A Comparative Efficacy of Antidepressants in the Treatment of Major Depressive Disorder: A Systematic Review and Meta-Analysis
DOI:
https://doi.org/10.53819/81018102t4218Abstract
Major Depressive Disorder (MDD) affects about 280, 000, 000 people globally, with a higher incidence among females than males. The increasing incidence implicates health burdens and clinical dilemmas regarding the low efficacy of the existing antidepressants. A literature search was performed on electronic databases, PubMed, the Cochrane Library of Randomized Trials, Scopus, and ProQuest, for studies reporting the efficacy of an SNRI (Desvenlafaxine 50 mg/d), a serotonin modulator (Vortioxetine 10-20 mg/d), and an aminoketone antidepressant (Bupropion). Study selection focused on randomized controlled trials (RCTs) and observational studies. All statistical analyses and visualization were performed using the Review Manager (RevMan) software and Python programming. The random effects model, ANOVA test, and Cohen’s d were used for statistical analyses. The present meta-analysis involved 17 studies, including 11, 533 participants. The results aligned with previous studies and accounts provided by literature regarding the efficacy of antidepressants used to manage MDD. Five studies, including 2, 377 MDD patients, reported a statistically significant outcome, that Desvenlafaxine 50 mg/d reduced MDD’s severity than placebo (OR: 0.52, 95% CI [0.44, 0.62], P < 0.00001, I2 = 0%). Three studies involving 742 MDD patients reported the efficacy of dextromethorphan-bupropion (AXS-50). The reduction of MADRS scores in the treatment group was statistically insignificant, with high variability, favouring the placebo (OR of 1.85 [95% CI: 0.93, 3.70], p = 0.08, I2 = 79%). Additionally, Vortioxetine 10-20 mg/d produced adverse effects, headache, vomiting, nausea, diarrhea, dizziness, nasopharyngitis, somnolence, and suicidal ideation among 6, 669 MDD patients reported by the 9 studies. The finding was statistically significant but with a high variability OR: 15.25, 95% CI [12.55, 18.52], P < 0.00001, I2 = 98%). A preliminary analysis of evidence collected following Desvenlafaxine, AXS-50, and Vortioxetine administration yielded compelling evidence on the efficacy of antidepressants in MDD treatment. Desvenlafaxine and AXS-50 reported reduced severity and symptomatology in MDD, respectively. On the other hand, Vortioxetine implicated adverse effects, which are common with most antidepressants. Despite adverse effects like headache, vomiting, nausea, diarrhea, dizziness, nasopharyngitis, somnolence, and suicidal ideation, antidepressants used to treat MDD yield clinically satisfying outcomes like decreased severity of depression and relief from symptoms. Clinicians should monitor patients to take care of any adverse effects resulting from the treatments.
Keywords: Antidepressant efficacy, adverse effects, major depressive disorder, MDD symptomatology, severity, improved outcomes.
References
B. S. Diniz et al., “Mild cognitive impairment and major depressive disorder are associated with molecular senescence abnormalities in older adults,” Alzheimer’s and Dementia: Translational Research and Clinical Interventions, vol. 7, no. 1, 2021, doi: 10.1002/trc2.12129.
Z. Pan et al., “Cognitive impairment in major depressive disorder,” CNS Spectrums, vol. 24, no. 1. 2019. doi: 10.1017/S1092852918001207.
N. Bains and A. Sara, “Major Depressive Disorder Continuing Education Activity,” Statpearls, 2022.
R. Karrouri, Z. Hammani, Y. Otheman, and R. Benjelloun, “Major depressive disorder: Validated treatments and future challenges,” World J Clin Cases, vol. 9, no. 31, 2021, doi: 10.12998/wjcc.v9.i31.9350.
D. Santarsieri and T. L. Schwartz, “Antidepressant efficacy and side-effect burden: A quick guide for clinicians,” Drugs in Context, vol. 4. 2015. doi: 10.7573/dic.212290.
L. M. Behlke, E. J. Lenze, and R. M. Carney, “The Cardiovascular Effects of Newer Antidepressants in Older Adults and Those With or At High Risk for Cardiovascular Diseases,” CNS Drugs, vol. 34, no. 11. 2020. doi: 10.1007/s40263-020-00763-z.
A. Wichniak, A. Wierzbicka, M. Walęcka, and W. Jernajczyk, “Effects of Antidepressants on Sleep,” 1920, doi: 10.1007/s11920-017-0816-4.
A. M. Methley, S. Campbell, C. Chew-Graham, R. Mcnally, and S. Cheraghi-Sohi, “PICO, PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews,” 2014, doi: 10.1186/s12913-014-0579-0.
H. J. Luijendijk, “How to create PICO questions about diagnostic tests,” BMJ Evidence-Based Medicine Month, vol. 0, 2021, doi: 10.1136/bmjebm-2021-111676.
Y. Cho, C. Kim, and B. Kang, “Risk of bias assessment of randomised controlled trials referenced in the 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care: a cross-sectional review,” BMJ Open, vol. 9, p. 23725, 2019, doi: 10.1136/bmjopen-2018-023725.
“The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials”, doi: 10.1136/bmj.d5928.
C. Luchini, B. Stubbs, M. Solmi, and N. Veronese, “Assessing the quality of studies in meta-analyses: Advantages and limitations of the Newcastle Ottawa Scale,” World J Metaanal, vol. 5, no. 4, 2017, doi: 10.13105/wjma.v5.i4.80.
H. Cooper, L. V. Hedges, and J. C. Valentine, The handbook of research synthesis and meta-analysis 2nd edition. 2009.
M. W. L. Cheung, “A Guide to Conducting a Meta-Analysis with Non-Independent Effect Sizes,” Neuropsychology Review, vol. 29, no. 4. 2019. doi: 10.1007/s11065-019-09415-6.
D. Carrozzino, C. Patierno, G. A. Fava, and J. Guidi, “The hamilton rating scales for depression: A critical review of clinimetric properties of different versions,” Psychotherapy and Psychosomatics, vol. 89, no. 3. 2020. doi: 10.1159/000506879.
K. J. Rohan et al., “A protocol for the Hamilton Rating Scale for Depression: Item scoring rules, Rater training, and outcome accuracy with data on its application in a clinical trial,” J Affect Disord, vol. 200, 2016, doi: 10.1016/j.jad.2016.01.051.
K. Kondo, J. R. Antick, C. K. Ayers, D. Kansagara, and P. Chopra, “Depression screening tools for patients with kidney failure a systematic review,” Clinical Journal of the American Society of Nephrology, vol. 15, no. 12, 2020, doi: 10.2215/CJN.05540420.
S. Borentain et al., “Montgomery-Åsberg Depression Rating Scale factors in treatment-resistant depression at onset of treatment: Derivation, replication, and change over time during treatment with esketamine,” 2022, doi: 10.1002/mpr.1927.
P. Mishra, U. Singh, C. M. Pandey, P. Mishra, and G. Pandey, “Application of student’s t-test, analysis of variance, and covariance,” Ann Card Anaesth, vol. 22, no. 4, 2019, doi: 10.4103/aca.ACA-94-19.
Z. Yu, M. Guindani, S. F. Grieco, L. Chen, T. C. Holmes, and X. Xu, “Beyond t test and ANOVA: applications of mixed-effects models for more rigorous statistical analysis in neuroscience research,” Neuron, vol. 110, no. 1. 2022. doi: 10.1016/j.neuron.2021.10.030.
A. Hazra and N. Gogtay, “Biostatistics series module 3: Comparing groups: Numerical variables,” Indian J Dermatol, vol. 61, no. 3, 2016, doi: 10.4103/0019-5154.182416.
Q. Li, J. Hu, J. Ding, and G. Zheng, “Fisher’s method of combining dependent statistics using generalizations of the gamma distribution with applications to genetic pleiotropic associations,” Biostatistics, vol. 15, no. 2, 2014, doi: 10.1093/biostatistics/kxt045.
W. Poole, D. L. Gibbs, I. Shmulevich, B. Bernard, and T. A. Knijnenburg, “Combining dependent P-values with an empirical adaptation of Brown’s method,” in Bioinformatics, 2016. doi: 10.1093/bioinformatics/btw438.
Lakens Daniel, “Calculating and reporting effect sizes to facilitate cumulative science: a practical primer for t-tests and ANOVAs,” Front Psychol, vol. 4, 2013.
D. Lakens, “Calculating and reporting effect sizes to facilitate cumulative science: A practical primer for t-tests and ANOVAs,” Front Psychol, vol. 4, no. NOV, 2013, doi: 10.3389/fpsyg.2013.00863.
L. Lin et al., “Empirical Comparison of Publication Bias Tests in Meta-Analysis,” J Gen Intern Med, vol. 33, no. 8, 2018, doi: 10.1007/s11606-018-4425-7.
L. Lin and H. Chu, “Quantifying publication bias in meta-analysis,” Biometrics, vol. 74, no. 3, 2018, doi: 10.1111/biom.12817.
A. Khan, J. Musgnung, T. Ramey, M. Messig, G. Buckley, and P. T. Ninan, “Abrupt discontinuation compared with a 1-week taper regimen in depressed outpatients treated for 24 weeks with desvenlafaxine 50 mg/d,” J Clin Psychopharmacol, vol. 34, no. 3, 2014, doi: 10.1097/JCP.0000000000000100.
A. H. Clayton, K. A. Tourian, K. Focht, E. Hwang, R. F. J. Cheng, and M. E. Thase, “Desvenlafaxine 50 and 100 mg/d versus placebo for the treatment of major depressive disorder: A phase 4, randomized controlled trial,” Journal of Clinical Psychiatry, vol. 76, no. 5, 2015, doi: 10.4088/JCP.13m08978.
S. G. Kornstein, A. Clayton, W. Bao, and C. J. Guico-Pabia, “Post hoc analysis of the efficacy and safety of desvenlafaxine 50 mg/day in a randomized, placebo-controlled study of perimenopausal and postmenopausal women with major depressive disorder,” Menopause, vol. 21, no. 8, 2014, doi: 10.1097/GME.0000000000000178.
A. H. Clayton et al., “Efficacy and safety of desvenlafaxine 50 mg/d in a randomized, placebo-controlled study of perimenopausal and postmenopausal women with major depressive disorder,” Journal of Clinical Psychiatry, vol. 74, no. 10, 2013, doi: 10.4088/JCP.12m08065.
J. Endicott, R. W. Lam, M. A. Hsu, R. Fayyad, M. Boucher, and C. J. Guico-Pabia, “Improvements in quality of life with desvenlafaxine 50 mg/d vs placebo in employed adults with major depressive disorder,” J Affect Disord, vol. 166, pp. 307–314, 2014, doi: 10.1016/j.jad.2014.05.011.
G. Wang et al., “Effectiveness and Safety of Vortioxetine for Major Depressive Disorder in Real-World Clinical Practice: Results from the Single-Arm RELIEVE China Study,” Neuropsychiatr Dis Treat, vol. 18, 2022, doi: 10.2147/NDT.S358253.
G. W. Mattingly et al., “Effectiveness of Vortioxetine in Patients With Major Depressive Disorder in Real-World Clinical Practice: Results of the RELIEVE Study,” Front Psychiatry, vol. 13, 2022, doi: 10.3389/fpsyt.2022.824831.
M. Di Nicola et al., “Effect of vortioxetine in subjects with major depressive and alcohol use disorders: A 6-month retrospective analysis,” CNS Spectr, vol. 27, no. 1, 2022, doi: 10.1017/S109285292000173X.
C. N. Chin et al., “Results of a real-world study on vortioxetine in patients with major depressive disorder in South East Asia (REVIDA),” Curr Med Res Opin, vol. 34, no. 11, 2018, doi: 10.1080/03007995.2018.1477746.
T. Inoue, A. Nishimura, K. Sasai, and T. Kitagawa, “Randomized, 8-week, double-blind, placebo-controlled trial of vortioxetine in Japanese adults with major depressive disorder, followed by a 52-week open-label extension trial,” Psychiatry Clin Neurosci, vol. 72, no. 2, 2018, doi: 10.1111/pcn.12623.
A. Nishimura, Y. Aritomi, K. Sasai, T. Kitagawa, and A. R. Mahableshwarkar, “Randomized, double-blind, placebo-controlled 8-week trial of the efficacy, safety, and tolerability of 5, 10, and 20 mg/day vortioxetine in adults with major depressive disorder,” Psychiatry Clin Neurosci, vol. 72, no. 2, 2018, doi: 10.1111/pcn.12565.
A. R. Mahableshwarkar, J. Zajecka, W. Jacobson, Y. Chen, and R. S. E. Keefe, “A randomized, placebo-controlled, active-reference, double-blind, flexible-dose study of the efficacy of vortioxetine on cognitive function in major depressive disorder,” Neuropsychopharmacology, vol. 40, no. 8, 2015, doi: 10.1038/npp.2015.52.
A. R. Mahableshwarkar, P. L. Jacobsen, Y. Chen, M. Serenko, and M. H. Trivedi, “A randomized, double-blind, duloxetine-referenced study comparing efficacy and tolerability of 2 fixed doses of vortioxetine in the acute treatment of adults with MDD,” Psychopharmacology (Berl), vol. 232, no. 12, 2015, doi: 10.1007/s00213-014-3839-0.
R. L. Findling et al., “Vortioxetine for Major Depressive Disorder in Adolescents: 12-Week Randomized, Placebo-Controlled, Fluoxetine-Referenced, Fixed-Dose Study,” J Am Acad Child Adolesc Psychiatry, vol. 61, no. 9, 2022, doi: 10.1016/j.jaac.2022.01.004.
H. Tabuteau, A. Jones, A. Anderson, M. Jacobson, and D. V Iosifescu, “Effect of AXS-05 (Dextromethorphan-Bupropion) in Major Depressive Disorder: A Randomized Double-Blind Controlled Trial,” Am J Psychiatry, vol. 179, pp. 490–499, 2022, doi: 10.1176/appi.ajp.21080800.
A. Jones, C. O’Gorman, C. Streicher, S. Feliz, D. V Iosifescu, and H. Tabuteau, “Efficacy and Safety of AXS-05, an Oral NMDA Receptor Antagonist With Multimodal Activity, in Major Depressive Disorder: results From the GEMINI Trial,” Annals of clinical psychiatry, vol. 33, no. 3 SUPPL, 2021.
D. V. Iosifescu et al., “Efficacy and Safety of AXS-05 (Dextromethorphan-Bupropion) in Patients With Major Depressive Disorder: A Phase 3 Randomized Clinical Trial (GEMINI),” Journal of Clinical Psychiatry, vol. 83, no. 4, 2022, doi: 10.4088/JCP.21m14345.
P. T. Von Hippel, “The heterogeneity statistic I2 can be biased in small meta-analyses,” BMC Med Res Methodol, vol. 15, no. 1, 2015, doi: 10.1186/s12874-015-0024-z.
W. R. Nugent, “Measurement equivalence, symmetry, effect sizes, and meta-analysis,” J Soc Social Work Res, vol. 12, no. 1, 2021, doi: 10.1086/713393.
F. Ijaz and N. I. Chaudhry, “Impact of Health Information Technology Adoption and its Drivers on Quality of Care & Patient Safety in the Health Care Sector of Pakistan,” Pakistan Journal of Commerce and Social Science, vol. 15, no. 1, 2021.
Y. K. Alotaibi and F. Federico, “The impact of health information technology on patient safety,” Saudi Medical Journal, vol. 38, no. 12. 2017. doi: 10.15537/smj.2017.12.20631.
Y. Bombard et al., “Engaging patients to improve quality care,” Implementation Science, vol. 13, no. 1, 2018.
Y. Bombard et al., “Engaging patients to improve quality of care: A systematic review,” Implementation Science, vol. 13, no. 1. 2018. doi: 10.1186/s13012-018-0784-z.
R. Perry and M. Cassagnol, “Desvenlafaxine: A new serotonin-norepinephrine reuptake inhibitor for the treatment of adults with major depressive disorder,” Clinical Therapeutics, vol. 31, no. SUPPL. 1. 2009. doi: 10.1016/j.clinthera.2009.07.012.
S. Jin, P. Verhaeghen, and D. Rahnev, “Across-subject correlation between confidence and accuracy: A meta-analysis of the Confidence Database,” Psychon Bull Rev, vol. 29, no. 4, 2022, doi: 10.3758/s13423-022-02063-7.
M. B. Mathur and T. J. Vanderweele, “Robust Metrics and Sensitivity Analyses for Meta-analyses of Heterogeneous Effects,” Epidemiology, vol. 31, no. 3, 2020, doi: 10.1097/EDE.0000000000001180.
G. I. Papakostas, L. Culpepper, R. S. Fayyad, J. Musgnung, and C. J. Guico-Pabia, “Efficacy of desvenlafaxine 50 mg compared with placebo in patients with moderate or severe major depressive disorder: A pooled analysis of six randomized, double-blind, placebo-controlled studies,” Int Clin Psychopharmacol, vol. 28, no. 6, 2013, doi: 10.1097/YIC.0b013e3283638fbd.
T. R. Norman and J. S. Olver, “Desvenlafaxine in the treatment of major depression: an updated overview,” Expert Opin Pharmacother, vol. 22, no. 9, 2021, doi: 10.1080/14656566.2021.1900826.
R. S. McIntyre, I. Florea, M. M. Pedersen, and M. C. Christensen, “Head-To-Head Comparison of Vortioxetine Versus Desvenlafaxine in Patients With Major Depressive Disorder With Partial Response to SSRI Therapy,” Journal of Clinical Psychiatry, vol. 84, no. 4, 2023, doi: 10.4088/JCP.23m14780.
M. R. Liebowitz and K. A. Tourian, “Efficacy, safety, and tolerability of desvenlafaxine 50 mg/d for the treatment of major depressive disorder: A systematic review of clinical trials,” Prim Care Companion J Clin Psychiatry, vol. 12, no. 3, 2010, doi: 10.4088/PCC.09r00845blu.
A. H. Linden and J. Hönekopp, “Heterogeneity of Research Results: A New Perspective From Which to Assess and Promote Progress in Psychological Science,” Perspectives on Psychological Science, vol. 16, no. 2, 2021, doi: 10.1177/1745691620964193.
N. N. Ivanets, M. A. Kinkul’kina, Y. G. Tikhonova, and T. A. Izyumina, “Venlafaxine in the Treatment of Moderate and Severe Depression: Approaches to Increasing Treatment Efficacy,” Neurosci Behav Physiol, vol. 46, no. 5, 2016, doi: 10.1007/s11055-016-0272-3.
J. R. Fann et al., “Venlafaxine extended-release for depression following spinal cord injury a randomized clinical trial,” JAMA Psychiatry, vol. 72, no. 3, 2015, doi: 10.1001/jamapsychiatry.2014.2482.
G. J. Lyndon, R. Prieto, D. B. Wajsbrot, C. Allgulander, and B. Bandelow, “Efficacy of venlafaxine extended release in major depressive disorder patients: Effect of baseline anxiety symptom severity,” Int Clin Psychopharmacol, vol. 34, no. 3, 2019, doi: 10.1097/YIC.0000000000000256.
X. Gonda, S. R. Sharma, and F. I. Tarazi, “Vortioxetine: a novel antidepressant for the treatment of major depressive disorder,” Expert Opin Drug Discov, vol. 14, no. 1, 2019, doi: 10.1080/17460441.2019.1546691.
A. Verma and A. Kumar, “Send Orders for Reprints to reprints@benthamscience.net Risks Associated with Vortioxetine in the Established Therapeutic Indication,” 2021, doi: 10.2174/1570159X18666200818195720.
Andrew D’Agostino, Clayton D. English, and Jose A. Ray, “Vortioxetine (Brintellix): A New Serotonergic Antidepressant,” 2015.
P. B. Imrey, “Limitations of Meta-analyses of Studies with High Heterogeneity,” JAMA Network Open, vol. 3, no. 1. 2020. doi: 10.1001/jamanetworkopen.2019.19325.
C. Uakarn, “Sample size estimation using Yamane and Cochran and Krejcie and Morgan and Green formulas and Cohen statistical power analysis by G*power and comparisons,” Apheit International Journal, vol. 10, no. 2, 2021.
F. Kaliyadan and V. Kulkarni, “Types of variables, descriptive statistics, and sample size,” Indian Dermatol Online J, vol. 10, no. 1, 2019, doi: 10.4103/idoj.IDOJ_468_18.
Q. Zhou, X. Li, D. Yang, C. Xiong, and Z. Xiong, “A comprehensive review and meta-analysis of neurological side effects related to second-generation antidepressants in individuals with major depressive disorder,” Behavioural Brain Research, vol. 447. 2023. doi: 10.1016/j.bbr.2023.114431.
T. M. Hillhouse and J. H. Porter, “A brief history of the development of antidepressant drugs: From monoamines to glutamate,” Exp Clin Psychopharmacol, vol. 23, no. 1, 2015, doi: 10.1037/a0038550.
J. C. Jakobsen, C. Gluud, and I. Kirsch, “Should antidepressants be used for major depressive disorder?,” BMJ, vol. 25, no. 4, 2020, doi: 10.1136/bmjebm-2019-111238.
B. Pedraz‐Petrozzi, M. Deuschle, and M. Gilles, “Improvement of depressive symptoms, after a suicide attempt, with dextromethorphan/bupropion combination treatment in a patient with treatment‐resistant depression and psychiatric comorbidities,” Clin Case Rep, vol. 11, no. 3, 2023, doi: 10.1002/ccr3.7045.
D. K. Pandey, S. Bhatt, A. Jindal, and B. Gautam, “Effect of combination of ketanserin and escitalopram on behavioral anomalies after olfactory bulbectomy: Prediction of quick onset of antidepressant action,” Indian J Pharmacol, vol. 46, no. 6, 2014, doi: 10.4103/0253-7613.144935.
P. Schumacher and C. Culmsee, “Psychedelic drugs – new approaches in the therapy of depression,” Med Monatsschr Pharm, vol. 45, no. 6, 2022.
