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Long-term stimulant medication treatment of attention-deficit/hyperactivity disorder: results from a population-based study.

The purpose of this study was to offer detailed information about stimulant medication treatment provided throughout childhood to 379 children with research-identified attention-deficit hyperactivity disorder (ADHD) in the 1976-1982 Rochester, MN, birth cohort. Subjects were retrospectively followed from birth until a mean of 17.2 years of age. The complete medical record of each subject was reviewed. The history and results of each episode of stimulant treatment were compared by gender, DSM-IV subtype of ADHD, and type of stimulant medication. Overall, 77.8% of subjects were treated with stimulants. Boys were 1.8 times more likely than girls to be treated. The median age at initiation (9.8 years), median duration of treatment (33.8 months), and likelihood of developing at least one side effect (22.3%) were not significantly different by gender. Overall, 73.1% of episodes of stimulant treatment were associated with a favorable response. The likelihood of a favorable response was comparable for boys and girls. Treatment was initiated earlier for children with either ADHD combined type or ADHD hyperactive-impulsive type than for children with ADHD predominantly inattentive type and duration of treatment was longer for ADHD combined type. There was no association between DSM-IV subtype and likelihood of a favorable response or of side effects. Dextroamphetamine and methylphenidate were equally likely to be associated with a favorable response, but dextroamphetamine was more likely to be associated with side effects. These results demonstrate that the effectiveness of stimulant medication treatment of ADHD provided throughout childhood is comparable to the efficacy of stimulant treatment demonstrated in clinical trials.

Adolescent↗

Psychostimulant plasma concentration and learning performance.

Six normal adults were administered an oral dose of 0.25 mg/kg of dextroamphetamine, and their learning performance on a paired-associate task and drug blood level were measured at hourly intervals for 5 hours postdrug intake. Dextroamphetamine plasma concentration peaked at 2 to 3 hours following the oral dose, and learning errors were lowest during the same period. A self-report measure of mood also yielded findings consistent with peak plasma concentration. Similar findings obtained with hyperactive children treated with methylphenidate (Ritalin) lead the authors to conclude that the paired-associate learning task may be useful as an indicator of psychostimulant plasma levels, as a predictor of clinical response after an acute dose, and as a highly controlled task for studying psychostimulant drug effects on learning.

Administration, Oral↗

Drug interactions with psychostimulants.

The psychostimulants methylphenidate, dextroamphetamine, and pemoline are among the most common medications used in child and adolescent psychiatry. Often, these agents are used in combination with other medications. This review summarizes reported drug interactions and assesses both causality and clinical significance. A computerized search was undertaken using MEDLINE (1966 to 1998) to obtain all pertinent reports of adverse events associated with the coadministration of psychostimulants and other drugs. A total of 38 reports involving 25 different drugs from various classes were systematically evaluated along with research studies conducted to specifically assess drug interactions. Methylphenidate appeared to be involved primarily in pharmacokinetic interactions suggestive of cytochrome P450 inhibition while dextroamphetamine and pemoline were more often involved in apparent pharmacodynamic interactions. The published data support the safe use of psychostimulants with most classes of medications with few absolute contraindications.

Anticonvulsants↗

Psychostimulants in post-stroke depression.

The hospital charts of 17 patients with post-stroke depression who were treated with either dextroamphetamine or methylphenidate during a 5-year period at the Massachusetts General Hospital were examined. Eighty-two percent of the patients showed improvement after psychostimulant treatment. Forty-seven percent of all patients showed marked or moderate improvement in depressive symptoms. The authors saw no significant differences in efficacy between the two psychostimulants or across the diagnostic categories for depression. Patients improved quickly, usually within the first 2 days of treatment. Adverse reactions necessitating the termination of psychostimulant treatment occurred in three patients. Anorexia was not observed as a side effect of either dextroamphetamine or methylphenidate treatment. Psychostimulants appear to be a safe and rapidly effective alternative to tricyclic antidepressants in inpatients with post-stroke depression.

Aged↗

Psychostimulants in psychiatry.

The use of the psychostimulants in psychiatry is reviewed. A brief historical perspective on dextroamphetamine is presented, and a brief review of the psychopharmacology of dextroamphetamine, methylphenidate and magnesium pemoline is given. The literature on the use of stimulants in the treatment of resistant depression, apathetic geriatric patients and patients medically ill with a secondary depression is summarized and two case histories given to illustrate the clinical usefulness of the stimulants. The literature on the use of stimulants as an adjunct to antidepressant therapy and as a diagnostic test is also discussed. Finally the use of stimulants in obsessional illness and adult attention deficit disorder is summarized. The writer concludes by commenting that the stimulants have a very useful role in the treatment of certain categories of depression as well as other psychiatric syndromes and such patients should not be deprived of symptom relief by these drugs. The approach to therapy should be much the same as the use of analgesics for chronic pain sufferers.

Adult↗

Central monoamines and hyperkinase of childhood.

Lumbar cerebrospinal fluid levels of homovanillic acid and 5-hydroxyindoleacetic acid, the major metabolites of dopamine and serotonin, respectively, in hyperactive children did not differ significantly from those of age-matched controls. Dextroamphetamine treatment substantially reduced the spinal fluid content of homovanillic acid but not of 5-hydroxyindoleacetic acid. No change in levels of either monoamine metabolite occurred with placebo therapy. In hyperactive children receiving dextroamphetamine, the amount of homovanillic acid decline correlated closely with the degree of clinical improvement. These results support the view that an alteration in central dopamine-mediated synaptic function may occur in children manifesting the hyperactive syndrome.

Adolescent↗

Gamma hydroxybutyrate in the monkey. IV. Dopaminergic mechanisms.

The electrical seizure activity and trancelike state induced in the rhesus monkey by gamma-hydroxybutyrate (GHB) were abolished by dextroamphetamine. Dextroamphetamine blockade of this neurophysiologic effect was overcome with chlorpromazine, a dopamine receptor blocker. These results suggest that the electroencephalographic (EEG) and behavioral effects of GHB are related to effects on dopaminergic systems. Such a relationship, if substantiated by further studies, might indicate that anticonvulsant drugs used to treat petit mal epilepsy have a dopaminergic mode of action.

Animals↗

Clinical behavioral pharmacology: methods for evaluating medications and contingency management.

We evaluated methods for comparing the effects of dextroamphetamine (Dexedrine), thioridazine (Mellaril), and contingency management in the control of severe behavior problems. A reversal design was used in which medications were systematically titrated and assessed in unstructured as well as structured settings with three clients. Subsequently, behavioral procedures including timeout, differential reinforcement of other behavior, and visual screening, were used in a multiple-baseline design across settings. The assessment and design methods were useful in comparing the interventions. Dextroamphetamine decreased inappropriate behaviors and improved academic behaviors in one client, but no reliable effects were observed in the other two clients. Thioridazine was variable across clients, settings, behaviors, and dosages. Contingency management produced consistent decreases in inappropriate behaviors and small improvements in academic performance.

Achievement↗

Psychostimulant treatment of depressive disorders secondary to medical illness.

Hospital charts were reviewed for 66 medical and surgical patients who received dextroamphetamine or methylphenidate to treat a depressive disorder. Approximately three-fourths showed some improvement; in half of the sample, improvement was marked or moderate. Of those who improved, 93% reached their peak response within the first 2 days. Relapse occurred in only 5 patients. Side effects were minimal. Nonsignificant trends suggested that dextroamphetamine was more effective for major depression than adjustment disorder, while methylphenidate tended to be more effective for adjustment disorder. Psychostimulants appear to be a therapeutic option in the medically ill depressed population and may be more rapidly effective with fewer side effects than tricyclic antidepressants.

Adjustment Disorders↗

Single dose of prednisone does not induce amphetamine-like subjective effects in healthy subjects.

Among the methods developed in assessing abuse liability, the behavioural and subjective effects of drugs can be recorded using the Addiction Research Center Inventory (ARCI) in drug-experienced subjects and normal volunteers. Sixteen healthy volunteers with no history of drug abuse participated in the study. The subjective, behavioural and physiological effects of prednisone (30 and 60 mg) were compared with those of dextroamphetamine (15 mg) and placebo in a randomized double-blind Latin square design. The self-questionnaires (ARCI, Profile of Mood States, Visual Analogue Scales and Sleep Questionnaire) were completed before, 1, 2, 4 and 8 h post single oral dosing. Results showed that subjective effects of the two studied doses of prednisone did not resemble those induced by dextroamphetamine (15 mg). These results indicate that oral single doses of prednisone do not possess amphetamine-like subjective effects in a healthy population. The well established psychostimulant effect of amphetamine have been replicated on almost all subjective assessments.

Adult↗

The use of amphetamines in U.S. Air Force tactical operations during Desert Shield and Storm.

Today's battleground requires round-the-clock air support. Modern aircraft systems enable tactical aircraft to be flown in all weather conditions, day or night, and for prolonged periods. U.S. Air Force Tactical Air Command (TAC) aircrew who deployed to the Southwest Asia Area of Responsibility (SWA AOR) for Operation Desert Shield/Desert Storm were retrospectively surveyed to determine the extent and effectiveness of dextroamphetamine use in support of sustained flying operations. Surveys were sent in May 1991 to each tactical squadron that participated in Desert Storm. Of pilots who were surveyed, 65% used amphetamines during the deployment to the SWA AOR and/or during Operation Desert Storm. Pilots who used amphetamines in air operations described it as "occasional." The most frequent indications for amphetamine use were "aircrew fatigue" and "mission type." Of pilots who used amphetamines, 58-61% considered their use beneficial or essential to operations. Dextroamphetamine (5 mg every 4 h) was used effectively and without major side effects in tactical flying operations. Amphetamine use enhanced cockpit performance and flight safety by reducing the effect of fatigue during critical stages of flight.

Aerospace Medicine↗

Amphetamines reduce embryonic size and produce caudal hematomas during early chick morphogenesis.

Experiments were designed to study some of the similarities and differences in the effects of amphetamines and trypan blue on early chick morphogenesis. Both dextroamphetamine sulfate (0.5 mg/egg) and methamphetamine hydrochloride (1.0 mg/egg) were capable of inducing, in 3-day chick embryos, caudal hematomas which were similar in appearance and location to those routinely observed following treatment with trypan blue. It was found, too, that both dextroamphetamine and methamphetamine treated embryos frequently exhibited a significant decrease in crown rump length and cross-sectional area of the notochord, neural tube, dorsal aortae and whole body section, when compared with unopened or saline injected controls. Trypan blue treated embryos had only a rare decrease or increase in the size of structures when compared to either control group. These findings suggest that the amphetamines have an ability to decrease or retard embryonic growth in the chick.

Abnormalities, Drug-Induced↗

Cardiomyopathy associated with amphetamine administration.

A 45-year-old woman with congestive heart failure, in whom there was no evidence of coronary heart disease, valve disease, or other demonstrable cause of heart failure, was found to have taken high doses of dextroamphetamine over a long period. Withdrawal of amphetamine resulted in deterioration, suggesting a physical cardiac dependence on the drug. The clinical and autopsy findings are presented and the similarities to the myocarditis associated with pheochromocytoma are discussed. The evidence presented suggests a causal relationship between administration of dextroamphetamine and the cardiomyopathy.

Amphetamines↗

Psychostimulant drugs potentiate morphine analgesia in the formalin test.

Recent research has shown that the psychostimulant drug dextroamphetamine can increase the analgesia produced by opioids. Despite the strong, positive results in human clinical subjects and in animals, this combination is rarely used in clinical practice. The purpose of this paper is to investigate whether the psychostimulant drug methylphenidate (MP) can potentiate morphine analgesia in the rat formalin test, and to compare its effectiveness to that of dextroamphetamine (AMP). The formalin test was used because its long-lasting pain of moderate intensity resembles human clinical pain. Two different drug administration times were used to observe whether the early phase of the formalin response would be differentially affected by the drugs. At Drug Administration Time 1, rats received morphine 30 min prior to the formalin injection (-30 min) and MP or AMP 20 min prior to the formalin injection (-20 min). At Drug Administration Time 2, rats received morphine 10 min prior to the formalin injection (-10 min) and MP or AMP immediately prior to the formalin injection (0 min). All drugs were given subcutaneously. The results indicate that low doses of MP or AMP potentiate the analgesic effects of morphine. The clinical value of these drug combinations merits further investigation in animals and in humans.

Analgesics, Opioid↗

Narcolepsy.

Narcolepsy is a neurological condition with a prevalence of up to 1 per 1,000 that is characterized by irresistible bouts of sleep. Associated features include the pathological manifestations of rapid-eye-movement (REM) sleep: cataplexy, sleep paralysis, hypnagogic hallucinations, and abnormal sleep-onset REM periods and disturbed nocturnal sleep. The condition is strongly associated with the HLA-DR2 and DQw1 phenotype. The phenomenology of narcolepsy is discussed, and diagnostic procedures are reviewed. Treatment modalities involving central nervous system stimulants for somnolence and tricyclic drugs for REM-sleep abnormalities are discussed. Sleep laboratory studies on the treatment efficacy of methylphenidate, pemoline, dextroamphetamine, protriptyline, and viloxazine are presented. Data suggest that: (1) methylphenidate and dextroamphetamine objectively improve somnolence; (2) pemoline, at doses up to 112.5 mg, is less effective in controlling somnolence but may improve certain aspects of performance; and (3) protriptyline and viloxazine are effective anticataplectic agents that produce little improvement in somnolence.

Adult↗

Amphetamines in the treatment of Parkinson's disease.

Twenty-two patients with Parkinsonism were treated with levoamphetamine and 12 of these with dextroamphetamine. Levoamphetamine resulted in a significant improvement in disability from Parkinsonism, although the reduction in total disability, tremor, akinesia, and rigidity scores was slight (ca 20 percent). Dextroamphetamine in lower dosage also reduced disability by some 17 percent. The most disabled patients, including those also on levodopa, showed the greatest response to amphetamines. Previously, amphetamines have been reported to be a selective treatment for the oculogyric crises of post-encephalitic Parkinsonism. Amphetamines are thought to cause the release of catecholamines from central neurones. Their action in Parkinson's disease may be limited because of pre-existing striatal dopamine deficiency. Side-effects of amphetamines, anorexia, and CNS stimulation are different from those caused by levodopa in patients with Parkinson's disease.

Aged↗

Treatment modalities for narcolepsy.

Narcolepsy, a lifelong disorder, requires long-term management of symptoms. Interventions may be nonpharmacologic, such as lifestyle changes, and pharmacologic for relief of daytime sleepiness. Pharmacologic treatment of narcolepsy has depended on the use of CNS stimulants to increase wakefulness, vigilance, and performance. The medications considered effective in the treatment of narcolepsy include dextroamphetamine, pemoline, methylphenidate, methamphetamine, and modafinil; only methylphenidate hydrochloride and dextroamphetamine are approved for use in the United States. The currently available stimulants are associated with sympathomimetic side effects, limitations in efficacy, and negative effects on nighttime sleep. This has led to the development of alternative agents. Modafinil, a new wake-promoting agent, has been shown to be effective in reducing daytime sleepiness in patients with narcolepsy. The results of a United States 18-center randomized, placebo-controlled, 9-week trial of modafinil in the treatment of patients with narcolepsy has recently been reported. Patients receiving modafinil demonstrated significant improvement in all subjective and objective measures of sleepiness. Treatment with modafinil 200 mg and 400 mg daily significantly reduced mean scores on the Epworth Sleepiness Scale compared with baseline and placebo (p < 0.001) and significantly increased mean scores on the Maintenance of Wakefulness Test (p < 0.001) and the Multiple Sleep Latency Test (p < 0.001) compared with baseline and placebo. More improvement, as recorded on the Clinical Global Impression of Change scale, was seen in the modafinil group than in the placebo group at all time points (p < 0.001). Modafinil was well tolerated, with headache the only adverse event to occur significantly more often in the active treatment group (p < 0.05). These results suggest that modafinil is an important new therapeutic option for the treatment of narcolepsy.

Adult↗

Illicit use of specific prescription stimulants among college students: prevalence, motives, and routes of administration.

OBJECTIVES: To explore the illicit use of specific prescription stimulants among college students and add to our understanding of reasons (motives) and routes of administration associated with illicit use of these drugs. METHODS: A random sample of 4580 college students self-administered a Web-based survey. The survey contained a variety of items pertaining to the illicit use of prescription stimulants. An extensive list of prescription stimulants was provided, and students were asked to select all the specific prescription stimulants that they had used illicitly. Items were also included to assess the motives and routes of administration associated with illicit use of prescription stimulants. RESULTS: Lifetime and past-year prevalence rates for illicit use of prescription stimulants were 8.3% (382 students) and 5.9% (269 students), respectively. Approximately three fourths (75.8%) of the 269 past-year illicit users of prescription stimulants reported using an amphetamine-dextroamphetamine combination agent (e.g., Adderall) in the past year, and approximately one fourth (24.5%) reported using methylphenidate (e.g., Ritalin, Concerta, Metadate, Methylin). Past-year illicit use of prescription stimulants was more than 3 times more likely among Caucasians (odds ratio [OR] 3.1, 95% confidence interval [CI] 1.5-6.6) and Hispanics (OR 3.8, 95% CI 1.6-9.3) compared with African-Americans, and more than twice as likely among Caucasians (OR 2.1, 95% CI 1.3-3.4) and Hispanics (OR 2.6, 95% CI 1.4-5.1) compared with Asians. The most commonly reported motives for illicit use were to help with concentration (65.2%), help study (59.8%), and increase alertness (47.5%). Other motives included getting high (31.0%) and experimentation (29.9%). Nearly every illicit user (95.3%) reported oral administration, and 38.1% reported snorting prescription stimulants. CONCLUSION: Illicit use of amphetamine-dextroamphetamine is more prevalent than illicit use of methylphenidate formulations among college students.

Adolescent↗