[Treatment of a serious autistic disorder in a child with Naltrexone in an oral suspension form].
CLINICAL BACKGROUND: Autism is a developmental disorder that is usually diagnosed in early childhood. According to ICD-10 criteria, autism can be characterized by delays in language skills, by impaired social interaction, verbal or non-verbal communication and by repetitive, stereotyped or severely restricted activities and interests. The causes of autism are not yet elucidated, but both genetics and environment seem to play a role in 10 to 25% of autism cases. Several biochemical abnormalities, such as impairment of serotoninergic, catecholinergic, dopaminergic, and opioid systems have been reported. Autism therapies are designed to treat symptoms, and medication can be associated with psychoeducational and environmental interventions. Generally, the medications that are currently used are not intended for autism, and must be used with caution and selected according to the type and intensity of symptoms. The most common medication consists of psychotropic therapies by administration of dopaminergic and/or serotoninergic receptor antagonists (haloperidol, risperidone, clomipramine). Several drugs, such as anxiolytics (buspirone), mood stabilisers (lithium, sodium valproate), vitamins (vitamins B6, B12) or opioid antagonists (naltrexone) can be prescribed, in second intention, in cases of severe behavioural disorders. The prescription of opioid antagonists is based on the possible implication of an opioid system disorder observed in some cases. Nevertheless, several clinical studies reveal its variable effectiveness. Naltrexone is a competitive antagonist of opioid receptors OPRM1, OPRD1 and OPRK1. In France, this drug is prescribed for treating opioid and alcohol dependence. Moreover, several studies describe naltrexone as a possible treatment of autistic children in cases of developmental disorder and hyperactivity.


METHODS
In the Child and Adolescent Psychopathology Department of Sainte-Anne's Hospital, autistic children benefit from a multidisciplinary treatment program that sometimes includes the administration of psychotropic medication. One of these children presented with a severe autistic disorder according to the Childhood Autism Rating Scale (CARS). Considering ICD-10 criteria, he benefited from a multidisciplinary program, associating cognitive psychotherapy, psychomotor rehabilitation, speech therapy and educational intervention. However, persistent sleep disorder and motor instability led to successive prescriptions of several different psychotropic drugs. Initial treatment by thioridazine (10mg per day) followed by propericiazine (2.5mg per day) improved sleep, but was not efficient in reducing self-mutilating behaviour. A new treatment by risperidone (from 0.5mg to 1.5mg per day) was therefore chosen; however it lost its efficacy after five months. Finally, an anxiolytic (cyamemazine) and a thymoregulator (sodium valproate) were successively tried without yielding any clinical improvement. Owing to the persistence of communication difficulties, major instability, self-mutilating behaviour and heteroaggressiveness, treatment with naltrexone was subsequently chosen with parental consent. In France, naltrexone hydrochloride is only available in tablet form (Nalorex 50mg and Revia 50mg), which is not adapted to children at the efficient dose. Consequently, an oral suspension form marketed in Spain (Antaxone 50mg) was imported, having obtained the Afssaps' (the French drug administration) authorisation for its temporary use. The Connors and Nisonger scales were used as outcome measures of behavioural symptom change. The Conners scale is used to assess attention deficit and hyperactivity, whereas the Nisonger scale analyses social skills and behaviour disorders in children and adolescents with mental retardation. The onset of treatment, at a dose of 1mg/kg/day, led to a transitory increase in negative behaviour. However, a dose of 0.75mg/kg per day subsequently led to significant improvements, as shown by outcome measurements. Self-mutilating behaviour disappeared completely. Certain side effects were observed, namely transitory sedation at the beginning of treatment and moderate constipation.


CONCLUSIONS
This clinical case confirms that treatment of a serious autistic disorder in children using Naltrexone in oral suspension form is a potentially interesting therapeutic alternative for treating behavioural symptoms resistant to classical drug therapy.
Desjardins
S
S
Département de pharmacie-stérilisation, centre hospitalier Sainte-Anne, 1, rue Cabanis, 75674 Paris cedex 14, France.
Doyen
C
C
Contejean
Y
Y
Kaye
K
K
Paubel
P
P
D000284:Administration, Oral; D001321:Autistic Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002648:Child; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D004519:Education, Special; D005602:France; D006801:Humans; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage* / Q000009:adverse effects; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D010348:Patient Care Team; D026741:Physical Therapy Modalities; D011596:Psychomotor Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000523:psychology; D013070:Speech Therapy; D013535:Suspensions; D016896:Treatment Outcome
D009292:Narcotic Antagonists; D013535:Suspensions; D009271:Naltrexone