Nocturnal enuresis: a placebo controlled trial of two antidepressant drugs.

A multicentre, randomised, double blind treatment trial was set up comparing imipramine (a tricyclic antidepressant with anticholinergic action), mianserin (a quadricyclic antidepressant without anticholinergic activity), and placebo, (a) possibly to identify an effective alternative drug and (b) to elucidate the action of imipramine in enuretic children. Eighty children (65 boys, 15 girls) aged 5-13 years, wet three or more nights a week, were studied. Exclusions were a urinary tract infection or abnormality, other organic illness, or severe emotional disorders. After a four week assessment, 25 children were randomised to eight weeks'' treatment with imipramine 25 mg, 26 to mianserin 10 mg and 29 to placebo, followed by four weeks without treatment. Dry nights and a wetness score were recorded throughout. During treatment, imipramine was superior to both placebo and mianserin (p < 0.001) in achieving dry nights and reducing wetness scores. It led to a definite improvement in 72% of children. Mianserin produced a mildly beneficial effect that was not superior to placebo. No side effects were recorded. Mianserin would not be a satisfactory alternative treatment for nocturnal enuresis. The efficacy of imipramine is unlikely to be the result of its antidepressant activity.     

DNA damage in children treated with imipramine for primary nocturnal enuresis

BACKGROUND: Despite the fact that primary nocturnal enuresis (PNE) is self-limited and pathologically benign, the emotional stress and inconvenience that it produces, warrants treatment. Imipramine is one of the widely used drugs in PNE treatment. Although some mutagenic effects were suggested in imipramine administration, this toxicity has never been investigated in enuretic patients. The aim of this study was to evaluate the association of exposure to imipramine with DNA damage. METHODS: Thirty-five children treated with imipramine for at least 4.5 months who were in otherwise good health were accepted into the investigation. Twenty healthy sisters or brothers of the patients who did not use any long-term drugs were studied simultaneously as the control group. Comet assay was used to evaluate DNA damage. RESULTS: Damaged (limited and extensive migrated) cells of the enuretic children who were taking imipramine were statically higher than that of the control group (P < 0.05) indicating a detectable DNA damaging effect of imipramine in human lymphocytes. CONCLUSIONS: Our finding suggests that the difference in comet scores between two groups was induced by the imipramine treatment. The other possibility to be considered is the psychological stress of the children who were concerned by the symptoms and their parent's anxiety. As our preliminary data were based on a limited number of children, further research is needed considering the importance of this possible toxic effects which may be associated with mutagenicity.     

Treatment of severe imipramine poisoning complicated by a negative history of drug ingestion

The wide use of imipramine (Tofranil) for the treatment of nocturnal enuresis continues in spite of the unique dangers associated with this drug. Young children are particularly susceptible to the potentially lethal central nervous system and cardiovascular toxicities, yet the toxic potential of imipramine remains unrecognized by both parents and too many physicians. Management of severe imipramine intoxication can be difficult. This report describes a 12-month-old patient with severe imipramine intoxication whose treatment was complicated by a negative history at presentation.     

Differentiation of subgroups of monosymptomatic enuresis according to prepulse inhibition of the startle reflex

Aim: Monosymptomatic enuresis (ME) is a common disorder in children with serious social and psychological consequences. Treatment is usually initiated with desamino‐arginine vasopressin (dDAVP) and/or alarm therapy as first‐line treatment and imipramine as second‐line. All treatments have proven efficacy, but are not successful with all patients. Therefore, a differentiation into subgroups according to treatment efficacy would be beneficial. Methods: A group of patients resistant to first‐line treatment was treated with imipramine and compared with matched controls successfully treated with dDAVP and/or alarm therapy. Prepulse inhibition (PPI) to acoustic startle reflexes was measured in all patients. Results: In a group of 23 nonresponders, the median PPI was 72% (range 43–94%) compared with the matched dDAVP/alarm – responders with a median PPI of 26% (range 0–61%) (p < 0.0001). The response rate to imipramine was 87%. Conclusion: The presented data provide evidence that PPI allows to identify two subgroups of ME. The results offer further insight into (at least) two different pathomechanisms involved in ME: (i) a maturational delay of reflex inhibition with reduced PPI and (ii) a normal PPI, possibly with abnormal sleep patterns, that can be influenced by imipramine.     

Enuresis—its background and management

Conclusions Enuresis was more frequent in boys (64.3%) as compared to girls (35.7%) and the incidence decreases as the age advances. The highest incidence (47.6%) was in the 4–6 years age group. Enuresis was more commonly seen in children of middle (46.4%) and lower (33.3%) socio-economic groups. The children of parents with an educational status up to class V (57.1% were more commonly affected. Regular bedwetters (60.7%) were more in number as compared to occasional bed wetters (39.3%). There was a greater prevalence of bedwetting among later born children (72.8%) of large families. 11.6% of sibs had the history of bedwetting. Enuretic children were apt to have a small bladder (bladder capacity 190–250 ml./sq.m.) and to void frequently during the day. A slightly higher percentage of recovery rate was noticed in regular bed wetters when put on both psychotherapy and imipramine hydrochloride (80.9% or 17 out of 21) as compared to those receiving imipramine only (72.8% or 16 out of 22). The response to combined therapy in occasional bedwetters was better (100%) as compared to imipramine only (90%). From the District Hospital, Hamirpur, U.P.     

Nocturnal enuresis: What is happening?

Primary nocturnal enuresis is common and has considerable psychological ramifications for children as they get older. It is a familial condition with complex inheritance patterns. The pathophysiology of the condition appears to be related to poor arousal from sleep, nocturia due to deficient vasopressin release in sleep and possibly a decrease in functional bladder capacity especially at night. The mainstay of treatment is the bed-wetting alarm. In recent years, desmopressin nasal spray has found a clinical niche as a short-term solution for children attending school camps or sleeping over at friends' houses and as treatment in the medium term for those unresponsive to treatment with a bed-wetting alarm. It may also be used as an adjunct to the use of the alarm. Treatment with imipramine is increasingly in disfavour because the relapse rate is unacceptably high and fatal overdose is a real possibility.     

Imipramine poisoning in a child: lack of efficacy of resin hemoperfusion

A three-year-old boy ingested up to 1,500 mg of the tricyclic antidepressant imipramine (Tofranil). He entered our facility within two hours of discovery, and multiple resuscitative efforts, which proved unsuccessful, followed. Resin hemoperfusion was used in an effort to remove imipramine from the systemic circulation. Serum concentrations of imipramine and its major metabolite desipramine were determined from serum drawn before, during, and after hemoperfusion. Serum concentrations of imipramine and desipramine did not change appreciably. No improvement in the clinical condition was noted during the hemoperfusion period, which was due in part to the fact that our patient was clinically brain dead upon arrival in our intensive care unit. Our subsequent literature review documents that this case represents the first reported use of hemoperfusion in a pediatric tricyclic antidepressant ingestion, hemoperfusion removes an insignificant portion of the total amount of tricyclic antidepressant ingested, and some pediatric literature misleadingly suggests that hemoperfusion may be useful in such patients. Physicians treating tricyclic antidepressant ingestion cases should avoid using hemoperfusion; standard supportive care remains the essential management response.     

Oxybutynin efficacy in the treatment of primary enuresis

The effectiveness of oxybutynin in the treatment of primary enuresis was evaluated in a double-blind study. A total of 30 children (25 boys, five girls), at least 6 years of age, with primary enuresis and no daytime incontinence or history of other urinary tract problems were selected at random from an enuresis clinic population. The study was explained to the families and they were told how to keep records of nocturnal bed-wetting episodes and side effects. The patients were treated with a 10 mg of oxybutynin at suppertime for 28 days. Before or after the treatment period, all children received an identical placebo for 4 weeks. Two-sided paired t tests were used to compare frequency of nocturnal enuresis. Frequency during the drug regimen did not differ significantly from that during the placebo study. There were no differences in findings between boys and girls or between children who had previously taken imipramine and those who had not. The study showed no evidence that oxybutynin is effective in treating primary enuresis.     

Early treatment of acute stress disorder in children with major burn injury.

OBJECTIVE: This study examines retrospectively the response rate of pediatric burn survivors with acute stress disorder to either imipramine or fluoxetine. METHODS: On retrospective chart review, 128 intensive care unit patients (85 boys, 43 girls) with 52%+/- 20% total body surface area burn, length of stay of 32.8+/- 25.2 days, mean age of 9.1+/- 4.7 yrs, and age range of 13 months to 19 yrs met criteria for acute stress disorder after >or=2 days of symptoms and were treated with either imipramine or fluoxetine. If significant improvement did not occur within 7 days, the medication was either increased or switched to the other class. RESULTS: Initially, 104 patients were treated with imipramine and 24 with fluoxetine. A total of 84 patients responded to imipramine: seven of these patients required a higher dose. A total of 18 patients responded to initial fluoxetine treatment. Of 26 nonresponders to the initial medication, 13 imipramine failures and one fluoxetine failure refused further treatment. The other 12 responded to the second medication. Therefore, 114 of 128 treated patients (89%) responded to either fluoxetine (mean dose, 0.30+/- 0.14 mg/kg) or imipramine (mean dose, 1.30+/- 0.55 mg/kg). Response was independent of sex and age but was less for those with burns of >60% total body surface area. The side effects of each medication were not significant. Most patients continued treatment for >or=3 months; some required 6 months of treatment before successful discontinuation. CONCLUSIONS: Early treatment of acute stress disorder with either imipramine or fluoxetine is often able to reduce its symptoms. This is a review of a single hospital's experience in managing psychiatric distress in this very high-risk group of burned children. Additional clinical studies are needed before generalizing these findings.     

Neural correlates of verbal and nonverbal semantic integration in children with autism spectrum disorders

Background: Autism is a pervasive developmental disorder characterized by deficits in social‐emotional, social‐communicative, and language skills. Behavioral and neuroimaging studies have found that children with autism spectrum disorders (ASD) evidence abnormalities in semantic processing, with particular difficulties in verbal comprehension. However, it is not known whether these semantic deficits are confined to the verbal domain or represent a more general problem with semantic processing. The focus of the current study was to investigate verbal and meaningful nonverbal semantic processing in high‐functioning children with autism (mean age = 5.8 years) using event‐related potentials (ERPs). Method: ERPs were recorded while children attended to semantically matching and mismatching picture–word and picture–environmental sound pairs. Results: ERPs of typically developing children exhibited evidence of semantic incongruency detection in both the word and environmental sound conditions, as indexed by elicitation of an N400 effect. In contrast, children with ASD showed an N400 effect in the environmental sound condition but not in the word condition. Conclusions: These results provide evidence for a deficiency in the automatic activation of semantic representations in children with ASD, and suggest that this deficit is somewhat more selective to, or more severe in, the verbal than the nonverbal domain.     

Management of neuropathic urinary incontinence in children by intermittent catheterisation.

Forty-nine children with urinary incontinence owing to neuropathic bladder were treated by intermittent catheterisation. Manometric studies to determine urethral closing pressures and intravesical pressure/volume relationships were performed before or during treatment in all children. Cystography and intravenous urography were carried out at the beginning of treatment and intravenous urography was repeated after treatment for at least 12 months. Routine long-term antibacterial therapy was not used. With a 3-hourly catheterisation regimen a total of 46 (93%) children achieved day-time control but 27 (55%) did so only with the help of propantheline or imipramine or both of these. Night-time control was also substantially improved in 43 (87%) children. The manometric studies enabled a reliable prediction to be made on whether drugs would be required to achieve success. One child with an undilated urinary tract before treatment developed unilateral dilatation owing to mechanical problems during treatment. Upper urinary tract dilatation which was present before treatment in 20 children (33 kidneys) disappeared or improved in all. Early renal failure in 2 children also responded favourably. The technique had to be abandoned in 2 children.     

The early intervention foster care program: permanent placement outcomes from a randomized trial

Preschool-aged foster children face multiple risks for poor long-term outcomes. These risks appear to increase with the number of placement changes experienced. The Early Intervention Foster Care Program (EIFC) targets the spectrum of challenges that preschool-aged foster children face via a team approach delivered in home and community settings. In this article, we report on permanent placement outcomes from the EIFC randomized clinical trial. Children in EIFC had significantly fewer failed permanent placements than children in the regular foster care comparison condition. The number of prior placements was positively associated with the risk of failed permanent placements for children in the comparison condition but not for children in EIFC. Type of prior maltreatment did not predict permanent placement outcomes. These results provide the foundation of an evidence base for the EIFC program as a preventive intervention to improve permanent placement outcomes for preschool-aged foster children.     

Suspected adverse methylphenidate-imipramine interactions in children

Two cases are presented which illustrate the dangers inherent in utilizing a polypharmacy approach in treating children with psychotropic medication. In each case, severe adverse effects, including cognitive and mood deterioration, were experienced by the child when treated with a combination of methylphenidate and imipramine. Possible mechanisms at the neurotransmitter level are described as postulated determinants for this pharmacological interaction.     

Considerations on respective roles of anxiety and depressive disorders in children]

Anxiety and depression are often clinically associated in children, but are very different in term of effect and symptoms. Family studies favor the hypothesis of a common diathesis for these disorders. Parental history of major depressive and/or anxiety disorders increase the risk of mood and anxiety disorders in children. At the present time, biological studies have not determined any biochemical conclusion for these disorders. It should be noted that although imipramine is efficient in both depressive disorder and separation anxiety, this does not implicate a common physiopathologic basis.     

Non-convulsive status epilepticus.

The clinical, electrographic and reported neuropsychological features of 50 children with non-convulsive status epilepticus (NCSE) were reviewed and the children''s progress followed for one to five years. NCSE occurred in a variety of epilepsies, especially the Lennox-Gastaut syndrome. Clinical manifestations ranged from obvious mental deterioration to subtle changes. The condition had often been overlooked or misinterpreted and many children had experienced repeated episodes over long periods. Following diagnosis, immediate treatment was often not attempted or was not successful. Further episodes of NCSE occurred in the majority of children during the follow up period. Failure to recognise NCSE and to treat episodes promptly, and the high rate of recurrence, is of particular concern in view of fears that repeated exposure to this condition might be brain damaging. At least 28 children in the present series showed evidence of intellectual or educational deterioration over the period during which NCSE had occurred, although the exact cause was difficult to determine.     

Challenging Ronald: McDonald versus McDonald's

Obesity is the most prevalent health condition affecting first world children in 2011. This article recounts a campaign that opposed the construction of a fast food outlet in close proximity to a large school complex. The epidemiologic evidence that there is a negative health impact on children that attend schools close to fast food outlets is reiterated. There is an urgent need for planning laws to be modernised to reflect that evidence.     

Cause and Effect Beliefs and Self-esteem of Overweight Children

In this study, beliefs of the cause and effect of weight were examined in a sample of 9- to 11-year-old clinically overweight children. Lower self-esteem was found in the children who believed they are responsible for their overweight as compared to those who attributed their overweight to an external cause. Lower self-esteem was also found in the children who believed that their overweight hinders their social interaction. Other evidence gathered here lends some support to the view that the overweight child is more vulnerable to low self-esteem. The negative experiences in school and at home that the children reported and the premise that childhood obesity is a stigmatising condition is discussed.     

Chronic Fatigue Syndrome in children and young people

Chronic Fatigue Syndrome/myalgic encephalomyopathy (CFS/ME) is a relatively common and serious condition in children and young people, having a significant impact on their physical, emotional and cognitive well being. Although some progress has been made in understanding this perplexing condition there is still a long way to go and controversies persist about terminology, aetiology and treatment. However, there is a general agreement that CFS is a heterogeneous condition and good evidence regarding management. This review explores the best practice approach to assessment, diagnosis and management of CFS/ME in children and young people. Early diagnosis and appropriate multi-disciplinary intervention facilitate recovery.There remains a pressing need for research to improve understanding of the condition and thereby ensure all children and young people with CFS/ME are understood and receive effective treatment.     

Japanese guidelines for the management of intussusception in children, 2011

Background: The Japanese Society of Emergency Pediatrics has formulated evidence‐based guidelines for the management of intussusception in children in order to diagnose intussusceptions promptly, to initiate appropriate treatment as early as possible, and to protect intussuscepted children from death. Methods: Literature was collected systematically via the Internet using the key words “intussusception” and “children.” The evidence level of each paper was rated in accordance with the levels of evidence of the Oxford Center for Evidence‐based Medicine. The guidelines consisted of 50 clinical questions and the answers. Grades of recommendation were added to the procedures recommended on the basis of the strength of evidence levels. Results: Three criteria of “diagnostic criteria,”“severity assessment criteria,” and “criteria for patient transfer” were proposed aiming at an early diagnosis, selection of appropriate treatment, and patient transfer for referral to a tertiary hospital in severe cases. Barium is no longer recommended for enema reduction (recommendation D) because the patient becomes severely ill once perforation occurs. Use of other contrast media, such as water‐soluble iodinated contrast, normal saline, or air, is recommended under either fluoroscopic or sonographic guidance. Delayed repeat enema improves reduction success rate, and is recommended if the initial enema partially reduced the intussusception and if the patient condition is stable. Conclusions: The guidelines offer standards of management, but it is not necessarily the purpose of the guidelines to regulate clinical practices. One should judge each individual clinical situation in accordance with experiences, available devices, and the patient's condition.