Nephrotic syndrome and behavior problems in children

Sir, Children with chronic physical illnesses are generally considered at increased risk for behavior difficulties. Illnesses not only affect their psychosocial development but also increase behavior problems in siblings and with added burden of disease on family life.[1] The literature on chronic illnesses provide evidence that conditions, such as insulin-dependent diabetes mellitus (IDDM),[2] cancer,[3] cystic fibrosis,[4] juvenile rheumatoid arthritis,[5] and asthma,[6] among others, are associated with increased psychopathology, including behavior problems in children. Nephrotic syndrome is one of the chronic illnesses of childhood that has significant association with behaviour problems, but there are not enough studies to study this in considerable details. Guha et al.,[7] are highly commendable for their efforts to support this notion, through their highly praiseworthy work on the topic. However, there are few points that need further clarifications from the authors, in order to make it easy for our understanding.

Firstly, authors could not find any association between use of corticosteroid therapy and behaviour disturbance, which is a significant finding considering the other studies providing the evidence for association and had been replicated in a number of studies. In this study, behavior disturbance was recorded in 34 (68%) of children. It is important to know how many of these children were on steroids at the time of assessment. As there is some evidence to suggest that corticosteroids significantly reduce the morbidity and mortality in children afflicted with leukemia, asthma, rheumatic diseases, and other inflammatory disorders, though often at the expense of behavioral problems, which may be either due to use of medication or the disease process (chronicity). [8] Secondly, hyperkinesis at 32% (16 children) was over-repre sented in the nephrotic syndrome (NS) group. It is not entirely clear whether overactivity was considered to be only a symptom of behavior disturbance or diagnostic for attention deficit hyperactivity disorder (ADHD). If that is the case, then it may have therapeutic implications, knowing that ADHD may be under-recognized and under-diagnosed in low-and middle-income countries.
Thirdly, 50% of children in the NS group were not attending school and yet still the authors claim that the presence of behavior disturbance and inability to attend school is an important finding of the study. We could argue that non-attendance may be due to other factors, such as parents' socioeconomic status (84% in the study were from lower socioeconomic background), effects of illness itself, and parenting style e,g, being overprotective, rather than mere behaviour disturbance as a sole factor. It will be interesting to know how many children out of the 50% non-attenders that never attended school at all in the first instance.
Fourthly, there appears to be a statistically significant finding of the presence of behavior problem and in relation to the frequency of relapses per year, thus signaling the possibility of a recall bias. It also raises doubt as to whether the patients in remission could not have had any behavior problems, as the authors did not make this clear in the study.
Fifthly, it is again not entirely clear why behavioral disturbances at baseline were not considered in the exclusion criteria.
Sixthly, it appears that 6% of the NS group had learning disorder bearing in mind that mental retardation (MR) was one of the exclusion criteria. It is also important to note that learning difficulties and learning disability (MR) are often used synonymously, although they both can convey different messages or meanings. [9] Finally, authors have not mentioned about the power of the study, which would have given us an indication of the significance of the study in relation to the results if they are to be considered valid.

Letters to Editor
First-generation vs second-generation antipsychotic drugs: The ongoing saga Sir, I have read the letter to editor by Dasgupta and Dasgupta with interest. [1] In this year, we have some more publications shedding more light in this area. It is a very intricate area and one should be cautious in interpreting the evidence. Firstly, we have evidences from both efficacy vs effectiveness trial like CATIE (Clinical antipsychotic trials in intervention effectiveness), and CUTLASS (Cost utility of the latest antipsychotics in severe schizophrenia). Effectiveness trials or practical clinical trials are more informative and can easily be applied to practice. Secondly, second-generation antipsychotic drugs (or atypical antipsychotics) are not a homogenous category, they differ both in terms of effects and side effects; hence, when comparing to first-generation drugs, we should be cautious about generalization of the findings. [2] The superiority of clozapine, especially in treatment-resistant patients, has been established. The position of other second-generation antipsychotic drugs, in comparison to first-generation antipsychotic drugs, remains uncertain.
Leucht et al. recently published a meta-analysis of 150 double blind clinical trials, involving 21,533 patients. [3] Four atypical antipsychotic drugs were found to be better than first-generation antipsychotic drugs for overall efficacy (both positive and negative symptoms). Among them, the effect size was largest for clozapine 20.52 (95% CI 20.75 to 20.29, P , 0.0001), which was not surprising. Clozapine was followed by amisulpride 20.31(20.44 to 20.19, P , 0.001), olanzapine 20.28 (20.38 to 0.18, P , 0.0001) and lastly risperidone 20.18 (20.22 to 20.05, P 5 0.002). The other second-generation antipsychotics (aripiprazole, quetiapine, zotepine, ziprasidone, sertindole) were not more efficacious than first-generation drugs, even on negative symptoms. Extrapyramidal (EP) symptoms, as expected, were more on first-generation antipsychotic drugs. On the other hand, second-generation antipsychotics drugs (except ziprasidone and aripiprazole) induced more weight gain. Similarly, certain drugs were better for depressive symptoms (amisulpride, clozapine, olanzapine, aripiprazole, and quetiapine). They also showed variable changes in overall efficacy of the individual drug when they compared the efficacy in industry-sponsored or non-sponsored trials.
In March 2009, NICE updated the previous guideline issued in 2002. [4] While in the previous guideline, they had recommended first-line use of atypical antipsychotic drug (second generation).In the current update, due to recent evidence casting doubts about alleged superiority of second-generation antipsychotic drugs, NICE have suggested that selection of the antipsychotic drug should be based on benefit and side-effect profile (EP symptoms vs metabolic side effects).NICE no longer recommends second-generation antipsychotic drugs as a first-line treatment.
The artificial classification of the antipsychotic drugs has caused more harm than benef it. The dichotomy of typical and atypical antipsychotic drugs has been abandoned. The current splitting, first generation and second generation, is also not satisfactory as second generation implies that these drugs are advanced and better than the previous ones. What are the implications of these findings? We should not restrict ourselves to second-generation antipsychotic drugs. In some patients, first-generation antipsychotic drugs may be more effective and better tolerated than the second-generation antipsychotic drugs. The long-term studies with global outcome measures (quality of life, functioning) rather than only symptomatic outcomes will help in understanding the risks and benefits of individual antipsychotic drug.