Bromocriptine for Patients With Schizophrenia and Prediabetes

Summary

This is a multicenter open-label, pilot study to evaluate the safety and tolerability of bromocriptine, a dopamine D2/D3 receptor and serotonin 5-HT2C receptor agonist, as an adjunct to preexisting standard-of-care antipsychotic drug (APD) regimens in the management of APD-associated impaired glucose tolerance (IGT)/insulin resistance (IR). The ultimate aim of the study team is to evaluate the efficacy of bromocriptine in treating the metabolic disturbances associated with APDs and the hypothesis is that bromocriptine will be a well-tolerated, safe, and inexpensive way to ameliorate these metabolic complications and prevent or delay the onset of type 2 diabetes (T2D). This study will be a small, short-duration pilot focusing on safety and tolerability. A total of 15 psychiatrically stable APD-treated adult outpatients, VA Pittsburgh , aged 18 to 65 years old, with a confirmed diagnosis of schizophrenia and comorbid IGT will be recruited and receive 6 weeks of bromocriptine (flexibly titrated, 2.5-5.0 mg PO daily). Key inclusion criteria are: 1) currently being treated with second generation APDs for 3 or more months with no change in dose in the 1 month prior to enrollment, 2) fasting glucose 100 to 125mg/dL and/or hemoglobin A1c (HbA1c) 5.7-6.4%. Key exclusions are: 1) prior APD nonadherence, 2) drug/alcohol abuse in the 3 months prior to screening, 3) a history of violent behavior/psychoses, 4) pregnancy, or 5) a diagnosis of diabetes. Subjects on other dopamine agonists or on medications that may interact with bromocriptine and those taking corticosteroids or other medications that may alter glucose levels will be excluded. The purposes of the study are to demonstrate safety/tolerability, demonstrate feasibility, provide proof of concept, and provide an open-label assessment of the metabolic and psychiatric effects of bromocriptine in patients with schizophrenia treated with APDs. The primary metabolic outcome measures will be change in IR as measured by the HOMA-IR and change in IGT measured by HbA1c. Secondary metabolic outcome measures include body weight, fasting lipids, and prolactin. The specific aims are as follows: Specific aim 1: To establish the safety and tolerability of bromocriptine in patients with schizophrenia and IGT/IR treated with APDs. Specific aim 2: To demonstrate feasibility/proof of concept for an improvement in APD-induced IGT/IR with bromocriptine.

Timeline

Start

2026-01-01

Primary completion

2026-07-31

Completion

2026-07-31

Publications

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• Background Chiu CC, Lu ML, Huang MC, Chen PY, Lin YK, Lin SK, Chen CH. Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study. PLoS One. 2016 Dec 14;11(12):e0168347. doi: 10.1371/journal.pone.0168347. eCollection 2016.
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• Background Gaziano JM, Cincotta AH, O'Connor CM, Ezrokhi M, Rutty D, Ma ZJ, Scranton RE. Randomized clinical trial of quick-release bromocriptine among patients with type 2 diabetes on overall safety and cardiovascular outcomes. Diabetes Care. 2010 Jul;33(7):1503-8. doi: 10.2337/dc09-2009. Epub 2010 Mar 23.
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• Background Kok P, Roelfsema F, Frolich M, van Pelt J, Stokkel MP, Meinders AE, Pijl H. Activation of dopamine D2 receptors simultaneously ameliorates various metabolic features of obese women. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1038-43. doi: 10.1152/ajpendo.00567.2005. Epub 2006 Jun 27.
• Background Lee MS, Song HC, An H, Yang J, Ko YH, Jung IK, Joe SH. Effect of bromocriptine on antipsychotic drug-induced hyperprolactinemia: eight-week randomized, single-blind, placebo-controlled, multicenter study. Psychiatry Clin Neurosci. 2010 Feb;64(1):19-27. doi: 10.1111/j.1440-1819.2009.02032.x. Epub 2009 Nov 24.
• Background Lehman AF, Lieberman JA, Dixon LB, McGlashan TH, Miller AL, Perkins DO, Kreyenbuhl J; American Psychiatric Association; Steering Committee on Practice Guidelines. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004 Feb;161(2 Suppl):1-56. No abstract available.
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• Background Maayan L, Vakhrusheva J, Correll CU. Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis. Neuropsychopharmacology. 2010 Jun;35(7):1520-30. doi: 10.1038/npp.2010.21. Epub 2010 Mar 24.
• Background Perovich RM, Lieberman JA, Fleischhacker WW, Alvir J. The behavioral toxicity of bromocriptine in patients with psychiatric illness. J Clin Psychopharmacol. 1989 Dec;9(6):417-22.
• Background Pijl H, Ohashi S, Matsuda M, Miyazaki Y, Mahankali A, Kumar V, Pipek R, Iozzo P, Lancaster JL, Cincotta AH, DeFronzo RA. Bromocriptine: a novel approach to the treatment of type 2 diabetes. Diabetes Care. 2000 Aug;23(8):1154-61. doi: 10.2337/diacare.23.8.1154.
• Background Pramyothin P, Khaodhiar L. Metabolic syndrome with the atypical antipsychotics. Curr Opin Endocrinol Diabetes Obes. 2010 Oct;17(5):460-6. doi: 10.1097/MED.0b013e32833de61c.
• Background Sykes DA, Moore H, Stott L, Holliday N, Javitch JA, Lane JR, Charlton SJ. Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors. Nat Commun. 2017 Oct 2;8(1):763. doi: 10.1038/s41467-017-00716-z.
• Background Valiquette G. Bromocriptine for diabetes mellitus type II. Cardiol Rev. 2011 Nov-Dec;19(6):272-5. doi: 10.1097/CRD.0b013e318229d2d2.

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Indications