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Theoharis C. Theoharides, BA, MS, MD, PhD*Þþ§ Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders affecting approx- imately 1% of children and characterized by varying degrees of deficiencies in social interac- tions, concentration, language, learning, and as stereotypic behaviors.1Y3 Many children develop ASDby regression at approximately age 3 years, often after a specific event such as vaccination or infec-tion, although they were developing normally.4,5 Some gene variants in ASD confer altered vulnera-bility to environmental stressors and exposures.6 Behavioral interventions alone are not sufficient to adequately address the disruptive nature of ASD symptoms and their persistence throughout life.7,8 Instead, psychotropic drug therapy is typicallyused to treat irritability, hyperactivity, inattention, obsessive-compulsive symptoms, aggression, andself-injury.9Y11 Many children with ASD also develop seizures with no apparent underlying patholog-ical cause,12Y14 but traditional antiseizure medications seem to worsen ASD symptoms.15 Overall, 70% of children with ASD take at least 10 different drugs, dietary supplements, vitamins, or other treatments10,16Y18 including intravenous immunoglobulin.19 Secretin is also commonly usedalthough it has no effect20 and could lead to the risk of possible inflammatory complications.21 Thereis little attention to unwanted drug-drug or drug-supplement interactions.
A cross-sectional study of a child and adolescent psychiatric sample nationwide in Denmark found that the prevalence of treatment with antipsychotic medications was 6.4%.22 Some pediatricpatients were prescribed additional medications, with 24% receiving antidepressants, 8% receivingsedative medications, and 4% receiving psychostimulants.22 Many children with ASD also take anti-psychotic medications.23 In a national sample of children and adolescents with ASD, the percentageof outpatients being treated with antipsychotic medications was almost 30%.24 Risperidone is the only antipsychotic drug with Food and Drug Administration approval for treating aggressiveness and stereotypic and self-injurious behaviors in ASD.25 This class of drugsalso includes haloperidol and the newer ‘‘atypical’’ compounds.26,27 Aripiprazole is an atypical anti-psychotic approved for treating irritability in children with ASD.28 A review of 21 randomizedplacebo-controlled trials using psychopharmacologic agents29 showed that only risperidone foraggressive behavior30,31 and methylphenidate for hyperactivity32 produced significant improvementin more than one study.29 A recent systemic review of medical treatments for children with ASDconcluded that only risperidone and aripiprazole had some benefit, but they had significant adverseeffects.33 For instance, they result in significant weight gain, whereas haloperidol use is limitedowing to higher risks of extrapyramidal effects and tardive dyskinesia. Another study of childrenwith ASD from a national registry showed that 35% of children with ASD received psychotropicmedications, but adding a second-generation antipsychotic to the stimulant did not have any sig-nificant additional benefit on any of the parameters studied.34 Moreover, the long-term safety ofantipsychotics in children remains unknown.23 Many children with ASD are also prescribed antidepressants, especially selective serotonin reuptake inhibitors (SSRIs).9 However, 2 recent reviews concluded that there is insufficient evidencefor any benefit of SSRIs or other psychotropic drugs in ASD.33,35 In fact, the results of a recent trial From the *Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Molecular Physiology andPharmacology, and Departments of †Biochemistry, ‡Internal Medicine, and §Psychiatry, Tufts University School of Medi-cine, ||Department of Pharmacy, Tufts Medical Center, Boston, MA.
Reprints: Theoharis C. Theoharides, BA, MS, MD, PhD, Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine,136 Harrison Avenue, Boston, MA 02111, USA (e-mail: theoharis.theoharides@tufts.edu).
Copyright * 2012 by Lippincott Williams & WilkinsISSN: 0271-0749DOI: 10.1097/JCP.0b013e31825e00e4 Journal of Clinical Psychopharmacology & Volume 32, Number 4, August 2012 Copyright 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Journal of Clinical Psychopharmacology & Volume 32, Number 4, August 2012 FIGURE 1. Diagrammatic representation of some of the most important interactions commonly seen among treatment of ASD.
NSAIDs, nonsteroidal anti-inflammatory drugs.
indicate that one SSRI, citalopram, not only was not effective for This broad category of flavonoids also includes the subgroups children with ASD but may actually be detrimental.36 These of flavonols (quercetin) and flavones (luteolin).51 Oral absorption findings highlight the fact that psychotropic agents have different and bioavailability of flavonoids are limited.54 These substances have varying antioxidant and anti-inflammatory properties, mostlydue to the degree of hydroxylation of their phenolic rings.51 The main metabolism of a flavonol such as quercetin is by glucur- Autistic children seem to have decreased capacity to sul- onidation (quercetin-3¶-glucuronide) and sulfation (quercetin-3¶- foconjugate acetaminophen and therefore are unable to effec- sulfate).55,56 Some children with ASD seem to be intolerant to tively metabolize particularly phenolic amines such as polyphenols, presenting with increased hyperactivity. Not all dopamine, tyramine, and serotonin.38 Some authors even hy- phenolic compounds carry the same potential risk. For instance, pothesized that the increased rate of ASD may be at least pycnogenol from pine bark has 15 hydroxyl groups and naringin partly due to acetaminophen39 through decrease of glutathione has 8 hydroxyl groups, as compared to quercetin’s 5 hydroxyl levels (Fig. 1).40 In view of this, parents have been shifting to groups and luteolin’s 4 hydroxyl groups. More detailed informa- ibuprofen. However, a recent study reported that using nonste- tion on interactions in general can be found elsewhere.53,57 roidal anti-inflammatory drugs, such as ibuprofen, with SSRIsreduces the antidepressant effect of the latter41 while increasing the risk of GI bleeding with SSRIs (Fig. 1).42 Quercetin and its structural analog luteolin are generally Taking multiple drugs increases the risk of adverse reac- safe.58,59 In addition, a number of papers report protective effects tions, especially in children and neonates.43 In a recent study of quercetin and luteolin both in the brain and liver.60,61 For ex- of spontaneous reporting of adverse drug-drug interactions ample, quercetin prevented liver toxicity induced by acetamino- in Italy, the incidence was 9.8% for 2 drugs but increased to phen62 and reduced haloperidol-induced dyskinesia in rodents.63 88.3% for 8 drugs or more.44 There is less information on drug- Quercetin also prevented methylmercury-induced DNA damage,64 supplement interactions. However, it was reported that 33.4% of whereas luteolin prevented mercury and thimerosal-induced in- patients using antipsychotics also took traditional Chinese med- flammatory mediator release from immune cells.65 Luteolin was icine concurrently; 7.2% of these patients had worse outcomes recently shown to inhibit microglial activation and is also neu- compared to 4.4% of those using antipsychotics alone.45 roprotective.66Y72 In fact, a luteolin analog was shown to mimic Risperidone is metabolized and can contribute to numer- the activity of brain-derived neurotrophic factor.73 A recent re- ous drug interactions because it is metabolized by CYP3A4, port also indicated that phenols in olive leaf extract can prevent the most common drug-metabolizing enzyme.46 Many children blood-brain barrier disruption,74 which has been proposed as have GI problems47 and are given numerous medications that a key pathogenetic factor in ASD.18,75 Formulations containing change the GI flora. In particular, they are often given antifungal luteolin in olive kernel extract are, therefore, likely not only to medications,16,17 such as fluconazole, which is a CYP3A inhib- permit higher absorption of luteolin in the brain but also provide itor and can affect the metabolism of many drugs (Fig. 1).48 the additional benefit of blood-brain barrier protection.
Moreover, concurrent use of fluconazole and amitriptyline has re- Patients may still develop idiosyncratic reactions through sulted in syncope49 and in serotonin toxicity presenting with de- activation of a unique immune cell, the mast cell, found in all lirium when given together with citalopram.50 tissues and responsible for allergic and inflammatory reactions.76The likelihood of idiosyncratic reactions may, therefore, be in- creased in the subgroup of patients with ASD who seem to have Treatment approaches for ASD have featured the use ‘‘allergic-like symptoms’’ 77 that involve mast cell activation by of polyphenolic compounds such as anthocyanidins, curcumin, pycnogenol (pine bark extract), green tea, and ginseng extract.
Given the high percentage of children with ASD being All of these are natural polyphenols present in plants, fruits, treated with multiple pharmacologic and nonpharmacologic in- vegetables, and tea.51 Oral administration of curcumin led to terventions, attention to interactions is a vital, but often overlooked, decreased intestinal P-glycoprotein and CYP3A and increased aspect of clinical management. Awareness of efficacy, safety, and serum levels of their respective substrates celiprolol and mid- unwanted interactions could increase the benefits of treatment azolam (Fig. 1).52 The main polyphenolic ingredients of grape- fruit juice, the coumarins, also inhibit the liver enzyme CYP3A,affecting the metabolism and/or activation of numerous drugs and natural substances, whereas the main polyphenolic flavonoid TCT is the inventor of US patents Nos. 6,624,148; 6,689, naringin can inhibit the organic anion-transporting polypeptide 748; 6,984,667, and EPO 1365777, which cover methods and family responsible for the transport of many hormones and drugs.53 compositions of mast cell blockers, including flavonoids; US Copyright 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Journal of Clinical Psychopharmacology & Volume 32, Number 4, August 2012 patents 7,906,153 and 12/861,152 (allowed) for treatment of medication in child and adolescent psychiatric treatment in Denmark.
neuroinflammatory conditions, as well as US patent applications A cross-sectional survey. Nord J Psychiatry. 2008;62:472Y480.
No. 12/534,571 and No. 13/009,282 for the diagnosis and treat- 23. Posey DJ, Stigler KA, Erickson CA, et al. Antipsychotics in the treatment of autism. J Clin Invest. 2008;118:6Y14.
24. Gerhard T, Chavez B, Olfson M, et al. National patterns in the outpatient pharmacological management of children and adolescents 1. Johnson CP, Myers SM. Identification and evaluation of children with with autism spectrum disorder. J Clin Psychopharmacol.
autism spectrum disorders. Pediatrics. 2007;120:1183Y1215.
2. Fombonne E. Epidemiology of pervasive developmental disorders.
25. McDougle CJ, Holmes JP, Carlson DC, et al. A double-blind, placebo-controlled study of risperidone in adults with autistic disorderand other pervasive developmental disorders. Arch Gen Psychiatry.
3. Kogan MD, Blumberg SJ, Schieve LA, et al. Prevalence of parent-reported diagnosis of autism spectrum disorder among childrenin the US, 2007. Pediatrics. 2009;5:1395Y1403.
26. Chavez B, Chavez-Brown M, Sopko MA Jr, et al. Atypical antipsychotics in children with pervasive developmental disorders.
4. Volkmar FR. Understanding the social brain in autism Dev Psychobiol.
27. McDougle CJ, Stigler KA, Erickson CA, et al. Atypical antipsychotics 5. Blenner S, Reddy A, Augustyn M. Diagnosis and management of in children and adolescents with autistic and other pervasive autism in childhood. BMJ. 2011;343:d6238.
developmental disorders. J Clin Psychiatry. 2008;69(suppl 4):15Y20.
6. Herbert MR. Contributions of the environment and environmentally 28. Curran MP. Aripiprazole: in the treatment of irritability associated vulnerable physiology to autism spectrum disorders. Curr Opin with autistic disorder in pediatric patients. Paediatr Drugs.
7. Lang R, Mahoney R, El ZF, et al. Evidence to practice: treatment 29. Parikh MS, Kolevzon A, Hollander E. Psychopharmacology of of anxiety in individuals with autism spectrum disorders.
aggression in children and adolescents with autism: a critical review Neuropsychiatr Dis Treat. 2011;7:27Y30.
of efficacy and tolerability. J Child Adolesc Psychopharmacol.
8. Warren Z, McPheeters ML, Sathe N, et al. A systematic review of early intensive intervention for autism spectrum disorders.
30. McCracken JT, McGough J, Shah B, et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med.
9. Nazeer A. Psychopharmacology of autistic spectrum disorders in children and adolescents. Pediatr Clin North Am. 2011;58:85Y97.
31. Scott LJ, Dhillon S. Risperidone: a review of its use in the treatment 10. Francis K. Autism interventions: a critical update. Dev Med Child of irritability associated with autistic disorder in children and adolescents. Paediatr Drugs. 2007;9:343Y354.
11. Munshi KR, Gonzalez-Heydrich J, Augenstein T, et al. Evidence-based 32. Research Units on Pediatric Psychparmacology Autism Network.
treatment approach to autism spectrum disorders. Pediatr Ann.
Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch Gen Psychiatry.
2005;62:1266Y1274.
12. Hughes JR. A review of recent reports on autism: 1000 studies published in 2007. Epilepsy Behav. 2008;13:425Y437.
33. Williams K, Wheeler DM, Silove N, et al. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane 13. Trevathan E. Seizures and epilepsy among children with language regression and autistic spectrum disorders. J Child Neurol.
2004;19(suppl 1):S49YS57.
34. Rosenberg RE, Mandell DS, Farmer JE, et al. Psychotropic medication use among children with autism spectrum disorders 14. Tuchman R, Rapin I. Epilepsy in autism. Lancet Neurol.
enrolled in a national registry, 2007-2008. J Autism Dev Disord.
15. Theoharides TC, Zhang B. Neuro-inflammation, blood-brain barrier, 35. McPheeters ML, Warren Z, Sathe N, et al. A systematic review seizures and autism. J Neuroinflammation. 2011;8:168.
of medical treatments for children with autism spectrum disorders.
16. Adams JB. Summary of Biomedical Treatments for Autism. ARI 36. King BH, Hollander E, Sikich L, et al. Lack of efficacy of citalopram 17. Bradstreet JJ, Smith S, Baral M, et al. Biomarker-guided interventions in children with autism spectrum disorders and high levels of repetitive of clinically relevant conditions associated with autism spectrum behavior: citalopram ineffective in children with autism. Arch Gen disorders and attention deficit hyperactivity disorder. Altern Med Rev.
37. Correll CU, Kratochvil CJ, March JS. Developments in pediatric 18. Theoharides TC, Doyle R, Francis K, et al. Novel therapeutic targets psychopharmacology: focus on stimulants, antidepressants, and for autism. Trends Pharmacol Sci. 2008;29:375Y382.
antipsychotics. J Clin Psychiatry. 2011;72:655Y670.
19. Feasby T, Banwell B, Benstead T, et al. Guidelines on the use of 38. Alberti A, Pirrone P, Elia M, et al. Sulphation deficit in intravenous immune globulin for neurologic conditions. Transfus Med ‘‘low-functioning’’ autistic children: a pilot study. Biol Psychiatry.
20. Krishnaswami S, McPheeters ML, Veenstra-Vanderweele J. A 39. Becker KG, Schultz ST. Similarities in features of autism and asthma systematic review of secretin for children with autism spectrum and a possible link to acetaminophen use. Med Hypotheses.
disorders. Pediatrics. 2011;127:e1322Ye1325.
21. Cunningham-Rundles C. Key aspects for successful immunoglobulin 40. Deth R, Muratore C, Benzecry J, et al. How environmental and therapy of primary immunodeficiencies. Clin Exp Immunol.
genetic factors combine to cause autism: a redox/methylation hypothesis. Neurotoxicology. 2008;29:190Y201.
22. Deurell M, Weischer M, Pagsberg AK, et al. The use of antipsychotic 41. Warner-Schmidt JL, Vanover KE, Chen EY, et al. Antidepressant Copyright 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Journal of Clinical Psychopharmacology & Volume 32, Number 4, August 2012 effects of selective serotonin reuptake inhibitors (SSRIs) are attenuated 61. Janbaz KH, Saeed SA, Gilani AH. Protective effect of rutin on by antiinflammatory drugs in mice and humans. Proc Natl Acad Sci paracetamol- and CCl4-induced hepatotoxicity in rodents. Fitoterapia.
42. Theoharides TC, Asadi S, Weng Z, et al. Serotonin-selective reuptake 62. Yousef MI, Omar SA, El-Guendi MI, et al. Potential protective inhibitors and nonsteroidal anti-inflammatory drugs-important effects of quercetin and curcumin on paracetamol-induced considerations of adverse interactions especially for the treatment histological changes, oxidative stress, impaired liver and kidney of myalgic encephalomyelitis/chronic fatigue syndrome1. J Clin functions and haematotoxicity in rat. Food Chem Toxicol.
43. de Wildt SN. Profound changes in drug metabolism enzymes 63. Naidu PS, Singh A, Kulkarni SK. Quercetin, a bioflavonoid, attenuates and possible effects on drug therapy in neonates and children.
haloperidol-induced orofacial dyskinesia. Neuropharmacology.
Expert Opin Drug Metab Toxicol. 2011;7:935Y948.
44. Leone R, Magro L, Moretti U, et al. Identifying adverse drug reactions 64. Barcelos GR, Grotto D, Serpeloni JM, et al. Protective properties associated with drug-drug interactions: data mining of a spontaneous of quercetin against DNA damage and oxidative stress induced reporting database in Italy. Drug Saf. 2010;33:667Y675.
by methylmercury in rats. Arch Toxicol. 2011;85(9):1151Y1157.
45. Zhang ZJ, Tan QR, Tong Y, et al. An epidemiological study of concomitant use of Chinese medicine and antipsychotics in 65. Asadi S, Zhang B, Weng Z, et al. Luteolin and thiosalicylate inhibit schizophrenic patients: implication for herb-drug interaction.
HgCl(2) and thimerosal-induced VEGF release from human mast cells. Int J Immunopathol Pharmacol. 2010;23:1015Y1020.
46. Berecz R, Dorado P, De La RA, et al. The role of cytochrome P450 66. Chen HQ, Jin ZY, Wang XJ, et al. Luteolin protects dopaminergic enzymes in the metabolism of risperidone and its clinical relevance neurons from inflammation-induced injury through inhibition of for drug interactions. Curr Drug Targets. 2004;5:573Y579.
microglial activation. Neurosci Lett. 2008;448:175Y179.
47. Buie T, Fuchs GJ III, Furuta GT, et al. Recommendations for 67. Dirscherl K, Karlstetter M, Ebert S, et al. Luteolin triggers global evaluation and treatment of common gastrointestinal problems in changes in the microglial transcriptome leading to a unique children with ASDs. Pediatrics. 2010;125(suppl 1):S19YS29.
anti-inflammatory and neuroprotective phenotype. J Neuroinflammation.
48. Ragueneau-Majlessi I, Boulenc X, Rauch C, et al. Quantitative correlations among CYP3A sensitive substrates and inhibitors: 68. Jang S, Dilger RN, Johnson RW. Luteolin inhibits microglia and literature analysis. Curr Drug Metab. 2007;8:810Y814.
alters hippocampal-dependent spatial working memory in aged mice.
49. Robinson RF, Nahata MC, Olshefski RS. Syncope associated with concurrent amitriptyline and fluconazole therapy. Ann Pharmacother.
69. Kimata M, Shichijo M, Miura T, et al. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from 50. Levin TT, Cortes-Ladino A, Weiss M, et al. Life-threatening human cultured mast cells. Clin Exp Allergy. 2000;30:501Y508.
serotonin toxicity due to a citalopram-fluconazole drug interaction: 70. Kao TK, Ou YC, Lin SY, et al. Luteolin inhibits cytokine expression case reports and discussion. Gen Hosp Psychiatry. 2008;30:372Y377.
in endotoxin/cytokine-stimulated microglia. J Nutr Biochem.
51. Middleton E Jr, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart 71. Kempuraj D, Tagen M, Iliopoulou BP, et al. Luteolin inhibits myelin disease and cancer. Pharmacol Rev. 2000;52:673Y751.
basic protein-induced human mast cell activation and mast cell 52. Zhang W, Tan TM, Lim LY. Impact of curcumin-induced changes in dependent stimulation of Jurkat T cells. Br J Pharmacol.
P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral celiprolol and midazolam in rats. Drug Metab Dispos.
72. Verbeek R, Plomp AC, van Tol EA, et al. The flavones luteolin and apigenin inhibit in vitro antigen-specific proliferation and 53. Hanley MJ, Cancalon P, Widmer WW, et al. The effect of grapefruit interferon-gamma production by murine and human autoimmune juice on drug disposition. Expert Opin Drug Metab Toxicol.
T cells. Biochem Pharmacol. 2004;68:621Y629.
73. Jang SW, Liu X, Yepes M, et al. A selective TrkB agonist with 54. Erlund I, Kosonen T, Alfthan G, et al. Pharmacokinetics of quercetin potent neurotrophic activities by 7,8-dihydroxyflavone. Proc Natl from quercetin aglycone and rutin in healthy volunteers. Eur J Clin 74. Mohagheghi F, Bigdeli MR, Rasoulian B, et al. The neuroprotective 55. Manach C, Donovan JL. Pharmacokinetics and metabolism of dietary effect of olive leaf extract is related to improved blood-brain barrier flavonoids in humans. Free Radic Res. 2004;38:771Y785.
permeability and brain edema in rat with experimental focal cerebral 56. Walle T. Absorption and metabolism of flavonoids. Free Radic Biol ischemia. Phytomedicine. 2011;18:170Y175.
75. Theoharides TC, Doyle R. Autism, gut-blood-brain barrier and mast 57. Theoharides TC. Essentials of pharmacology. In: Theoharides TC, ed.
cells. J Clin Psychopharmacol. 2008;28:479Y483.
Essentials of Pharmacology. Boston, MA: Little, Brown & Co.; 1986.
76. Theoharides TC, Alysandratos KD, Angelidou A, et al. Mast cells 58. Formica JV, Regelson W. Review of the biology of quercetin and and inflammation. Biochim Biophys Acta. 2010;1822:21Y33.
related bioflavonoids. Food Chem Toxicol. 1995;33:1061Y1080.
77. Angelidou A, Alysandratos KD, Asadi S, et al. Brief report: 59. Li L, Gu L, Chen Z, et al. Toxicity study of ethanolic extract of ‘‘allergic symptoms’’ in children with autism spectrum disorders.
Chrysanthemum morifolium in rats. J Food Sci. 2010;75:T105YT109.
More than meets the eye? J Autism Dev Disord. 2011;41: 60. Domitrovic R, Jakovac H, Milin C, et al. Dose- and time-dependent effects of luteolin on carbon tetrachloride-induced hepatotoxicity 78. Theoharides TC, Angelidou A, Alysandratos KD, et al. Mast cell in mice. Exp Toxicol Pathol. 2009;61:581Y589.
activation and autism. Biochim Biophys Acta. 2012;1822:34Y41.
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