ABSTRACT
INTRODUCTION: Psychoactive drug prescription for preschoolers has increased over the past decade and has been a controversial topic for those who prescribe, regulate, and research the use of psychotropics in this population. Children and adolescents are deemed vulnerable populations, at risk of being harmed by unethical or suboptimal practice and research and are in need of special protection. Historically, preschoolers have been therapeutic and research "orphans," excluded from pharmacological studies so that the evidence base for their treatment has to be extrapolated from other ages. Within the past few decades, several ethical principles guiding pediatric psychopharmacological research have been developed. The same principles could effectively guide the treatment of these patients. CONCLUSION: Further studies are needed to elucidate the safety and effectiveness of psychotropics, and sound ethical guidelines for their involvement in psychiatric research are needed. This article reviews some challenges facing mental health care providers involved in prescribing or researching the use of psychoactive drugs in preschoolers. Some of these challenges are general to medical treatment and research with children, and others are particular to child psychopharmacological treatment and research.
Subject(s)
Clinical Trials as Topic/ethics , Mental Disorders/drug therapy , Psychology, Child/ethics , Psychopharmacology/ethics , Psychotropic Drugs/therapeutic use , Child, Preschool , Clinical Trials as Topic/methods , Ethics, Clinical , Ethics, Medical , Humans , Mental Disorders/psychology , Patient Selection , Practice Guidelines as Topic , Psychotropic Drugs/adverse effects , Research Design , Treatment OutcomeABSTRACT
OBJECTIVE: Stress is believed to be a risk factor for systemic lupus erythematosus (SLE) flare. Two serotonin-related gene polymorphisms, the serotonin receptor 1A (5-HT1A) polymorphism at -1019C>G and the serotonin transporter LS polymorphism, have been reported to affect stress-related behaviors. The purpose of this study was to assess the relationship between self-perceived stress (SPS), variability in SPS, and the 2 serotonin-related gene polymorphisms as risk factors for SLE flare. METHODS: Seventy-seven SLE patients (50 with lupus nephritis) were evaluated every 2 months (mean +/- SD total followup 18.5 +/- 8.5 months), and patients recorded their daily SPS levels (0-10 scale). Values for mean SPS and coefficient of variation (CV) for SPS were calculated from the 60-day block of daily measurements between study visits. Serotonin-related gene polymorphism genotypes were determined by polymerase chain reaction-based methods. RESULTS: Of the 77 patients, 53 experienced 80 flares of SLE (32 renal flares) based on prespecified criteria. Multivariate analysis revealed that whereas neither the serotonin-related gene polymorphisms nor the mean SPS was predictive of an SLE flare, an increased CV for SPS was predictive (P = 0.0031). Interaction between the CV for SPS and the 5-HT1A -1019C>G polymorphism was also found to be a predictor of SLE flare (P = 0.0039). Subset analysis revealed that only in lupus nephritis patients were increasing CVs for SPS (P = 0.0002) and the interaction between CVs for SPS and 5-HT1A (P < 0.0001) predictive of a flare. Odds ratio curves demonstrated that the predictive effect of increasing CVs for SPS required the presence of the 5-HT1A -1019 G allele, but appeared to be independent of the G allele number. CONCLUSION: Fluctuation in the level of SPS is a risk factor for the onset of flare in SLE patients with major renal manifestations when it occurs on the background of a stress-related susceptibility gene (the 5-HT1A -1019 G allele).
