Level III.

BACKGROUND: Treatment of the complications arising from Prenatal Alcohol Exposure (PAE) has largely been focused on psychosocial and environmental approaches. Research on the use of medications, especially psychotropic medications, has lagged behind. OBJECTIVES: This systematic review sought to investigate psychotropic medication related findings and outcomes in those diagnosed with Fetal Alcohol Spectrum Disorder (FASD). METHODS: Comprehensive searches were conducted in seven major databases (Medline/ PubMed, Scopus, Web of Knowledge, Embase, PsycINFO, Cochrane Library, and PsycARTICLES) up to February 2017. Key search terms with synonyms were mapped on these databases. There were no timeline restrictions and no grey literature searches. Two reviewers independently assessed 25 studies that met the inclusion criteria. Most studies were reviews of treatment and retrospective case series. RESULTS: Two crossover randomized trials were reported, and the findings were not amenable to meta-analysis. Several conditions (depression, agitation, seizures, and outburst) combined with the most frequent presentation, ADHD, to represent the rationale for prescribing psychotropic medications. Second-generation antipsychotics were found to improve social skills, but the paucity of data limited the extent of clinical guidance necessary for the field. CONCLUSIONS: The systematic review showed that there are some clinical evidence displaying the validity of psychopharmacological interventions in people with FASD, which varies across the spectrum of disease severity, age, and gender. There is a need for more clinical evidencebased studies in addition to clinical expert opinions to substantiate an optimal ground for individualized management of FASD.The study protocol for this review was registered in PROSPERO with registration number CRD42016045703.

BackgroundBronchoprovocation challenges use direct or indirect acting stimuli to induce airflow obstruction. Indirect stimuli either non-allergic/non-IgE mediated (e.g. exercise, mannitol) or allergic/IgE mediated (i.e. allergen) trigger mast cells to release bronchoconstricting mediators (e.g. cysteinyl leukotrienes, histamine). Performing repeat challenges within a short timeframe (e.g. 3 h) with non-allergic indirect stimuli results in a diminished, refractory response to the second challenge that is inhibited by non-steroidal anti-inflammatory medications. Cross refractoriness occurs between indirect stimuli. It follows that repeat bronchoprovocation with allergen might exhibit refractoriness that might be altered by ibuprofen. We assessed the response to a second allergen challenge performed 24 h after an initial allergen challenge to determine if the response is refractory. If refractoriness developed, the study aimed to determine whether a single dose of ibuprofen would alter the refractory response to the second allergen challenge. In the absence of a refractory response, the study design allowed for the assessment of the effect of ibuprofen on allergen challenge outcomes, including indices of airway inflammation.MethodsThirteen mild atopic asthmatics were enrolled in a randomized, double-blind, placebo controlled, cross-over study. Ibuprofen (400 mg) or placebo was administered 1 h prior to the first of two allergen challenges, performed 24 h apart. Blood and sputum eosinophils, airway responsiveness to methacholine and levels of fractional exhaled nitric oxide were assessed before and 7 h after each allergen challenge. All data were log transformed and differences in geometric means were analyzed by paired t-tests.ResultsAfter placebo, early asthmatic responses for the two challenges were not significantly different (p = 0.82). A single 400 mg dose of ibuprofen decreased both the early (p = 0.03; n = 12) and late asthmatic responses (p = 0.03; n = 3).ConclusionAllergen challenges conducted 24 h apart do not exhibit refractoriness. Single dose ibuprofen inhibits early and late asthmatic responses to allergen bronchoprovocation. Ibuprofen should be withheld for at least 24 h prior to investigations utilizing allergen bronchoprovocation.Trial registration clinicaltrials.gov #NCT02327234

Background and objectiveIndividuals with Fetal Alcohol Spectrum Disorder (FASD) tend to be prescribed a high number of psychotropic medications to treat high rates of comorbid psychiatric disorders. A lack of guidance regarding best practices for prescribing psychotropic medications to individuals with FASD probably accounts for this reliance on polypharmacy. The objective of this study is to describe the types of medications prescribed to individuals with prenatal alcohol exposure, comparing rates between individuals diagnosed with FASD and individuals without FASD as well as how medications are prescribed based on age, sex, and comorbid psychiatric disorders. Material and methodsData were drawn from Canada’s national FASD database. This database includes information collected during an FASD assessment related to diagnostic outcomes, secondary challenges, and medical and mental health information. Descriptive statistics were calculated for four diagnostic groups (FASD with sentinel facial features [FASD + SFF], FASD without sentinel facial features [FASD - SFF], at risk for FASD [“at risk”], and no FASD). Group demographics were compared using Chi-Square, Fisher’s Exact Test, and ANOVA, as appropriate. Differences in the proportion of individuals between these four diagnostic groups were calculated using each of the following six classes of psychotropic medications—antipsychotics, antidepressants/anxiolytic, anticonvulsants/mood stabilizers, stimulants, melatonin, and others—using ANOVA. Considering just the individuals with FASD by combining the FASD + SFF and FASD - SFF groups, independent sample tests were used to compare differences in the proportion of males and females prescribed different medications. Chi-Square and Fisher’s Exact Test were used to compare the proportion of individuals using psychotropic medications, according to category, within the FASD group based on the presence or absence of 13 comorbid psychiatric disorders. ResultsThe overall sample included 2349 participants (mean value = 18.1 years, SD = 10.3). The sample included 1453 participants with an FASD diagnosis (n = 218, FASD + SFF, mean = 23.7 years, SD = 15.8, and n = 1235, FASD - SFF, mean = 19.5 years, SD = 10.0 years) and 896 participants who were assessed but did not receive an FASD diagnosis (n = 653, no FASD, mean = 16.1 years and n = 261, “at risk” for FASD, mean = 12.2 years). The FASD groups had a significantly higher rates of anxiety disorders, depressive disorders, and the presence of at least one comorbid psychiatric disorder compared to the no FASD and the “at risk” groups. Both FASD groups had a higher proportion of individuals taking antipsychotic and antidepressant/anxiolytic medications compared to the no FASD and “at risk” groups. Females with FASD were more often prescribed antidepressants/anxiolytics compared to males with FASD, while males with FASD were more often prescribed stimulants than females with FASD. The prevalence of antidepressants/anxiolytics, stimulants, and melatonin use by individuals with FASD differed across the lifespan. The prevalence of the prescription of six medication categories was found to differ according to psychiatric disorder. ConclusionCompared to individuals assessed as not fulfilling criteria for FASD, those with FASD had higher rates of psychiatric disorders and were prescribed significantly more antidepressants/anxiolytics and antipsychotics. The class and rate of prescriptions may support efforts in devising treatment guidelines for a complex disorder with known high comorbidity such as FASD.

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