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International Journal of Clinical... Apr 2015To describe the efficacy and safety of lisdexamfetamine dimesylate (LDX) for the treatment of binge eating disorder (BED). (Review)
Review
Lisdexamfetamine for binge eating disorder in adults: a systematic review of the efficacy and safety profile for this newly approved indication - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?
OBJECTIVE
To describe the efficacy and safety of lisdexamfetamine dimesylate (LDX) for the treatment of binge eating disorder (BED).
DATA SOURCES
The pivotal registration trials were accessed by querying http://www.ncbi.nlm.nih.gov/pubmed/, http://www.clinicaltrials.gov and http://www.clinicaltrialsregister.eu for the search terms 'lisdexamfetamine' and 'binge', and by also querying the Web of Science (Thomson Reuters) and Embase (Elsevier) commercial databases, and by asking the manufacturer for copies of posters presented at congresses. Product labelling provided additional information.
STUDY SELECTION
All available clinical reports of studies were identified.
DATA EXTRACTION
Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.
DATA SYNTHESIS
LDX is a central nervous system stimulant indicated for the treatment of moderate to severe BED. The recommended dose range is 50-70 mg/day. Approval for the treatment of BED was based on a clinical development programme that included an 11-week Phase II proof-of-concept, placebo-controlled study, testing fixed doses of LDX 30, 50 and 70 mg/day, and two 12-week Phase III placebo-controlled studies examining LDX 50-70 mg/day. Statistically significant reductions in binge eating days/week, the primary outcome measure, were observed for LDX doses of 50 and 70 mg/day, with effect sizes in the Phase III trials ranging from 0.83 to 0.97. The pooled NNT for response across all trials (as defined by a Clinical Global Impressions-Improvement score of 'very much improved' or 'much improved') for LDX vs. placebo was 3 (95% CI 3-4), and NNT for remission (as defined by 4-week cessation of binge eating) for LDX vs. placebo was 4 (95% CI 4-6). Reductions in weight ranged between 5.2% and 6.25% for LDX 50 or 70 mg/day. Discontinuation rates because of adverse events (AEs) were low; NNH for discontinuation because of an AE for LDX vs. placebo was 44 (95% CI 23-1971). The most commonly encountered AEs (incidence ≥ 10% and greater than the rate for placebo) were dry mouth, decreased appetite, insomnia and headache, with NNH values vs. placebo of 4 (95% CI 3-5), 11 (95% CI 8-17), 11 (95% CI 8-18) and 19 (95% CI 11-75), respectively.
CONCLUSIONS
LDX is the first pharmacological agent that has received regulatory approval for the treatment of BED. LDX 50 or 70 mg/day significantly reduced BED symptoms as measured by the number of binge eating days per week. Effect sizes were highly robust. Pending clinical trials include a long-term study examining maintenance of efficacy.
Topics: Antipsychotic Agents; Binge-Eating Disorder; Central Nervous System Stimulants; Clinical Trials as Topic; Dopamine Uptake Inhibitors; Humans; Lisdexamfetamine Dimesylate; Numbers Needed To Treat
PubMed: 25752762
DOI: 10.1111/ijcp.12639 -
Drug Design, Development and Therapy 2014Recent studies have promised that lisdexamfetamine (LDX) is effective in the treatment of adults with attention-deficit hyperactivity disorder (ADHD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent studies have promised that lisdexamfetamine (LDX) is effective in the treatment of adults with attention-deficit hyperactivity disorder (ADHD).
OBJECTIVES
This systematic review was undertaken to summarize LDX efficacy, acceptability, and tolerability in adult ADHD. All randomized controlled trials (RCTs) of lisdexamfetamine compared with placebo were included for synthesis. Clinical trials published between January 1991 and January 2014 were evaluated.
METHODS
The database of MEDLINE(®), EMBASE™, CINAHL(®), PsycINFO(®) and Cochrane Controlled Trials Register were searched in January 2014. Studies were also searched in ClinicalTrials.gov and the EU Clinical Trials Register database. Study eligibility criteria, participants, and interventions were considered. All RCTs of LDX vs placebo reporting final results of: 1) severity of ADHD symptoms and executive function deficit, 2) response or remission rates, 3) overall discontinuation rate, or 4) discontinuation rate due to adverse events were included. The language of the papers was not restricted. All abstracts of studies gathered from the database were examined. After excluding irrelevant trials, the full text version of relevant studies were assessed and extracted for outcomes of interest. Examination of risks of bias, based on the Cochrane bias assessment, was carried out. The efficacy outcomes consisted of the mean end point or change scores for ADHD rating scales, the response rate, and the remission rate. The overall discontinuation rate and the discontinuation rate due to adverse events were measured for acceptability and tolerability, respectively. A random effect model was applied for the synthesis of relative risks (RRs), and weighted mean differences or standardized mean differences (SMDs) with 95% confidence intervals (CIs).
RESULTS
A total of 806 final study or safety participants were included. The dosage of lisdexamfetamine was 30 to 70 mg/day. The pooled mean scores of mean change and mean end point scores between LDX- and placebo-treated groups also had a significant difference (SMD [95% CI] of -0.97 [-1.15, -0.78], I(2)=18%). The pooled response rates for adult ADHD between the two groups had a significant difference (RR [95% CI] of 1.99 [1.50, 2.63], I(2)=0%). Based on the Behavior Rating Inventory of Executive Function - Adult version (BRIEF-A), the pooled end point mean scores for the Global Executive Composite (GEC) for the LDX-treated groups was greater than that of placebo-treated groups (MD [95% CI] of -9.20 [-14.11, -4.29], I(2)=34%). The pooled overall discontinuation rates between the two groups had no significant difference (RR [95% CI] of 0.82 [0.59, 1.14], I(2)=0%). Similarly, the pooled discontinuation rates due to adverse events between the two groups was not significantly different (RR [95% CI] of 1.77 [0.71, 4.40], I(2)=0%).
CONCLUSION
The number of included studies was limited (five RCTs), but based on this meta-analysis, LDX is efficacious and well tolerated in the treatment of adult ADHD. Additionally, it also improved the executive function deficits in this population. However, its acceptability is no higher than placebo. These findings should be carefully interpreted and considered as preliminary outcomes. To confirm these results, further studies are warranted. LDX is a viable alternative psychostimulant for adult ADHD.
Topics: Attention Deficit Disorder with Hyperactivity; Databases, Factual; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Placebos; Registries
PubMed: 25336914
DOI: 10.2147/DDDT.S68393 -
CNS Drugs Jun 2014Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of... (Review)
Review
BACKGROUND
Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD).
METHODS
A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]).
RESULTS
In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX.
CONCLUSIONS
The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants.
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Clinical Trials, Phase III as Topic; Dextroamphetamine; Dose-Response Relationship, Drug; Humans; Lisdexamfetamine Dimesylate; Prodrugs; Randomized Controlled Trials as Topic; Time Factors
PubMed: 24788672
DOI: 10.1007/s40263-014-0166-2 -
American Journal of Alzheimer's Disease... Mar 2014The objective of this review is to summarize the current data on the pharmacological treatments for frontotemporal dementias from randomized controlled trials. A... (Review)
Review
The objective of this review is to summarize the current data on the pharmacological treatments for frontotemporal dementias from randomized controlled trials. A systematic search of 4 major databases, PubMed, Medline, PsychINFO and Cochrane, found a total of 9 randomized controlled, double-blinded clinical trials. Of these, 2 trials used the selective serotonin reuptake inhibitor (SSRI), paroxetine; 1 trial used trazodone; 2 trials used stimulants (methylphenidate and dextroamphetamine); 1 trial used the acetylcholinesterase inhibitor, galantamine; 2 trials used the N-methyl-d-aspartate antagonist, memantine; and 1 trial used the neuropeptide oxytocin. The analysis of the available data indicates that SSRIs, trazodone, and the amphetamines may be effective in reducing some behavioral symptoms, but none of these medications had an impact on cognition. Available data indicate that these medications were well tolerated in all the trials.
Topics: Cognition; Dopamine Agents; Frontotemporal Dementia; Humans; Memantine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 24164931
DOI: 10.1177/1533317513507375 -
Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review.BMC Cardiovascular Disorders Jun 2012There is increasing concern that prescription stimulants may be associated with adverse cardiovascular events such as stroke, myocardial infarction, and sudden death.... (Review)
Review
BACKGROUND
There is increasing concern that prescription stimulants may be associated with adverse cardiovascular events such as stroke, myocardial infarction, and sudden death. Public health concerns are amplified by increasing use of prescription stimulants among adults.
METHODS
The objective of this study was to conduct a systematic review of the evidence of an association between prescription stimulant use and adverse cardiovascular outcomes. PUBMED, MEDLINE, EMBASE and Google Scholar searches were conducted using key words related to these topics (MESH): ADHD; Adults; Amphetamine; Amphetamines; Arrhythmias, Cardiac; Cardiovascular Diseases; Cardiovascular System; Central Nervous Stimulants; Cerebrovascular; Cohort Studies; Case-control Studies; Death; Death, Sudden, Cardiac; Dextroamphetamine; Drug Toxicity; Methamphetamine; Methylphenidate; Myocardial Infarction; Stimulant; Stroke; Safety. Eligible studies were population-based studies of children, adolescents, or adults using prescription stimulant use as the independent variable and a hard cardiovascular outcome as the dependent variable.
RESULTS
Ten population-based observational studies which evaluated prescription stimulant use with cardiovascular outcomes were reviewed. Six out of seven studies in children and adolescents did not show an association between stimulant use and adverse cardiovascular outcomes. In contrast, two out of three studies in adults found an association.
CONCLUSIONS
Findings of an association between prescription stimulant use and adverse cardiovascular outcomes are mixed. Studies of children and adolescents suggest that statistical power is limited in available study populations, and the absolute risk of an event is low. More suggestive of a safety signal, studies of adults found an increased risk for transient ischemic attack and sudden death/ventricular arrhythmia. Interpretation was limited due to differences in population, cardiovascular outcome selection/ascertainment, and methodology. Accounting for confounding and selection biases in these studies is of particular concern. Future studies should address this and other methodological issues.
Topics: Adolescent; Adult; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Death, Sudden, Cardiac; Humans; Myocardial Infarction; Prescription Drugs; Risk; Stroke
PubMed: 22682429
DOI: 10.1186/1471-2261-12-41 -
Neuropsychopharmacology : Official... Jun 2010Antipsychotic-related weight gain and metabolic effects are a critical outcome for patients requiring these medications. A literature search using MEDLINE, Web of... (Meta-Analysis)
Meta-Analysis Review
Antipsychotic-related weight gain and metabolic effects are a critical outcome for patients requiring these medications. A literature search using MEDLINE, Web of Science, PsycNET, and EMBASE for randomized, open and double-blind, placebo-controlled trials of medications targeting antipsychotic-induced weight gain was performed. Primary outcome measures were change and endpoint values in body weight and body mass index (BMI). Secondary outcomes included >or=7% weight gain, all-cause discontinuation, change in waist circumference, glucose and lipid metabolism parameters, and psychiatric symptoms. Sensitivity analyses were conducted to explain heterogeneity of the results. Across 32 studies including 1482 subjects, 15 different medications were tested: amantadine, dextroamphetamine, d-fenfluramine, famotidine, fluoxetine, fluvoxamine, metformin, nizatidine, orlistat, phenylpropanolamine, reboxetine, rosiglitazone, sibutramine, topiramate, and metformin+sibutramine. Compared with placebo, metformin had the greatest weight loss (N=7, n=334, -2.94 kg (confidence interval (CI:-4.89,-0.99)), followed by d-fenfluramine (N=1, n=16, -2.60 kg (CI:-5.14,-0.06)), sibutramine (N=2, n=55, -2.56 kg (CI:-3.91,-1.22)), topiramate (N=2, n=133, -2.52 kg (CI:-4.87,-0.16)), and reboxetine (N=2, n=79, -1.90 kg (CI:-3.07,-0.72)). Weight loss remained significant with metformin initiation after weight gain had occurred, but not when started concomitantly with antipsychotics. Nausea rates were not higher with any treatment compared with placebo. In all, 5 of 15 psychopharmacologic interventions aimed at ameliorating antipsychotic-induced weight gain outperformed placebo. Results were most robust for metformin, although these were modest and heterogeneous. Only one (negative) combination treatment study was available and head-to-head studies are absent. None of the agents were able to entirely reverse weight gain because of antipsychotics. At present, no treatment has sufficient evidence to recommend broad clinical usage. Antipsychotics with no or minimal cardiometabolic liability, as well as interventions that prevent or normalize adverse antipsychotic cardiometabolic effects are needed.
Topics: Animals; Antidepressive Agents; Databases, Factual; Humans; Hypoglycemic Agents; Metabolic Diseases; Randomized Controlled Trials as Topic; Weight Gain
PubMed: 20336059
DOI: 10.1038/npp.2010.21 -
BMC Neurology Oct 2009Fragile X syndrome (FXS) is considered the most common cause of inherited mental retardation. Affected people have mental impairment that can include Attention Deficit... (Review)
Review
BACKGROUND
Fragile X syndrome (FXS) is considered the most common cause of inherited mental retardation. Affected people have mental impairment that can include Attention Deficit and/or Hyperactivity Disorder (ADHD), autism disorder, and speech and behavioural disorders. Several pharmacological interventions have been proposed to treat those impairments.
METHODS
Systematic review of the literature and summary of the evidence from clinical controlled trials that compared at least one pharmacological treatment with placebo or other treatment in individuals with diagnosis of FXS syndrome and assessed the efficacy and/or safety of the treatments. Studies were identified by a search of PubMed, EMBASE and the Cochrane Databases using the terms fragile X and treatment. Risk of bias of the studies was assessed by using the Cochrane Collaboration criteria.
RESULTS
The search identified 276 potential articles and 14 studies satisfied inclusion criteria. Of these, 10 studies on folic acid (9 with crossover design, only 1 of them with good methodological quality and low risk of bias) did not find in general significant improvements. A small sample size trial assessed dextroamphetamine and methylphenidate in patients with an additional diagnosis of ADHD and found some improvements in those taking methylphenidate, but the length of follow-up was too short. Two studies on L-acetylcarnitine, showed positive effects and no side effects in patients with an additional diagnosis of ADHD. Finally, one study on patients with an additional diagnosis of autism assessed ampakine compound CX516 and found no significant differences between treatment and placebo. Regarding safety, none of the studies that assessed that area found relevant side effects, but the number of patients included was too small to detect side effects with low incidence.
CONCLUSION
Currently there is no robust evidence to support recommendations on pharmacological treatments in patients with FXS in general or in those with an additional diagnosis of ADHD or autism.
Topics: Acetylcarnitine; Dioxoles; Folic Acid; Fragile X Syndrome; Humans; Methylphenidate; Piperidines; Treatment Outcome
PubMed: 19822023
DOI: 10.1186/1471-2377-9-53 -
The Cochrane Database of Systematic... Apr 2009Few studies examined treatments for amphetamine withdrawal, although it is a common problem among amphetamine users. Its symptoms, in particular intense craving, may be... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Few studies examined treatments for amphetamine withdrawal, although it is a common problem among amphetamine users. Its symptoms, in particular intense craving, may be a critical factor leading to relapse to amphetamine use. In clinical practice, medications for cocaine withdrawal are commonly used to manage amphetamine withdrawal although the pharmacodynamic and pharmacokinetic properties of these two illicit substances are different.
OBJECTIVES
To assess the effectiveness of pharmacological alone or in combination with psychosocial treatment for amphetamine withdrawals on discontinuation rates, global state, withdrawal symptoms, craving, and other outcomes.
SEARCH STRATEGY
MEDLINE (1966 - 2008), CINAHL (1982 - 2008), PsycINFO (1806 - 2008), CENTRAL (Cochrane Library 2008 issue 2), references of obtained articles.
SELECTION CRITERIA
All randomised controlled and clinical trials evaluating pharmacological and or psychosocial treatments (alone or combined) for people with amphetamine withdrawal symptoms.
DATA COLLECTION AND ANALYSIS
Two authors evaluated and extracted data independently. The data were extracted from intention-to-treat analyses. The Relative Risk (RR) with the 95% confidence interval (95% CI) was used to assess dichotomous outcomes. The Weighted Mean Difference (WMD) with 95% CI was used to assess continuous outcomes.
MAIN RESULTS
Four randomised controlled trials (involving 125 participants) met the inclusion criteria for the review. Two studies found that amineptine significantly reduced discontinuation rates and improved overall clinical presentation, but did not reduce withdrawal symptoms or craving compared to placebo. The benefits of mirtazapine over placebo for reducing amphetamine withdrawal symptoms were not as clear. One study suggested that mirtazapine may reduce hyperarousal and anxiety symptoms associated with amphetamine withdrawal. A more recent study failed to find any benefit of mirtazapine over placebo on retention or on amphetamine withdrawal symptoms.
AUTHORS' CONCLUSIONS
No medication is effective for treatment of amphetamine withdrawal. Amineptine showed reduction in discontinuation rates and improvement in clinical presentation compared to placebo, but had no effect on reducing withdrawal symptoms or craving. In spite of these limited benefits, amineptine is not available for use due to concerns over abuse liability when using the drug. The benefits of mirtazapine as a withdrawal agent are less clear based on findings from two randomised controlled trials: one report showed improvements in amphetamine withdrawal symptoms over placebo; a second report showed no differences in withdrawal symptoms compared to placebo. Further potential treatment studies should examine medications that increase central nervous system activity involving dopamine, norepinephrine and/or serotonin neurotransmitters, including mirtazapine.
Topics: Amphetamine; Antidepressive Agents, Tricyclic; Dextroamphetamine; Dibenzocycloheptenes; Dopamine Uptake Inhibitors; Humans; Methamphetamine; Randomized Controlled Trials as Topic; Substance Withdrawal Syndrome
PubMed: 19370579
DOI: 10.1002/14651858.CD003021.pub2 -
BMJ Clinical Evidence Oct 2008Prevalence estimates of attention deficit hyperactivity disorder (ADHD) vary according to the diagnostic criteria used and the population sampled. DSM-IV prevalence... (Review)
Review
INTRODUCTION
Prevalence estimates of attention deficit hyperactivity disorder (ADHD) vary according to the diagnostic criteria used and the population sampled. DSM-IV prevalence estimates among school children in the US are 3-5%, but other estimates vary from 1.7% to 16.0%. No objective test exists to confirm the diagnosis of ADHD, which remains a clinical diagnosis. Other conditions frequently co-exist with ADHD.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmacological treatments for ADHD in children and adolescents? What are the effects of psychological treatments for ADHD in children and adolescents? What are the effects of combination treatments for ADHD in children and adolescents? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 34 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: atomoxetine, bupropion, clonidine, dexamfetamine sulphate, homeopathy, methylphenidate, modafinil, omega 3-polyunsaturated fatty acids, and psychological/behavioural treatment (either alone or in combination with a drug treatment).
Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Attention Deficit and Disruptive Behavior Disorders; Child; Dextroamphetamine; Diagnostic and Statistical Manual of Mental Disorders; Humans; Methylphenidate
PubMed: 19445793
DOI: No ID Found -
Health Technology Assessment... Jul 2006To assess the clinical and cost-effectiveness of oral methylphenidate hydrochloride (MPH), dexamfetaminesulphate (DEX) and atomoxetine (ATX) in children and adolescents... (Review)
Review
A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents.
OBJECTIVES
To assess the clinical and cost-effectiveness of oral methylphenidate hydrochloride (MPH), dexamfetaminesulphate (DEX) and atomoxetine (ATX) in children and adolescents (<18 years of age) diagnosed with attention deficit hyperactivity disorder (ADHD) (including hyperkinetic disorder).
DATA SOURCES
Electronic databases covering 1999--July 2004 for MPH, 1997--July 2004 for DEX and 1981--July 2004 for ATX.
REVIEW METHODS
Selected studies were assessed using modified criteria based on CRD Report No. 4. Clinical effectiveness data were reported separately for each drug and by the type of comparison. Data for MPH were also analysed separately based on whether it was administered as an immediate release (IR) or extended release (ER) formulation. For all drugs, the data were examined by dose. Data for the core outcomes of hyperactivity (using any scale), Clinical Global Impression [as a proxy of quality of life (QoL)] and adverse events were reported. For crossover studies, the mean and standard deviation (SD) for each outcome were data extracted for end of trial data (i.e. baseline data were not considered). For parallel studies, change scores were reported where given, otherwise means and SDs were presented for end of trial data. In addition, mean differences with 95% confidence intervals were calculated for each study. For adverse events, self-ratings were reported when used, otherwise, parent reports were utilised. Percentages of participants reporting adverse events were used to calculate numbers of events in each treatment arm. All the clinical effectiveness data and economic evaluations (including accompanying models) included in the company submissions were assessed. A new model was developed to assess the cost-effectiveness of the alternative treatments in terms of cost per quality-adjusted life-year. To achieve this, a mixed treatment comparison model was used to estimate the differential mean response rates. Monte Carlo simulation was used to reflect uncertainty in the cost-effectiveness results.
RESULTS
In total, 65 papers met the inclusion criteria. The results suggest that MPH and DEX are effective at reducing hyperactivity and improving QoL (as determined by Clinical Global Impression) in children, although the reliability of the MPH study results is not known and there were only a small number of DEX studies. There was consistent evidence that ATX was superior to placebo for hyperactivity and Clinical Global Impression. Studies on ATX more often reported the study methodology well, and the results were likely to be reliable. Very few studies made direct head-to-head comparisons between the drugs or examined a non-drug intervention in combination with MPH, DEX or ATX. Adequate and informative data regarding the potential adverse effects of the drugs were also lacking. The results of the economic evaluation clearly identified an optimal treatment strategy of DEX first-line, followed by IR-MPH for treatment failures, followed by ATX for repeat treatment failures. Where DEX is unsuitable as a first-line therapy, the optimal strategy is IR-MPH first-line, followed by DEX and then ATX. For patients contraindicated to stimulants, ATX is preferred to no treatment. For patients in whom a midday dose of medication is unworkable, ER-MPH is preferred to ATX, and ER-MPH12 appears more cost-effective than ER-MPH8. As identified in the clinical effectiveness review, the reporting of studies was poor, therefore this should be borne in mind when interpreting the model results.
CONCLUSIONS
Drug therapy seems to be superior to no drug therapy, no significant differences between the various drugs in terms of efficacy or side effects were found, mainly owing to lack of evidence, and the additional benefits from behavioural therapy (in combination with drug therapy) are uncertain. Given the lack of evidence for any differences in effectiveness between the drugs, the economic model tended to be driven by drug costs, which differed considerably. Future trials examining MPH, DEX and ATX should include the assessment of tolerability and safety as a priority. Longer term follow-up of individuals participating in trials could further inform policy makers and health professionals. Such data could potentially distinguish between these drugs in a clinically useful way. In addition, research examining whether somatic complaints are actually related to drug treatment or to the disorder itself would be informative.
Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Child; Child, Preschool; Cost-Benefit Analysis; Dextroamphetamine; Humans; Methylphenidate; Models, Economic; Propylamines; Treatment Outcome
PubMed: 16796929
DOI: 10.3310/hta10230