Bumetanide for autism spectrum disorder in children: a review of randomized controlled trials
Abstract
OBJECTIVE: To evaluate clinical trials using bumetanide in autism spectrum disorder (ASD) treatment. DATA SOURCES: PubMed and Ovid MEDLINE (1946 to October 2018) were searched using terms bumetanide and autism. Bibliographies were reviewed for other relevant trials. STUDY SELECTION AND DATA EXTRACTION: English language, randomized, controlled, clinical trials in humans were evaluated. Three trials met all inclusion criteria. DATA SYNTHESIS: Oral bumetanide was studied in 208 patients, 2 to 18 years old, with ASD. Trials evaluated bumetanide's impact on core behavioral features using several different autism assessment scales. All trials used the Childhood Autism Rating Scale to assess improvement at 90 days, with one trial finding statistical significance. The Clinical Global Impressions Scale identified statistically significant improvements in 2 of the 3 trials. The Autism Behavioral Checklist and Social Responsiveness Scales identified statistical benefit in the 2 trials utilizing those outcomes. Behaviors most improved by bumetanide included social communication, interactions, and restricted interest. No dose-effect correlation was identified in the dose-ranging trial. Adverse effects, including hypokalemia and polyuria, occurred more often with higher doses and resulted in withdrawal rates of 17% to 43%. Bumetanide 0.5 mg twice daily was the most studied and best tolerated dose. Limitations included unclear clinical success definitions and evaluation methodology variability. Relevance to Patient Care and Clinical Practice: No effective treatment options for core ASD symptoms have been approved. This review presents preliminary safety and efficacy data for bumetanide in ASD. CONCLUSIONS: Low-dose oral bumetanide may be useful in patients with moderate to severe ASD when behavioral therapies are not available.
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Based on current literature, there is inconclusive evidence for the role of bumetanide in addressing the core symptoms of ASD.
“Regardless, based on current literature, there is inconclusive evidence for the role of bumetanide in addressing the core symptoms of ASD [102, 103].”
From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [103]
Cites
Standardizing ADOS Scores for a Measure of Severity in Autism Spectrum Disorders
Gotham, K., Pickles, A., & Lord, C. (2009) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-008-0674-3 · Cited by 1,605 · see citing works
Spearing, M. K., Post, R. M., Leverich, G. S., Brandt, D., & Nolen, W. (1997) · Psychiatry Research · doi:10.1016/s0165-1781(97)00123-6 · Cited by 978 · see citing works
Krug, D. A., Arick, J. R., & Almond, P. (1980) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.1980.tb01797.x · Cited by 903 · see citing works
Volkmar, F. R., Siegel, M. S., Woodbury‐Smith, M., King, B. H., McCracken, J. T., & State, M. W. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2013.10.013 · Cited by 858 · see citing works
Test Review: Social Responsiveness Scale–Second Edition (SRS-2)
Bruni, T. P. (2014) · Journal of Psychoeducational Assessment · doi:10.1177/0734282913517525 · Cited by 705 · see citing works
Autism Diagnostic Observation Schedule--Generic
Lord, C., Rutter, M. L., DiLavore, P. C., & Risi, S. (1999) · PsycTESTS Dataset · doi:10.1037/t17256-000 · Cited by 487 · see citing works
Using the Childhood Autism Rating Scale to Diagnose Autism Spectrum Disorders
Chlebowski, C., Green, J. A., Barton, M. L., & FEIN, D. A. (2010) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-009-0926-x · Cited by 341 · see citing works
A randomised controlled trial of bumetanide in the treatment of autism in children
Lemonnier, E., Degrez, C., Phelep, M., Tyzio, R., Josse, F., Grandgeorge, M., Hadjikhani, N., & Ben-Ari, Y. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.124 · Cited by 322 · see citing works
Rellini, E., Tortolani, D., Trillo, S., Carbone, S., & Montecchi, F. (2004) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-004-5290-2 · Cited by 292 · see citing works
NKCC1 Chloride Importer Antagonists Attenuate Many Neurological and Psychiatric Disorders
Ben‐Ari, Y. (2017) · Trends in Neurosciences · doi:10.1016/j.tins.2017.07.001 · Cited by 246 · see citing works
Lemonnier, E., Villeneuve, N., Sonie, S., Serret, S., Rosier, A., Roue, M., Brosset, P., Viellard, M., Bernoux, D., Rondeau, S., et al. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.10 · Cited by 218 · see citing works
Siegel, M. S., & Beaulieu, A. (2011) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-011-1399-2 · Cited by 143 · see citing works
Hadjikhani, N., Zürcher, N. R., Rogier, O., Ruest, T., Hippolyte, L., Ben-Ari, Y., & Lemonnier, E. (2015) · Autism · doi:10.1177/1362361313514141 · Cited by 129 · see citing works
Psychopharmacological interventions in autism spectrum disorder
Accordino, R. E., Kidd, C. L., Politte, L. C., Henry, C. A., & McDougle, C. J. (2016) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2016.1154536 · Cited by 128 · see citing works
Aman, M. G., Findling, R. L., Hardan, A. Y., Hendren, R. L., Melmed, R. D., Kehinde-Nelson, O., Hsu, H.-A., Trugman, J. M., Palmer, R. H., Graham, S. M., et al. (2016) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2015.0146 · Cited by 107 · see citing works
Bumetanide for autism: more eye contact, less amygdala activation
Hadjikhani, N., Åsberg Johnels, J., Lassalle, A., Zürcher, N. R., Hippolyte, L., Gillberg, C., Lemonnier, E., & Ben-Ari, Y. (2018) · Scientific Reports · doi:10.1038/s41598-018-21958-x · Cited by 90 · see citing works
Du, L., Shan, L., Wang, B., Li, H., Xu, Z., Staal, W. G., & Jia, F. (2015) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2015.0045 · Cited by 87 · see citing works
Brief Report: The Social Responsiveness Scale for Adults (SRS-A): Initial Results in a German Cohort
Bölte, S. (2011) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-011-1424-5 · Cited by 84 · see citing works
Paradoxical Benzodiazepine Response: A Rationale for Bumetanide in Neurodevelopmental Disorders?
Bruining, H., Passtoors, L., Goriounova, N. A., Jansen, F. E., Hakvoort, B. E., de Jonge, M. V., & Poil, S. (2015) · PEDIATRICS · doi:10.1542/peds.2014-4133 · Cited by 62 · see citing works
Herbal Medicine Treatment for Children with Autism Spectrum Disorder: A Systematic Review
Bang, M.-R., Lee, S. H., Cho, S., Yu, S.-A., Kim, K., Lu, H. Y., Chang, G. T., & Min, S. Y. (2017) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2017/8614680 · Cited by 40 · see citing works
The effect of bumetanide treatment on the sensory behaviours of a young girl with Asperger syndrome
Grandgeorge, M., Lemonnier, É., Degrez, C., & Jallot, N. (2014) · BMJ Case Reports · doi:10.1136/bcr-2013-202092 · Cited by 26 · see citing works
Flagged first, then by citations
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Targeting peripheral somatosensory neurons to improve tactile-related phenotypes in ASD models
Orefice, L. L., Mosko, J. R., Morency, D. T., Wells, M. F., Tasnim, A., Mozeika, S. M., Ye, M., Chirila, A. M., Emanuel, A. J., Rankin, G., et al. (2019) · Cell · doi:10.1016/j.cell.2019.07.024 · Cited by 247 · see citing works
An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
Aishworiya, R., Valica, T., Hagerman, R., & Restrepo, B. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01183-1 · Cited by 233 · see citing works
GABAergic System Dysfunction in Autism Spectrum Disorders
Zhao, H., Mao, X., Zhu, C., Zou, X., Peng, F., Yang, W., Li, B., Li, G., Ge, T., & Cui, R. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.781327 · Cited by 172 · see citing works
Chakraborty, P., Dey, A., Gopalakrishnan, A. V., Swati, K., Ojha, S. K., Prakash, A., Kumar, D., Ambasta, R. K., Jha, N. K., Jha, S. K., et al. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101838 · Cited by 58 · see citing works
Carnovale, C., Perrotta, C., Baldelli, S., Cattaneo, D., Montrasio, C., Barbieri, S. S., Pompilio, G., Vantaggiato, C., Clementi, E., & Pozzi, M. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac110 · Cited by 54 · see citing works
Therapeutic innovation in drug repurposing: Challenges and opportunities
Recino, A., Rayner, M., Rohn, J. L., Pasqua, O. E. D., Recino, A., Rayner, M. L. D., Rohn, J. L., Carter, B., Cupani, A., Dahlmann-Noor, A. H., et al. (2025) · Drug Discovery Today · doi:10.1016/j.drudis.2025.104390 · Cited by 48 · see citing works
Targeting epigenetic dysregulation in autism spectrum disorders
Herrera, M. L., Paraíso‐Luna, J., Bustos-Martínez, I., & Barco, Á. (2024) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2024.06.004 · Cited by 43 · see citing works
Bumetanide for autism: open-label trial in six children
Fernell, E., Gustafsson, P., & Gillberg, C. (2021) · Acta Paediatrica · doi:10.1111/apa.15723 · Cited by 34 · see citing works
Gillespie, B., Panthi, S., Sundram, S., & Hill, R. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105488 · Cited by 30 · see citing works
Wang, T., Shan, L., Miao, C., Xu, Z., & Jia, F. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.751575 · Cited by 28 · see citing works
Ichinose, W., Михайлович, Ч. С., Shabalova, A. A., Yokoyama, S., Yuhi, T., Yamaguchi, H., Watanabe, A., Yamamoto, Y., Okamoto, H., Horike, S., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01691 · Cited by 30 · see citing works
Why do children with autism spectrum disorder have abnormal visual perception?
Zhou, R., Xie, X., Wang, J., Ma, B., & Hao, X. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1087122 · Cited by 27 · see citing works
Ben‐Ari, Y., & Cherubini, E. (2022) · Cells · doi:10.3390/cells11030396 · Cited by 24 · see citing works
Zarepour, L., Gharaylou, Z., Hadjighassem, M., Shafaghi, L., Majedi, H., Behzad, E., Hosseindoost, S., Ramezani, F., & Nasirinezhad, F. (2020) · Journal of Clinical Neuroscience · doi:10.1016/j.jocn.2020.10.010 · Cited by 19 · see citing works
Autism under the umbrella of ESSENCE
Fernell, E., & Gillberg, C. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1002228 · Cited by 18 · see citing works
Li, Q., Zhang, L., Shan, H., Yu, J., Dai, Y., He, H., Li, W., Langley, C., Sahakian, B. J., Yao, Y., et al. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-01987-x · Cited by 16 · see citing works
Available Treatments for Autism Spectrum Disorder: From Old Strategies to New Options
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Lv, H., Gu, X. Q., Shan, X., Zhu, T., Ma, B., Zhang, H.-T., Bambini-Júnior, V., Zhang, T., Li, W., Gao, X., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.870577 · Cited by 13 · see citing works
Persico, A. M., Cucinotta, F., Ricciardello, A., & Turriziani, L. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-814409-1.00003-3 · Cited by 14 · see citing works
An Update on Psychopharmacological Treatment of Autism Spectrum Disorder
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van Andel, D. M., Sprengers, J. J., Keijzer‐Veen, M. G., Schulp, A. J. A., Lillien, M. R., Scheepers, F. E., & Bruining, H. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.780281 · Cited by 11 · see citing works
Treatment experience in two adults with creatinfe transporter deficiency
Schjelderup, J., Hope, S., Vatshelle, C., & van Karnebeek, C. (2021) · Molecular Genetics and Metabolism Reports · doi:10.1016/j.ymgmr.2021.100731 · Cited by 8 · see citing works
Kirkovski, M., Hill, A. T., Rogasch, N. C., Saeki, T., Fitzgibbon, B. M., Yang, J. S. C., Do, M., Donaldson, P. H., Albein‐Urios, N., Fitzgerald, P. B., et al. (2021) · Brain stimulation · doi:10.1016/j.brs.2021.12.010 · Cited by 8 · see citing works
Is the awakening produced by benzodiazepines due to excitatory actions of GABA?
Ben‐Ari, Y. (2021) · Translational Medicine Communications · doi:10.1186/s41231-021-00085-2 · Cited by 6 · see citing works
Bumetanide: A review of its neuroplasticity and behavioral effects after stroke
Tao, D., Liu, F., Sun, X., Qu, H., Zhao, S., Zhou, Z., Xiao, T., Zhao, C., & Zhao, M. (2019) · Restorative Neurology and Neuroscience · doi:10.3233/rnn-190926 · Cited by 6 · see citing works
Analgesic Effect of Bumetanide on Neuropathic Pain in Patients with Spinal Cord Injury
Nasirinezhad, F., Zarepour, L., Hadjighassem, M., Gharaylou, Z., Majedi, H., & Ramezani, F. (2021) · Basic and Clinical Neuroscience Journal · doi:10.32598/bcn.2021.2049.1 · Cited by 4 · see citing works
Neurobiology of Autism Spectrum Disorder
Casanova, M. F., Constantino, J. N., Ecker, C., Frye, R. E., Martínez‐Cerdeño, V., Rossignol, D. A., & Scherer, S. W. (2024) · Springer eBooks · doi:10.1007/978-3-030-51366-5_32 · Cited by 3 · see citing works
Pharmacologic management of autism spectrum disorder: A review of 7 studies
Kothadia, R. J., Krause, M., & Saeed, S. A. (2021) · Current Psychiatry · doi:10.12788/cp.0078 · Cited by 2 · see citing works
Drug Repurposing Patent Applications July–September 2021
Mucke, H. A. (2021) · Assay and Drug Development Technologies · doi:10.1089/adt.2021.126 · Cited by 1 · see citing works
Crossing borders in neurodevelopmental disorders
van Andel, D. M. (2021) · doi:10.33540/943
BUMETANIDE IN AUTISM SPECTRUM DISORDER
Moreira, L. D. S., & Aragão, G. F. (2022) · Arquivos de Ciências da Saúde da UNIPAR · doi:10.25110/arqsaude.v26i3.2022.8774
Neurobiology of Autism Spectrum Disorder
Casanova, M. F., Constantino, J. N., Ecker, C., Frye, R. E., Martínez‐Cerdeño, V., Rossignol, D. A., & Scherer, S. W. (2023) · Springer eBooks · doi:10.1007/978-3-030-42825-9_32-1
Tratamento farmacológico atual do transtorno do espectro autista
Kleis, E. T. C., & Soares, L. M. (2025) · Revista Científica Multidisciplinar Núcleo do Conhecimento · doi:10.32749/nucleodoconhecimento.com.br/saude/tratamento-farmacologico
d’Albis, M.-A. (2020) · theses.fr (ABES) · doi:10.70675/206f79f9z2fd3z499fz9abdz096c72713a99
- Authors
- James, B. J., Gales, M. A., & Gales, B. J.
- Affiliations
- Southwestern Oklahoma State University (US)
- INTEGRIS Baptist Medical Center (US)
- Corresponding author
- Gales, Mark A.
- ORCID
- Gales, Mark A.
- Venue
- Annals of Pharmacotherapy
- Publisher
- SAGE Publications
- Published
- 2018-12-02
- Volume
- 53
- Issue
- 5
- Pages
- 537-544
- ISSN
- 0012-6578 (ISSN-L)
- 1060-0280
- 1542-6270
- OpenAlex
- W2903304724
- Cited by
- 35
- References
- 21
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 5 · 2022: 8 · 2021: 9 · 2020: 4 · 2019: 3
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Pharmacotherapy (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Child Nutrition and Feeding Issues
- Keywords
- bumetanide, autism spectrum disorder, children, diuretic therapy, behavioral symptoms, social communication, restricted interests, hypokalemia, polyuria, drug safety, dose-response relationship, treatment efficacy
- MeSH terms
- Autism Spectrum Disorder, Adolescent, Bumetanide, Child, Child, Preschool, Female, Humans, Male, Randomized Controlled Trials as Topic, Treatment Outcome
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