Childhood Disintegrative Disorder Treatment & Management
- Author: Bettina E Bernstein, DO; Chief Editor: Caroly Pataki, MD more...
The principles of therapy for childhood disintegrative disorder are generally supportive in nature but do include specific behavioral interventions designed to halt behavioral deterioration and to improve communication, self-help, and social skills, thereby stabilizing the child’s reality testing scores and global functional level.
No known medications address the core processes of childhood disintegrative disorder. No specific medications treat this disorder; generally, medications only address specific symptoms. Only haloperidol and risperidone have been approved by the US Food and Drug Administration (FDA) to treat autism in children. Children who present with markedly impaired attention may improve with very low-dose (and carefully monitored) treatment with stimulants or nonstimulants (eg, atomoxetine).
Generally, inpatient care is unnecessary for childhood disintegrative disorder in the absence of the following:
An associated medical condition (eg, seizures, head injury)
A severe psychiatric problem (eg, behavioral disturbances that warrant closer observation, supervision, and/or stabilization)
Neuroleptic malignant syndrome (NMS)
Alteration of electrolytes levels (such as hyponatremia related to treatment with selective serotonin reuptake inhibitors [SSRIs] or atypical antipsychotics), which may necessitate intravenous (IV) therapy
Medications in various classes, including atypical antipsychotics, stimulants, SSRIs, and nonselective serotonin reuptake inhibitors (NSRIs), have been used to treat a wide range of behavioral and mood problems that may occur in children with childhood disintegrative disorder.
Haloperidol and risperidone are the only medications that have been approved by the FDA for the treatment of irritability associated with childhood autism.[13, 26, 36, 37] These medications can be useful in treating associated symptoms of irritability, aggression, and hyperactivity. Citalopram has not been proved effective, and fluoxetine often causes undesirable gastrointestinal (GI) side effects in this population.[13, 26, 36, 37, 38]
Children who present with markedly impaired attention may improve when treated with very low doses of stimulants or nonstimulants (eg, methylphenidate or atomoxetine), and they should show signs of improvement within 4 weeks if these agents are tolerated and effective.[13, 39]
The dosages are much lower than those usually employed to treat attention deficit/hyperactivity disorder (ADHD), and close monitoring is required. During pharmacotherapy, the clinician must be vigilant for signs of adverse reactions, including insomnia, crying spells, anorexia, weight loss, and frank or worsening psychosis.
If neuroleptic medications are used (eg, risperidone, haloperidol, or molindone), neuroleptic malignant syndrome (NMS) is a significant risk. NMS is a potentially irreversible and life-threatening syndrome that manifests with fever, rigidity, rhabdomyolysis, altered mental status, and lethargy. Laboratory studies used to diagnose NMS include creatine phosphokinase (CPK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase, blood urea nitrogen (BUN), and creatinine levels.
If NMS is left untreated, it may progress to coma and respiratory depression. Appropriate treatment includes immediate cessation of the neuroleptic medication and immediate consultation with an anesthetist for respiratory support and possible treatment with dantrolene.[41, 42, 43, 44, 45, 46, 47]
Antipsychotic agents are also associated with a potential risk of QTc prolongation.
If seizure control is an issue and valproic acid or valproate is used along with an atypical antipsychotics (especially risperidone), the patient should be closely monitored for abnormal levels of ammonia, which are generally accompanied by alterations in mental status (often nonspecific slowing) and abnormalities of liver function.[48, 41, 45, 46, 47]
If an atypical antipsychotics (eg, risperidone, quetiapine, ziprasidone, or aripiprazole) is being given, ongoing monitoring should include screening for metabolic syndrome, new-onset diabetes, or diabetic ketoacidosis, both through physical examination (including waist circumference, blood pressure, and proportion of weight to height) and through laboratory studies (eg, serum glucose and, when indicated, hemoglobin A1c [HbA1c]).[13, 26]
Many children and (in particular) adolescents with childhood disintegrative disorder have difficulty maintaining a regular sleep-wake cycle. This chronic poor sleep may exacerbate aggressive behavior problems, especially intermittent assaultive behaviors in preteens and adolescents. Some individuals experience improvement in their sleep cycle with a short trial of a melatonin agonist such as agomelatine, provided that there is no contraindication (eg, seizures).[21, 26]
Some investigators have found memantine to be useful in childhood disintegrative disorder, but more studies, especially randomized placebo-controlled trials, are needed for confirmation.[13, 49]
Some children with childhood disintegrative disorder who were treated with corticosteroids have shown improvements in motor, language, and behavioral regression.
More randomized placebo-controlled trials are needed to determine if other medications, such as antiepileptic mood stabilizers, are helpful in the management of childhood disintegrative disorder.
Benzodiazepines (eg, diazepam, lorazapam, midazolam, clonazepam) are an alternative choice, but generally are not the first choice, owing to their addictive potential and the fact that they decrease alertness and impair attention, which couldd potentially interfere with a child’s ability to learn in school. However, for children with acutely disturbed behavior and psychotic symptoms, these medications should be considered for short-term use or to decrease the antipsychotic dose when used in combination. They do not cause malignant neuroleptic or metabolic syndrome or prolongation of the QT interval, which can occur with antipsychotics (eg, haloperidol) or atypical antipsychotics.
In situations in which symptoms of catatonia are present (silence [mutism], tenseness and rigidity [holds back acts that are compelled by memories], refusal to obey commands, and displacing rising emotions and tension into motor acts that shut out reality [posturing, grimacing, staring, stereotypes]) and that appear to worsen or not respond to other medications, treatment with benzodiazepines should be considered. If a positive response occurs, the diagnosis of catatonia should be included in the differential diagnosis, especially because a state of extreme excitement can cause potentially fatal medical illness such as pneumonia, blood clotting problems (thrombosis), malnutrition or dehydration, concussion (due to head banging), or other cutaneous infection due to self-injurious behaviors while catatonic.
Additional randomized placebo-controlled trials are necessary to determine whether novel interventions such as hyperbaric oxygen therapy are safe and effective in patients with childhood disintegrative disorder. Other novel treatments, such as secretin, initially seemed to show promise but have not been proven to improve behavioral symptoms.
Although several more novel treatments (eg, cranial manipulation, vitamin B-6 therapy, magnesium therapy, and dimethylglycine therapy) have been used in attempts to “quiet” the brain, there are no data supporting their efficacy in childhood disintegrative disorder or pervasive developmental disorder (PDD). In addition, they all involve some risk of harm (eg, fracture, subluxation, dislocation, or metabolic toxicity). Consequently, they are not recommended at present.[53, 54]
Diet and Activity
No special diet is known to improve the clinical course or prognosis of childhood disintegrative disorder. Salicylate-free diets (ie, Feingold diets), diets low in yeast, and diets high in certain megavitamins or minerals (eg, zinc, magnesium, vitamin B-6, vitamin B-12, fatty acids) have not resulted in measurable and predictable improvements; however, some anecdotal reports have shown limited responses in individual cases.
If a parent wishes to try a special diet, it is advisable to obtain a nutrition consultation before and after the special diet is tried so that any undesirable diet-induced vitamin, mineral, or calorie changes can be prevented or reversed. Particular attention should be paid to ensuring adequate (but not excessive) caloric intake so as to prevent growth retardation.
No specific activity limitations are necessary unless the degree of motor deterioration is sufficient to suggest that activity restriction is warranted. This decision must be made on a case-by-case basis.
A neurologic consultation should be obtained to exclude neurologic conditions, which, if present, may be reversible. The neurology consult should include awake and sleep electroencephalography (EEG), magnetic resonance imaging (MRI), or positron emission tomography (PET). (See Workup.)
A child psychiatrist or a behavioral/developmental pediatrician should be consulted in conjunction with the pediatrician, family, or caregivers to assist with appropriate educational placement, therapeutic interventions, psychopharmacologic interventions, and psychotherapeutic interventions. Consider specific family support therapy for each individual with childhood disintegrative disorder.
Consultation with a speech pathologist should be sought, especially if language delay is significant (delay of 25% or more).
Collaboration of the primary clinician with an early childhood intervention specialist may facilitate appropriate educational placement.
Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res. 2009 Jun. 65(6):591-8. [Medline].
Barone R, Sturiale L, Fiumara A, Palmigiano A, Bua RO, Rizzo R, et al. CSF N-glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder. Autism Res. 2016 Apr. 9 (4):423-8. [Medline].
Volkmar FR, State M, Klin A. Autism and autism spectrum disorders: diagnostic issues for the coming decade. J Child Psychol Psychiatry. 2009 Jan. 50(1-2):108-15. [Medline].
Palomo R, Thompson M, Colombi C, Cook I, Goldring S, Young GS, et al. A case study of childhood disintegrative disorder using systematic analysis of family home movies. J Autism Dev Disord. 2008 Nov. 38(10):1853-8. [Medline].
Rossignol DA, Rossignol LW, Smith S, Schneider C, Logerquist S, Usman A, et al. Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial. BMC Pediatr. 2009 Mar 13. 9:21. [Medline]. [Full Text].
Libbey JE, Coon HH, Kirkman NJ, Sweeten TL, Miller JN, Stevenson EK, et al. Are there enhanced MBP autoantibodies in autism?. J Autism Dev Disord. 2008 Feb. 38(2):324-32. [Medline].
Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. 2003 Apr. 160(4):636-45. [Medline].
Berry-Kravis E, Sumis A, Hervey C, Nelson M, Porges SW, Weng N, et al. Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. J Dev Behav Pediatr. 2008 Aug. 29(4):293-302. [Medline].
Jyonouchi H, Geng L, Streck DL, Toruner GA. Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): case study. J Neuroinflammation. 2012 Jan 7. 9:4. [Medline]. [Full Text].
Strug LJ, Clarke T, Chiang T, Chien M, Baskurt Z, Li W, et al. Centrotemporal sharp wave EEG trait in rolandic epilepsy maps to Elongator Protein Complex 4 (ELP4). Eur J Hum Genet. 2009 Sep. 17(9):1171-81. [Medline]. [Full Text].
Ortega-Hernandez OD, Kivity S, Shoenfeld Y. Olfaction, psychiatric disorders and autoimmunity: is there a common genetic association?. Autoimmunity. 2009 Jan. 42(1):80-8. [Medline].
Lillywhite LM, Saling MM, Harvey AS, Abbott DF, Archer JS, Vears DF, et al. Neuropsychological and functional MRI studies provide converging evidence of anterior language dysfunction in BECTS. Epilepsia. 2009 Oct. 50(10):2276-84. [Medline].
Posey DJ, Erickson CA, McDougle CJ. Developing drugs for core social and communication impairment in autism. Child Adolesc Psychiatr Clin N Am. 2008 Oct. 17(4):787-801, viii-ix. [Medline]. [Full Text].
Miller MT, Ventura L, Strömland K. Thalidomide and misoprostol: Ophthalmologic manifestations and associations both expected and unexpected. Birth Defects Res A Clin Mol Teratol. 2009 Aug. 85(8):667-76. [Medline].
Tedrus GM, Fonseca LC, Melo EM, Ximenes VL. Educational problems related to quantitative EEG changes in benign childhood epilepsy with centrotemporal spikes. Epilepsy Behav. 2009 Aug. 15(4):486-90. [Medline].
Watemberg N, Leitner Y, Fattal-Valevski A, Kramer U. Epileptic negative myoclonus as the presenting seizure type in rolandic epilepsy. Pediatr Neurol. 2009 Jul. 41(1):59-64. [Medline].
Enstrom AM, Van de Water JA, Ashwood P. Autoimmunity in autism. Curr Opin Investig Drugs. 2009 May. 10(5):463-73. [Medline].
Critchfield JW, van Hemert S, Ash M, Mulder L, Ashwood P. The potential role of probiotics in the management of childhood autism spectrum disorders. Gastroenterol Res Pract. 2011. 2011:161358. [Medline]. [Full Text].
Finegold SM, Downes J, Summanen PH. Microbiology of regressive autism. Anaerobe. 2012 Apr. 18(2):260-2. [Medline].
Jyonouchi H, Geng L, Ruby A, et al. Evaluation of an association between gastrointestinal symptoms and cytokine production against common dietary proteins in children with autism spectrum disorders. J Pediatr. 2005 May. 146(5):605-10. [Medline].
Stigler KA, Posey DJ, McDougle CJ. Ramelteon for insomnia in two youths with autistic disorder. J Child Adolesc Psychopharmacol. 2006 Oct. 16(5):631-6. [Medline].
Malhotra S, Subodh BN, Parakh P, Lahariya S. Brief report: childhood disintegrative disorder as a likely manifestation of vitamin B12 deficiency. J Autism Dev Disord. 2013 Sep. 43(9):2207-10. [Medline].
Rosman NP, Bergia BM. Childhood disintegrative disorder: distinction from autistic disorder and predictors of outcome. J Child Neurol. 2013 Dec. 28(12):1587-98. [Medline].
Creten C, van der Zwaan S, Blankespoor RJ, Maatkamp A, Klinkenberg S, van Kranen-Mastenbroek VH, et al. [Anti-NMDA-receptor encephalitis: a new axis-III disorder in the differential diagnosis of childhood disintegrative disorder, early onset schizophrenia and late onset autism]. Tijdschr Psychiatr. 2012. 54(5):475-9. [Medline].
American Psychiatric Association. Childhood Disintegrative Disorder 299.10. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. 1994. 73-5.
Stigler KA, McDougle CJ. Pharmacotherapy of irritability in pervasive developmental disorders. Child Adolesc Psychiatr Clin N Am. 2008 Oct. 17(4):739-52, vii-viii. [Medline].
Agarwal V, Sitholey P, Mohan I. Childhood Disintegrative Disorder, an atypical presentation: a case report. J Autism Dev Disord. 2005 Dec. 35(6):873-4. [Medline].
Mordekar SR, Prendergast M, Chattopadhyay AK, Baxter PS. Corticosteroid treatment of behaviour, language and motor regression in childhood disintegrative disorder. Eur J Paediatr Neurol. 2008 Jul 13. [Medline].
Russo M, Perry R, Kolodny E, Gillberg C. Heller syndrome in a pre-school boy. Proposed medical evaluation and hypothesized pathogenesis. Eur Child Adolesc Psychiatry. 1996 Sep. 5(3):172-7. [Medline].
Akshoomoff N, Farid N, Courchesne E, Haas R. Abnormalities on the neurological examination and EEG in young children with pervasive developmental disorders. J Autism Dev Disord. 2007 May. 37(5):887-93. [Medline].
Kurita H, Koyama T, Osada H. Comparison of childhood disintegrative disorder and disintegrative psychosis not diagnosed as childhood disintegrative disorder. Psychiatry Clin Neurosci. 2005 Apr. 59(2):200-5. [Medline].
A Message From APA President Dilip Jeste, M.D., on DSM-5. Available at http://www.psychnews.org/files/DSM-message.pdf. Accessed: December 1, 2012.
Young EC, Diehl JJ, Morris D, et al. The use of two language tests to identify pragmatic language problems in children with autism spectrum disorders. Lang Speech Hear Serv Sch. 2005 Jan. 36(1):62-72. [Medline].
Gibson RC, Walcott G. Benzodiazepines for catatonia in people with schizophrenia and other serious mental illnesses. Cochrane Database Syst Rev. 2008 Oct 8. CD006570. [Medline].
Cohen IL, Schmidt-Lackner S, Romanczyk R, Sudhalter V. The PDD Behavior Inventory: a rating scale for assessing response to intervention in children with pervasive developmental disorder. J Autism Dev Disord. 2003 Feb. 33(1):31-45. [Medline].
Findling RL. Atypical antipsychotic treatment of disruptive behavior disorders in children and adolescents. J Clin Psychiatry. 2008. 69 Suppl 4:9-14. [Medline].
Stigler KA, Diener JT, Kohn AE, Li L, Erickson CA, Posey DJ, et al. Aripiprazole in pervasive developmental disorder not otherwise specified and Asperger's disorder: a 14-week, prospective, open-label study. J Child Adolesc Psychopharmacol. 2009 Jun. 19(3):265-74. [Medline].
King BH, Hollander E, Sikich L, McCracken JT, Scahill L, Bregman JD, et al. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Arch Gen Psychiatry. 2009 Jun. 66(6):583-90. [Medline].
Biederman J, Hammerness P, Doyle R, Joshi G, Aleardi M, Mick E. Risperidone treatment for ADHD in children and adolescents with bipolar disorder. Neuropsychiatr Dis Treat. 2008 Feb. 4(1):203-7. [Medline]. [Full Text].
Posey DJ, Aman MG, McCracken JT, Scahill L, Tierney E, Arnold LE, et al. Positive effects of methylphenidate on inattention and hyperactivity in pervasive developmental disorders: an analysis of secondary measures. Biol Psychiatry. 2007 Feb 15. 61(4):538-44. [Medline].
Carlson T, Reynolds CA, Caplan R. Case report: valproic Acid and risperidone treatment leading to development of hyperammonemia and mania. J Am Acad Child Adolesc Psychiatry. 2007 Mar. 46(3):356-61. [Medline].
Chakraborty N, Johnston T. Aripiprazole and neuroleptic malignant syndrome. Int Clin Psychopharmacol. 2004 Nov. 19(6):351-3. [Medline].
Chungh DS, Kim BN, Cho SC. Neuroleptic malignant syndrome due to three atypical antipsychotics in a child. J Psychopharmacol. 2005 Jul. 19(4):422-5. [Medline].
Nielsen J, Bruhn AM. Atypical neuroleptic malignant syndrome caused by olanzapine. Acta Psychiatr Scand. 2005 Sep. 112(3):238-40; discussion 240. [Medline].
Segura-Bruna N, Rodriguez-Campello A, Puente V, Roquer J. Valproate-induced hyperammonemic encephalopathy. Acta Neurol Scand. 2006 Jul. 114(1):1-7. [Medline].
Soares-Fernandes JP, Machado A, Ribeiro M, et al. Hippocampal involvement in valproate-induced acute hyperammonemic encephalopathy. Arch Neurol. 2006 Aug. 63(8):1202-3. [Medline].
Stewart JT. Treatment of valproate-induced hyperammonemia. J Am Geriatr Soc. 2005 Jun. 53(6):1080. [Medline].
[Guideline] Kagan-Kushnir T, Roberts SW, Snead OC 3rd. Screening electroencephalograms in autism spectrum disorders: evidence-based guideline. J Child Neurol. 2005 Mar. 20(3):197-206. [Medline].
Chez MG, Burton Q, Dowling T, Chang M, Khanna P, Kramer C. Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability. J Child Neurol. 2007 May. 22(5):574-9. [Medline].
Leskovec TJ, Rowles BM, Findling RL. Pharmacological treatment options for autism spectrum disorders in children and adolescents. Harv Rev Psychiatry. 2008. 16(2):97-112. [Medline].
Sonnier L, Barzman D. Pharmacologic management of acutely agitated pediatric patients. Paediatr Drugs. 2011 Feb 1. 13(1):1-10. [Medline].
Levy SE, Hyman SL. Complementary and alternative medicine treatments for children with autism spectrum disorders. Child Adolesc Psychiatr Clin N Am. 2008 Oct. 17(4):803-20, ix. [Medline]. [Full Text].
Duncan B, McDonough-Means S, Worden K, Schnyer R, Andrews J, Meaney FJ. Effectiveness of osteopathy in the cranial field and myofascial release versus acupuncture as complementary treatment for children with spastic cerebral palsy: a pilot study. J Am Osteopath Assoc. 2008 Oct. 108(10):559-70. [Medline].
Nye C, Brice A. Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database Syst Rev. 2005 Oct 19. CD003497. [Medline].
Murch S. Diet, immunity, and autistic spectrum disorders. J Pediatr. 2005 May. 146(5):582-4. [Medline].