Sulpiride (Eglonil) in the treatment of somatoform and anxiety disorders. A review of the literature

   Sulpiride (Eglonil), the progenitor of the substituted benzamide class, has retained its clinical relevance for over half a century thanks to its unique combination of a dose-dependent spectrum of action and a high safety profile. At low and medium doses (100–400 mg/day), the drug, alongside mild neuroleptic effects, exhibits a triple anxiolytic, stimulant and somatotropic effects due to selective blockade of presynaptic dopamine D2/D3 receptors, followed by an increase in dopaminergic transmission in the mesolimbic pathways. This pharmacological profile determines sulpiride's leading role in the treatment of somatoform disorders and generalised anxiety disorder with predominant somato-vegetative symptoms, where the primary complaints are cardialgia, dyspepsia, tachycardia, hyperhidrosis and polymorphic bodily sensations without an organic basis. Sulpiride (Eglonil) is the drug of choice for somatised forms of anxiety, comorbidity with somatic diseases, functional disorders of the gastrointestinal tract and somatoform disorders.

1. Galstyan DS, Lebedev AS, Ilyin NP, et al. Acute Behavioral and Neurochemical Effects of Sulpiride in Adult Zebrafish. Neurochem Res. 2024;50(1):11. doi: 10.1007/s11064-024-04268-9

2. Liang Y, Yang Y, Huang R, et al. Conjugation of sulpiride with a cell penetrating peptide to augment the antidepressant efficacy and reduce serum prolactin levels. Biomed Pharmacother. 2024;174:116610. doi: 10.1016/j.biopha.2024.116610

3. Tawfeek HM, Mekkawy AI, Abdelatif AAH, et al. Intranasal delivery of sulpiride nanostructured lipid carrier to central nervous system; in vitro characterization and in vivo study. Pharm Dev Technol. 2024;29(8):841-54. doi: 10.1080/10837450.2024.2404034

4. Herrmann W, Wacker J. The Selective Dopamine D2 Blocker Sulpiride Modulates the Relationship Between Agentic Extraversion and Executive Functions. Cogn Affect Behav Neurosci. 2021;21(4):852-67. doi: 10.3758/s13415-021-00887-9

5. Van Dijk H, Köke AJA, Elbers S, et al. Physiotherapists Using the Biopsychosocial Model for Chronic Pain: Barriers and Facilitators - A Scoping Review. Int J Environ Res Public Health. 2023;20(2):1634. doi: 10.3390/ijerph20021634

6. Bolton D. A revitalized biopsychosocial model: core theory, research paradigms, and clinical implications. Psychol Med. 2023;53(16):7504-11. doi: 10.1017/s0033291723002660

7. Zhuo C, Li C, Ma X, et al. KarXT combines the partial benefits of haloperidol for positive symptoms and sulpiride for negative symptoms: Evidence from computational biology. J Psychopharmacol. 2025;39(11):1307-19. doi: 10.1177/02698811251353268

8. Leucht S, Priller J, Davis JM. Antipsychotic Drugs : A Concise Review of History, Classification, Indications, Mechanism, Efficacy, Side Effects, Dosing, and Clinical Application. Am J Psychiatry. 2024;181(10):865-78. doi: 10.1176/appi.ajp.20240738

9. Ohmann HA, Kuper N, Wacker J. A low dosage of the dopamine D2-receptor antagonist sulpiride affects effort allocation for reward regardless of trait extraversion. Personal Neurosci. 2020;3:e7. doi: 10.1017/pen.2020.7

10. McCutcheon RA, Nour MM, Dahoun T, et al. Mesolimbic Dopamine Function Is Related to Salience Network Connectivity: An Integrative Positron Emission Tomography and Magnetic Resonance Study. Biol Psychiatry. 2019;85(5):368-78. doi: 10.1016/j.biopsych.2018.09.010

11. Labrakakis C. The Role of the Insular Cortex in Pain. Int J Mol Sci. 2023;24(6):5736. doi: 10.3390/ijms24065736

12. Takeuchi H, Suzuki T, Bies RR, et al. Estimated dopamine D2 receptor occupancy from plasma concentrations of atypical antipsychotics and subjective experience/drug attitude in schizophrenia: an analysis of the CATIE data. Schizophr Res. 2013;150(2-3):373-9. doi: 10.1016/j.schres.2013.08.033

13. Siafis S, Wu H, Wang D, et al. Antipsychotic dose, dopamine D2 receptor occupancy and extrapyramidal side-effects : a systematic review and dose-response meta-analysis. Mol Psychiatry. 2023;28(8):3267-77. doi: 10.1038/s41380-023-02203-y

14. Cohen J, Mathew A, Dourvetakis KD, et al. Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders. Cells. 2024;13(6):511. doi: 10.3390/cells13060511

15. Alfi MA, Naim J, Ahmed I, et al. Altered Serum IL-6 and TGF-β1 Levels Are Associated With Generalized Anxiety Disorder: A Case-Control Study. Dev Neurobiol. 2025;85(4):e23004. doi: 10.1002/dneu.23004

16. Mamun-or-Rashid R, Roknuzzaman ASM, Sarker R, et al. Altered serum interleukin-17A and interleukin-23A levels may be associated with the pathophysiology and development of generalized anxiety disorder. Sci Rep. 2024;14:15097. doi: 10.1038/s41598-024-66131-9

17. Altamura M, D'Andrea G, Angelini E, et al. Psychosomatic syndromes are associated with IL-6 pro-inflammatory cytokine in heart failure patients. PLoS One. 2022;17(3):e0265282. doi: 10.1371/journal.pone.0265282

18. Muscatell KA, Dedovic K, Slavich GM, et al. Greater amygdala activity and dorsomedial prefrontal-amygdala coupling are associated with enhanced inflammatory responses to stress. Brain Behav Immun. 2015;43:46-53. doi: 10.1016/j.bbi.2014.06.201

19. Ugalde-Muniz P, Hernandez-Luna MG, Garcia-Velasco S, et al. Activation of dopamine D2 receptors attenuates neuroinflammation and ameliorates the memory impairment nduced by rapid eye movement sleep deprivation in a murine model. Front Neurosci. 2022;16:988167. doi: 10.3389/fnins.2022.988167

20. Tolokonin AO. Models of pathogenesis of psychosomatic disorders and the concept of psychosomatic scenario. Medical Herald of the South of Russia. 2023;14(2):61-6 (In Russ.). doi: 10.21886/2219-8075-2023-14-2-61-66

21. Birolo R, Bravetti F, Bordignon S, et al. Overcoming the Drawbacks of Sulpiride by Means of New Crystal Forms. Pharmaceutics. 2022;14(9):1754. doi: 10.3390/pharmaceutics14091754

22. Ayoub AM, Ibrahim MM, Abdallah MH, Mahdy MA. Sulpiride Microemulsions as Antipsychotic Nasal Drug Delivery Systems: In-Vitro and Pharmacodynamic Study. J Drug Deliv Sci Technol. 2016;36:10-22. doi: 10.1016/j.jddst.2016.09.002

23. M'bitsi-Ibouily GC, Marimuthu T, du Toit LC, et al. In Vitro, Ex Vivo and in Vivo Evaluation of a Novel Metal-Liganded Nanocomposite for the Controlled Release and Improved Oral Bioavailability of Sulpiride. J Drug Deliv Sci Technol. 2021;66:102909. doi: 10.1016/j.jddst.2021.102909

24. Zarrindast MR, Khakpai F. The Modulatory Role of Dopamine in Anxiety-like Behavior. Arch Iran Med. 2015;18(9):591-603.

25. Muthuraju S, Talbot T, Brandаo ML. Dopamine D2 receptors regulate unconditioned fear in deep layers of the superior colliculus and dorsal periaqueductal gray. Behav Brain Res. 2016;297:116-23. doi: 10.1016/j.bbr.2015.10.005

26. Bandelow B, Michaelis S, Wedekind D. Treatment of anxiety disorders. Dialogues Clin Neurosci. 2017;19(2):93-107. doi: 10.31887/DCNS.2017.19.2/bbandelow

27. Vilianov VB, Kremenitskaya SA, Solov'eva NV. The efficacy of sulpiride in patients with anxiety disorders depending on the serum serotonin concentrations. S.S. Korsakov Journal of Neurology and Psychiatry. 2015;115(10):62-5 (In Russ.). doi: 10.17116/jnevro201511510162-65

28. Pohontsch NJ, Zimmermann T, Lehmann M, et al. ICD-10-Coding of Medically Unexplained Physical Symptoms and Somatoform Disorders - A Survey with German GPs. Front Med (Lausanne). 2021;8:598810. doi: 10.3389/fmed.2021.598810

29. Mewes R. Recent developments on psychological factors in medically unexplained symptoms and somatoform disorders. Front Public Health. 2022;10:1033203. doi: 10.3389/fpubh.2022.1033203

30. Gaebel W, Stricker J, Kerst A. Changes from ICD-10 to ICD-11 and future directions in psychiatric classification. Dialogues Clin Neurosci. 2020;22(1):7-15. doi: 10.31887/DCNS.2020.22.1/wgaebel

31. Hirsch JA, Nicola G, McGinty G, et al. ICD-10: History and Context. AJNR Am J Neuroradiol. 2016;37(4):596-9. doi: 10.3174/ajnr.A4696

32. Ying-Chih C, Yu-Chen H, Wei-Lieh H. Heart rate variability in patients with somatic symptom disorders and functional somatic syndromes : A systematic review and meta-analysis. Neurosci Biobehav Rev. 2020;112:336-44. doi: 10.1016/j.neubiorev.2020.02.007

33. Vreijling SR, Troudart Y, Brosschot JF. Reduced Heart Rate Variability in Patients With Medically Unexplained Physical Symptoms: A Meta-Analysis of HF-HRV and RMSSD. Psychosom Med. 2021;83(1):2-15. doi: 10.1097/psy.0000000000000874

34. Wangler J, Jansky M. Somatoform Disorders in Primary Care-An Exploratory Mixed-Methods Study on Experiences, Challenges and Coping Strategies of General Practitioners in the Federal Republic of Germany. Int J Environ Res Public Health. 2024;21(7):901. doi: 10.3390/ijerph21070901

35. Rouillon F, Rahola G, Van Moffaert M, et al.; Soma-D Study Team. Study Observing Multicultural Attitudes to Dogmatil. Sulpiride in the treatment of somatoform disorders: results of a European observational study to characterize the responder profile. J Int Med Res. 2001;29(4):304-13. doi: 10.1177/147323000102900407

36. Haller H, Cramer H, Lauche R, Dobos G. Somatoform disorders and medically unexplained symptoms in primary care. Dtsch Arztebl Int. 2015;112(16):279-87. doi: 10.3238/arztebl.2015.0279

37. Kolyutskaya EV. Role of sulpiride in the treatment of somatoform disorders. Meditsinskiy sovet = Medical Council. 2017;(17):20-4 (In Russ.). doi: 10.21518/2079-701X-2017-17-20-24

38. Ferreri M, Florent C, Gerard D. Sulpiride: study of 669 patient presenting with pain of psychological origin. Encephale. 2000;26(4):58-66.

39. Leutgeb R, Berger S, Szecsenyi J, Laux G. Patients with somatoform disorders: More frequent attendance and higher utilization in primary Out-of-Hours care? PLoS One. 2018;13(8):e0202546. doi: 10.1371/journal.pone.0202546

40. Iloson C, Praetorius Björk M, Möller A, et al. Awareness of somatisation disorder among Swedish physicians at emergency departments: a cross-sectional survey. BMC Psychiatry. 2024;24(1):223. doi: 10.1186/s12888-024-05652-z

41. Zhao JJ, Han CY, Xu GX, et al. Effect of lurasidone plus sulpiride on treatment efficacy, psychiatric manifestations, and quality of life among patients with schizophrenia. World J Psychiatry. 2025;15(10):105932. doi: 10.5498/wjp.v15.i10.105932

42. Rautio D, Vilaplana-Perez A, Gumpert M, et al. Validity and reliability of the diagnostic codes for hypochondriasis and dysmorphophobia in the Swedish National Patient Register : a retrospective chart review. BMJ Open. 2021;11(12):e051853. doi: 10.1136/bmjopen-2021-051853

43. Mataix-Cols D, Isomura K, Sidorchuk A, et al. All-Cause and Cause-Specific Mortality Among Individuals With Hypochondriasis. JAMA Psychiatry. 2024;81(3):284-91. doi: 10.1001/jamapsychiatry.2023.4744

44. Katz J, Rosenbloom BN, Fashler S. Chronic Pain, Psychopathology, and DSM-5 Somatic Symptom Disorder. Can J Psychiatry. 2015;60(4):160-7. doi: 10.1177/070674371506000402

45. Petrak F, Hardt J, Kappis B, et al. Determinants of health-related quality of life in patients with persistent somatoform pain disorder. Eur J Pain. 2003;7(5):463-71. doi: 10.1016/s1090-3801(03)00014-4

46. Huang Y, Chen H, Chen SR, Pan HL. Duloxetine and Amitriptyline Reduce Neuropathic Pain by Inhibiting Primary Sensory Input to Spinal Dorsal Horn Neurons via α1- and α2-Adrenergic Receptors. ACS Chem Neurosci. 2023;14(7):1261-77. doi: 10.1021/acschemneuro.2c00780

47. Tyuvina NA, Prokhorova SV, Maksimova TN. Comparative efficacy of sulpiride in the treatment of obsessions of different genesis. Sotsial'naya i klinicheskaya psikhiatriya. 2013;23(3):83-8 (In Russ.).

48. Kishimoto T, Hagi K, Kurokawa S, et al. Efficacy and safety/tolerability of antipsychotics in the treatment of adult patients with major depressive disorder : a systematic review and meta-analysis. Psychol Med. 2023;53(9):4064-82. doi: 10.1017/s0033291722000745

49. Ho CS, Chen HJ, Chiu NC, et al. Short-term sulpiride treatment of children and adolescents with Tourette syndrome or chronic tic disorder. J Formos Med Assoc. 2009;108(10):788-93. doi: 10.1016/s0929-6646(09)60406-x

50. El-Kassas M, Tawheed A, El Halwagy H, et al. Evaluation of safety and efficacy of the combination of mebeverine and sulpiride in treatment of patients with functional gastrointestinal disorders: A prospective cohort. J Int Med Res. 2026;54(1):3000605251410412. doi: 10.1177/03000605251410412

51. Belova EV. The effect of sulpirid in treatment of patients with gastric and duodenal erosions and ulcers. Klinicheskaya meditsina. 2007;85(7):70-3 (In Russ.).

52. Veyn AM, Sinyachkin MS. Sulpiride in the prophylactic treatment of migraine. S.S. Korsakov Journal of Neurology and Psychiatry. 1997;97(11):28-32 (In Russ.).

53. Zhukova NV, Kilessa VV, Turna EY, Ulchenko IG. Positive effect of rabeprazole/sulpiride combination therapy on bronchial asthma combined with gastroesophageal reflux disease. Pravara Med Rev. 2020;12(3):11-22. doi: 10.36848/PMR/2020/13100.51285

54. Ford AC, Moayyedi P, Black CJ, et al. Systematic review and network meta-analysis: efficacy of drugs for functional dyspepsia. Aliment Pharmacol Ther. 2021;53(1):8-21. doi: 10.1111/apt.16072

55. Liang L, Yu J, Xiao L, Wang G. Comparative Efficacy of Various Pharmacological Interventions in the Treatment of Functional Dyspepsia: A Network Meta-Analysis. Dig Dis Sci. 2022;67(1):187-207. doi: 10.1007/s10620-021-06846-1

56. Mukhtar I, Anwar H, Mirza OA, et al. Sulpiride Serves, a Substrate for the Gut Microbiome. Dose Response. 2021;19(1):1559325820987943. doi: 10.1177/1559325820987943