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Noropsikiyatri 2011-2 siraliAripiprazole-Induced Enuresis in a Child with Autistic Disorder Otizm Tan›l› Bir Çocukta Aripiprazole Ba¤l› Enürezis
Hasan BOZKURT, Osman ABALI ‹stanbul Üniversitesi ‹stanbul T›p Fakültesi, Çocuk Ruh Sa¤l›¤› ve Hastal›klar› Anabilim Dal›, ‹stanbul, Türkiye ABSTRACT
Aripiprazole is being increasingly reported to be effective in treating behavioral Aripiprazolün otistik çocuklarda görülen davran›ﬂsal problemleri tedavi etmede problems of children with autism. It has fewer side effects with respect to other etkili olmas›yla ilgili yay›nlar›n say›s› giderek artmaktad›r. Aripiprazolün di¤er atypical antipsychotics. However, to our knowledge, in the literature, there is no atipik antipsikotiklere nazaran daha az yan etkisi bulunmaktad›r. Oral aripiprazol report on aripiprazole-induced enuresis in children and adolescents diagnosed henüz piyasaya sürülmeden önce yap›lan de¤erlendirmelerde enürezis çok nadir with autism, although enuresis has been a very rare adverse event observed dur- bir yan etki olarak gözlenmesine ra¤men, bilindi¤i kadar›yla yaz›nda, otizm tan›l› ing the premarketing evaluation of oral aripiprazole. Here, we present a sixteen- çocuk ve ergenlerde aripiprazole ba¤l› enürezis ile ilgili bir vaka bildirimi yoktur.
year-old boy with diagnosis of autism and epilepsy who developed enuresis after Biz bu yaz›da on alt› yaﬂ›nda otizm ve epilepsi tan›s› ile takip etti¤imiz, aripiprazole starting aripiprazole and had rapid remission after the discontinuation of the baﬂlad›ktan sonra enürezisi olan ve ilac› kestikten sonra alt kaç›rmas› h›zla düze- drug. (Archives of Neuropsychiatry 2011; 48: 164-6) len bir olgu sunduk.(Nöropsikiyatri Arﬂivi 2011; 48: 164-6) Key words: Aripiprazole, enuresis, autism, children
Anahtar kelimeler: Aripiprazol, enürezis, otizm, çocuk
Aripiprazole anovel atypical antipsychotic, is being adminis- H, a nonverbal 16-year-old male, was brought to our tered to children and adolescents for the management of mood outpatient clinic by his parents due to his aggressiveness and instability, aggression, and psychosis. Recently, the U.S. Food self-injurious behaviors. Information regarding his developmental and Drug Administration (FDA) has approved it for the treatment and psychiatric history was taken from his mother. According to of irritability associated with autistic disorder in pediatric her, he was diagnosed with autistic disorder due to his severe patients aged 6-17 years and including symptoms of aggression impairment in language development and social-emotional towards others, deliberate self-injuriousness, temper tantrums, reciprocity, and repetitive behaviors when he was 3. His medical and quickly changing moods (1). Compared to other atypical history was also positive for epilepsy. He was on valproic acid antipsychotics, aripiprazole is reported to cause fewer side 2000 mg/day and lamotrigine 100 mg/day since the age of 12.
effects e.g., weight gain, elevation in glucose and lipid levels, Risperidone was initiated at 0.5 mg/day to cope with his prolactin elevation, QTc prolongation, and onset of diabetes behavioral problems, but ceased because of excessive vomiting mellitus. Other untoward events include headache, insomnia, and gastrointestinal problems. Thus, we switched to olanzapine nausea, vomiting, lightheadedness, somnolence, constipation, 5 mg/day. However, he began to have epileptic seizures soon increased appetite and dyspepsia (2). Here, we present a case of after olanzapine treatment, so the medication was stopped.
aripiprazole-induced enuresis in an adolescent with autistic Then, he was given quetiapine, haloperidol and escitalopram, respectively, but all these drugs also induced epilepsy by Address for Correspondence/Yaz›ﬂma Adresi: Dr. Hasan Bozkurt, ‹stanbul Üniversitesi ‹stanbul T›p Fakültesi, Çocuk Ruh Sa¤l›¤› ve Hastal›klar› Anabilim Dal›, ‹stanbul, Türkiye
Gsm: +90 554 237 19 32 E-mail: [email protected] Received/Geliﬂ tarihi: 05.09.2010 Accepted/Kabul tarihi: 31.10.2010
Archives of Neuropsychiatry, published by Galenos Publishing. / Nöropsikiyatri Arﬂivi Dergisi, Galenos Yay›nevi taraf›ndan bas›lm›ﬂt›r.
Archives of Neuropsychiatry 2011; 48: 164-6 Nöropsikiyatri Arﬂivi 2011; 48: 164-6 Aripiprazole-Induced Enuresis in an Adolescent with Autistic Disorder decreasing the seizure threshold. Hence, we decided to although it had no noticeable anticholinergic effects. As use aripiprazole to control the symptoms and he was given serotonin can indirectly potentiate cholinergic neuromuscular aripiprazole 10 mg/day. But, he developed new-onset diurnal transmission in isolated human detrusor muscle strips (10) and enuresis within the first day of the treatment and it continued there are a number of case reports on SSRI-induced enuresis 10-15 times a day till we stopped the medication a week later. His (11-14), aripiprazole may be responsible for enuresis because of medical history and workup, including physical and neurological its serotonin reuptake properties (SERT). Besides, possible examination and urinalysis, were unremarkable. The patient had reduced dopamine transmission due to partial agonist activity of urinary bladder control at 3 years of age, and he and his family aripiprazole at D2 receptors might also cause urinary had no previous history of urinary incontinence. His enuresis incontinence in our autistic case despite the fact that the other resolved rapidly after discontinuation of aripiprazole. We then partial agonist activity at 5-HT1A receptors can reduce bladder decided to restart aripiprazole to understand whether the diurnal dysfunction, while selective 5-HT1A antagonists inhibit bladder enuresis was associated with the use of aripiprazole or not.
Enuresis reemerged on the first day of the treatment and repeated On the other hand, aripiprazole had no clinically important 10-15 times a day again. Meanwhile, he benefited from interactions with the drugs, valproic acid and lamotrigine, which aripiprazole and his behavioral symptoms resolved substantially our patient was using (2). Because enuresis remitted rapidly without emerging an epileptic seizure, but we could not keep upthe treatment because his parents requested the discontinua- after discontinuation of aripiprazole and reemerged after tion of aripiprazole due to the severity of enuresis, thus, we starting again, the improvement of enuresis in this case cannot ceased aripiprazole a week after the beginning and decided to be explained by the other drugs. Our patient was using these antiepileptics for four years and there was no dose increase thatmay contribute to the emergence of enuresis. Moreover, the risk Discussion
of seizures with aripiprazole is reported to be 0.1%, the lowestamong atypical agents (1,2).
We reported the case of an autistic patient who developed It is known that antipsychotic-induced enuresis happens to diurnal enuresis after starting aripiprazole and had rapid be mostly a transient and time-limited phenomenon (16,17). As remission after the discontinuation of the drug. Although our case had severe behavioral problems and communicational antipsychotic-induced enuresis may be more common than difficulties and his parents did not cope with the severity of generally reported (3), urinary incontinence associated with enuresis, we could not apply behavioral treatment and could not aripiprazole has been a very rare adverse event observed during the premarketing evaluation of its oral form.
Urinary incontinence associated with aripiprazole seems to Possible mechanisms have been described in the be very rare like the other cases with antipsychotic-induced pathophysiology of antipsychotic-induced enuresis. They enuresis (18) and our autistic case is probably the first report include decreased internal bladder sphincter tone due to alfa 1 according to litereture (PubMed). Additionally, there are adrenergic blockade (4), reduced dopamine transmission in the two case reports describing the efficacy of combined use of basal ganglia (5), urinary retention and subsequent overflow aripiprazole in the treatment of clozapine-induced enuresis (19).
incontinence due to antimuscarinic properties of antipsychotics However, the use of aripiprazole has become widely (6) and blockade of pudendal reflexes via antagonism of 5-HT2 or common in treating behavioral problems associated with 3 (7) and the activation of neuronal 5 HT4 receptors in the autistic spectrum disorders; thus, our case report shows that detrusor muscle (8). The sedative effects of antipsychotics may aripiprazole-induced enuresis should be born in mind when also lead to inability to wake up during sleep and might cause using this drug especially in children with developmental Moreover, efficacy of aripiprazole is mediated through a disabilities. However, further research is needed to better combination of partial agonist activity at D2 and 5-HT1A understand the pathophysiology of enuresis with aripiprazole.
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