 1 | 1 | 0 | 2 | 2 | 29 | |
Category score | 48 | 23 | 25 | 2 | 13 | 50 | 45 | 50 | 50 | 41 | 29 | 47 | 47 | 39 | 37 | 12 | 25 | 26 | 0 | 19 | 37 | 665 | |
Maximum score | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 50 | 1050 | |
Ratio | 0.96 | 0.46 | 0.50 | 0.04 | 0.26 | 1.00 | 0.90 | 1.00 | 1.00 | 0.82 | 0.58 | 0.94 | 0.94 | 0.78 | 0.74 | 0.24 | 0.50 | 0.52 | 0.00 | 0.38 | 0.74 | 0.63 |
Drug | Affinity | |||||
---|---|---|---|---|---|---|
SERT | DA | 5-HT | H | M | Others | |
Fluoxetine | ||||||
Prozac | H2 | α2, α3, β4 | ||||
Fluoxetine hydrochloride | SERT | 5-HT2C | ||||
Eli Lilly | ||||||
Paroxetine | ||||||
Seroxat | 5-HT1 | α1, α2, β | ||||
Paroxetine hydrochloride | SERT | D2 | 5-HT2 | H1 | ||
GlaxoSmithKline (GSK) | 5-HT3 | |||||
Sertraline | ||||||
Zoloft | σ1 | |||||
Sertraline hydrochloride | SERT | |||||
Pfizer | ||||||
Citalopram | ||||||
Cipramil | ||||||
Citalopram hydrobromide | SERT | |||||
Lundbeck | H1 | |||||
Escitalopram | ||||||
Lexapro | 5-HT1A | M1 | ||||
Escitalopram oxalate | SERT | D2 | 5-HT2A | H1 | ||
Lundbeck | 5-HT2C | α2 |
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Ratajczak, P.; Martyński, J.; Zięba, J.K.; Świło, K.; Kopciuch, D.; Paczkowska, A.; Zaprutko, T.; Kus, K. Comparative Efficacy of Animal Depression Models and Antidepressant Treatment: A Systematic Review and Meta-Analysis. Pharmaceutics 2024, 16, 1144. https://doi.org/10.3390/pharmaceutics16091144
Ratajczak P, Martyński J, Zięba JK, Świło K, Kopciuch D, Paczkowska A, Zaprutko T, Kus K. Comparative Efficacy of Animal Depression Models and Antidepressant Treatment: A Systematic Review and Meta-Analysis. Pharmaceutics. 2024; 16(9):1144. https://doi.org/10.3390/pharmaceutics16091144
Chicago/Turabian StyleRatajczak, Piotr, Jakub Martyński, Jan Kazimierz Zięba, Katarzyna Świło, Dorota Kopciuch, Anna Paczkowska, Tomasz Zaprutko, and Krzysztof Kus. 2024. "Comparative Efficacy of Animal Depression Models and Antidepressant Treatment: A Systematic Review and Meta-Analysis" Pharmaceutics 16, no. 9: 1144. https://doi.org/10.3390/pharmaceutics16091144