Impact of endometriosis on women's life decisions and goal attainment: a cross-sectional survey of members of an online patient community.

OBJECTIVES: To examine women's perceptions of endometriosis-associated disease burden and its impact on life decisions and goal attainment. DESIGN: An anonymous online survey was distributed in October 2018 through the social media network MyEndometriosisTeam.com. PARTICIPANTS: Women aged 19 years and older living in several English-speaking countries who self-identified as having endometriosis. OUTCOME MEASURES: Patients' perspectives on how endometriosis has affected their work, education, relationships, overall life decisions and attainment of goals. Subanalyses were performed for women who identified as 'less positive about the future' (LPAF) or had 'not reached their full potential' (NRFP) due to endometriosis. RESULTS: 743 women completed the survey. Women reported high levels of pain when pain was at its worst (mean score, 8.9 on severity scale of 0 (no pain) to 10 (worst imaginable pain)) and most (56%, n=415) experienced pain daily. Women reported other negative experiences attributed to endometriosis, including emergency department visits (66%, n=485), multiple surgeries (55%, n=406) and prescription treatments for symptoms of endometriosis (72%, n=529). Women indicated that they believed endometriosis had a negative impact on their educational and professional achievements, social lives/relationships and overall physical health. Most women 'somewhat agreed'/'strongly agreed' that endometriosis caused them to lose time in life (81%, n=601), feel LPAF (80%, n=589) and feel they had NRFP (75%, n=556). Women who identified as LPAF or NRFP generally reported more negative experiences than those who were non-LPAF or non-NRFP. CONCLUSIONS: Women who completed this survey reported pain and negative experiences related to endometriosis that were perceived to negatively impact major life-course decisions and attainment of goals. Greater practitioner awareness of the impact that endometriosis has on a woman's life course and the importance of meaningful dialogue with patients may be important for improving long-term management of the disease and help identify women who are most vulnerable.

Development of a visual, patient-reported tool for assessing the multi-dimensional burden of endometriosis.

OBJECTIVE: Inadequate communication about endometriosis symptom burden between women and healthcare providers is a barrier for optimal treatment. This study describes the development of the EndoWheel, a patient-reported assessment tool that visualizes the multi-dimensional burden of endometriosis to facilitate patient-provider communication. METHODS: Assessment questions for the tool were developed using an iterative Delphi consensus process. A consensus phase included additional practitioners and specialists to broaden perspectives and select revised statements. Semi-structured qualitative interviews were conducted with 13 women with endometriosis to assess the scoring and content of the measures. RESULTS: Symptoms included in the tool were pelvic pain, vaginal bleeding, bowel/bladder symptoms, energy levels, fertility, impact on activities, emotional and sexual well-being, and self-perceived global health. Additional life impact areas included relationships, social and occupational activity, and self-perception. The 13 interviewees completed the tool in approximately 5-6 min (range 4.0-7.5 min). Most participants (92%) perceived that the tool would enable better patient-provider communication, including addressing symptoms and areas of impact not normally discussed during office visits. CONCLUSION: Similar to visual circular tools used in burden assessment of other chronic diseases, the tool may facilitate improved patient dialogue with providers around endometriosis treatment goals and options.

Impact of Endometriosis on Life-Course Potential: A Narrative Review.

Endometriosis may exert a profound negative influence on the lives of individuals with the disorder, adversely affecting quality of life, participation in daily and social activities, physical and sexual functioning, relationships, educational and work productivity, mental health, and well-being. Over the course of a lifetime, these daily challenges may translate into limitations in achieving life goals such as pursuing or completing educational opportunities; making career choices or advancing in a chosen career; forming stable, fulfilling relationships; or starting a family, all of which ultimately alter one's life trajectory. The potential for endometriosis to impact the life course is considerable, as symptom onset generally occurs at a time of life (menarche through menopause, adolescence through middle age) when multiple life-changing and trajectory-defining decisions are made. Using a life-course approach, we examine how the known effects of endometriosis on life-domain satisfaction may impact health and well-being across the life course of affected individuals. We provide a quasi-systematic, narrative review of the literature as well as expert opinion on recommendations for clinical management and future research directions.

The effects of concomitant immunomodulators on the pharmacokinetics, efficacy and safety of adalimumab in paediatric patients with Crohn's disease: a post hoc analysis.

BACKGROUND: In the IMAgINE 1 study, adalimumab induced and maintained remission of moderate-to-severe Crohn's disease in children. AIM: To assess the efficacy, pharmacokinetics, immunogenicity and safety of immunomodulator and adalimumab combination therapy vs adalimumab monotherapy in paediatric patients with Crohn's disease. METHODS: Patients 6-17 years old with moderate-to-severe Crohn's disease (n = 192) received weight-based adalimumab induction at baseline and week 2. At week 4, 188 patients were randomised to high-dose or low-dose adalimumab. Patients receiving immunomodulators (investigator's decision) at baseline maintained a stable dose until week 26; patients could then discontinue immunomodulators. Adalimumab serum concentrations were measured at weeks 4, 26 and 52. Safety was evaluated at each study visit. Data were analysed using non-responder imputation (NRI; week 4) or modified NRI (weeks 26; 52). RESULTS: At week 4, patients with (n = 117) and without (n = 71) baseline immunomodulator use had similar response (79%; 87%; P = 0.235) and remission (26%; 30%; P = 0.737) rates. At week 26, patients with and without baseline immunomodulators had no significant difference in response (68%; 55%; P = 0.086) or remission (41%; 30%; P = 0.122). At week 52, patients with (n = 82) and without (n = 106) immunomodulator use had no significant difference in response (56%; 46%; P = 0.189) or remission (38%; 33%; P = 0.539). Adalimumab serum trough concentrations and serious infection rates (7%; 6%) were not significantly different between groups. CONCLUSIONS: Analyses found no statistically significant difference in response or remission between patients receiving adalimumab monotherapy vs immunomodulator and adalimumab combination therapy. Serious and infectious adverse event rates were similar between groups.

Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2.

BACKGROUND AND AIMS: Adalimumab has been shown to be more effective than placebo in healing fistulae in adults with moderately to severely active Crohn's disease. The efficacy and safety of adalimumab in healing fistulae in children/adolescents with Crohn's disease from the 52-week IMAgINE 1 clinical trial, and its open-label extension IMAgINE 2, are reported. METHODS: Children/adolescents with perianal fistulae at baseline of IMAgINE 1 were assessed for fistula closure and improvement during IMAgINE 1 [Weeks 0-52] and from Week 0 of IMAgINE 2 [Week 52 of IMAgINE 1] through to Week 240 of IMAgINE 2 using non-responder imputation. RESULTS: A total of 36 children/adolescents had fistulae at baseline of IMAgINE 1 and were included in the analysis. Fistula closure and improvement were observed in 44.4% and 52.8%, respectively, at Week 12. Rates of closure and improvement were maintained throughout the analysis period to Week 292. No new safety signals were identified. CONCLUSIONS: In children/adolescents with moderately to severely active, fistulizing Crohn's disease, adalimumab induced perianal fistula closure and improvement within 12 weeks of treatment, with rates that were sustained for more than 5 years. The safety profile of adalimumab in patients with fistulae at baseline was similar to that of the overall population in IMAgINE 1/2. ClinicalTrials.gov identifiers: IMAgINE 1 (NCT00409682); IMAgINE 2 (NCT00686374).

Extraintestinal Manifestations in Vedolizumab and Anti-TNF-Treated Patients With Inflammatory Bowel Disease.

BACKGROUND: Extra-intestinal manifestations (EIMs) can impact morbidity in patients with inflammatory bowel diseases (IBD; Crohn's disease [CD] and ulcerative colitis [UC]). This study compared incidence rates of EIMs in patients with moderate to severe IBD receiving gut-selective vedolizumab (VDZ) vs those receiving systemic anti-tumor necrosis factor (anti-TNF) therapies. METHODS: Adult IBD patients receiving VDZ or anti-TNFs were identified from the MarketScan claims database from September 28, 2012, through September 30, 2016. Incidence rates of EIMs were compared between the 2 cohorts. Descriptive analyses were performed for all courses of treatment. Generalized linear models estimated the impact of treatment on the likelihood of developing EIMs. RESULTS: Compared with patients receiving anti-TNF therapy, VDZ-treated CD patients were 28% more likely to develop "any EIMs" (adjusted incident rate ratio [IRR], 1.28; 95% confidence interval [CI], 1.02-1.62). Specifically, CD patients treated with VDZ were more likely to develop erythema nodosum (IRR, 4.29; 95% CI, 1.73-10.64), aphthous stomatitis (IRR, 3.73; 95% CI, 1.51-9.23), episcleritis/scleritis (IRR, 2.51; 95% CI, 1.02-6.14), arthropathy (IRR, 1.45; 95% CI, 1.15-1.84), primary sclerosing cholangitis (PSC) (IRR, 7.79; 95% CI, 3.32-18.27), and uveitis/iritis (IRR, 2.89; 95% CI, 1.35-6.18). UC patients receiving VDZ did not have a statistically significant increase in "any EIMs" vs patients receiving anti-TNFs, but were more likely to develop specific EIMs (aphthous stomatitis: IRR, 3.67; 95% CI, 1.30-10.34; pyoderma gangrenosum: IRR, 4.42; 95% CI, 1.00-19.45; and PSC: IRR, 3.44; 95% CI, 1.23-9.68). CONCLUSIONS: IBD patients receiving VDZ may be more likely to develop EIMs vs patients receiving anti-TNF therapies. The gut-selective inflammatory control of VDZ may potentially limit its clinical effect on EIM prevention.

Comparison of Health Care Utilization and Costs Between Patients with Perianal Fistulizing Crohn's Disease Treated with Biologics with or Without Previous Seton Placement.

BACKGROUND: Fistulas are a common and often debilitating complication of Crohn's disease (CD). Tumor necrosis factor inhibitors and/or seton drainage are effective treatment options. We compared health care utilization and costs for patients with perianal CD who had setons placed before treatment with biologics versus those who did not. METHODS: Patients with CD (≥18 yr) were identified from the Truven Health MarketScan Database by ICD-9 code 555.x (January 1, 2006-March 31, 2015); those with external fistulas were identified by ICD-9 codes 565.1. Biological treatment and seton procedures were identified with the National Drug Codes or Current Procedural Terminology codes. Patients were grouped into 2 cohorts: seton before biological (SBB) treatment or no seton before biological (NSBB) treatment. RESULTS: SBB (N = 326) and NSBB (N = 1519) groups were similar in baseline age, sex, use of immunosuppressants and steroids, and comorbidity score. Baseline prevalence of asthma and cardiovascular disease, and use of antibiotics and 5-aminosalicylic acid were significantly greater in the SBB group versus the NSBB group. Baseline number of all-cause and fistula-related hospitalizations were greater for the SBB group than in the NSBB group. However, during follow-up, the NSBB group required significantly more hospitalizations than the SBB group (all-cause: 0.41 versus 0.23; fistula related: 0.16 versus 0.07) and had significantly greater health care costs (all-cause: $9711 versus $5514; fistula related: $4156 versus $1900). Results were confirmed in multivariate regressions adjusting for baseline characteristics and prescription drug use. CONCLUSIONS: Patients who had the setons placed before treatment with biologics used fewer health care resources and incurred lower health care costs compared with those who did not have the procedure.

Growth Improvement with Adalimumab Treatment in Children with Moderately to Severely Active Crohn's Disease.

BACKGROUND: Growth failure is common in children with Crohn's disease. The effect of adalimumab (ADA), a fully human antitumor necrosis factor antagonist, on height velocity in pediatric patients with baseline (BL) linear growth impairment in the IMAgINE 1 trial is presented. METHODS: This analysis included female and male patients with growth potential (bone age ≤13 and ≤14 yr, respectively), with BL Pediatric Crohn's disease Activity Index >30, and who failed or were intolerant to conventional therapy. Patients received open-label induction ADA at weeks 0 and 2 by body weight (≥40 kg, 160 and 80 mg and <40 kg, 80 and 40 mg). At week 4, patients were randomized to double-blind high (40 or 20 mg for ≥40 kg or <40 kg) or low dose (20 or 10 mg for ≥40 kg or <40 kg) every other week ADA to week 52. Height velocity z-score was summarized at BL, week 26, and week 52 by patients with BL growth impairment (z-score ≤-1.0) or normal growth (z-score >-1.0). RESULTS: ADA therapy significantly improved and normalized growth rate at weeks 26 and 52 in patients with BL growth impairment (median z-score, BL, -3.25; week 26, -0.34; and week 52, 0.21; P < 0.001 versus BL for both), but not in patients with normal growth. Growth improvement was significantly greater at week 26 in week 4 responders to induction therapy compared with nonresponders (median z-score 0.09 versus -2.92; P = 0.02). CONCLUSIONS: ADA treatment resulted in growth rate normalization as early as week 26 in children with moderately to severely active Crohn's disease and growth impairment.

Long-term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease.

BACKGROUND: IMAgINE 1 assessed 52-week efficacy and safety of adalimumab in children with moderate to severe Crohn's disease. Long-term efficacy and safety of adalimumab for patients who entered the IMAgINE 2 extension are reported. METHODS: Patients who completed IMAgINE 1 could enroll in IMAgINE 2. Endpoints assessed from weeks 0 to 240 of IMAgINE 2 were Pediatric Crohn's Disease Activity Index remission (Pediatric Crohn's Disease Activity Index ≤ 10) and response (Pediatric Crohn's Disease Activity Index decrease ≥15 from IMAgINE 1 baseline) using observed analysis and hybrid nonresponder imputation (hNRI). For hNRI, discontinued patients were imputed as failures unless they transitioned to commercial adalimumab (with study site closure) or adult care, where last observation was carried forward. Corticosteroid-free remission in patients receiving corticosteroids at IMAgINE 1 baseline, discontinuation of immunomodulators (IMMs) in patients receiving IMMs at IMAgINE 2 baseline, and linear growth improvement were reported as observed. Adverse events were assessed for patients receiving ≥1 adalimumab dose in IMAgINE 1 and 2 through January 2015. RESULTS: Of 100 patients enrolled in IMAgINE 2, 41% and 48% achieved remission and response (hNRI) at IMAgINE 2 week 240. Remission rates were maintained by 45% (30/67, hNRI) of patients who entered IMAgINE 2 in remission. At IMAgINE 2 week 240, 63% (12/19) of patients receiving corticosteroids at IMAgINE 1 baseline achieved corticosteroid-free remission and 30% (6/20) of patients receiving IMMs at IMAgINE 2 baseline discontinued IMMs. Adalimumab treatment led to growth velocity normalization. No new safety signals were identified. CONCLUSIONS: Efficacy and safety profiles of prolonged adalimumab treatment in children with Crohn's disease were consistent with IMAgINE 1 and adult Crohn's disease adalimumab trials.

Characterisation of Mucosal Healing with Adalimumab Treatment in Patients with Moderately to Severely Active Crohn's Disease: Results from the EXTEND Trial.

BACKGROUND AND AIMS: Mucosal healing [MH] is an important goal for patients with Crohn's disease [CD], yet is incompletely characterised. We investigated whether MH differed by segments across the colon and ileum in patients who received adalimumab maintenance treatment in the EXTEND study. METHODS: In this double-blind study in adults with moderate to severe ileocolonic CD and mucosal ulceration, all patients received adalimumab induction [Week 0, 160 mg; Week 2, 80 mg]. At Week 4, patients were randomised to 40 mg adalimumab or placebo every other week until Week 52. In this post-hoc analysis, MH was assessed by CD Endoscopic Index of Severity [CDEIS], Simple Endoscopic Score for CD [SES-CD], and Colonic and Ileal Global Histologic Disease Activity Scores [CGHAS/IGHAS]. RESULTS: Baseline endoscopic severity was similar across segments. At Week 52, mean changes in CDEIS surface involved and ulcerated surface were -68.5% to -90.6% in the rectum, sigmoid/left colon, and transverse colon compared with -22.3% to -50.0% in the right colon and ileum. Favourable shifts by Week 52 in ulcer size and ulcerated surfaces per SES-CD were more pronounced in the rectum, sigmoid/left colon, and transverse colon vs the right colon and ileum. At Week 52, CGHAS and IGHAS healing was more common in the colon [28.3%] vs the ileum [21.2%]. CONCLUSIONS: This analysis suggests differing propensities of the ileocolonic segments to heal endoscopically during adalimumab treatment. In the sigmoid/left and transverse colon, higher MH rates may be achieved, compared with the ileum, in patients with moderate to severe CD.

Interpreting Registrational Clinical Trials of Biological Therapies in Adults with Inflammatory Bowel Diseases.

BACKGROUND: The use of biologics to treat inflammatory bowel disease is supported by robust randomized controlled trials in both ulcerative colitis and Crohn's disease. Nonetheless, an understanding of the principles of clinical trial design is necessary to extrapolate study findings to clinical practice. METHODS: We conducted a review of inflammatory bowel disease registrational clinical trials of biologics to determine how differences in trial design potentially influence results and interpretation. RESULTS: Registrational trials of biological agents have used diverse patient populations, outcome measures, and designs, which makes comparisons of results among studies difficult. Key differences among trials include patient populations, choice of symptom-based measures or objective outcomes as endpoints, and overall trial design. Additional factors, including analytical methods, can also influence the interpretation of outcomes. CONCLUSIONS: The most robust evidence is derived from comparative effectiveness trials. In the absence of these, clinicians should be aware of the various methodological issues which could impact interpretation of efficacy and safety outcomes, including differences in patient population, study design, and analytic methodology.

Efficacy and Safety of Escalation of Adalimumab Therapy to Weekly Dosing in Pediatric Patients with Crohn's Disease.

BACKGROUND: The efficacy of adalimumab in inducing and maintaining remission in children with moderately to severely active Crohn's disease was shown in the IMAgINE 1 trial (NCT00409682). As per protocol, nonresponders or patients experiencing flare(s) on every other week (EOW) maintenance dosing could escalate to weekly dosing; we aimed to determine the therapeutic benefits of weekly dose escalation in this subpopulation. METHODS: Week 52 remission and response rates were assessed in patients who escalated to weekly dosing from their previous EOW schedule, which was according to randomized treatment dose (higher dose [HD] adalimumab [≥40 kg, 40 mg EOW; <40 kg, 20 mg EOW] or lower dose [LD; ≥40 kg, 20 mg EOW; <40 kg, 10 mg EOW]). Adverse events were reported for patients remaining on EOW dosing and patients receiving weekly dosing. RESULTS: Escalation to weekly dosing occurred in 48/95 (50.5%) patients randomized to LD and 35/93 (37.6%) patients randomized to HD adalimumab (P = 0.076). Week 52 remission and response rates were 18.8% and 47.9% for patients receiving LD adalimumab weekly and 31.4% and 57.1% for patients receiving HD adalimumab weekly, respectively (LD versus HD, P = 0.19 for remission; P = 0.41 for response). Adverse event rates were similar for patients receiving EOW and weekly adalimumab. CONCLUSIONS: Weekly adalimumab dosing was clinically beneficial for children with Crohn's disease who experienced nonresponse or flare on EOW dosing. No increased safety risks were observed with weekly dosing.

Weekly active-learning activities in a drug information and literature evaluation course.

OBJECTIVES: To incorporate learning activities into the weekly 2-hour Drug Information and Literature Evaluation class sessions to improve student ability and confidence in performing course objectives, as well as to assess student perception of the value of these activities. METHODS: In-class activities that emphasized content and skills taught within class periods were created and implemented. Three different surveys assessing student ability and confidence in completing drug information and literature retrieval and evaluation tasks were administered prior to and following the appropriate class sessions. At the completion of the course, an additional evaluation was administered to assess the students' impressions of the value of the learning activities. RESULTS: Students reported increased ability and confidence in all course objectives. The teaching activities were also stated to be useful in students' learning of the material. CONCLUSIONS: Incorporation of weekly learning activities resulted in an improvement in student ability and confidence to perform course objectives. Students considered these activities to be beneficial and to contribute to the completion of course objectives.

Evaluating the accuracy of health news publications in a drug literature evaluation course.

OBJECTIVES: To design an assignment for second-professional year pharmacy students to assess the accuracy and quality of health information published in the news. DESIGN: Students in a literature evaluation course were assigned a health-related news publication to review and find the original published research article. They then critically evaluated the quality and accuracy of the news publication based on the original research. All students wrote a critique focusing on the quality and accuracy of the news article and potential responses the lay public might have. ASSESSMENT: Eighty-four percent of students agreed the writing assignment reinforced critical literature evaluation skills, while 90% agreed the assignment contributed to completion of course objectives. CONCLUSIONS: A writing assignment requiring comparison of a news publication to the original research reinforces critical literature evaluation and communication skills, as well as stimulates thought about the accuracy, quality, and public responses to health information published in the news.

Propofol-related infusion syndrome in critically ill pediatric patients: coincidence, association, or causation?

Over the past two decades numerous reports have described the development of a propofol-related infusion syndrome (PRIS) in critically ill adult and pediatric patients who received continuous infusion propofol for anesthesia or sedation. The syndrome is generally characterized by progressive metabolic acidosis, hemodynamic instability and bradyarrhythmias that are refractory to aggressive pharmacological treatments. PRIS may occur with or without the presence of hepatomegaly, rhabdomyolysis or lipemia. To date, the medical literature contains accounts of 20 deaths in critically ill pediatric patients who developed features consistent with PRIS. These reports have generated considerable discussion and debate regarding the relationship, if any, between propofol and a constellation of clinical symptoms and features that have been attributed to its use in critically ill pediatric patients. This paper reviews the literature concerning PRIS, its clinical presentation, proposed mechanisms for the syndrome, and potential management should the syndrome occur.

Evaluation of accuracy of health studies reported in mass media.

OBJECTIVE: To evaluate communication of clinical research in the written media for completeness and accuracy. DESIGN: Observational assessment. SETTING: United States. PARTICIPANTS: Not applicable. INTERVENTIONS: Content of media articles discussing randomized controlled trials was assessed by three reviewers on the basis of the Consolidated Standards of Reporting Trials (CONSORT) criteria modified for the mass media. Reports from October 1 through December 31, 2002, published in the top two U.S. daily newspapers (USA Today and Wall Street Journal), weekly news magazines (Time and Newsweek), and daily news Web sources (CNN.com and MSNBC.com) and the corresponding published RCTs were analyzed. MAIN OUTCOME MEASURES: Total score and score in 10 specific content areas, leading to classification of coverage as poor, fair, or excellent. RESULTS: A total of 60 media reports discussing results of 25 RCTs appeared in these media during the study period. All reports were categorized as fair, and no content area was rated excellent. Several content areas received poor rankings in all and/or most media, including reporting of adverse effects, outcomes data, and statistical tests used. Media reports written by newswire services were rated more highly than were those prepared by nonnewswire services, but only 1 of 10 criteria had statistically significant differences. CONCLUSION: Mass media reports of RCTs are often incomplete. This type of reporting may misinform the lay public and may lead to questions about the applicability of the results to individual patients.

Nebulized morphine for relief of dyspnea due to chronic lung disease.

OBJECTIVE: To evaluate the efficacy and safety of nebulized morphine for the management of dyspnea in chronic pulmonary diseases. DATA SOURCES: MEDLINE (1966-May 2004), EMBASE (1980-May 2004), and International Pharmaceutical Abstracts (1970-May 2004) searches were performed. Key search terms included morphine, dyspnea, and inhalation. DATA SYNTHESIS: Nine studies have evaluated the efficacy of nebulized morphine in relieving dyspnea. Three trials had positive results, but the rest failed to show improvement after treatment with doses ranging from 1 to 40 mg nebulized morphine. The small number of subjects, variety of disease states, and different outcome measures limit interpretation of the studies. CONCLUSIONS: Results from several small studies do not support the use of nebulized morphine for treatment of dyspnea; however, several positive case reports have been published.

Treatment of migraine headaches with sumatriptan in pregnancy.

OBJECTIVE: To review the literature for treatment of migraine headaches with sumatriptan during pregnancy. DATA SOURCES: Studies and reports were located in International Pharmaceutical Abstracts (1970-September 2003) and MEDLINE (1966-week 3 September 2003). DATA SYNTHESIS: Research has been performed to evaluate the risk of teratogenesis after sumatriptan exposure in pregnant patients. Data have been collected in areas including placental transmission of sumatriptan, prospective pregnancy registries, open-labeled and controlled prospective studies, and a retrospective prescription-linked study. As of August 6, 2004, no randomized controlled trials have been conducted with exposure to sumatriptan during pregnancy. CONCLUSIONS: Teratogenesis occurs in approximately 150 000 births per year which represents an incidence of 3-5%. Available literature to date indicates that exposure to sumatriptan during pregnancy has no additional risk of birth defects compared with the incidence in the general population.

Treating functional impairment of autism with selective serotonin-reuptake inhibitors.

OBJECTIVE: To review literature describing use of selective serotonin-reuptake inhibitors (SSRIs) in the management of functional impairments associated with autistic disorder. DATA SOURCES: EMBASE (1980-3rd quarter of 2003), International Pharmaceutical Abstracts (1970-August 2003), and MEDLINE (1966-August 2003) were searched. Search terms included autism, autistic disorder, citalopram, fluoxetine, fluvoxamine, paroxetine, selective serotonin-reuptake inhibitors, and sertraline. DATA SYNTHESIS: Studies and case reports evaluating treatment outcomes associated with the use of SSRIs in managing impairments of autism were reviewed. Multiple SSRI dosing ranges were evaluated in autistic patients of different ages with various functional impairments. No specific SSRI or dose range has been shown to improve a specific autistic symptom although some patients have demonstrated improvements. CONCLUSIONS: Benefits with SSRIs in treating functional impairments in autism have been observed. Response to therapy and adverse effects are individualized. Current evidence does not support selection of one SSRI over another for any impairment associated with autism.