Approach Considerations
The principles of therapy for childhood disintegrative disordere (CDD) 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. [2]
No known medications address the core processes of CDD. 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:
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An associated medical condition (eg, seizures, head injury)
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A severe psychiatric problem (eg, behavioral disturbances that warrant closer observation, supervision, and/or stabilization)
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Neuroleptic malignant syndrome (NMS)
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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
Pharmacologic 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 (CDD).
Haloperidol and risperidone are the only medications that have been approved by the FDA for the treatment of irritability associated with childhood autism. [13, 29, 39, 40] 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, 29, 39, 40, 41]
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, 42]
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. [43]
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. [44, 45, 46, 47, 48, 49, 50]
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. [51, 44, 48, 49, 50]
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, 29]
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). [23, 29]
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, 52]
Some children with childhood disintegrative disorder who were treated with corticosteroids have shown improvements in motor, language, and behavioral regression. [31]
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. [53]
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. [54]
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. [37]
Novel Therapies
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. [4] Other novel treatments, such as secretin, initially seemed to show promise but have not been proven to improve behavioral symptoms. [55]
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. [56, 57]
Diet and Activity
No special diet is known to improve the clinical course or prognosis of childhood disintegrative disorder. [58] 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.
Consultations
A neurologic consultation should be obtained to exclude neurologic conditions, which, if present, may be reversible. [33] 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.
