Treatments for ADHD in Children and Adolescents: A Systematic Review.

CONTEXT: Effective treatment of attention-deficit/hyperactivity disorder (ADHD) is essential to improving youth outcomes. OBJECTIVES: This systematic review provides an overview of the available treatment options. DATA SOURCES: We identified controlled treatment evaluations in 12 databases published from 1980 to June 2023; treatments were not restricted by intervention content. STUDY SELECTION: Studies in children and adolescents with clinically diagnosed ADHD, reporting patient health and psychosocial outcomes, were eligible. Publications were screened by trained reviewers, supported by machine learning. DATA EXTRACTION: Data were abstracted and critically appraised by 1 reviewer and checked by a methodologist. Data were pooled using random-effects models. Strength of evidence and applicability assessments followed Evidence-based Practice Center standards. RESULTS: In total, 312 studies reported in 540 publications were included. We grouped evidence for medication, psychosocial interventions, parent support, nutrition and supplements, neurofeedback, neurostimulation, physical exercise, complementary medicine, school interventions, and provider approaches. Several treatments improved ADHD symptoms. Medications had the strongest evidence base for improving outcomes, including disruptive behaviors and broadband measures, but were associated with adverse events. LIMITATIONS: We found limited evidence of studies comparing alternative treatments directly and indirect analyses identified few systematic differences across stimulants and nonstimulants. Identified combination of medication with youth-directed psychosocial interventions did not systematically produce better results than monotherapy, though few combinations have been evaluated. CONCLUSIONS: A growing number of treatments are available that improve ADHD symptoms and other outcomes, in particular for school-aged youth. Medication therapies remain important treatment options but are associated with adverse events.

Combat and Operational Stress Control Interventions and PTSD: A Systematic Review and Meta-Analysis.

INTRODUCTION: Military personnel must prepare for and respond to life-threatening crises on a daily basis. This lifestyle places stress on personnel, and particularly so on deployed service members who are isolated from support systems and other resources. As part of a larger systematic review on the acceptability, efficacy, and comparative effectiveness of interventions designed to prevent, identify, and manage stress reactions, we assessed posttraumatic stress disorder (PTSD) outcomes. MATERIALS AND METHODS: We searched the electronic databases PsycINFO, PubMed, PTSDPubs, the Defense Technical Information Center, and Cochrane Central, as well as bibliographies of existing systematic reviews, to identify English-language studies evaluating the efficacy or comparative effectiveness of stress control interventions published since 1990. Controlled trials and cohort comparisons of interventions with military, law enforcement, and first responders were included. Two independent reviewers screened literature using predetermined eligibility criteria. Researchers individually abstracted study-level information and outcome data and assessed the risk of bias of included studies; data were reviewed for accuracy by the project leader. Changes in PTSD symptom scores from baseline to post-intervention were converted to standardized mean differences for comparison across studies. Risk ratios were calculated for PTSD case rates post-deployment. When several studies that compared an intervention group with a similar control/comparator reported the same outcome category and measure type, we conducted meta-analysis. We conducted meta-regression by adding a categorical variable, representing setting (i.e., in theater) or population (military vs. law enforcement or first responders) to the meta-analysis model to assess whether this variable was associated with the outcome across studies. The quality of the body of evidence (QoE) was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, which considers study limitations (risk of bias), directness, consistency, precision, and publication bias. RESULTS: Sixteen controlled trials and 13 cohort comparisons reporting PTSD outcomes met inclusion criteria. Eight controlled trials and two cohort studies had high risk of bias, primarily due to poor, differential, or unknown response rate at follow-up. Twenty-four of the 29 studies included military personnel. Interventions included Acceptance-based Skills training, Attention Bias Modification training, stress inoculation with biofeedback, Critical Incident Stress Debriefing, group psychological debriefing, Eye Movement Desensitization and Reprocessing for sub-clinical stress, embedding mental health providers in theater, Third Location Decompression, reintegration programs, and a 3-week post-deployment residential program for psychological resource strengthening.Meta-analyses of studies comparing a group that received a stress control intervention to a group that did not receive an intervention found no significant difference in reduction in PTSD symptom scores (moderate QoE) or PTSD case rate post-deployment (low QoE). A meta-analysis of studies comparing a specific stress control intervention to an active comparator (usually standard stress management education) found no significant effect on PTSD symptom scores (moderate QoE). CONCLUSION: Although combat and operational stress control (COSC) interventions may play a valuable role in decreasing stress, decreasing absenteeism, and enabling return to duty, a systematic review of 29 studies that included a control/comparison group found little evidence that COSC is effective in preventing PTSD or decreasing PTSD symptom scores in military personnel.

Efficacy of mindfulness meditation for smoking cessation: A systematic review and meta-analysis.

BACKGROUND: Smokers increasingly seek alternative interventions to assist in cessation or reduction efforts. Mindfulness meditation, which facilitates detached observation and paying attention to the present moment with openness, curiosity, and acceptance, has recently been studied as a smoking cessation intervention. AIMS: This review synthesizes randomized controlled trials (RCTs) of mindfulness meditation (MM) interventions for smoking cessation. METHODS: Five electronic databases were searched from inception to October 2016 to identify English-language RCTs evaluating the efficacy and safety of MM interventions for smoking cessation, reduction, or a decrease in nicotine cravings. Two independent reviewers screened literature using predetermined eligibility criteria, abstracted study-level information, and assessed the quality of included studies. Meta-analyses used the Hartung-Knapp-Sidik-Jonkman method for random-effects models. The quality of evidence was assessed using the GRADE approach. FINDINGS: Ten RCTs of MM interventions for tobacco use met inclusion criteria. Intervention duration, intensity, and comparison conditions varied considerably. Studies used diverse comparators such as the American Lung Association's Freedom from Smoking (FFS) program, quitline counseling, interactive learning, or treatment as usual (TAU). Only one RCT was rated as good quality and reported power calculations indicating sufficient statistical power. Publication bias was detected. Overall, mindfulness meditation did not have significant effects on abstinence or cigarettes per day, relative to comparator groups. The small number of studies and heterogeneity in interventions, comparators, and outcomes precluded detecting systematic differences between adjunctive and monotherapy interventions. No serious adverse events were reported. CONCLUSIONS: MM did not differ significantly from comparator interventions in their effects on tobacco use. Low-quality evidence, variability in study design among the small number of existing studies, and publication bias suggest that additional, high-quality adequately powered RCTs should be conducted.

Mindfulness Meditation for Chronic Pain: Systematic Review and Meta-analysis.

BACKGROUND: Chronic pain patients increasingly seek treatment through mindfulness meditation. PURPOSE: This study aims to synthesize evidence on efficacy and safety of mindfulness meditation interventions for the treatment of chronic pain in adults. METHOD: We conducted a systematic review on randomized controlled trials (RCTs) with meta-analyses using the Hartung-Knapp-Sidik-Jonkman method for random-effects models. Quality of evidence was assessed using the GRADE approach. Outcomes included pain, depression, quality of life, and analgesic use. RESULTS: Thirty-eight RCTs met inclusion criteria; seven reported on safety. We found low-quality evidence that mindfulness meditation is associated with a small decrease in pain compared with all types of controls in 30 RCTs. Statistically significant effects were also found for depression symptoms and quality of life. CONCLUSIONS: While mindfulness meditation improves pain and depression symptoms and quality of life, additional well-designed, rigorous, and large-scale RCTs are needed to decisively provide estimates of the efficacy of mindfulness meditation for chronic pain.

Omega-3 Fatty Acids and Maternal and Child Health: An Updated Systematic Review.

OBJECTIVES: To update a prior systematic review on the effects of omega-3 fatty acids (n-3 FA) on maternal and child health and to assess the evidence for their effects on, and associations with, additional outcomes. DATA SOURCES: MEDLINE®, Embase®, the Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Centre for Agriculture and Biosciences (CAB) Abstracts from 2000 to August 2015; eligible studies from the original report; and relevant systematic reviews. REVIEW METHODS: We included randomized controlled trials (RCTs) of any defined dose of n-3 FA (or combination) compared to placebo, any other n-3 FA, or alternative dose with an outcome of interest conducted in pregnant or breastfeeding women or neonates (preterm or term). We also included prospective observational studies that analyzed the association between baseline n-3 FA intake or biomarker level and followup outcomes. Postnatal interventions began within a week of birth for term infants and within a week of beginning enteral or oral feeding for preterm infants. Standard methods were used for data abstraction and analysis, according to the Evidence-based Practice Center Methods Guide. RESULTS: We identified 4,275 potentially relevant titles from our searches, of which 95 RCTs and 48 observational studies met the inclusion criteria. Risk of bias was a concern with both RCTs and observational studies. Outcomes for which evidence was sufficient to draw a conclusion are summarized here with the Strength of Evidence (SoE). (Outcomes for which the evidence was insufficient to draw a conclusion are summarized in Appendix G of the report.).Maternal Exposures and Outcomes: Gestational length and risk for preterm birth: Prenatal algal docosahexaenoic acid (DHA) or DHA-enriched fish oil supplementation had a small positive effect on length of gestation (moderate SoE), but no effect on risk for preterm birth (low SoE). Prenatal EPA (eicosapentaenoic acid) plus DHA-containing fish oil supplementation has no effect on length of gestation (low SoE). Supplementation with DHA, or EPA plus DHA-, or DHA-enriched fish oil does not decreaserisk for preterm birth (low SoE).Birth weight and risk for low birth weight: Changes in maternal n-3 FA biomarkers were significantly associated with birth weight. Prenatal algal DHA or DHA-enriched fish oil supplementation had a positive effect on birth weight among healthy term infants (moderate SoE), but prenatal DHA supplementation had no effect on risk for low birth weight (low SoE). Prenatal EPA plus DHA or alpha-linolenic acid (ALA) supplementation had no effect on birth weight (low SoE).Risk for peripartum depression: Maternal n-3 FA biomarkers had no association with risk for peripartum depression. Maternal DHA, EPA, or DHA-enriched fish oil supplementation had no effect on risk for peripartum depression (low SoE).Risk for gestational hypertension/preeclampsia: Prenatal DHA supplementation among high-risk pregnant women had no effect on the risk for gestational hypertension or preeclampsia (moderate SoE). Prenatal supplementation of any n-3 FA in normal-risk women also had no significant effect on risk for gestational hypertension or preeclampsia (low SoE).Fetal, Infant, and Child Exposures and Outcomes: Postnatal growth patterns: Maternal fish oil or DHA plus EPA supplementation had no effect on postnatal growth patterns (attainment of weight, length, and head circumference) when administered prenatally (moderate SoE) or both pre- and postnatally (low SoE). Fortification of infant formulas with DHA plus arachidonic acid (AA, an n-6 FA) had no effect on growth patterns of preterm or term infants (low SoE).Visual acuity: Prenatal supplementation with DHA had no effect on development of visual acuity (low SoE). Supplementing or fortifying preterm infant formula with any n-3 FA had no significant effect on visual acuity assessed by visual evoked potentials (VEP) at 4 or 6 months corrected age (low SoE). Data conflicted on the effectiveness of supplementing infant formula for term infants with n-3 FA depending on when and how visual acuity was assessed (i.e. by VEP or by behavioral methods) and the type of essential FA provided (low SoE).Neurological development: Prenatal or postnatal n-3 FA supplementation had no consistent effect on neurological development (low SoE).Cognitive development: Prenatal DHA supplementation with AA or EPA had no effect on cognitive development (moderate SoE). Supplementing breastfeeding women with DHA plus EPA also had no effect on cognitive development in infants and children (low SoE). Supplementing or fortifying preterm infants' formula with DHA plus AA had a positive effect on infant cognition at some short-term followup times (moderate SoE). Supplementing or fortifying infant formula for term infants with any n-3 FA had no effect on cognitive development (low SoE). Evidence is insufficient to support any effect of n-3 FA infant supplementation on long-term cognitive outcomes.Autism spectrum disorder, attention deficit hyperactivity disorder (ADHD), and learning disorders: Maternal or infant n-3 FA supplementation had no effect on risk for autism spectrum disorders or ADHD (low SoE). No studies on other learning disorders were identified.Atopic dermatitis (AD), allergies, and respiratory disorders: Pre- and postnatal (maternal and infant) n-3 FA supplementation had no consistent effect on the risk for AD/eczema, allergies, asthma, and other respiratory illnesses (moderate SoE). Biomarkers and intakes had no consistent association with the risk for AD, allergies, and respiratory disorders (low SoE).Adverse events: Prenatal and infant supplementation with n-3 FA or fortification of foods with n-3 FA did not result in any serious or nonserious adverse events (moderate SoE); with the exception of an increased risk for mild gastrointestinal symptoms. CONCLUSIONS: Most studies in this report examined the effects of fish oil (or other combinations of DHA and EPA) supplements on pregnant or breastfeeding women or the effects of infant formula fortified with DHA plus AA. As with the original report, with the exception of small increases in birth weight and length of gestation,n-3 FA supplementation or fortification has no consistent evidence of effects on peripartum maternal or infant health outcomes. No effects of n-3 FA were seen on gestational hypertension, peripartum depression, or postnatal growth. Apparent effects of n-3 FA supplementation were inconsistent across assessment methods and followup times for outcomes related to infant visual acuity, cognitive development and prevention of allergy and asthma. Future RCTs need to assess standardized preparations of n-3 and n-6 FA, using a select group of clinically important outcomes, on populations with baseline n-3 FA intakes typical of those of most western populations.

Bariatric surgery in women of reproductive age: special concerns for pregnancy.

CONTEXT: The use of bariatric surgery for treating severe obesity has increased dramatically over the past 10 years; about half of patients who undergo these procedures are women of reproductive age. This report was commissioned to measure the incidence of bariatric surgery in this population and review the evidence on the impact of bariatric surgery on fertility and subsequent pregnancy. OBJECTIVES: To measure the incidence of contemporary bariatric surgery procedures in women age 18-45 and to assess its impact on fertility, contraception, prepregnancy risk factors, and pregnancy outcomes, including those of neonates. DATA SOURCES AND STUDY SELECTION: Nationwide Inpatient Sample (NIS), a national sample of over 1,000 hospitals, to measure the trend in the number of women of reproductive age who underwent bariatric procedures from 1998-2005. We searched numerous electronic databases, including MEDLINE and Embase, for potentially relevant studies involving bariatric surgery (gastric bypass, laparoscopic adjustable gastric band, vertical-banded gastroplasty, biliopancreatic diversion), and consequent fertility, contraception, pregnancy, weight management, maternal and neonatal outcomes, and nutritional deficiencies. We scanned reference lists for additional relevant articles and contacted experts in the fields of bariatric surgery and obstetrics/gynecology (OB/GYN). Of 223 screened articles, we accepted 57 that reported on fertility following surgery (19 articles), contraception use/recommendations (11), maternal weight or nutrition management (28), maternal outcomes including morbidity and mortality (48), cesarean-section rates (16), and neonatal outcomes (44). These articles included reports on gastric bypass, both open and laparoscopic (27 articles), laparoscopic adjustable band (15), biliopancreatic diversion (16), and vertical-banded gastroplasty (6). Studies could contribute to one or more analyses. We found one case-control study and the observational data accepted included 12 cohort studies, 21 case series, and 23 individual case reports. DATA EXTRACTION: We abstracted information about study design, fertility history, fertility outcomes, prepregnancy weight loss, nutritional management, outcomes following pregnancy, and adverse events (during pregnancy) related to surgery. DATA SYNTHESIS: Nationally representative data showed a six-fold increase in bariatric surgery inpatient procedures from 1998 to 2005. Women age 18-45 accounted for about half of the patients undergoing bariatric surgery; over 50,000 have these procedures as inpatients annually. An unknown number have outpatient bariatric procedures. We identified one case-control study that directly addressed some of the key questions, but no randomized controlled trials or prospective cohort studies, which would be the strongest study designs to answer questions about effectiveness, risk and prognosis. Consequently, all of our conclusions are limited by the available data, and are cautious.The evidence suggests that bariatric surgery results in improved fertility; the strongest evidence is in women with the polycystic ovarian syndrome, where biochemical studies showing normalization of hormones after surgery support case series data. Observational studies (retrospective cohorts and case series) suggest that fertility improves following bariatric procedures and weight loss; similar to that seen when obese women lose weight through nonsurgical means. There is almost no evidence on post-surgical contraceptive efficacy or use. Research is needed to determine whether differences in absorption, particularly for oral contraceptives, affect contraceptive efficacy. Nutrient deficiencies were reported in infants born to women who underwent procedures that resulted in malabsorption, as well as women who did not take prenatal vitamins or had difficulty with their own nutrition (i.e., from chronic vomiting). Literature suggests that gastric bypass and laparoscopic adjustable band procedures confer only minimal, if any, increased risk of nutritional or congenital problems if supplemental vitamins are taken and maternal nutrition is otherwise adequate. Biliopancreatic diversion has an appreciable risk for nutritional problems in some patients. Women who have undergone bariatric surgery may have less risk than obese women for certain pregnancy complications such as gestational diabetes, preeclampsia, and pregnancy induced hypertension. There is no evidence that cesarean section rates and delivery complications are higher in the post-surgery group, but data are limited. CONCLUSIONS: Weight loss procedures are being performed more frequently to treat morbid obesity, with a six-fold increase over a recent 7-year time span; almost half of all patients are women of reproductive age. The level of evidence on fertility, contraception, and pregnancy outcomes is limited to observational studies. Data suggest that fertility improves after bariatric surgical procedures, nutritional deficiencies for mother and child are minimal, and maternal and neonatal outcomes are acceptable with laparoscopic adjustable band and gastric bypass as long as adequate maternal nutrition and vitamin supplementation are maintained. There is no evidence that delivery complications are higher in post-surgery pregnancies.

Psychiatric symptoms associated with ephedra use.

The objective of this review is to describe psychiatric adverse events occurring after ingestion of dietary supplements containing herbal ephedra and to assess the possible relationship between supplement use and the events. The authors reviewed all adverse event reports related to dietary supplements containing herbal ephedra from US FDA MedWatch files as of 30 September, 2001. Psychosis, mania or severe agitation, severe depression, hallucinations, delusions, suicide attempts, paranoia and violent behaviour were classified as serious psychiatric events. Events were categorised based on the amount of information supporting a causal relationship. Out of almost 1800 total adverse events, 57 were classified as both psychiatric in nature and serious. Two-thirds of these psychiatric cases involved patients with pre-existing psychological/psychiatric conditions and/or use of other mood-altering medications or illicit substances. The majority of case reports were insufficiently documented to make an informed judgment about a relationship between the use of ephedra and the adverse event in question. The case reports evaluated do not prove a definitive causal link between ephedra and psychiatric complications. However, they do raise concern that such a relationship may exist.

Psychiatric effects of ephedra use: an analysis of Food and Drug Administration reports of adverse events.

OBJECTIVE: As part of a synthesis of evidence regarding the efficacy and safety of ephedra, the authors describe data on psychiatric adverse events from reports submitted to the Food and Drug Administration (FDA). METHOD: The authors reviewed all 1,820 adverse event reports related to dietary supplements containing herbal ephedra from FDA MedWatch files as of Sept. 30, 2001. Fifty-seven serious psychiatric events were reported. RESULTS: The most commonly reported events were psychosis, severe depression, mania or agitation, hallucinations, sleep disturbance, and suicidal ideation. Ten events involved physical harm to self or others; five events resulted in legal action due to criminal behavior. Twenty-six events resulted in hospitalization, at least six of which were involuntary. Of importance, two-thirds of all cases involved patients with preexisting psychiatric conditions and /or use of other medications or illicit substances. CONCLUSIONS: Clinicians should be aware that serious psychiatric symptoms could be associated with ephedra use.

Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis.

CONTEXT: Ephedra and ephedrine sometimes are used for weight loss or enhanced athletic performance, but the efficacy and safety of these compounds are uncertain. OBJECTIVE: To assess the efficacy and safety of ephedra and ephedrine used for weight loss and enhanced athletic performance. DATA SOURCES: We searched 9 databases using the terms ephedra, ephedrine, adverse effect, side effect, efficacy, effective, and toxic. We included unpublished trials and non-English-language documents. Adverse events reported to the US Food and Drug Administration MedWatch program were assessed. STUDY SELECTION: Eligible studies were controlled trials of ephedra or ephedrine used for weight loss or athletic performance and case reports of adverse events associated with such use. Eligible studies for weight loss were human studies with at least 8 weeks of follow-up; and for athletic performance, those having no minimum follow-up. Eligible case reports documented that ephedra or ephedrine was consumed within 24 hours prior to an adverse event or that ephedrine or an associated product was found in blood or urine, and that other potential causes had been excluded. Of the 530 articles screened, 52 controlled trials and 65 case reports were included in the adverse events analysis. Of more than 18 000 other case reports screened, 284 underwent detailed review. DATA EXTRACTION: Two reviewers independently identified trials of efficacy and safety of ephedra and ephedrine on weight loss or athletic performance; disagreements were resolved by consensus. Case reports were reviewed with explicit and implicit methods. DATA SYNTHESIS: No weight loss trials assessed duration of treatment greater than 6 months. Pooled results for trials comparing placebo with ephedrine (n = 5), ephedrine and caffeine (n = 12), ephedra (n = 1), and ephedra and herbs containing caffeine (n = 4) yielded estimates of weight loss (more than placebo) of 0.6 (95% confidence interval, 0.2-1.0), 1.0 (0.7-1.3), 0.8 (0.4-1.2), and 1.0 (0.6-1.3) kg/mo, respectively. Sensitivity analyses did not substantially alter the latter 3 results. No trials of ephedra and athletic performance were found; 7 trials of ephedrine were too heterogeneous to synthesize. Safety data from 50 trials yielded estimates of 2.2- to 3.6-fold increases in odds of psychiatric, autonomic, or gastrointestinal symptoms, and heart palpitations. Data are insufficient to draw conclusions about adverse events occurring at a rate less than 1.0 per thousand. The majority of case reports are insufficiently documented to allow meaningful assessment. CONCLUSIONS: Ephedrine and ephedra promote modest short-term weight loss (approximately 0.9 kg/mo more than placebo) in clinical trials. There are no data regarding long-term weight loss, and evidence to support use of ephedra for athletic performance is insufficient. Use of ephedra or ephedrine and caffeine is associated with increased risk of psychiatric, autonomic, or gastrointestinal symptoms, and heart palpitations.