Minocycline as adjunctive treatment to risperidone in children with autistic disorder: A randomized, double-blind placebo-controlled trial

Journal of Child and Adolescent Psychopharmacology

Volumn 26, Issue 9, 2016, Pages 784-791

  Ghaleiha, Ali ^a   Alikhani, Rosa ^b   Kazemi, Mohammad Reza ^c   Mohammadi, Mohammad Reza ^b   Mohammadinejad, Payam ^b   Zeinoddini, Atefeh ^b   Hamedi, Mehdi ^b   Shahriari, Mona ^b   Keshavarzi, Zahra ^a   Akhondzadeh, Shahin ^a  

^a HAMADAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^c AJA UNIVERSITY OF MEDICAL SCIENCES   (Iran)

Author keywords

Autistic disorder; Glutamate; Minocycline

Indexed keywords

MINOCYCLINE; PLACEBO; RISPERIDONE; NEUROLEPTIC AGENT;

ADD ON THERAPY; ADJUVANT THERAPY; ARTICLE; AUTISM; CHILD; CLINICAL ARTICLE; CONTROLLED STUDY; DIARRHEA; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG FATALITY; DRUG RESPONSE; DRUG SAFETY; FEMALE; HEADACHE; HUMAN; HYPERACTIVITY; INCREASED APPETITE; INSOMNIA; IRRITABILITY; LETHARGY; MALE; NAUSEA; PARALLEL DESIGN; PSYCHOSOCIAL WITHDRAWAL; RANDOMIZED CONTROLLED TRIAL; SCHOOL CHILD; SEDATION; SIDE EFFECT; STEREOTYPY; UNSPECIFIED SIDE EFFECT; COMBINATION DRUG THERAPY; DRUG EFFECTS; PATHOPHYSIOLOGY; PRESCHOOL CHILD; STATISTICAL MODEL; TREATMENT OUTCOME;

ANTIPSYCHOTIC AGENTS; AUTISTIC DISORDER; CHILD; CHILD, PRESCHOOL; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; IRRITABLE MOOD; LINEAR MODELS; MALE; MINOCYCLINE; RISPERIDONE; TREATMENT OUTCOME;

EID: 84997161386     PISSN: 10445463     EISSN: 15578992     Source Type: Journal    
DOI: 10.1089/cap.2015.0175     Document Type: Article

References (64)

1. Abdallah MW, Pearce BD, Larsen N, Greaves-Lord K, Nørgaard-Pedersen B, Hougaard DM, Mortensen EL, Grove J: Amniotic fluid MMP-9 and neurotrophins inautism spectrum disorders: An exploratory study. Autism Res 5:428-433, 2012.
2. Akhondzadeh S, Fallah J, Mohammadi MR, Imani R, Mohammadi M, Salehi B, Ghanizadeh A, Raznahan M, Mohebbi-Rasa S, Rezazadeh SA, Forghani S: Double-blindplacebo-controlled trial of pentoxifylline added to risperidone: Effects onaberrant behavior in children with autism. Prog Neuropsychopharmacol Biol Psychiatry 34:32-36, 2010.
3. Akhondzadeh S, Tajdar H, Mohammadi MR, Mohammadi M, Nouroozinejad GH, Shabstari OL, Ghelichnia HA: A double-blind placebo controlled trial of piracetamadded to risperidone in patients with autistic disorder. Child Psychiatry Hum Dev 39:237-245, 2008.
4. Aman MG, Farmer CA, Hollway J, Arnold LE: Treatment of inattention, overactivity, and impulsiveness in autism spectrum disorders. Child Adolesc Psychiatr Clin N Am 17:713-738, vii, 2008.
5. Aman MG, Singh NN, Stewart AW, Field CJ: The Aberrant Behavior Checklist: A behavior rating scale for the assessment of treatment effects. Am J Ment Defic 89:485-491, 1985.
6. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision. Washington, DC: American Psychiatric Association; 2000.
7. Asadabadi M, Mohammadi MR, Ghanizadeh A, Modabbernia A, Ashrafi M, Hassanzadeh E, Forghani S, Akhondzadeh S: Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: A randomized, double-blind, placebo-controlled trial. Psychopharmacology (Berl) 225:51-59, 2013.
8. Ashwood P, Corbett BA, Kantor A, Schulman H, Van de Water J, Amaral DG: In search of cellular immunophenotypes in the blood of children with autism. PLoS One 6:e19299, 2011.
9. Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J: Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 25:40-45, 2011.
10. Bilousova TV, Dansie L, Ngo M, Aye J, Charles JR, Ethell DW, Ethell IM: Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model. J Med Genet 46:94-102, 2009.
11. Boris M, Kaiser CC, Goldblatt A, Elice MW, Edelson SM, Adams JB, Feinstein DL: Effect of pioglitazone treatment on behavioral symptoms in autistic children. J Neuroinflammation 4, 2007.
12. Brundula V, Rewcastle NB, Metz LM, Bernard CC, Yong VW: Targeting leukocyte MMPs and transmigration: Minocycline as a potential therapy for multiple sclerosis. Brain 125:1297-1308, 2002.
13. Carty ML, Wixey JA, Colditz PB, Buller KM: Post-insult minocycline treatment attenuates hypoxia-ischemia-induced neuroinflammation and white matter injury in the neonatal rat: A comparison of two different dose regimens. Int J Dev Neurosci 26:477-485, 2008.
14. Chaste P, Leboyer M: Autism risk factors: Genes, environment, and gene-environment interactions. Dialogues Clin Neurosci 14:281- 292, 2012.
15. Chaves C, Marque CR, Trzesniak C, Machado de Sousa JP, Zuardi AW, Crippa JA, Dursun SM, Hallak JE: Glutamate-N-methyl-daspartate receptor modulation and minocycline for the treatment of patients with schizophrenia: An update. Braz J Med Biol Res 42:1002-1014, 2009.
16. Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM: Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 6:797-801, 2000.
17. Chouinard G, Margolese HC: Manual for the Extrapyramidal Symptom Rating Scale (ESRS). Schizophr Res 76:247-265, 2005.
18. Dziembowska M, Pretto DI, Janusz A, Kaczmarek L, Leigh MJ, Gabriel N, Durbin-Johnson B, Hagerman RJ, Tassone F: High MMP-9 activity levels in fragile X syndrome are lowered by minocycline. Am J Med Genet A 161A:1897-1903, 2013.
19. Elewa HF, Hilali H, Hess DC, Machado LS, Fagan SC: Minocycline for short-term neuroprotection. Pharmacotherapy 26:515-521, 2006.
20. Elsabbagh M, Divan G, Koh YJ, Kim YS, Kauchali S, Marcin C, Montiel-Nava C, Patel V, Paula CS, Wang C, Yasamy MT, Fombonne E: Global prevalence of autism and other pervasive developmental disorders. Autism Res 5:160-179, 2012.
21. Erickson CA, Posey DJ, Stigler KA, Mullett J, Katschke AR, McDougle CJ: A retrospective study of memantine in children and adolescents with pervasive developmental disorders. Psychopharmacology (Berl) 191:141-147, 2007.
22. Ganguly K, Rejmak E, Mikosz M, Nikolaev E, Knapska E, Kaczmarek L: Matrix metalloproteinase (MMP) 9 transcription in mouse brain induced by fear learning. J Biol Chem 288:20978-20991, 2013.
23. Ghaleiha A, Asadabadi M, Mohammadi MR, Shahei M, Tabrizi M, Hajiaghaee R, Hassanzadeh E, Akhondzadeh S: Memantine as adjunctive treatment to risperidone in children with autistic disorder: A randomized, double-blind, placebo-controlled trial. Int J Neuropsychopharmacol 16:783-789, 2013a.
24. Ghaleiha A, Ghyasvand M, Mohammadi MR, Farokhnia M, Yadegari N, Tabrizi M, Hajiaghaee R, Yekehtaz H, Akhondzadeh S: Galantamine efficacy and tolerability as an augmentative therapy in autistic children: A randomized, double-blind, placebo-controlled trial. J Psychopharmacol 28:677-685, 2013b.
25. Ghaleiha A, Mohammadi E, Mohammadi MR, Farokhnia M, Modabbernia A, Yekehtaz H, Ashrafi M, Hassanzadeh E, Akhondzadeh S: Riluzole as an adjunctive therapy to risperidone for the treatment of irritability in children with autistic disorder: A double-blind, placebo-controlled, randomized trial. Paediatr Drugs 15:505-514, 2013c.
26. Ghaleiha A, Rasa SM, Nikoo M, Farokhnia M, Mohammadi MR, Akhondzadeh S: A pilot double-blind placebo-controlled trial of pioglitazone as adjunctive treatment to risperidone: Effects on aberrant behavior in children with autism. Psychiatry Res 30: 229:181-187, 2015.
27. Grieco JC, Ciarlone SL, Gieron-Korthals M, Schoenberg MR, Smith AG, Philpot RM, Heussler HS, Banko JL, Weeber EJ: An openlabel pilot trial of minocycline in children as a treatment for Angelman syndrome. BMC Neurol 14:232, 2014.
28. Gupta S, Aggarwal S, Rashanravan B, Lee T: Th1- and Th2-like cytokines in CD4+ and CD8+ T cells in autism. J Neuroimmunol 85:106-109, 1998.
29. Hansen SN, Schendel DE, Parner ET: Explaining the increase in the prevalence of autism spectrum disorders: The proportion attributable to changes in reporting practices. JAMA Pediatr 169:56-62, 2015.
30. Harris SW, Hessl D, Goodlin-Jones B, Ferranti J, Bacalman S, Barbato I, Tassone F, Hagerman PJ, Herman H, Hagerman RJ: Autism profiles of males with fragile X syndrome. Am J Ment Retard 113:427-438, 2008.
31. Hasanzadeh E, Mohammadi MR, Ghanizadeh A, Rezazadeh SA, Tabrizi M, Rezaei F, Akhondzadeh S: A double-blind placebo controlled trial of Ginkgo biloba added torisperidone in patients with autistic disorders. Child Psychiatry Hum Dev 43:674-682, 2012.
32. Heuer L, Ashwood P, Schauer J, Goines P, Krakowiak P, Hertz- Picciotto I, Hansen R, Croen LA, Pessah IN, Van de Water J: Reduced levels of immunoglobulin in children with autism correlates with behavioral symptoms. Autism Res 1:275-283, 2008.
33. Jin WJ, Feng SW, Feng Z, Lu SM, Qi T, Qian YN: Minocycline improves postoperative cognitive impairment in aged mice by inhibiting astrocytic activation. Neuroreport 25:1-6, 2014.
34. Jyonouchi H, Sun S, Le H: Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. J Neuroimmunol 120:170-179, 2001.
35. Kaplan A, Spiller KJ, Towne C, Kanning KC, Choe GT, Geber A, Akay T, Aebischer P, Henderson CE: Neuronal matrix metalloproteinase-9 is a determinant of selective neurodegeneration. Neuron 81:333-348, 2014.
36. Kenny EM, Cormican P, Furlong S, Heron E, Kenny G, Fahey C, Kelleher E, Ennis S, Tropea D, Anney R, Corvin AP, Donohoe G, Gallagher L, Gill M, Morris DW: Excess of rare novel loss-offunction variants in synaptic genes in schizophrenia and autism spectrum disorders. Mol Psychiatry 19:872-879, 2014.
37. Khodaie-Ardakani MR, Mirshafiee O, Farokhnia M, Tajdini M, Hosseini SM, Modabbernia A, Rezaei F, Salehi B, Yekehtaz H, Ashrafi M, Tabrizi M, Akhondzadeh S: Minocycline add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: Randomized double-blind placebo-controlled study. Psychiatry Res 215:540-546, 2014.
38. Lee EJ, Choi SY, Kim E: NMDA receptor dysfunction in autism spectrum disorders. Curr Opin Pharmacol 20:8-13, 2015.
39. Leigh MJ, Nguyen DV, Mu Y, Winarni TI, Schneider A, Chechi T, Polussa J, Doucet P, Tassone F, Rivera SM, Hessl D, Hagerman RJ: A randomized double-blind, placebo-controlled trial of minocycline in children and adolescents with fragile x syndrome. J Dev Behav Pediatr 34:147-155, 2013.
40. Lord C, Rutter M, Le Couteur A: Autism diagnostic interviewrevised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. J Autism Dev Disord 24:659-685, 1994.
41. Miyaoka T, Wake R, Furuya M, Liaury K, Ieda M, Kawakami K, Tsuchie K, Taki M, Ishihara K, Araki T, Horiguchi J: Minocycline as adjunctive therapy for patients with unipolar psychotic depression: An open-label study. Prog Neuropsychopharmacol Biol Psychiatry 37:222-226, 2012.
42. Miyaoka T, Yasukawa R, Yasuda H, Hayashida M, Inagaki T, Horiguchi J: Minocycline as adjunctive therapy for schizophrenia: An open-label study. Clin Neuropharmacol 31:287-292, 2008.
43. Mohammadi MR, Yadegari N, Hassanzadeh E, Farokhnia M, Yekehtaz H, Mirshafiee O, Akhondzadeh S: Double-blind, placebocontrolled trial of risperidone plus amantadine in children with autism: A 10-week randomized study. Clin Neuropharmacol 36:179-184, 2013.
44. Morgan JT, Chana G, Pardo CA, Achim C, Semendeferi K, Buckwalter J, Courchesne E, Everall IP: Microglial activation and increased microglial density observed in the dorsolateral prefrontal cortex in autism. Biol Psychiatry 68:368-376, 2010.
45. Myers SM, Johnson CP; and American Academy of Pediatrics Council on Children with Disabilities: Management of children with autism spectrum disorders. Pediatrics 120:1162-1182, 2007.
46. Niederhofer H: Glutamate antagonists seem to be slightly effective in psychopharmacologic treatment of autism. J Clin Psychopharmacol 27:317-318, 2007.
47. Nikoo M, Radnia H, Farokhnia M, Mohammadi MR, Akhondzadeh S: N-acetylcysteine as an adjunctive therapy to risperidone for treatment of irritability in autism: A randomized, double-blind, placebocontrolled clinical trial of efficacy and safety. Clin Neuropharmacol 38:11-17, 2015.
48. NINDS NET-PD Investigators: A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology. 66:664-671, 2006.
49. NINDS NET-PD Investigators: A pilot clinical trial of creatine and minocycline in early Parkinson disease: 18-month results. Clin Neuropharmacol. 31:141-150, 2008.
50. O'Roak BJ, Vives L, Fu W, Egertson JD, Stanaway IB, Phelps IG, Carvill G, Kumar A, Lee C, Ankenman K, Munson J, Hiatt JB, Turner EH, Levy R, O'Day DR, Krumm N, Coe BP, Martin BK, Borenstein E, Nickerson DA, Mefford HC, Doherty D, Akey JM, Bernier R, Eichler EE, Shendure J: Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders. Science 338:1619-1622, 2012a.
51. O'Roak BJ, Vives L, Girirajan S, Karakoc E, Krumm N, Coe BP, Levy R, Ko A, Lee C, Smith JD, Turner EH, Stanaway IB, Vernot B, Malig M, Baker C, Reilly B, Akey JM, Borenstein E, Rieder MJ, Nickerson DA, Bernier R, Shendure J, Eichler EE: Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations. Nature 485:246-250, 2012b.
52. Pardo CA, Buckley A, Thurm A, Lee LC, Azhagiri A, Neville DM, Swedo SE: A pilot open-label trial of minocycline in patients with autism and regressive features. J Neurodev Disord 5:9, 2013.
53. Paribello C, Tao L, Folino A, Berry-Kravis E, Tranfaglia M, Ethell IM, Ethell DW: Open-label add-on treatment trial of minocycline in fragile X syndrome. BMC Neurol 10:91, 2010.
54. Rezaei V, Mohammadi MR, Ghanizadeh A, Sahraian A, Tabrizi M, Rezazadeh SA, Akhondzadeh S: Double-blind, placebo-controlled trial of risperidone plustopiramate in children with autistic disorder. Prog Neuropsychopharmacol Biol Psychiatry 34:1269-1272, 2010.
55. Schildknecht S, Pape R, Muller N, Robotta M, Marquardt A, Burkle A, Drescher M, Leist M: Neuroprotection by minocycline caused by direct and specific scavenging of peroxynitrite. J Biol Chem 286:4991-5002, 2011.
56. Singh VK, Warren R, Averett R, Ghaziuddin M: Circulating autoantibodies to neuronal and glial filament proteins in autism. Pediatr Neurol 17:88-90, 1997.
57. Stolp HB, Ek CJ, Johansson PA, Dziegielewska KM, Potter AM, Habgood MD, Saunders NR: Effect of minocycline on inflammationinduced damage to the blood-brain barrier and white matter during development. Eur J Neurosci 26:3465-3474, 2007.
58. Suk K: Minocycline suppresses hypoxic activation of rodent microglia in culture. Neurosci Lett 366:167-171, 2004.
59. Tikka TM, Koistinaho JE: Minocycline provides neuroprotection against N-methyl-d-aspartate neurotoxicity by inhibiting microglia. J Immunol 166:7527-7533, 2001.
60. Towbin KE: Strategies for pharmacologic treatment of high functioning autism and Asperger syndrome. Child Adolesc Psychiatr Clin N Am 12:23-45, 2003.
61. Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA: Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 57:67-81, 2005.
62. WangLW, Berry-KravisE, HagermanRJ: FragileX:Leading theway for targeted treatments in autism. Neurotherapeutics 7:264-274, 2010.
63. Zeinoddini A, Ahadi M, Farokhnia M, Rezaei F, Tabrizi M, Akhondzadeh S: L-lysine as an adjunct to risperidone in patients with chronic schizophrenia: A double-blind, placebo-controlled, randomized trial. J Psychiatr Res 59:125-131, 2014.
64. Zhang W, Narayanan M, Friedlander RM: Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS. Ann Neurol 53:267-270, 2003.