Topiramate vs Metformin on Cardio-Metabolic Profile in Schizophrenia on Atypical Antipsychotics

NCT05663749 | Completed Phase 4

• 1 other identifier: AIIMS BBSR/PG Thesis/2021-22
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Metabolic syndrome is common in patients of schizophrenia. It can add to morbidity, loss of functionality and discontinuation of antipsychotic medication. Apart from metformin, there are limited treatment options as add on-s to antipsychotics for treatment of metabolic syndrome. There have been placebo-controlled studies of Topiramate as an adjuvant but the present study would be the first head-on trial between these drugs for treatment of metabolic syndrome in patients of schizophrenia. If the outcome measures show a significant improvement with add on topiramate when compared with Metformin, then add on Topiramate can be a preferred treatment for metabolic syndrome in patients with schizophrenia on atypical antipsychotics. The adverse effects of Metformin can be side-stepped and Topiramate can also be given in conditions which are contraindications for Metformin. Thus, Topiramate can be a good alternative to metformin especially in conditions like liver, cardiac and renal impairment where metformin use should be avoided. Topiramate can not only improve metabolic parameters but can also have a beneficial effect on the symptom severity of schizophrenia. Thus, it can be a good augmentation drug to be used along with antipsychotics in these patients.

Conditions

Metabolic Syndrome; Schizophrenia

Keywords

Metabolic Syndrome; Schizophrenia; Atypical antipsychotics; Topiramate; Metformin

Outcome Measures

Primary Outcomes (1)

• Change in the QRISK3 score.

  QRISK3 (QRESEARCH cardiovascular risk algorithm)2018 algorithm- used for calculating the cardiovascular risk in the upcoming 10 years. It is measured for the age group of 25 to 84 years using information like age, weight, height, BMI, Lipid profile, past history of CKD, angina, migraine etc. Higher score indicates higher risk.

  8 weeks

Secondary Outcomes (4)

• Change in the LDL/HDL ratio(Low density lipoprotein/High density lipoprotein).Higher ratio indicates higher risk

  8 weeks

• Change in Insulin Resistance (HOMA-IR)(homeostasis model assessment-estimated insulin resistance ).

  8 weeks

• Change in Positive and negative syndrome scale

  8 weeks

• Change in Clinical Global Impression-Schizophrenia scale

  8 weeks

Study Arms (2)

Metformin arm

ACTIVE COMPARATOR

1000mg for 8 weeks

Drug: Metformin

Topiramate arm

EXPERIMENTAL

50mg for 8 weeks

Drug: Topiramate

Interventions

Metformin DRUG

1000mg for 8 weeks

Also known as: Dibeta SR, Metgen, Glycomet

Metformin arm

Topiramate DRUG

50mg for 8 weeks

Also known as: Topamax, Topirol, Topaz

Topiramate arm

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients clinically diagnosed with schizophrenia (F20 according to ICD-10 DCR) on a stable dose of atypical antipsychotic for more than 3 months.
• Patients with metabolic syndrome (as per NCEP ATP III Definition).
• Patients above 25 years of age of either gender.
• Legally authorized representative (LAR) giving voluntary written consent for participation in the study.

You may not qualify if:

• Patients on combination of antipsychotics.
• Patients having any contraindication for Metformin/Topiramate.
• History of any psychoactive substance use in harmful use or dependence pattern except tobacco.
• Any co-morbid medical, psychiatric or neurological disorders like hypertension, coronary artery disease, hypothyroidism, arthritis.
• History of any significant head injury or organic diseases.
• Pregnant and breastfeeding females.

Sponsors & Collaborators

• All India Institute of Medical Sciences, Bhubaneswar: lead

Study Sites (1)

Dept of Psychiatry, Aiims, Bhubaneswar

Bhubaneswar, Odisha, 751019, India

Location

Related Publications (17)

• Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry. 2007 Oct;64(10):1123-31. doi: 10.1001/archpsyc.64.10.1123.

  PMID: 17909124 BACKGROUND

• DE Hert M, Schreurs V, Vancampfort D, VAN Winkel R. Metabolic syndrome in people with schizophrenia: a review. World Psychiatry. 2009 Feb;8(1):15-22. doi: 10.1002/j.2051-5545.2009.tb00199.x.

  PMID: 19293950 BACKGROUND

• Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, Lobos CA, Kissling W, Davis JM, Leucht S. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res. 2010 Nov;123(2-3):225-33. doi: 10.1016/j.schres.2010.07.012. Epub 2010 Aug 7.

  PMID: 20692814 BACKGROUND

• Zheng W, Li XB, Tang YL, Xiang YQ, Wang CY, de Leon J. Metformin for Weight Gain and Metabolic Abnormalities Associated With Antipsychotic Treatment: Meta-Analysis of Randomized Placebo-Controlled Trials. J Clin Psychopharmacol. 2015 Oct;35(5):499-509. doi: 10.1097/JCP.0000000000000392.

  PMID: 26280837 BACKGROUND

• Flory J, Lipska K. Metformin in 2019. JAMA. 2019 May 21;321(19):1926-1927. doi: 10.1001/jama.2019.3805.

  PMID: 31009043 BACKGROUND

• Goh KK, Chen CH, Lu ML. Topiramate mitigates weight gain in antipsychotic-treated patients with schizophrenia: meta-analysis of randomised controlled trials. Int J Psychiatry Clin Pract. 2019 Mar;23(1):14-32. doi: 10.1080/13651501.2018.1449864. Epub 2018 Mar 20.

  PMID: 29557263 BACKGROUND

• Lawrence D, Hancock KJ, Kisely S. The gap in life expectancy from preventable physical illness in psychiatric patients in Western Australia: retrospective analysis of population based registers. BMJ. 2013 May 21;346:f2539. doi: 10.1136/bmj.f2539.

  PMID: 23694688 BACKGROUND

• Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999 Nov;156(11):1686-96. doi: 10.1176/ajp.156.11.1686.

  PMID: 10553730 BACKGROUND

• Praharaj SK, Jana AK, Goyal N, Sinha VK. Metformin for olanzapine-induced weight gain: a systematic review and meta-analysis. Br J Clin Pharmacol. 2011 Mar;71(3):377-82. doi: 10.1111/j.1365-2125.2010.03783.x.

  PMID: 21284696 BACKGROUND

• Chen CH, Chiu CC, Huang MC, Wu TH, Liu HC, Lu ML. Metformin for metabolic dysregulation in schizophrenic patients treated with olanzapine. Prog Neuropsychopharmacol Biol Psychiatry. 2008 May 15;32(4):925-31. doi: 10.1016/j.pnpbp.2007.11.013. Epub 2007 Nov 17.

  PMID: 18082302 BACKGROUND

• de Silva VA, Suraweera C, Ratnatunga SS, Dayabandara M, Wanniarachchi N, Hanwella R. Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. BMC Psychiatry. 2016 Oct 3;16(1):341. doi: 10.1186/s12888-016-1049-5.

  PMID: 27716110 BACKGROUND

• Narula PK, Rehan HS, Unni KE, Gupta N. Topiramate for prevention of olanzapine associated weight gain and metabolic dysfunction in schizophrenia: a double-blind, placebo-controlled trial. Schizophr Res. 2010 May;118(1-3):218-23. doi: 10.1016/j.schres.2010.02.001. Epub 2010 Mar 7.

  PMID: 20207521 BACKGROUND

• Egger C, Muehlbacher M, Schatz M, Nickel M. Influence of topiramate on olanzapine-related weight gain in women: an 18-month follow-up observation. J Clin Psychopharmacol. 2007 Oct;27(5):475-8. doi: 10.1097/jcp.0b013e31814b98e5.

  PMID: 17873679 BACKGROUND

• Ellinger LK, Ipema HJ, Stachnik JM. Efficacy of metformin and topiramate in prevention and treatment of second-generation antipsychotic-induced weight gain. Ann Pharmacother. 2010 Apr;44(4):668-79. doi: 10.1345/aph.1M550. Epub 2010 Mar 16.

  PMID: 20233913 BACKGROUND

• Ince B, Altinbas K. [Ten-Year Risk of Cardiovascular Disease in Patients with Bipolar Disorder]. Turk Psikiyatri Derg. 2020 Winter;31(4):225-231. doi: 10.5080/u25270. Turkish.

  PMID: 33454933 BACKGROUND

• Tang Q, Li X, Song P, Xu L. Optimal cut-off values for the homeostasis model assessment of insulin resistance (HOMA-IR) and pre-diabetes screening: Developments in research and prospects for the future. Drug Discov Ther. 2015 Dec;9(6):380-5. doi: 10.5582/ddt.2015.01207.

  PMID: 26781921 BACKGROUND

• Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261-76. doi: 10.1093/schbul/13.2.261.

  PMID: 3616518 BACKGROUND

MeSH Terms

Conditions

Metabolic Syndrome; Schizophrenia

Interventions

Metformin; Topiramate; Topaz resin

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Study Officials

• Biswa Ranjan Mishra, MD, DPM

  All India Institute of Medical Sciences, Bhubaneswar

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Additional Professor

Study Record Dates

• First Submitted: December 4, 2021
• First Posted: December 23, 2022
• Study Start: September 20, 2022
• Primary Completion: July 30, 2023
• Study Completion: August 20, 2023
• Last Updated: August 22, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)