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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 -
Psychopharmacology Jan 2012Several psychoactive drugs are known to influence episodic memory. However, these drugs' effects on false memory, or the tendency to incorrectly remember nonstudied... (Comparative Study)
Comparative Study Randomized Controlled Trial
RATIONALE
Several psychoactive drugs are known to influence episodic memory. However, these drugs' effects on false memory, or the tendency to incorrectly remember nonstudied information, remain poorly understood.
OBJECTIVES
Here, we examined the effects of two commonly used psychoactive drugs, one with memory-enhancing properties (dextroamphetamine; AMP), and another with memory-impairing properties (Δ(9)-tetrahydrocannabinol; THC), on false memory using the Deese/Roediger-McDermott (DRM) illusion.
METHODS
Two parallel studies were conducted in which healthy volunteers received either AMP (0, 10, and 20 mg) or THC (0, 7.5, and 15 mg) in within-subjects, randomized, double-blind designs. Participants studied DRM word lists under the influence of the drugs, and their recognition memory for the studied words was tested 2 days later, under sober conditions.
RESULTS
As expected, AMP increased memory of studied words relative to placebo, and THC reduced memory of studied words. Although neither drug significantly affected false memory relative to placebo, AMP increased false memory relative to THC. Across participants, both drugs' effects on true memory were positively correlated with their effects on false memory.
CONCLUSIONS
Our results indicate that AMP and THC have opposing effects on true memory, and these effects appear to correspond to similar, albeit more subtle, effects on false memory. These findings are consistent with previous research using the DRM illusion and provide further evidence that psychoactive drugs can affect the encoding processes that ultimately result in the creation of false memories.
Topics: Adolescent; Adult; Dextroamphetamine; Double-Blind Method; Dronabinol; Female; Humans; Male; Memory; Psychomotor Performance; Psychotropic Drugs; Recognition, Psychology; Young Adult
PubMed: 21647577
DOI: 10.1007/s00213-011-2374-5 -
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 -
The American Journal of Managed Care May 2009Although symptoms of attention-deficit/ hyperactivity disorder (ADHD) are certainly most visible in children, the syndrome persists into adolescence in 40% to 70% of... (Review)
Review
Although symptoms of attention-deficit/ hyperactivity disorder (ADHD) are certainly most visible in children, the syndrome persists into adolescence in 40% to 70% of cases and into adulthood in 50% or more of cases. Accurate recognition of the disorder is clouded by the frequent presence of psychiatric comorbidities. Contributing to these challenges, managed care providers in primary care are often inexperienced in identifying and treating ADHD in adults because of a lack of formalized training. As such, special consideration must be given to each individual age group and includes identifying common clinical presentations, characterizing the disorder and its comorbidities, applying validated rating scales as screening and treatment outcome measures, and individually assessing patients' optimal response to determine the best course of therapy. Pharmacotherapy is often initiated to target ADHD symptoms with either a stimulant medication or nonstimulants. In addition, behavioral interventions are often applied to treat comorbidities and associated impairments of ADHD.
Topics: Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Diagnostic and Statistical Manual of Mental Disorders; Dopamine Uptake Inhibitors; Humans; Managed Care Programs; Methylphenidate; Propylamines
PubMed: 19601688
DOI: No ID Found -
NTP CERHR MON Jul 2005The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for amphetamines to cause... (Review)
Review
The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for amphetamines to cause adverse effects on reproduction and development in humans. Amphetamines evaluated were D- and D,L-amphetamine and methamphetamine. Amphetamine is approved by the U.S. Food and Drug Administration for the treatment of attention deficit hyperactivity disorder (ADHD) in persons over 3 years of age and narcolepsy; methamphetamine is approved for the treatment of ADHD in persons 6 years of age and older and for short-term treatment of obesity. Amphetamines were selected for evaluation because of 1) widespread usage in children, 2) availability of developmental studies in children and experimental animals, and 3) public concern about the effect of this stimulant on child development. The results of this evaluation on amphetamines are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Methylphenidate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to methylphenidate on human development and reproduction. First, there is some concern for developmental effects, specifically for potential neurobehavioral alterations, from prenatal amphetamine exposure in humans both in therapeutic and non-therapeutic settings. After prenatal exposure to therapeutic doses of amphetamine, rat pups demonstrated neurobehavioral alterations. Data from human and animal studies were judged insufficient for an evaluation of the effect of amphetamine exposure on growth and other related developmental effects. Second, there is concern for methamphetamine-induced adverse developmental effects, specifically on growth and neurobehavioral development, in therapeutic and non-therapeutic settings. This conclusion is based on evidence from studies in experimental animals that prenatal and postnatal exposures to methamphetamine produce neurobehavioral alterations, small litter size, and low birth weight. Results from studies in humans suggest that methamphetamine may cause low birth weight and shortened gestation, but study confounders such as possible multiple drug usage prevent a definite conclusion. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511).
Topics: Amphetamine; Animals; Attention Deficit Disorder with Hyperactivity; Behavior, Animal; Central Nervous System Stimulants; Dextroamphetamine; Female; Government Agencies; Government Programs; Humans; Infant, Low Birth Weight; Infant, Newborn; Learning; Litter Size; Memory; Methamphetamine; Narcolepsy; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Reproduction; Substance-Related Disorders
PubMed: 16130031
DOI: No ID Found -
British Medical Journal Oct 1974
Topics: Adolescent; Adult; Age Factors; Child; Child, Preschool; Delayed-Action Preparations; Dextroamphetamine; Epilepsy; Humans; Phenobarbital; Phenytoin; Primidone; Sleep Wake Disorders
PubMed: 4414391
DOI: 10.1136/bmj.4.5936.104 -
Canadian Medical Association Journal Jun 1950
Topics: Amphetamine; Amphetamines; Dextroamphetamine; Drug Overdose
PubMed: 15420660
DOI: No ID Found -
British Medical Journal Sep 1964
Topics: Amobarbital; Antidepressive Agents; Chlordiazepoxide; Depression; Depressive Disorder; Dextroamphetamine; Imipramine; Monoamine Oxidase Inhibitors; Psychoses, Substance-Induced; Psychotic Disorders; Toxicology
PubMed: 14172048
DOI: 10.1136/bmj.2.5411.756 -
Substance Abuse Treatment, Prevention,... Sep 2021A high proportion of people receiving both oral and injectable opioid agonist treatment report concurrent use of stimulants (i.e. cocaine and or amphetamines), which has...
Exploring the effectiveness of dextroamphetamine for the treatment of stimulant use disorder: a qualitative study with patients receiving injectable opioid agonist treatment.
BACKGROUND
A high proportion of people receiving both oral and injectable opioid agonist treatment report concurrent use of stimulants (i.e. cocaine and or amphetamines), which has been associated with higher rates of continued illicit opioid use and treatment dropout. A recent randomized controlled trial demonstrated the effectiveness of dextroamphetamine (a prescribed stimulant) at reducing craving for and use of cocaine among patients receiving injectable opioid agonist treatment. Following this evidence, dextroamphetamine has been prescribed to patients with stimulant use disorder at a clinic in Vancouver. This study investigates perceptions of the effectiveness of dextroamphetamine from the perspective of these patients.
METHODS
Data were collected using small focus groups and one-on-one interviews with patients who were currently or formerly receiving dextroamphetamine (n = 20). Thematic analysis was conducted using an iterative approach, moving between data collection and analysis to search for patterns in the data across transcripts. This process led to the defining and naming of three central themes responding to the research question.
RESULTS
Participants reported a range of stimulant use types, including cocaine (n = 8), methamphetamine (n = 8), or both (n = 4). Three central themes were identified as relating to participants' perceptions of the effectiveness of the medication: 1) achieving a substitution effect (i.e. extent to which dextroamphetamine provided a substitution for the effect they received from use of illicit stimulants); 2) Reaching a preferred dose (i.e. speed of titration and effect of the dose received); and 3) Ease of medication access (i.e. preference for take home doses (i.e. carries) vs. medication integrated into care at the clinic).
CONCLUSION
In the context of continued investigation of pharmacological treatments for stimulant use disorder, the present study has highlighted how the study of clinical outcomes could be extended to account for factors that contribute to perceptions of effectiveness from the perspective of patients. In practice, elements of treatment delivery (e.g. dosing and dispensation protocols) can be adjusted to allow for various scenarios (e.g. on site vs. take home dosing) by which dextroamphetamine and other pharmacological stimulants could be implemented to provide "effective" treatment for people with a wide range of treatment goals and needs.
Topics: Analgesics, Opioid; Central Nervous System Stimulants; Dextroamphetamine; Humans; Methamphetamine; Opioid-Related Disorders
PubMed: 34530878
DOI: 10.1186/s13011-021-00399-2 -
Medscape Journal of Medicine Jan 2008The names assigned to attention-deficit/hyperactive disorder (ADHD) have changed over the years. ADHD cannot be cured, and the patient with ADHD journeys through life... (Review)
Review
The names assigned to attention-deficit/hyperactive disorder (ADHD) have changed over the years. ADHD cannot be cured, and the patient with ADHD journeys through life with a burden. Although ADHD is most commonly studied in school-aged children, it is a syndrome that spans the life cycle, through adolescence and into adulthood. Improvements in patient adherence to pharmacologic treatment, attributable to the launch of new formulations, the availability of new non-schedule II drugs, and the development of novel drugs in late-stage clinical trials, are transforming the treatment of ADHD. For example, atomoxetine is a nonstimulant treatment, and lisdexamfetamine was developed with the goal of providing an extended duration of effect with a reduced potential for abuse, overdose toxicity, and drug tampering. Known adverse effects of stimulant treatment of ADHD include appetite suppression and sleep disturbance. Other adverse effects, such as growth suppression and substance use disorder, are controversial. The US Food and Drug Administration (FDA) recently issued a public health advisory for drugs approved for the treatment of ADHD to provide more information for patients about potential risks of ADHD medications. Additional research is needed on approaches for treating ADHD in adolescents transitioning into adulthood, as are studies on the relationships between ADHD and comorbidities such as substance use disorder.
Topics: Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Clinical Trials as Topic; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Practice Patterns, Physicians'; Prodrugs; Propylamines; Treatment Outcome
PubMed: 18324315
DOI: No ID Found