Five-Year Trends in SSRI Consumption: A Precision Medicine Approach to Comparative Analysis Between Serbia and European Countries
Abstract
:1. Introduction
2. Materials and Methods
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
DDD | Defined daily doses |
DDD/TID | Defined daily doses per 1000 inhabitants per day |
References
- Wu, Y.; Wang, L.; Tao, M.; Cao, H.; Yuan, H.; Ye, M.; Chen, X.; Wang, K.; Zhu, C. Changing Trends in the Global Burden of Mental Disorders from 1990 to 2019 and Predicted Levels in 25 Years. Epidemiol. Psychiatr. Sci. 2023, 32, e63. [Google Scholar] [CrossRef]
- GBD 2019 Diseases and Injuries Collaborators. Global Burden of 369 Diseases and Injuries in 204 Countries and Territories, 1990–2019: A Systematic Analysis for the Global Burden of Disease Study 2019. Lancet 2020, 396, 1204–1222. [Google Scholar] [CrossRef] [PubMed]
- Kalin, N.H. The Critical Relationship between Anxiety and Depression. Am. J. Psychiatry 2020, 177, 365–367. [Google Scholar] [CrossRef] [PubMed]
- Vigo, D.; Thornicroft, G.; Atun, R. Estimating the True Global Burden of Mental Illness. Lancet Psychiatry 2016, 3, 171–178. [Google Scholar] [CrossRef] [PubMed]
- Hock, R.S.; Or, F.; Kolappa, K.; Burkey, M.D.; Surkan, P.J.; Eaton, W.W. A New Resolution for Global Mental Health. Lancet 2012, 379, 1367–1368. [Google Scholar] [CrossRef]
- Jha, P.; Subedi, S.; Paudyal, S.; Panta, P.P. Suicidal Attempt among Psychiatry Patients Presented to the Department of Emergency of a Tertiary Care Centre: A Descriptive Cross-Sectional Study. JNMA J. Nepal Med. Assoc. 2023, 61, 442–445. [Google Scholar] [CrossRef]
- Alshaya, D.S. Genetic and Epigenetic Factors Associated with Depression: An Updated Overview. Saudi J. Biol. Sci. 2022, 29, 103311. [Google Scholar] [CrossRef]
- Javaid, S.F.; Hashim, I.J.; Hashim, M.J.; Stip, E.; Samad, M.A.; Ahbabi, A.A. Epidemiology of Anxiety Disorders: Global Burden and Sociodemographic Associations. Middle East Curr. Psychiatry 2023, 30, 44. [Google Scholar] [CrossRef]
- Luft, M.J.; Lamy, M.; DelBello, M.P.; McNamara, R.K.; Strawn, J.R. Antidepressant-Induced Activation in Children and Adolescents: Risk, Recognition and Management. Curr. Probl. Pediatr. Adolesc. Health Care 2018, 48, 50–62. [Google Scholar] [CrossRef]
- Gabriel, M.; Sharma, V. Antidepressant Discontinuation Syndrome. Can. Med Assoc. J. 2017, 189, E747. [Google Scholar] [CrossRef]
- Jing, E.; Straw-Wilson, K. Sexual Dysfunction in Selective Serotonin Reuptake Inhibitors (SSRIs) and Potential Solutions: A Narrative Literature Review. Ment. Health Clin. 2016, 6, 191–196. [Google Scholar] [CrossRef]
- Zhao, Y.; Zhang, Y.; Yang, L.; Zhang, K.; Li, S. Safety Profile of Selective Serotonin Reuptake Inhibitors in Real-World Settings: A Pharmacovigilance Study Based on FDA Adverse Event Reporting System. Ann. Pharmacother. 2024, 58, 1105–1116. [Google Scholar] [CrossRef] [PubMed]
- Mikkelsen, N.; Damkier, P.; Pedersen, S.A. Serotonin Syndrome-A Focused Review. Basic Clin. Pharmacol. Toxicol. 2023, 133, 124–129. [Google Scholar] [CrossRef] [PubMed]
- Grimsley, S.R.; Jann, M.W. Paroxetine, Sertraline, and Fluvoxamine: New Selective Serotonin Reuptake Inhibitors. Clin. Pharm. 1992, 11, 930–957. [Google Scholar] [PubMed]
- Nawaz, A.; Mamoon, B.; Batool, T.E.; Khattak, M.I.; Amir, F.; Akbar, A.; Khan, S. Advances in Antidepressant Therapy: Comparing the Efficacy of Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), and Novel Agents. Cureus 2024, 16, e76318. [Google Scholar] [CrossRef]
- Milijašević, B.Ž.; Vlajankov, A.L.; Ubavić, M.B.; Rašković, A.L.; Martić, N.B.; Tomić, Z.S. Analysis of Antidepressant Use in Republic of Serbia from 2013 to 2015. Hosp. Pharmacol.-Int. Multidiscip. J. 2018, 5, 607–616. [Google Scholar] [CrossRef]
- Muijsers, R.B.R.; Plosker, G.L.; Noble, S. Spotlight on Sertraline in the Management of Major Depressive Disorder in Elderly Patients. CNS Drugs 2002, 16, 789–794. [Google Scholar] [CrossRef]
- Dwyer, J.B.; Bloch, M.H. Antidepressants for Pediatric Patients. Curr. Psychiatr. 2019, 18, 26–42. [Google Scholar]
- Pinheiro, E.; Bogen, D.L.; Hoxha, D.; Ciolino, J.D.; Wisner, K.L. Sertraline and Breastfeeding: Review and Meta-Analysis. Arch. Womens Ment. Health 2015, 18, 139–146. [Google Scholar] [CrossRef]
- Cuomo, A.; Maina, G.; Neal, S.M.; De Montis, G.; Rosso, G.; Scheggi, S.; Beccarini Crescenzi, B.; Bolognesi, S.; Goracci, A.; Coluccia, A.; et al. Using Sertraline in Postpartum and Breastfeeding: Balancing Risks and Benefits. Expert Opin. Drug Saf. 2018, 17, 719–725. [Google Scholar] [CrossRef]
- Edinoff, A.N.; Akuly, H.A.; Hanna, T.A.; Ochoa, C.O.; Patti, S.J.; Ghaffar, Y.A.; Kaye, A.D.; Viswanath, O.; Urits, I.; Boyer, A.G.; et al. Selective Serotonin Reuptake Inhibitors and Adverse Effects: A Narrative Review. Neurol. Int. 2021, 13, 387–401. [Google Scholar] [CrossRef]
- Huddart, R.; Hicks, J.K.; Ramsey, L.B.; Strawn, J.R.; Smith, D.M.; Bobonis Babilonia, M.; Altman, R.B.; Klein, T.E. PharmGKB Summary: Sertraline Pathway, Pharmacokinetics. Pharmacogenet. Genom. 2020, 30, 26–33. [Google Scholar] [CrossRef]
- Mauri, M.C.; Fiorentini, A.; Paletta, S.; Altamura, A.C. Pharmacokinetics of Antidepressants in Patients with Hepatic Impairment. Clin. Pharmacokinet. 2014, 53, 1069–1081. [Google Scholar] [CrossRef]
- Apseloff, G.; Wilner, K.D.; von Deutsch, D.A.; Henry, E.B.; Tremaine, L.M.; Gerber, N.; Lazar, J.D. Sertraline Does Not Alter Steady-State Concentrations or Renal Clearance of Lithium in Healthy Volunteers. J. Clin. Pharmacol. 1992, 32, 643–646. [Google Scholar] [CrossRef]
- Vaughn, S.E.; Strawn, J.R.; Poweleit, E.A.; Sarangdhar, M.; Ramsey, L.B. The Impact of Marijuana on Antidepressant Treatment in Adolescents: Clinical and Pharmacologic Considerations. J. Pers. Med. 2021, 11, 615. [Google Scholar] [CrossRef] [PubMed]
- Cavanah, L.R.; Ray, P.K.; Goldhirsh, J.L.; Huey, L.Y.; Piper, B.J. Patterns in (Es)Citalopram Prescriptions to Medicaid and Medicare Patients in the United States: The Potential Effects of Evergreening. Front. Psychiatry 2025, 16, 1450111. [Google Scholar] [CrossRef] [PubMed]
- Hyttel, J.; Bøgesø, K.P.; Perregaard, J.; Sánchez, C. The Pharmacological Effect of Citalopram Residues in the (S)-(+)-Enantiomer. J. Neural Transm. Gen. Sect. 1992, 88, 157–160. [Google Scholar] [CrossRef] [PubMed]
- Rao, N. The Clinical Pharmacokinetics of Escitalopram. Clin. Pharmacokinet. 2007, 46, 281–290. [Google Scholar] [CrossRef]
- von Moltke, L.L.; Greenblatt, D.J.; Giancarlo, G.M.; Granda, B.W.; Harmatz, J.S.; Shader, R.I. Escitalopram (S-Citalopram) and Its Metabolites in Vitro: Cytochromes Mediating Biotransformation, Inhibitory Effects, and Comparison to R-Citalopram. Drug Metab. Dispos. 2001, 29, 1102–1109. [Google Scholar]
- Malling, D.; Poulsen, M.N.; Søgaard, B. The Effect of Cimetidine or Omeprazole on the Pharmacokinetics of Escitalopram in Healthy Subjects. Br. J. Clin. Pharmacol. 2005, 60, 287–290. [Google Scholar] [CrossRef]
- Molden, E.; Spigset, O. Interactions between metoprolol and antidepressants. Tidsskr. Nor. Laegeforen. 2011, 131, 1777–1779. [Google Scholar] [CrossRef]
- Zakaraya, Z.; Abu Assab, M.; Tamimi, L.N.; Karameh, N.; Hailat, M.; Al-Omari, L.; Abu Dayyih, W.; Alasasfeh, O.; Awad, M.; Awad, R. Pharmacokinetics and Pharmacodynamics: A Comprehensive Analysis of the Absorption, Distribution, Metabolism, and Excretion of Psychiatric Drugs. Pharmaceuticals 2024, 17, 280. [Google Scholar] [CrossRef]
- Laine, K.; Kytölä, J.; Bertilsson, L. Severe Adverse Effects in a Newborn with Two Defective CYP2D6 Alleles after Exposure to Paroxetine during Late Pregnancy. Ther. Drug Monit. 2004, 26, 685–687. [Google Scholar] [CrossRef] [PubMed]
- Parker, R.B.; Soberman, J.E. Effects of Paroxetine on the Pharmacokinetics and Pharmacodynamics of Immediate-Release and Extended-Release Metoprolol. Pharmacotherapy 2011, 31, 630–641. [Google Scholar] [CrossRef] [PubMed]
- Spina, E.; Avenoso, A.; Salemi, M.; Facciolá, G.; Scordo, M.G.; Ancione, M.; Madia, A. Plasma Concentrations of Clozapine and Its Major Metabolites during Combined Treatment with Paroxetine or Sertraline. Pharmacopsychiatry 2000, 33, 213–217. [Google Scholar] [CrossRef]
- Alderman, J.; Preskorn, S.H.; Greenblatt, D.J.; Harrison, W.; Penenberg, D.; Allison, J.; Chung, M. Desipramine Pharmacokinetics When Coadministered with Paroxetine or Sertraline in Extensive Metabolizers. J. Clin. Psychopharmacol. 1997, 17, 284–291. [Google Scholar] [CrossRef]
- Albers, L.J.; Reist, C.; Helmeste, D.; Vu, R.; Tang, S.W. Paroxetine Shifts Imipramine Metabolism. Psychiatry Res. 1996, 59, 189–196. [Google Scholar] [CrossRef]
- Bannister, S.J.; Houser, V.P.; Hulse, J.D.; Kisicki, J.C.; Rasmussen, J.G. Evaluation of the Potential for Interactions of Paroxetine with Diazepam, Cimetidine, Warfarin, and Digoxin. Acta Psychiatr. Scand. Suppl. 1989, 350, 102–106. [Google Scholar] [CrossRef]
- Hillhouse, T.M.; Porter, J.H. A Brief History of the Development of Antidepressant Drugs: From Monoamines to Glutamate. Exp. Clin. Psychopharmacol. 2015, 23, 1–21. [Google Scholar] [CrossRef]
- Stevens, J.C.; Wrighton, S.A. Interaction of the Enantiomers of Fluoxetine and Norfluoxetine with Human Liver Cytochromes P450. J. Pharmacol. Exp. Ther. 1993, 266, 964–971. [Google Scholar] [CrossRef]
- Mandrioli, R.; Forti, G.C.; Raggi, M.A. Fluoxetine Metabolism and Pharmacological Interactions: The Role of Cytochrome P450. Curr. Drug Metab. 2006, 7, 127–133. [Google Scholar] [CrossRef] [PubMed]
- Deodhar, M.; Rihani, S.B.A.; Darakjian, L.; Turgeon, J.; Michaud, V. Assessing the Mechanism of Fluoxetine-Mediated CYP2D6 Inhibition. Pharmaceutics 2021, 13, 148. [Google Scholar] [CrossRef] [PubMed]
- Eleftheriou, G.; Zandonella Callegher, R.; Butera, R.; De Santis, M.; Cavaliere, A.F.; Vecchio, S.; Lanzi, C.; Davanzo, R.; Mangili, G.; Bondi, E.; et al. Consensus Panel Recommendations for the Pharmacological Management of Breastfeeding Women with Postpartum Depression. Int. J. Environ. Res. Public Health 2024, 21, 551. [Google Scholar] [CrossRef]
- Vitale, S.G.; Laganà, A.S.; Muscatello, M.R.A.; La Rosa, V.L.; Currò, V.; Pandolfo, G.; Zoccali, R.A.; Bruno, A. Psychopharmacotherapy in Pregnancy and Breastfeeding. Obstet. Gynecol. Surv. 2016, 71, 721–733. [Google Scholar] [CrossRef] [PubMed]
- Taylor, C.; Crosby, I.; Yip, V.; Maguire, P.; Pirmohamed, M.; Turner, R.M. A Review of the Important Role of CYP2D6 in Pharmacogenomics. Genes 2020, 11, 1295. [Google Scholar] [CrossRef]
- Sánchez, C.; Bøgesø, K.P.; Ebert, B.; Reines, E.H.; Braestrup, C. Escitalopram versus Citalopram: The Surprising Role of the R-Enantiomer. Psychopharmacology 2004, 174, 163–176. [Google Scholar] [CrossRef]
- Dackehag, M.; Ellegård, L.M.; Gerdtham, U.; Nilsson, T. Macroeconomic fluctuations and individual use of psychotropic medications: Evidence from Swedish administrative data. Eur. J. Public Health 2023, 33, 93–98. [Google Scholar] [CrossRef]
- Zivanovic, M.; Vukcevic Markovic, M.; Dimoski, J.; Gvozden, M. Mental Health in Serbia: Assessment of Needs, Risk Factors and Barriers to Obtaining Professional Help; Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) GmbH: Belgrade, Serbia, 2022. [Google Scholar]
SSRI | Depression | Panic Attacks | OCD | Social Phobia | GAD | PTSD | Bulimia Nervosa | PTSD |
---|---|---|---|---|---|---|---|---|
fluoxetine | X (8+) | X | X (7+) | X | X | X | X | |
citalopram | X | |||||||
paroxetine | X | X | X | X | X | X | X | |
sertraline | X | X | X (6+) | X | X | X | ||
escitalopram | X (12+) | X |
SSRI | Time to Maximum Concentration | Bioavailability | Bound Fraction | Volume of Distribution | Half-Life |
---|---|---|---|---|---|
fluoxetine | 6–8 h | 60–80% | 94% | 20–40 L/kg | 96 h |
citalopram | 2–4 h | 80% | 80% | 12–16 L/kg | 30–35 h |
paroxetine | 5–6 h | 30–60% | 95% | 3–12 L/kg | 21 h |
sertraline | 4–8 h | 44% | 98% | 25 L/kg | 22–36 h |
escitalopram | 3–4 h | 80% | 56% | 12–26 L/kg | 27–33 h |
Medicine | DID 2018 | DID 2019 | DID 2020 | DID 2021 | DID 2022 |
---|---|---|---|---|---|
fluoxetine | 2.40943 | 2.81899 | 3.40094 | 2.68469 | 3.22032 |
citalopram | 0.97396 | 0.95170 | 0.91167 | 0.87061 | 0.78152 |
paroxetine | 4.16225 | 4.32504 | 4.79192 | 7.40698 | 5.25851 |
sertraline | 14.8493 | 11.0207 | 11.8468 | 9.85769 | 9.24536 |
escitalopram | 6.13398 | 7.44041 | 8.46109 | 8.51289 | 9.73523 |
Medicine | Trend Equation | R2 | Adjusted R2 | p-Value |
---|---|---|---|---|
fluoxetine | y = 0.1487x + 2.4606 | 0.342 | 0.1227 | 0.300 |
citalopram | y = −0.0466x + 1.0377 | 0.9376 | 0.9168 | 0.007 * |
paroxetine | y = 0.5274x + 3.6066 | 0.4042 | 0.2056 | 0.249 |
sertraline | y = −1.2371x + 15.075 | 0.7948 | 0.7263 | 0.042 * |
escitalopram | y = 0.8275x + 5.5742 | 0.9424 | 0.9233 | 0.006 * |
SSRI | y = 0.22x + 27.754 | 0.0908 | −0.2123 | 0.622 |
Year | DID SSRI |
---|---|
2018 | 28.52887 |
2019 | 26.55683 |
2020 | 29.41245 |
2021 | 29.33288 |
2022 | 28.24096 |
Country | DID 2018 | DID 2019 | DID 2020 | DID 2021 | DID 2022 |
---|---|---|---|---|---|
Serbia | 28.53 | 26.56 | 29.41 | 29.33 | 28.24 |
Italy | 29.70 | 29.90 | 30.6 | 31.20 | 31.70 |
Iceland | 103.3 | 106.3 | 111.7 | 118.9 | 116.3 |
Spain | 49.09 | 50.27 | 52.11 | 55.07 | 57.71 |
Croatia | 21.66 | 22.19 | 22.69 | 23.85 | 24.61 |
Norway | 35.46 | 35.97 | 36.35 | 37.58 | / |
The Netherlands | 42.35 | 44.41 | 46.5 | 48.21 | 49.71 |
Estonia | 18.91 | 20.58 | 21.72 | 24.06 | 26.26 |
Finland | 41.39 | 43.40 | 44.58 | 46.45 | / |
Latvia | 10.42 | 11.45 | 13.17 | 14.26 | 15.76 |
Lithuania | 20.127 | 22.50 | 23.22 | 23.86 | 25.74 |
Slovenia | 40.30 | 41.00 | 41.30 | 42.90 | 44.20 |
Denmark | 46.70 | 47.80 | 49.50 | 52.50 | 55.20 |
Title 1 | Serbia | Denmark | Spain | Latvia | ||||
---|---|---|---|---|---|---|---|---|
2019 | 2020 | 2019 | 2020 | 2019 | 2020 | 2019 | 2020 | |
fluoxetine | 2.82 | 3.4 | 2 | 1.8 | 6.94 | 7.06 | 0.51 | 0.63 |
citalopram | 0.95 | 0.91 | 13.9 | 13 | 6.11 | 6.09 | 0.86 | 0.94 |
paroxetine | 4.33 | 4.79 | 2.2 | 2.1 | 8.8 | 8.9 | 3.1 | 3.52 |
sertraline | 11.02 | 11.85 | 25.9 | 28.7 | 14.56 | 15.78 | 1.4 | 1.63 |
escitalopram | 7.44 | 8.46 | 4.4 | 4.4 | 13.46 | 13.88 | 5.39 | 6.24 |
Country | DID SSRI (2019) | GDP Per Capita (2019) | DID SSRI (2020) | GDP Per Capita (2020) |
---|---|---|---|---|
Serbia | 26.56 | 9927.1 | 29.41 | 9809.7 |
Italy | 29.90 | 21,336.7 | 30.60 | 19,772.8 |
Iceland | 106.3 | 26,029.8 | 111.7 | 24,937.5 |
Spain | 50.27 | 19,497.2 | 52.11 | 17,253.5 |
Croatia | 22.19 | 14,168.2 | 22.69 | 14,004.4 |
Norway | 35.97 | 27,761.2 | 36.35 | 26,073.7 |
The Netherlands | 44.41 | 23,939.2 | 46.50 | 23,281.6 |
Estonia | 20.58 | 15,760.0 | 21.72 | 15,771.9 |
Finland | 43.40 | 23,237.4 | 44.58 | 23,047.9 |
Latvia | 11.45 | 14,628.4 | 13.17 | 14,325.5 |
Lithuania | 22.50 | 18,444.7 | 23.22 | 18,053.4 |
Slovenia | 41 | 17,652.1 | 41.30 | 16,907.5 |
Denmark | 47.80 | 25,277.4 | 49.50 | 25,457.2 |
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Samardžić, J.; Simović, F.; Sekanić, K.; Branković, M. Five-Year Trends in SSRI Consumption: A Precision Medicine Approach to Comparative Analysis Between Serbia and European Countries. Healthcare 2025, 13, 1174. https://doi.org/10.3390/healthcare13101174
Samardžić J, Simović F, Sekanić K, Branković M. Five-Year Trends in SSRI Consumption: A Precision Medicine Approach to Comparative Analysis Between Serbia and European Countries. Healthcare. 2025; 13(10):1174. https://doi.org/10.3390/healthcare13101174
Chicago/Turabian StyleSamardžić, Janko, Filip Simović, Kristina Sekanić, and Milica Branković. 2025. "Five-Year Trends in SSRI Consumption: A Precision Medicine Approach to Comparative Analysis Between Serbia and European Countries" Healthcare 13, no. 10: 1174. https://doi.org/10.3390/healthcare13101174
APA StyleSamardžić, J., Simović, F., Sekanić, K., & Branković, M. (2025). Five-Year Trends in SSRI Consumption: A Precision Medicine Approach to Comparative Analysis Between Serbia and European Countries. Healthcare, 13(10), 1174. https://doi.org/10.3390/healthcare13101174