Dynamics of Somatic and Comorbid Mental Disorders (Distress, Anxiety, Somatisation and Depression) in Patients with Irritable Bowel Syndrome during Therapy with Alimemazine: Results of an Non-Interventional Observational Programme (“Terra”)

Aim. This study is aimed at investigating the efficacy and safety of alimemazine (Teraligen®) therapy in patients with irritable bowel syndrome (IBS) associated with comorbid mental disorders (distress, anxiety, somatisation and depression).

Materials and methods. During an open-label, non-comparative and non-interventional study, 60 patients diagnosed with the K58 (K 58.0, K58.9) irritable bowel syndrome were observed (12 men and 48 women, average age 39.6 ± 11.1 years) and treated with Teraligen® (alimemazine) with a gradual dose increase from 2.5 to 15 mg per day against the background of the standard symptomatic treatment used for such states. The observational study lasted for 4 weeks. The Four-Dimensional Symptom Questionnaire (4DSQ) was used to assess the dynamics and effectiveness of the treatment in terms of the patients’ mental state, while the “7 symptoms per 7 days” (“7 × 7”) questionnaire was used to assess the dynamics of IBS symptoms and concomitant functional dyspepsia (FD). Both questionnaires were offered to the patients three times: before the start of the treatment and following 2 and 4 weeks of the therapy.

Results. Teraligen therapy along with the standard symptomatic treatment has shown a significant positive dynamics of the patients’ state due to the reduction of such symptoms, as pain and burning sensation in the epigastrium, postprandial fullness, early satiety, abdominal pain before defecation, abdominal distension, impaired frequency and quality of defecation. This is confirmed by a reliable and consistent decrease in the total scores of the “7 × 7” questionnaire, with the scores changing from 19.7 ± 7.1 to 11.6 ± 5.9 and 7.3 ± 5.6 before treatment, on the 14th day (p <0.0001) and on the 28th day of therapy (p <0.0001), respectively. The number of patients reporting no symptoms increased by 18.3 %, indicating a complete reduction of severe disorders. The proportion of patients with the minimal or mild severity of complaints increased by 36.7 % and 8.2 % (from 3.3 % to 40.0 % and from 11.8 % to 20.0 %), respectively. In addition, alimemazine treatment contributed to a statistically significant positive dynamics of the patients’ psychoemotional state. The average level of distress decreased from 14.9 ± 10.0 to 7.5 ± 6.2 (14th day) and to 4.4 ± 5.8 scores (28th day). The number of patients reporting no distress symptoms increased by 49.4 %, reaching 91.1 % (n = 51) on the 28th day of treatment. The mean level of depression decreased from 1.7 ± 2.7 to 0.5 ± 1.2 (14th day) and to 0.5 ± 1.6 (28th day), while the proportion of patients without depression increased by 17.9 % and reached 94.6 % (n = 53). The anxiety level was reduced from 6.0 ± 6.3 to 2.9 ± 4.3 (14th day) and to 1.5 ± 3.8 scores (28th day), and the proportion of patients without anxiety increased by 21.4 % reaching 96.4 % (n = 54) (28th day). The level of somatisation decreased from 13.5 ± 7.3 to 8.7 ± 5.6 (14th day) and to 5.1 ± 4.4 scores (28th day), and the proportion of patients without somatisation increased by 52.9 % and comprised 92.9 % (n = 52) (28th day) (according to the 4DSQ). Most of the patients tolerated alimemazine at a dose of 15 mg/day. In 15 patients, minor adverse reactions were observed; however, no cases of pronounced and severe side effects were recorded. In 4 patients, the treatment was cancelled due to increased drowsiness.

Conclusion. It is shown that the application of alimemazine (Teraligen®) in patients with IBS and concomitant FD associated with comorbid mental disorders (distress, anxiety, somatisation and depression) reduces gastroenterological (somatic) and mental (affective, somatoform) symptoms, improves the patients’ state of health, thus being confirmed as effective and safe.

1. Poluektova E.A., Ivashkin V.T., Sheptulin A.A. The rationale for the use of psychotropic drugs in patients with irritable bowel syndrome. Russian Medical Journal. 2007;9 (1, Appendix):1–3 (In Rus.)

2. Van Oudenhove L., Crowell M.D., Drossman D.A., Halpert A.D. et al. Biopsychosocial Aspects of Functional Gastrointestinal Disorders: How Central and Environmental Processes Contribute to the Development and Expression of Functional Gastrointestinal Disorders. Gastroenterology. 2016;150(6):1355–67.

3. Drossman D.A. Do psychosocial factors define symptom severity and patient status in irritable bowel syndrome? Am J Med. 1999;107(5A):41–50.

4. Hausteiner-Wiehle C., Henningsen P. Irritable bowel syndrome: relations with functional, mental, and somatoform disorders. World J Gastroenterol. 2014;20(20):6024–30.

5. Cho H.S., Park J.M., Lim C.H., Cho Y.K. et al. Anxiety, depression and quality of life in patients with irritable bowel syndrome. Gut Liver. 2011;5(1):29–36.

6. Greenwood-Van Meerveld B., Moloney R.D., Johnson A.C., Vicario M. Mechanisms of stress-induced visceral pain: implications in irritable bowel syndrome. J Neuroendocrinol. 2016;28(8). DOI: 10.1111/jne.12361

7. Wilson A., Longstreth G., Knight K., Wong J. et al. Quality of life in managed care patients with irritable bowel syndrome. Manage Care Interface. 2004;17:24.

8. Dekel R., Drossman D.A., Sperber A.D. The use of psychotropic drugs in irritable bowel syndrome. Expert Opin Investig Drugs. 2013;22(3):329–39.

9. Hausteiner-Wiehle С., Henningsen P. Irritable bowel syndrome: Relations with functional, mental, and somatoform disorders. World J Gastroenterol. 2014;20(20):6024–30.

10. Ivashkin V.T., Shelygin Yu.A., Baranskaya Ye.K. et al. Diagnosis and treatment of the irritable bowel syndrome: clinical guidelines of the Russian gastroenterological association and Russian association of coloproctology. Rus J Gastroenterol Hepatol Coloproctol. 2017;27(5):76–93 (In Rus.) DOI: 10.22416/1382-4376-2017-27-5-76-93

11. Terluin B., van Marwijk H.W., Adèr H.J., de Vet H.C. et al. The Four-Dimensional Symptom Questionnaire (4DSQ): a validation study of a multidimensional selfreport questionnaire to assess distress, depression, anxiety and somatization. BMC Psychiatry. 2006;6:34.

12. Langerak W., Langeland W. et al. A validation study of the Four-Dimensional Symptom Questionnaire (4DSQ) in insurance medicine. Work. 2012;43(3):369–80.

13. Nagasako C.K., Garcia Montes C., Silva Lorena S.L., Mesquita M.A. Irritable bowel syndrome subtypes: Clinical and psychological features, body mass index and comorbidities. Rev Esp Enferm Dig. 2016;108(2):59–64.

14. Wong H.Y., Chang L. Stress and the gut: Central influences. In: Spiller R., Grundy D. (eds) A basis for understanding functional diseases. Blackwell, 2004. P. 45–51.

15. Hausteiner-Wiehle C., Henningsen P. Irritable bowel syndrome: relations with functional, mental, and somatoform disorders. World J Gastroenterol. 2014;20(20):6024–30.

16. Pae C.U., Lee S.J., Han C., Patkar A.A. et al. Atypical antipsychotics as a possible treatment option for irritable bowel syndrome. Expert Opin Investig Drugs. 2013;22(5):565–72.

17. Albert U., Carmassi C., Cosci F., De Cori D. et al. Role and clinical implications of atypical antipsychotics in anxiety disorders, obsessive-compulsive disorder, traumarelated, and somatic symptom disorders: a systematized review. Int Clin Psychopharmacol. 2016;31(5):249–58.