Implementation of Advanced Methods for Reproductive Pharmacovigilance in Autism: A Meta-Analysis of the Effects of Prenatal Antidepressant Exposure.

OBJECTIVE: Observational studies of prenatal antidepressant safety are hindered by methodological concerns, including susceptibility to surveillance bias. Some studies address potential bias by using alternative strategies to operationalize study comparison groups. In a meta-analysis of the association between prenatal antidepressant exposure and autism risk, the authors examined the utility of comparison group operationalization in reducing surveillance bias. METHODS: A systematic search of multiple databases through August 2017 was conducted, selecting controlled observational studies of the association of prenatal antidepressant exposure with autism. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis produced summary effect measures with 95% confidence intervals stratified by comparator group composition, antidepressant class, and trimester of exposure. RESULTS: Fourteen studies were included, with 13 reporting results using a population-based comparison group, five using a psychiatric control group, and four using a discordant-sibling control group. Eight of the 14 studies were rated poor because of inadequate control for prenatal depression and maternal ethnicity. Autism risk estimates after prenatal exposure to any antidepressant were decidedly different for population-based designs (hazard ratio=1.42, 95% CI=1.18, 1.70; odds ratio=1.58, 95% CI=1.25, 1.99) compared with psychiatric control (hazard ratio=1.14, 95% CI=0.84, 1.53; odds ratio=1.24, 95% CI=0.93, 1.66) and discordant-sibling (hazard ratio=0.97, 95% CI=0.68, 1.37; odds ratio=0.85, 95% CI=0.54, 1.35) designs. Findings for prenatal exposure to selective serotonin reuptake inhibitors were similar. Meta-regression of population-based studies demonstrated that despite statistical adjustment, ethnicity differences remained a significant source of study heterogeneity. CONCLUSIONS: In this meta-analysis, neither psychiatric control nor discordant-sibling designs supported an association between prenatal antidepressant exposure and autism. Discordant-sibling designs effectively addressed surveillance bias in pharmacovigilance reports derived from national registries and other large databases.

Anesthetic Management During Electroconvulsive Therapy in Children: A Systematic Review of the Available Literature.

Electroconvulsive therapy (ECT) is indicated in a myriad of pediatric psychiatric conditions in children, and its use is increasing. Literature on the clinical features salient to anesthetic care is lacking. The objective of this systematic review is to describe the available literature on the anesthetic considerations of pediatric ECT. Original publications were screened for inclusion criteria: (1) manuscript written in English; (2) persons under 18 years of age; and (3) use of ECT. Data tabulation included demographic information, details of anesthetic management and ECT procedure, and adverse events. The mean age was 15 years, 90% were 12-17 years of age, and no cases involving children <6 years of age were identified. The psychiatric diagnoses most commonly represented were major depressive disorder (n = 185) and schizophrenia/schizoaffective disorders (n = 187). ECT was also used to treat many neurological disorders. Medical comorbidities were reported in 16% of all cases. Common coexisting conditions included developmental delay (n = 21) and autism (n = 18). Primary ECT indications included severe psychosis (n = 190), symptoms refractory to pharmacotherapy (n = 154), and suicidality (n = 153). ECT courses per patient ranged from 2 to 156. Duration averaged 91.89 ± 144.3 seconds. The most commonly reported induction agents were propofol and methohexital, and the most commonly reported paralytic agent was succinylcholine. Reported adverse events included headache, nausea, sedation, and short-term amnesia, as well as rare cases of benign dysrhythmias and prolonged seizure. Negative perception and diminished access to care result in treatment delays; thus, these children present in an advanced state of disease. In examining the details of modern ECT performed in 592 children, no major anesthetic morbidity was identified. Further study should start with retrospective analysis of anesthesia data during ECT to compare various effects of anesthesia medications and technique on adverse events and outcomes.

Steroid-Induced Psychosis in the Pediatric Population: A New Case and Review of the Literature.

OBJECTIVES: Iatrogenic steroid-induced psychosis is a rare but serious adverse side effect seen largely in the adult population that less commonly affects children and adolescents. Given the significant distress steroid-induced psychosis may cause, recommendations are needed for effective management. Here we conducted a systematic review of the literature and report a new case of steroid-induced psychosis in a 12-year-old patient. METHODS: We performed a systematic search using Embase, PubMed, Scopus, and PsychInfo. Key terms included ("steroid induced" or "corticosteroid induced" or "glucocorticoid induced") and ("psychosis" or "hallucinations" or "delusions") and ("child" or "adolescent" or "pediatric"). A total of 15 articles of steroid-induced psychosis in children and adolescents were found in the scientific literature. This report includes those articles and a novel case of steroid-induced psychosis. RESULTS: Children with asthma, autoimmune diseases, and cancer have been reported to experience steroid-induced psychosis. The mean age of children with steroid-induced psychosis was 12 ± 3.6 years. Our team presents a report of steroid-induced psychosis in a 12-year-old patient with discoid-type lupus erythematosus. Within days of treatment with 40 mg prednisone daily, this patient began to drool, became mute, and was responding to internal stimuli. Treatment was difficult secondary to the acute exacerbation of lupus, requiring ongoing therapy. It was initially unclear whether the acute psychosis was a manifestation of lupus, a side effect of medication, or a combination of the two risk factors. Neurology consultation ruled out lupus cerebritis. Psychosis was treated with haloperidol 5 mg. Psychosis did not resolve until the steroid taper was complete and the patient was no longer taking any prednisone. CONCLUSIONS: Given the common use of glucocorticoid therapy in children, it is important that physicians and parents recognize the signs of steroid-induced psychosis and are aware of the data on treating this complication.