Pharmacological treatments for fatigue in patients with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Multiple sclerosis (MS) is a chronic immune-mediated inflammatory disease. Fatigue is the most common symptom of MS patients, affecting >80% subjects. Medical treatment is an important method for managing fatigue. Currently, although many drugs have been tested in treatment of MS fatigue, the efficacy of these drugs remain largely unclear. METHODS: We researched available literatures in PubMed, Embase, Medline, Google Scholar, Cochrane Library (August 31, 2016). Search terms included multiple sclerosis, fatigue, medication treatments, amantadine, modafinil, aspirin, acetyl-l-carnitine, pemoline, 4-aminopyridine and randomized controlled trial (RCT). Two researchers were required to independently assess the quality of literatures, and finish data extraction. Meta-analysis was conducted using RevMan 5.3 software. FINDINGS: A total of 11 RCTs involving 723 patients were included. The therapeutic effects were quantified by different scales, such as Modified Fatigue Impact Scale (MFIS) or Fatigue Severity Scale (FSS). Here, meta-analysis suggested that amantadine, not modafinil, was effective for treating the fatigue in MS. Moreover, two studies implied that l-carnitine might have similar therapeutic effect with amantadine. However, the reliability of this finding was greatly weakened by the limited sample sizes. Additionally, current data could not answer whether treatment of MS fatigue using aspirin or 4-aminopyridine was beneficial. Finally, we found that all drugs except pemoline were relatively safe for treating MS fatigue. CONCLUSIONS: Current limited data suggest that amantadine may be the only drug that has relatively sufficient evidences in treatment of fatigue symptoms in MS. Further RCT studies recruiting larger samples sizes are required to validate the therapeutic effect of these candidate drugs.

Pharmacological treatments for fatigue associated with palliative care.

BACKGROUND: This review updates the original review, 'Pharmacological treatments for fatigue associated with palliative care' and also incorporates the review 'Drug therapy for the management of cancer-related fatigue'.In healthy individuals, fatigue is a protective response to physical or mental stress, often relieved by rest. By contrast, in palliative care patients' fatigue can be severely debilitating and is often not counteracted with rest, thereby impacting daily activity and quality of life. Fatigue frequently occurs in patients with advanced disease (e.g. cancer-related fatigue) and modalities used to treat cancer can often contribute. Further complicating issues are the multidimensionality, subjective nature and lack of a consensus definition of fatigue. The pathophysiology is not fully understood and evidence-based treatment approaches are needed. OBJECTIVES: To evaluate the efficacy of pharmacological treatments for fatigue in palliative care, with a focus on patients at an advanced stage of disease, including patients with cancer and other chronic diseases. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO and EMBASE, and a selection of cancer journals up to 28 April 2014. We searched the references of identified articles and contacted authors to obtain unreported data. To validate the search strategy we selected sentinel references. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) concerning adult palliative care with a focus on pharmacological treatment of fatigue compared to placebo, application of two drugs, usual care or a non-pharmacological intervention. The primary outcome had to be non-specific fatigue (or related terms such as asthenia). We did not include studies on fatigue related to antineoplastic treatment (e.g. chemotherapy, radiotherapy, surgical intervention). We also included secondary outcomes that were assessed in fatigue-related studies (e.g. exhaustion, tiredness). DATA COLLECTION AND ANALYSIS: Two review authors (MM and MC) independently assessed trial quality and extracted data. We screened the search results and included studies if they met the selection criteria. If we identified two or more studies that investigated a specific drug with the same dose in a population with the same disease and using the same assessment instrument or scale, we conducted meta-analysis. In addition, we compared the type of drug investigated in specific populations, as well as the frequent adverse effects of fatigue treatment, by creating overview tables. MAIN RESULTS: For this update, we screened 1645 publications of which 45 met the inclusion criteria (20 additional studies to the previous reviews). In total, we analysed data from 18 drugs and 4696 participants. There was a very high degree of statistical and clinical heterogeneity in the trials and we discuss the reasons for this in the review. There were some sources of potential bias in the included studies, including a lack of description of the methods of blinding and allocation concealment, and the small size of the study populations. We included studies investigating pemoline and modafinil in participants with multiple sclerosis (MS)-associated fatigue and methylphenidate in patients suffering from advanced cancer and fatigue in meta-analysis. Treatment results pointed to weak and inconclusive evidence for the efficacy of amantadine, pemoline and modafinil in multiple sclerosis and for carnitine and donepezil in cancer-related fatigue. Methylphenidate and pemoline seem to be effective in patients with HIV, but this is based only on one study per intervention, with only a moderate number of participants in each study. Meta-analysis shows an estimated superior effect for methylphenidate in cancer-related fatigue (standardised mean difference (SMD) 0.49, 95% confidence interval (CI) 0.15 to 0.83). Therapeutic effects could not be described for dexamphetamine, paroxetine or testosterone. There were a variety of results for the secondary outcomes in some studies. Most studies had low participant numbers and were heterogeneous. In general, adverse reactions were mild and had little or no impact. AUTHORS' CONCLUSIONS: Based on limited evidence, we cannot recommend a specific drug for the treatment of fatigue in palliative care patients. Fatigue research in palliative care seems to focus on modafinil and methylphenidate, which may be beneficial for the treatment of fatigue associated with palliative care although further research about their efficacy is needed. Dexamethasone, methylprednisolone, acetylsalicylic acid, armodafinil, amantadine and L-carnitine should be further examined. Consensus is needed regarding fatigue outcome parameters for clinical trials.

Trends in office-based treatment of adults with stimulants in the United States.

OBJECTIVE: The authors investigated trends and patterns in stimulant treatment of adults visiting office-based medical practices in the United States. METHOD: A time series analysis of data from the 1994 to 2009 National Ambulatory Medical Care Surveys (no. of visits = 372,702) was performed, focusing on adult (aged ≥ 18 years) visits in which stimulant medications (amphetamine salts, methylphenidate, or pemoline) were prescribed. The authors computed trends in the percentage of visits in which a stimulant was prescribed stratified by background and clinical patient characteristics. Results are reported as odds ratios (ORs) over the 1994 to 2009 period. The authors also compare visits to psychiatrists and nonpsychiatrist physicians that yielded a stimulant prescription to an adult. RESULTS: The percentage of visits in which stimulants were prescribed increased from 0.11% (1994-1997) to 0.70% (2006-2009) (OR = 13.72, 95% confidence interval [CI], 9.40-20.03). Among adults aged 18 to 29 years, the corresponding increase in stimulant visits was from 0.17% to 1.83% (OR = 30.14, 95% CI, 15.84-57.36). Stimulant prescriptions increased significantly more rapidly among visits without a clinical ADHD diagnosis (OR = 11.86, 95% CI, 7.49-18.80) than among visits with such a diagnosis (OR = 5.45, 95% CI, 2.96-10.04) (interaction P = .04) and among visits to nonpsychiatrist physicians (OR = 21.54, 95% CI, 12.84-36.12) than psychiatrists (OR = 10.64, 95% CI, 6.72-16.86) (interaction P = .03). By 2006-2009, nonpsychiatrist physicians provided most (57.7%) of the stimulant prescriptions linked to adult office-based visits. As compared with psychiatrists, nonpsychiatrist physicians diagnosed ADHD in a significantly smaller proportion of their adult visits in which stimulants were prescribed (62.5% vs 34.4%, P < .0001). CONCLUSIONS: Between 1994 and 2009, there was a substantial increase in stimulant prescriptions during adult outpatient visits, especially during visits of younger adults. The increase in stimulant treatment occurred significantly more rapidly in the practices of nonpsychiatrist physicians than in those of psychiatrists.

Fatigue in multiple sclerosis - a brief review.

Fatigue is the most common and debilitating symptom in multiple sclerosis (MS) and is believed to be distinctly different from fatigue seen in other chronic conditions. It can affect a patient's mood, sleep and have a detrimental effect on their quality of life. In the recent years much literature has emerged in an attempt to elucidate the potential causes and treatment of this common symptom. This review article aims to examine the most recent theories on the pathophysiology of fatigue in MS as well as its association with sleep and depression. We describe the pharmacological and non-pharmacological approaches to its treatment and propose a multidisciplinary, patient enabled and individualised manner to the management of fatigue in MS.

Safety assessment in pediatric studies.

It typically takes many years before an association of a drug with a rare, serious adverse reaction is established. As related to pediatric drug use, evidence is even more erratic, as most drugs are used off labels. To enhance child safety, there is an urgent need to develop robust and rapid methods to identify such associations in as timely a manner as possible. In this chapter, several novel methods, both clinically based pharmacoepidemiological approaches and laboratory-based methods, are described.

Stimulant adherence and academic performance in urban youth with attention-deficit/hyperactivity disorder.

OBJECTIVE: This analysis assessed whether stimulant adherence was associated with improvement in academic grade point average (GPA) among children diagnosed with and treated for attention-deficit/hyperactivity disorder (ADHD). METHOD: Medicaid claims were merged with academic records from Philadelphia public schools of Medicaid-eligible children in first through eighth grades who were diagnosed with ADHD and who had filled one or more stimulant prescription. Students diagnosed with mental retardation, autism, or speech, hearing, visual, or language impairments were excluded. Marking periods were scored for GPA (range: 0-4.0) based on English, mathematics, social studies, and science grades and for stimulant adherence (medication possession ratio ≥ 0.70). Random and fixed-effects models estimated the effects of stimulant adherence on GPA, between all adherent and nonadherent marking periods in aggregate and within individual student's marking periods, respectively. RESULTS: A total of 3,543 students contributed 29,992 marking periods, of which 18.6% were adherent. Mean GPA was significantly higher during stimulant-adherent (2.18) than stimulant-nonadherent (1.99) marking periods in aggregate (p < .0001). The regression coefficient representing within-student association between stimulant adherence and GPA over time was 0.108 (p < .0001), indicating that adherence was associated with a 0.108 increase in GPA. In stratified analyses, analogous coefficients were 0.106 for boys, 0.111 for girls, 0.078 for elementary students, and 0.118 for middle school students (all p < .0001). The association was stronger among students with (0.139) than without (0.088) comorbid disruptive behavior disorders (both p < .0001). CONCLUSIONS: Stimulant adherence, although found to be low among urban elementary and middle school students diagnosed with ADHD, was associated with a marginal improvement in GPA.

Pharmacological treatments for fatigue associated with palliative care.

BACKGROUND: In healthy individuals, fatigue is a protective response to physical or mental stress, often relieved by rest. By contrast, in palliative care patients fatigue can be severely debilitating, thereby impacting daily activity and quality of life, often with rest not counteracting fatigue. Fatigue frequently occurs in patients with advanced disease and modalities treating cancer often contribute or cause fatigue. Further complicating issues are its multidimensionality, subjective nature, and lack of a consensus definition of fatigue. Pathophysiology is not fully understood and evidence-based treatment approaches are needed. OBJECTIVES: The objective was to determine efficacy of pharmacological treatments on non-specific fatigue in palliative care. The focus was on patients at an advanced stage of disease, including cancer and other chronic diseases associated with fatigue, aiming to relieve fatigue. Studies aiming at curative treatment (e.g. surgical intervention for early breast cancer) were not included. SEARCH STRATEGY: We searched EMBASE; Psych Lit, CENTRAL and MEDLINE to June 2009. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) concerning adult palliative care with focus on pharmacological treatment of fatigue. The primary outcome had to be non-specific fatigue (or related terms such as asthenia). DATA COLLECTION AND ANALYSIS: Results were screened and included if they met the selection criteria. If two or more studies were identified that investigated a specific drug in a population with the same disease, meta-analysis was conducted. In addition, comparison of type of drug investigated in a specific population as well as comparison of frequent adverse effects of fatigue treatment was done by creating overview tables. MAIN RESULTS: More than 2000 publications were screened, and 22 met inclusion criteria. In total, data from 11 drugs and 1632 participants were analysed. Studies investigating amantadine, pemoline, and modafinil in participants with Multiple Sclerosis (MS)-associated fatigue and methylphenidate in patients suffering from advanced cancer and fatigue could be used for meta-analysis. Amantadine in MS and methylphenidate in cancer patients showed a superior effect. Most studies had low participant numbers and were heterogenous. AUTHORS' CONCLUSIONS: Based on limited evidence, we cannot recommend a specific drug for treatment of fatigue in palliative care patients. Surprisingly, corticosteroids have not been a research focus for fatigue treatment, although these drugs are frequently used. Recent fatigue research seems to focus on modafinil, which may be beneficial although there is no evidence currently. Amantadine and methylphenidate should be further examined. Consensus regarding fatigue assessment in advanced disease is needed.

Psychostimulant treatment and the developing cortex in attention deficit hyperactivity disorder.

OBJECTIVE: While there has been considerable concern over possible adverse effects of psychostimulants on brain development, this issue has not been examined in a prospective study. The authors sought to determine prospectively whether psychostimulant treatment for attention deficit hyperactivity disorder (ADHD) was associated with differences in the development of the cerebral cortex during adolescence. METHOD: Change in cortical thickness was estimated from two neuroanatomic MRI scans in 43 youths with ADHD. The mean age at the first scan was 12.5 years, and at the second scan, 16.4 years. Nineteen patients not treated with psychostimulants between the scans were compared with an age-matched group of 24 patients who were treated with psychostimulants. Further comparison was made against a template derived from 620 scans of 294 typically developing youths without ADHD. RESULTS: Adolescents taking psychostimulants differed from those not taking psychostimulants in the rate of change of the cortical thickness in the right motor strip, the left middle/inferior frontal gyrus, and the right parieto-occipital region. The group difference was due to more rapid cortical thinning in the group not taking psychostimulants (mean cortical thinning of 0.16 mm/year [SD=0.17], compared with 0.03 mm/year [SD=0.11] in the group taking psychostimulants). Comparison against the typically developing cohort without ADHD showed that cortical thinning in the group not taking psychostimulants was in excess of age-appropriate rates. The treatment groups did not differ in clinical outcome, however. CONCLUSIONS: These findings show no evidence that psychostimulants were associated with slowing of overall growth of the cortical mantle.

Idiopathic hypersomnia: clinical features and response to treatment.

OBJECTIVE: A recent American Academy of Sleep Medicine publication identified a need for research regarding idiopathic hypersomnia. We describe various clinical and polysomnographic features of patients with idiopathic hypersomnia, with an emphasis on response to pharmacotherapy. METHODS: A retrospective review of our database initially identified 997 patients, utilizing "idiopathic hypersomnia", "hypersomnia NOS", and "primary hypersomnia" as keywords. The charts of eligible patients were examined in detail, and data were abstracted and analyzed. Response to treatment was graded utilizing an internally developed scale. RESULTS: Eighty-five patients were ultimately identified (65% female). Median (interquartile range) ages of onset and diagnosis were 19.6 (15.5) and 33.7 (15.5), respectively. During a median follow-up duration of 2.4 (4.7) years, 65% of patients demonstrated a "complete response" to pharmacotherapy as assessed by the authors' grading schema. Methylphenidate was most commonly used as a first-line agent prior to December 1998, but subsequently, modafinil became the most common first drug. At the last recorded follow-up visit, 92% of patients were on monotherapy, with greater representation of methylphenidate versus modafinil (51% vs. 32%). Among these patients, methylphenidate produced a higher percentage of "complete" or "partial" responses than modafinil, although statistical significance was not reached (38/40 [95%] vs. 22/25 [88%], respectively, p = 0.291). CONCLUSIONS: The majority of patients with idiopathic hypersomnia respond well to treatment. Methylphenidate is chosen more often than modafinil as final monotherapy in the treatment of idiopathic hypersomnia, despite the fact that it is less commonly used initially. Further prospective comparisons of medications should be explored.

A surveillance method for the early identification of idiosyncratic adverse drug reactions.

BACKGROUND: Pemoline is a CNS stimulant that was introduced in 1975 in the US and was used to treat children with attention deficit hyperactivity disorder. Pemoline was withdrawn from the market 30 years later because of fatal hepatotoxicity associated with its use. OBJECTIVE: To create a system that will estimate the potential association between a serious adverse event and a medication early in its marketing cycle. METHOD: All case reports of acute liver failure associated with pemoline and reported to the US FDA from 1975 through 1999 were reviewed. All published articles on pemoline-induced hepatotoxicity were reviewed, and the Naranjo adverse drug reaction probability scale was applied. The incidence rate of idiopathic acute liver failure was estimated from the published literature. The data were analyzed using Fisher's Exact test and relative risks (RR) were calculated. RESULTS: As early as 1978, there was a significant signal indicating that pemoline was associated with acute liver failure, with an RR of 24.08 (95% CI 4.67, 124.10; p < 0.05). With an increased number of cases, the significance of the association had been steadily increased. CONCLUSION: This method enables researchers, clinicians, drug companies and regulators to identify uncommon adverse drug reactions, caused mostly by new medications, earlier than they currently are in the course of marketing and thus quantify serious adverse events.

Methylphenidate use in children and risk of cancer at 18 sites: results of surveillance analyses.

PURPOSE: A recent report linked methylphenidate (MPH) use in children to cytologic abnormalities in plasma lymphocytes, a possible cancer biomarker. The purpose of this study was to investigate the association of MPH use and childhood cancer risk. METHODS: Using automated pharmacy databases and the SEER-affiliated cancer registry of the Kaiser Permanente Medical Care Program (KPMCP), we compared cancer rates at 18 sites among 35,400 MPH users who received it before age 20 to rates among KPMCP membership (age, sex, and calendar year standardized). Medical records of MPH exposed cancer cases were reviewed to identify the presence of established risk factors. RESULTS: There were 23 cancers among MPH users, versus 20.4 expected (standardized morbidity ratio, SMR = 1.13, 95% confidence interval (0.72, 1.70)). Given the small number of cancers, site-specific SMR estimates were imprecise. Only one SMR was statistically significant at the p < 0.05 level, which given the number of comparisons is consistent with the absence of a true association at any site. MPH use was associated with increased risk of lymphocytic leukemia (SMR = 2.64 (1.14, 5.20)), based on eight observed cases). The medical records of these exposed cases did not reveal any lymphocytic leukemia risk factors (prior cancer, radiotherapy or chemotherapy, or Down syndrome). CONCLUSIONS: Our results are consistent with no moderate or strong association between MPH use and cancer risk in children, although our ability to examine dose and duration of use or risk at specific sites was limited by small numbers. Further study of MPH use and lymphocytic leukemia risk is needed to determine whether our results are due to chance alone.

Treating fatigue.

Fatigue is recognized as one of the most disabling and common symptoms of MS. However, no universal consensus has been reached regarding a formal definition for fatigue, and its mechanisms and causes are not understood. This review summarizes important research in this field and recommends a multidisciplinary approach to managing MS patients with fatigue. Such an approach should include proven pharmaceutical and non-pharmaceutical treatments.

Eficacia del bupropión en el tratamiento de la dependencia de pemolina / Efficacy of bupropion in the treatment of pemoline dependence

Presentamos el caso de una mujer que solicita evaluación psiquiátrica por llevar 6 meses consumiendo pemolina en unas dosis de entre 100 y 150 mg/día, encontrándose con dificultades para abandonar el consumo de dicha sustancia. La instauración de 300 mg/día de bupropión resuelve la dependencia que tenía la enferma. Proponemos el uso de antidepresivos como el bupropión para el tratamiento de conductas adictivas sobre estimulantes del sistema nervioso central

We present the case of a woman who requested psychiatric evaluation because she had been taking pemoline for six months at a dose between 100-150 mg/day, and was finding it difficult to discontinue taking this substance. Initiation of 300 mg/day of bupropion solved the patient's dependence problem. We propose using antidepressants such as bupropion for the treatment of addictive behaviors due to central nervous system stimulants

Trastorno por déficit de atención con hiperactividad: una actualización / Attention deficit hyperactivity disorder: an up-date

El trastorno por déficit de atención con hiperactividad es al mismo tiempo el trastorno mental más estudiado en niños y adolescentes y el más controvertido. Este artículo describe la clasificación, epidemiología, manifestaciones clínicas, diagnóstico, etiología, pronóstico y tratamiento del trastorno por déficit de atención con hiperactividad. El objetivo principal del artículo es que pueda ser utilizado como una guía práctica para que los pediatras identifiquen a los niños en situación de riesgo de ser hiperactivos, inatentos o sufrir por su conducta impulsiva. Una vez identificados correctamente, los niños con trastorno por déficit de atención con hiperactividad deben ser tratados. En este sentido, el tratamiento farmacológico ha demostrado claramente su eficacia en el control de los síntomas nucleares del trastorno a corto y medio plazo y en general se considera que la medicación psicoestimulante es segura y bien tolerada en la mayoría de los pacientes (AU)

Attention-deficit/hiperactivity disorder has the distinction of being both the most extensively studied child mental disorder and yet the most controversial. This article describes the classification, epidemiology, clinical description, diagnostic considerations, etiology, prognosis and treatment of attention-deficit/hyperactivity disorder. Therefore the main objective of this article is that it can be used as a practice guide to paediatrician to identify children at risk of being hyperactive, inattentive and suffering for their impulsive conduct. Once correctly identified children with attention-deficit/ hyperactivity disorder should be treated. At this point medication treatment is clearly established as effective in terms of suppressing the core symptoms of the disorder in the short and the middle term, and in general it appears that stimulant medication is safe and well tolerated by the majority of patients (AU)

Effectiveness of risk management plans: a case study of pemoline using pharmacy claims data.

PURPOSE: To assess the effectiveness of a pharmaceutical risk management plan using pemoline as a case study and pharmacy claims as the data source. METHODS: Prescription claims from a continuously enrolled US population (September 1, 2000-September 30, 2002) from Caremark, a pharmacy benefit manager, were evaluated for patients with one or more pemoline claims. Patients were categorized using pemoline as second-line or first-line therapy depending on presence or absence of other central nervous system (CNS) stimulants prescriptions 90 days prior to the first pemoline claim. Logistic regression was performed to compare second-line and first-line usage with regard to patient age, gender and prescribing physician specialty and region of practice. RESULTS: Of 1,279,296 prescription claims for CNS stimulants, 17,256 (1.3%) were for pemoline. Nine hundred thirteen patients received pemoline and had 90 days or more prior enrollment. Overall, 10% of patients receiving pemoline received it as second-line therapy (95%CI: 8-12%). After adjusting for age, gender, specialty, and region, the odds of receiving pemoline as second-line therapy were significantly greater in pediatrics relative to adults (OR = 2.82, 95%CI: 1.58-5.03), and among those whose prescribers were psychiatrists versus primary care physicians (OR = 2.48, 95%CI: 1.37-4.50). Children treated by a psychiatrist had the greatest likelihood for use as second-line therapy (36%, 95%CI: 19-56%). CONCLUSIONS: Among patients who received pemoline, concordance with second-line therapy recommendations was low, even among the primary target audience of children. These results in a large geographically diverse patient population are consistent with an earlier regional study.

[Pathophysiology and treatment of fatigue in multiple sclerosis]. / Physiopathologie et traitement de la fatigue dans la sclérose en plaques.

Patients suffering from multiple sclerosis (MS) frequently complain of fatigue (53 to 92 percent depending on studies). Fatigue can be one of the most disabling symptoms of MS and presents as physical or mental fatigue in daily living activities. Besides this permanent feeling of exhaustion, MS patients can suffer from an abnormal tiredness and lack of energy after a given motor or mental task, which defines fatigability. A number of studies explored the origins of fatigue and fatigability by means of subjective and objective tools. The implication of central nervous system dysfunctions has been established in several studies; however the contribution of peripheral nervous system factors and systemic abnormalities associated with inflammatory and immunological parameters was also suggested. The aim of this review is to present the different types of fatigue and fatigability occurring in MS patients, their origins, the investigation tools which allow the quantification of fatigue and fatigability and characterization of their mechanisms. The currently available therapeutic strategies that have been proposed to relieve this disabling symptom are presented.

Treatment of attention-deficit/hyperactivity disorder: overview of the evidence.

The American Academy of Pediatrics' Committee on Quality Improvement, Subcommittee on Attention-Deficit/Hyperactivity Disorder, reviewed and analyzed the current literature for the purpose of developing an evidence-based clinical practice guideline for the treatment of the school-aged child with attention-deficit/hyperactivity disorder (ADHD). This review included several key reports, including an evidence review from the McMaster Evidence-Based Practice Center (supported by the Agency for Healthcare Research and Quality), a report from the Canadian Coordinating Office for Health Technology Assessment, the Multimodal Treatment for ADHD comparative clinical trial (supported by the National Institute of Mental Health), and supplemental reviews conducted by the subcommittee. These reviews provided substantial information about different treatments for ADHD and their efficacy in improving certain characteristics or outcomes for children with ADHD as well as adverse effects and benefits of multiple modes of treatment compared with single modes (eg, medication or behavior therapies alone). The reviews also compared the effects of different medications. Other evidence documents the long-term nature of ADHD in children and its classification as a chronic condition, meriting the application of general concepts of chronic-condition management, including an individual treatment plan with a focus on ongoing parent and child education, management, and monitoring. The evidence strongly supports the use of stimulant medications for treating the core symptoms of children with ADHD and, to a lesser degree, for improving functioning. Behavior therapy alone has only limited effect on symptoms or functioning of children with ADHD, although combining behavior therapy with medication seems to improve functioning and may decrease the amount of (stimulant) medication needed. Comparison among stimulants (mainly methylphenidate and amphetamines) did not indicate that 1 class outperformed the other.