Skip to main content

Advertisement

Log in

Reduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder

  • Letter to the Editor
  • Published:
Journal of Autism and Developmental Disorders Aims and scope Submit manuscript

Abstract

Aggression remains a major cause of morbidity in patients with autism spectrum disorder (ASD). Current pharmacotherapy for aggression is not always effective and is often associated with morbidity. Nicotinic acetylcholinergic neurotransmission may play a prominent role in ASD pathophysiology based on human and animal studies, and preclinical studies show nicotine administration can reduce aggression-related behaviors. Transdermal nicotine has been used to treat agitation in neuropsychiatric conditions with cholinergic dysfunction. Here we report the use of transdermal nicotine as an adjunctive medication to treat aggression in a hospitalized adolescent with ASD. Nicotine patch was recurrently well tolerated, and reduced the need for emergency medication and restraint. These findings suggest further study of transdermal nicotine for aggression comorbid with ASD is warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  • Adler, B. A., Wink, L. K., Early, M., Shaffer, R., Minshawi, N., McDougle, C. J., & Erickson, C. A. (2014). Drug-refractory aggression, self-injurious behavior, and severe tantrums in autism spectrum disorders: A chart review study. Autism: The International Journal of Research and Practice,. doi:10.1177/1362361314524641.

    Google Scholar 

  • Allen, M. H., Debanné, M., Lazignac, C., Adam, E., Dickinson, L. M., & Damsa, C. (2011). Effect of nicotine replacement therapy on agitation in smokers with schizophrenia: A double-blind, randomized, placebo-controlled study. The American Journal of Psychiatry, 168(4), 395–399. doi:10.1176/appi.ajp.2010.10040569.

    Article  PubMed  Google Scholar 

  • Arnold, L. E., Aman, M. G., Hollway, J., Hurt, E., Bates, B., Li, X., et al. (2012). Placebo-controlled pilot trial of mecamylamine for treatment of autism spectrum disorders. Journal of Child and Adolescent Psychopharmacology, 22(3), 198–205. doi:10.1089/cap.2011.0056.

    Article  PubMed Central  PubMed  Google Scholar 

  • Arnold, L. E., Anand, R., & Aman, M. (2013). Varencline in autistic disorder: Hypothesis and case report of single-patient crossover. Journal of Child and Adolescent Psychopharmacology,. doi:10.1089/cap.2012.0025.

    Google Scholar 

  • Berntson, G. G., Beattie, M. S., & Walker, J. M. (1976). Effects of nicotinic and muscarinic compounds on biting attack in the cat. Pharmacology, Biochemistry and Behavior, 5(3), 235–239.

    Article  PubMed  Google Scholar 

  • Buckley, A. W., Sassower, K., Rodriguez, A. J., Jennison, K., Wingert, K., Buckley, J., et al. (2011). An open label trial of donepezil for enhancement of rapid eye movement sleep in young children with autism spectrum disorders. Journal of Child and Adolescent Psychopharmacology, 21, 353–357. doi:10.1089/cap.2010.0121.

    Article  PubMed Central  PubMed  Google Scholar 

  • Carmel, H., & Sheitman, B. B. (2007). Adjunctive transdermal nicotine reduced behavioral agitation in severe dementia. The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry, 15(5), 449. doi:10.1097/01.JGP.0000235688.05709.e2.

    Article  Google Scholar 

  • Deutsch, S. I., Urbano, M. R., Neumann, S. A., Burket, J. A., & Katz, E. (2010). Cholinergic abnormalities in autism: Is there a rationale for selective nicotinic agonist interventions? Clinical Neuropharmacology, 33(3), 114–120. doi:10.1097/WNF.0b013e3181d6f7ad.

    Article  PubMed  Google Scholar 

  • Driscoll, P., & Baettig, K. (1981). Selective inhibition by nicotine of shock-induced fighting in the rat. Pharmacology, Biochemistry and Behavior, 14(2), 175–179.

    Article  PubMed  Google Scholar 

  • Hajek, P., McRobbie, H., & Gillison, F. (2007). Dependence potential of nicotine replacement treatments: Effects of product type, patient characteristics, and cost to user. Preventive Medicine, 44, 230–234. doi:10.1016/j.ypmed.2006.10.005.

    Article  PubMed  Google Scholar 

  • Handen, B. L., Johnson, C. R., McAuliffe-Bellin, S., Murray, P. J., & Hardan, A. Y. (2011). Safety and efficacy of donepezil in children and adolescents with autism: Neuropsychological measures. Journal of Child and Adolescent Psychopharmacology, 21, 43–50. doi:10.1089/cap.2010.0024.

    Article  PubMed Central  PubMed  Google Scholar 

  • Hardan, A. Y., & Handen, B. L. (2002). A retrospective open trial of adjunctive donepezil in children and adolescents with autistic disorder. Journal of Child and Adolescent Psychopharmacology, 12, 237–241. doi:10.1089/104454602760386923.

    Article  PubMed  Google Scholar 

  • Hartley, S., Sikora, D., & McCoy, R. (2008). Prevalence and risk factors of maladaptive behaviour in young children with Autistic Disorder. Journal of Intellectual Disability Research, 52(10), 819–829. doi:10.1111/j.1365-2788.2008.01065.x.Prevalence.

    Article  PubMed Central  PubMed  Google Scholar 

  • Hellings, J. A., Zarcone, J. R., Crandall, K., Wallace, D., & Schroeder, S. R. (2001). Weight gain in a controlled study of risperidone in children, adolescents and adults with mental retardation and autism. Journal of Child and Adolescent Psychopharmacology, 11(3), 229–238. doi:10.1089/10445460152595559.

    Article  PubMed  Google Scholar 

  • Hoppman-Chaney, N., Wain, K., Seger, P. R., Superneau, D. W., & Hodge, J. C. (2013). Identification of single gene deletions at 15q13.3: Further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype. Clinical Genetics, 83, 345–351. doi:10.1111/j.1399-0004.2012.01925.x.

    Article  PubMed  Google Scholar 

  • Hughes, J. R., Pillitteri, J. L., Callas, P. W., Callahan, R., & Kenny, M. (2004). Misuse of and dependence on over-the-counter nicotine gum in a volunteer sample. Nicotine and Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco, 6, 79–84. doi:10.1080/14622200310001656894.

    Article  Google Scholar 

  • Johnson, S. K., Carlson, K. M., Lee, J., Burr, L. E., & Wagner, G. C. (2003). Effects of nicotine on target biting and resident-intruder attack. Life Sciences, 73(3), 311–317.

    Article  PubMed  Google Scholar 

  • Joseph, A. M., Norman, S. M., Ferry, L. H., Prochazka, A. V., Westman, E. C., Steele, B. G., et al. (1996). The safety of transdermal nicotine as an aid to smoking cessation in patients with cardiac disease. The New England Journal of Medicine, 335, 1792–1798. doi:10.1056/NEJM199612123352402.

    Article  PubMed  Google Scholar 

  • Kanne, S. M., & Mazurek, M. O. (2011). Aggression in children and adolescents with ASD: Prevalence and risk factors. Journal of Autism and Developmental Disorders, 41(7), 926–937. doi:10.1007/s10803-010-1118-4.

    Article  PubMed  Google Scholar 

  • Karvat, G., & Kimchi, T. (2014). Acetylcholine elevation relieves cognitive rigidity and social deficiency in a mouse model of autism. Neuropsychopharmacology, 39, 831–840. doi:10.1038/npp.2013.274.

    Article  PubMed Central  PubMed  Google Scholar 

  • Kemper, T. L., & Bauman, M. (1998). Neuropathology of infantile autism. Journal of Neuropathology and Experimental Neurology, 57, 645–652. doi:10.1097/00005072-199807000-00001.

    Article  PubMed  Google Scholar 

  • Leblond, C. S., Heinrich, J., Delorme, R., Proepper, C., Betancur, C., Huguet, G., et al. (2012). Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. PLoS Genetics, 8(2), e1002521. doi:10.1371/journal.pgen.1002521.

    Article  PubMed Central  PubMed  Google Scholar 

  • Lee, M., Martin-Ruiz, C., Graham, A., Court, J., Jaros, E., Perry, R., et al. (2002). Nicotinic receptor abnormalities in the cerebellar cortex in autism. Brain: A Journal of Neurology, 125(Pt 7), 1483–1495.

    Article  Google Scholar 

  • Levin, E. D. (2013). Complex relationships of nicotinic receptor actions and cognitive functions. Biochemical Pharmacology,. doi:10.1016/j.bcp.2013.07.021.

    Google Scholar 

  • Martin-Ruiz, C. M., Lee, M., Perry, R. H., Baumann, M., Court, J. A., & Perry, E. K. (2004). Molecular analysis of nicotinic receptor expression in autism. Brain Research. Molecular Brain Research, 123(1–2), 81–90. doi:10.1016/j.molbrainres.2004.01.003.

    Article  PubMed  Google Scholar 

  • McDougle, C. J., Stigler, K. A., & Posey, D. J. (2003). Treatment of aggression in children and adolescents with autism and conduct disorder. Journal of Clinical Psychiatry, 64, 16–25.

    PubMed  Google Scholar 

  • McTighe, S. M., Neal, S. J., Lin, Q., Hughes, Z. A., & Smith, D. G. (2013). The BTBR mouse model of autism spectrum disorders has learning and attentional impairments and alterations in acetylcholine and kynurenic acid in prefrontal cortex. PLoS ONE,. doi:10.1371/journal.pone.0062189.

    PubMed Central  PubMed  Google Scholar 

  • Mikhail, F. M., Lose, E. J., Robin, N. H., Descartes, M. D., Rutledge, K. D., Rutledge, S. L., et al. (2011). Clinically relevant single gene or intragenic deletions encompassing critical neurodevelopmental genes in patients with developmental delay, mental retardation, and/or autism spectrum disorders. American Journal of Medical Genetics, Part A, 155, 2386–2396. doi:10.1002/ajmg.a.34177.

    Article  Google Scholar 

  • Murray, R. P., Bailey, W. C., Daniels, K., Bjornson, W. M., Kurnow, K., Connett, J. E., et al. (1996). Safety of nicotine polacrilex gum used by 3,094 participants in the Lung Health Study. Chest, 109, 438–445. doi:10.1378/chest.109.2.438.

    Article  PubMed  Google Scholar 

  • Newhouse, P., Kellar, K., Aisen, P., White, H., Wesnes, K., Coderre, E., et al. (2012). Nicotine treatment of mild cognitive impairment: A 6-month double-blind pilot clinical trial. Neurology, 78, 91–101. doi:10.1212/WNL.0b013e31823efcbb.

    Article  PubMed Central  PubMed  Google Scholar 

  • Perry, E. K., Lee, M. L., Martin-Ruiz, C. M., Court, J. A., Volsen, S. G., Merrit, J., et al. (2001). Cholinergic activity in autism: Abnormalities in the cerebral cortex and basal forebrain. The American Journal of Psychiatry, 158(7), 1058–1066.

    Article  PubMed  Google Scholar 

  • Picciotto, M. R., Higley, M. J., & Mineur, Y. S. (2012). Acetylcholine as a neuromodulator: Cholinergic signaling shapes nervous system function and behavior. Neuron, 76(1), 116–129. doi:10.1016/j.neuron.2012.08.036.

    Article  PubMed Central  PubMed  Google Scholar 

  • Rodgers, R. J. (1979). Effects of nicotine, mecamylamine, and hexamethonium on shock-induced fighting, pain reactivity, and locomotor behaviour in rats. Psychopharmacology (Berl), 66(1), 93–98.

    Article  Google Scholar 

  • Rosin, R. A., Levine, M. D., & Peskind, E. (2001). Transdermal nicotine for agitation in dementia. The American Journal of Geriatric Psychiatry: Official Journal of the American Association for Geriatric Psychiatry, 9(4), 443–444. doi:10.1176/appi.ajgp.9.4.443.

    Article  Google Scholar 

  • Srivastava, E. D., Russell, M. A., Feyerabend, C., Masterson, J. G., & Rhodes, J. (1991). Sensitivity and tolerance to nicotine in smokers and nonsmokers. Psychopharmacology (Berl), 105, 63–68. doi:10.1007/BF02316865.

    Article  Google Scholar 

  • Stigler, K. A., & McDougle, C. J. (2008). Pharmacotherapy of irritability in pervasive developmental disorders. Child and Adolescent Psychiatric Clinics of North America, 17(4), 739–752. doi:10.1016/j.chc.2008.06.002.

    Article  PubMed  Google Scholar 

  • Snaedal, J., Johannesson, T., Jonsson, J. E., & Gylfadottir, G. (1996). The effects of nicotine in dermal plaster on cognitive functions in patients with Alzheimer’s disease. Dementia (Basel, Switzerland) 7: 47–52.

  • Waldbillig, R. J. (1980). Suppressive effects of intraperitoneal and intraventricular injections of nicotine on muricide and shock-induced attack on conspecifics. Pharmacology, Biochemistry and Behavior, 12(4), 619–623.

    Article  PubMed  Google Scholar 

  • West, R., Hajek, P., Foulds, J., Nilsson, F., May, S., & Meadows, A. (2000). A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. Psychopharmacology (Berl), 149, 198–202. doi:10.1007/s002130000382.

    Article  Google Scholar 

  • White, H. K., & Levin, E. D. (1999). Four-week nicotine skin patch treatment effects on cognitive performance in Alzheimer’s disease. Psychopharmacology (Berl), 143, 158–165. doi:10.1007/s002130050931.

    Article  Google Scholar 

  • White, H. K., & Levin, E. D. (2004). Chronic transdermal nicotine patch treatment effects on cognitive performance in age-associated memory impairment. Psychopharmacology (Berl), 171, 465–471. doi:10.1007/s00213-003-1614-8.

    Article  Google Scholar 

  • Yasui, D. H., Scoles, H. A., Horike, S.-I., Meguro-Horike, M., Dunaway, K. W., Schroeder, D. I., & Lasalle, J. M. (2011). 15q11.2-13.3 chromatin analysis reveals epigenetic regulation of CHRNA7 with deficiencies in Rett and autism brain. Human Molecular Genetics, 20(22), 4311–4323. doi:10.1093/hmg/ddr357.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by National Institute of Mental Health T32MH014276 and T32MH19961 (ASL). We thank Dr. Roger Jou for constructive comments on the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gerrit I. Van Schalkwyk.

Additional information

Gerrit I. Van Schalkwyk and Alan S. Lewis have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Van Schalkwyk, G.I., Lewis, A.S., Qayyum, Z. et al. Reduction of Aggressive Episodes After Repeated Transdermal Nicotine Administration in a Hospitalized Adolescent with Autism Spectrum Disorder. J Autism Dev Disord 45, 3061–3066 (2015). https://doi.org/10.1007/s10803-015-2471-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10803-015-2471-0

Keywords

Navigation