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Use of psychostimulants in medically ill patients with neurological disease and major depression.

The effective therapeutic response to dextroamphetamine and methylphenidate by five depressed patients with neurological disease is described. In four of these patients tricyclic antidepressants had to be discontinued due to the concomitant deterioration of their cognitive functions, and in one case they were not used due to cardiovascular complications. There was a rapid remission of depressive symptomatology with no adverse side effects, consistent with the findings of other investigators. The possible association of right hemisphere strokes and depression is also discussed. Further evaluation of the therapeutic role of psychostimulants in the treatment of depressed patients with structurally-compromised brain function is recommended.

Aged↗

Psychostimulant treatment of geriatric depressive disorders secondary to medical illness.

The records were reviewed for 129 medically ill geriatric inpatients treated with either dextroamphetamine or methylphenidate for secondary depression during a five year period at the Massachusetts General Hospital. Eighty-one percent of patients demonstrated at least some improvement following psychostimulant treatment. Sixty-six percent of these experienced marked to moderate amelioration of their depressive symptoms. Improvement was rapid and usually occurred within the first or second day of treatment. No significant difference in efficacy was noted between the two psychostimulants or across diagnostic categories for depression. Only 8% of patients experienced adverse reactions significant enough to warrant termination of the psychostimulant trial. No instances of anorexia due to psychostimulant treatment were observed.

Age Factors↗

Amphetamine-induced dysphoria in postmenopausal women.

Dextroamphetamine (0.15 mg/kg) intravenously administered to a group of normal postmenopausal women induced a dysphoric reaction with drowsiness, annoyance, sadness and anger. Young normal men, receiving the same dosage, responded with elation of mood and alertness. It is suggested that age and hypoestrogenism may alter the behavioural response to amphetamine.

Adult↗

Prevalence and characteristics of adolescents patients with co-occurring ADHD and substance dependence.

Estimates of co-morbidity of SUD and ADHD in addiction treatment settings range from 30% to 50%. The Schedule II psychostimulant medications, methylphenidate and dextroamphetamine, generally considered to be safe and effective in treating ADHD in adolescent patients, may be risky for an SUD population since individuals with SUD may have a higher likelihood of abusing or diverting the medications. One hundred sixty-two adolescent patients admitted to a residential addictions treatment program were administered a structured interview concerning ADHD and psychostimulant abuse as part of the clinical psychological evaluation administered by the staff psychologist. Results indicate 31% of patients have current ADHD diagnosis and 20% reported illicit diversion of Schedule II medication. One-third of entire adolescent patient population reported prior psychostimulant abuse. Results are discussed in terms of appropriate treatment for adolescents with co-occurring substance abuse or dependence and ADHD.

Adolescent↗

Stimulant medication withdrawal during long-term therapy in children with comorbid attention-deficit hyperactivity disorder and chronic multiple tic disorder.

OBJECTIVES: In this study we examined changes in attention-deficit hyperactivity disorder behaviors and motor and vocal tics during withdrawal from long-term maintenance therapy with stimulant medication. METHODS: Subjects were 19 children with attention-deficit hyperactivity disorder and chronic tic disorder who had received methylphenidate (n = 17) or dextroamphetamine (n = 2) for a minimum of 1 year. Children were switched to placebo under double-blind conditions. Treatment effects were assessed by using direct observations of child behavior in a simulated (clinic-based) classroom and behavior rating scales completed by parents and clinician. RESULTS: There was no change (group data) in the frequency or severity of motor tics or vocal tics during the placebo condition compared with maintenance dose of stimulant medication (ie, no evidence of tic exacerbation while receiving medication or of a withdrawal reaction). There was no evidence of tic exacerbation in the evening as a rebound effect. Treatment with the maintenance dose was also associated with behavioral improvement in attention-deficit hyperactivity disorder behaviors, indicating continued efficacy. CONCLUSIONS: Abrupt withdrawal of stimulant medication in children receiving long-term maintenance therapy does not appear to result in worsening of tic frequency or severity. Nevertheless, these findings do not preclude the possibility of drug withdrawal reactions in susceptible individuals.

Adolescent↗

Drug treatment for hyperactive children. Therapeutic guidelines.

Attention deficit hyperactivity disorder (ADHD) is a common childhood behavioural disorder and medication is one of the principal treatments. Methylphenidate and dexamphetamine (dextroamphetamine) have a long record of use in children and well proven efficacy, and are the preferred drugs. Current clinical guidelines recommend a trial of methylphenidate and of dexamphetamine for each child meeting criteria for the disorder in order to maximise response rate and minimise adverse effects.

Antidepressive Agents, Tricyclic↗

Dramatic favorable responses of children with learning disabilities or dyslexia and attention deficit disorder to antimotion sickness medications: four case reports.

Responses of four learning disabled children who showed dramatic improvements to one or more antimotion-sickness-antihistamines and -stimulants are described qualitatively. These cases were selected from a prior quantitative study in which three antihistamines (meclizine, cyclizine, dimenhydrinate) and three stimulants (pemoline, methylphenidate, dextroamphetamine) were tested in variable combinations (using a specific clinical method) for favorable responses by 100 children characterized by diagnostic evidence of learning disabilities and cerebellar-vestibular dysfunctioning. Pending validation in double-blind controlled studies, these qualitative results suggest that the "cerebellar-vestibular (CV) stabilizing" antimotion-sickness medications, Piracetam included, and their combinations may be shown to be therapeutically useful in treating children with learning disabilities or dyslexia and attention deficit disorder.

Attention Deficit Disorder with Hyperactivity↗

Does hair zinc predict amphetamine improvement of ADD/hyperactivity?

In 18 boys with ADHD (ages 6-12) in a balanced crossover design, parent and teacher hyperactivity rating differences between one month of dextroamphetamine and one month of placebo correlated significantly (p less than .05, 2 tailed) on Pearson's r with baseline hair zinc levels and nonsignificantly with 24-hour urinary zinc excretion. The signs of the correlations were such that a higher baseline zinc predicted a better placebo-controlled response to amphetamine. Patient baseline urinary zinc was significantly (p less than .02) lower than 7 normal controls. These findings are compatible with the possibility that some ADHD children may be mildly deficient in zinc and constitute poorer stimulant responders. Correlations of zinc levels with 24-hour urinary MHPG were in the expected direction but nonsignificantly by 2-tailed test.

Attention Deficit Disorder with Hyperactivity↗

The effect of stimulants on nocturnal motor activity and sleep quality in adults with ADHD: an open-label case-control study.

OBJECTIVE: Sleep disturbances are common in adults with attention-deficit/hyperactivity disorder (ADHD). In a case-control study, adult ADHD was associated with increased nocturnal motor activity and reduced self-perceived quality of sleep. METHOD: Eight adults with DSM-IV-diagnosed ADHD (combined type, N = 7; inattentive type, N = 1) were treated with stimulants in open-label form at 8:00 a.m., 12:00 noon, and 4:00 p.m. The mean daily dose was 51 mg of methylphenidate (range, 30-90 mg) in 7 subjects and 30 mg of dextroamphetamine in 1 subject. Actimeters were used to assess nocturnal motor activity during 6 consecutive nights both at baseline and after 3 weeks of treatment. The data were compared with those of 8 matched normal controls. RESULTS: ADHD patients slept worse and showed significantly higher nocturnal motor activity at baseline compared with controls. No baseline differences between patients and controls were found in sleep latency, number of awakenings, and total time in bed. Changes from baseline to week 3 within the ADHD patients indicated improvement of sleep quality (p = .05) and reduction of Activity Level (p = .10) and Movement Index (p = .07) scores. When within-group changes were compared between ADHD subjects and controls, treatment with stimulants tended to be associated with a reduction of Activity Level (p < .01) and Movement Index (p = .04) scores and improved sleep quality (p = .02) in ADHD patients. Sleep latency, number of awakenings, and total time in bed were unaffected in within-group and between-group analyses. CONCLUSION: The results should be interpreted cautiously given the open-label design and small sample size. Further study is warranted into the influence of stimulants on sleep in larger samples of ADHD patients by using controlled designs, multiple dose levels, and polysomnographic measures.

Adult↗

[Central nervous system stimulants and their potential risk of abuse in hyperkinetic disorders].

The literature on the medical use of methylphenidate for hyperkinetic disorder/AD/HD does not support that its use implies a substantial risk for substance abuse, serious complications or drug dependence. Recent pharmacokinetic studies with PET throw light on the empirical findings of low rate of abuse, as the euforigenic potential of methylphenidate taken orally appears to be very modest. Methylphenidate should be the drug of choice in the treatment of adults with hyperkinetic disorder/AD/HD. However, current substance abuse precludes use of the drug and former abuse liability and social adjustment problems are relative contraindications. There is a lack of scientific data on the use of dextroamphetamine in adults with hyperkinetic disorder/AD/HD. The drug has a higher potential for abuse than methylphenidate and should be considered as a second choice only after an individual consideration of compliance and if methylphenidate proves ineffective. Rigid control of the prescription is necessary, and a medical history of substance abuse should in our opinion preclude its use.

Adult↗

Treatment of attention-deficit/hyperactivity disorder.

OBJECTIVES: To determine (a) the long-term and short-term effectiveness and safety of pharmacological and nonpharmacological interventions for attention-deficit/hyperactivity disorder (ADHD) in children and adults and (b) whether combined interventions are more effective than individual interventions. SEARCH STRATEGY: MEDLINE (from 1966), CINAHL (from 1982), HEALTHStar (from 1975), PsycINFO (from 1984), EMBASE (from 1984), and the Cochrane Library searches were completed in November 1997. Reference lists of eligible studies and files of members of the research team and partner organizations were also searched. SELECTION CRITERIA: Studies were selected if they focused on the treatment of ADHD in humans and were published in any language as a full report in peer-reviewed journals. Studies including conditions other than ADHD were reported if separate subgroup analyses for patients with ADHD were provided. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data for 41 variables on general characteristics, along with detailed information on interventions, outcomes, and tests. Differences were resolved by consensus or by a third researcher. Studies were not combined quantitatively because the quality of reporting was low and heterogeneity existed across outcome measures and tests. MAIN RESULTS: Seventy-eight studies (77 randomized controlled trials) met the inclusion criteria. Twenty-three studies compared drugs and showed few, if any, differences among methylphenidate (MPH), dextroamphetamine (DEX), and pemoline; studies comparing stimulants with tricyclic antidepressants (2) were inconclusive. Six studies compared drugs with nondrug interventions and showed consistently that stimulants, particularly MPH, may be more effective than nonpharmacological interventions. Twenty studies compared combination therapies with a stimulant or a nondrug intervention alone; no additional beneficial effects for combination therapies were shown. Nine studies compared tricyclic antidepressants with placebo and showed that desipramine may be more effective than placebo; no consistent effect was shown for imipramine. Fourteen studies (13 in school children and 1 in adults) evaluated long-term therapy (> or = 12 weeks) and showed a trend to general improvement regardless of treatment, but the length of followup was inadequate. MPH may reduce behavioral disturbance in children with ADHD while it is taken. Academic performance does not appear to be improved with stimulants. Twelve studies evaluated treatment in adults with ADHD. For MPH vs. placebo, the results were contradictory. Antidepressants may be effective in adults, but no beneficial effect was seen with pemoline, nicotine, or phenylalanine compared with placebo. Thirty-two reports (29 studies) evaluated adverse effects of drug therapy; many of the side effects associated with stimulant use appear to be relatively mild and of short duration and to respond to dosing or timing adjustments. Data are inadequate on the long-term effects and severity of adverse effects of most interventions. CONCLUSIONS: This report describes rigorous systematic reviews on the treatment of ADHD, ready for incorporation into evidence-based clinical practice guidelines or performance measures. The report also provides a detailed description of the many limitations of the evidence available and provides recommendations to fill existing knowledge gaps. Studies on ADHD have low reporting quality, methodological flaws, and heterogeneity across outcome measures and tests. A detailed description is included of the many limitations of the available evidence plus recommendations to fill existing knowledge gaps. Fulfilling such knowledge gaps will not be easy and will require genuine collaboration among decisionmakers.

Adrenergic Uptake Inhibitors↗

Comparison of treatment strategies for Space Motion Sickness.

Treatment strategies for Space Motion Sickness were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of Space Motion Sickness were graded as mild, moderate or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through Private Medical Conferences with the crew. A symptom matrix was analyzed for 19 crewmembers treated with an oral combination of scopolamine and dextroamphetamine (scopdex) and 15 crewmembers treated with promethazine delivered by intramuscular (IM) or suppository routes. Scopdex has been given preflight as prophaxis for Space Motion Sickness but analysis showed delayed symptom presentation in 9 crewmembers or failed to prevent symptoms in 7. Only three crewmembers who took scopdex had no symptoms inflight. Fourteen out of 15 crewmembers treated with IM promethazine and 6 of 8 treated with promethazine suppositories after symptom development had immediate (within 12 h) symptom relief and required no additional medication. There were no cases of delayed symptom presentation in the crewmembers treated with promethazine. This response is in contrast to untreated crewmembers who typically have slow symptom resolution over 72-96 h. We conclude that promethazine is an effective treatment of Space Motion Sickness symptoms inflight. NASA policy currently recommends treating crewmembers with Space Motion Sickness after symptom development, and no longer recommends prophylaxis with scopdex due to delayed symptom development and apparent variable absorption of oral medications during early flight days.

Aerospace Medicine↗

Central nervous system stimulants as symptomatic treatments for AIDS-related neuropsychiatric impairment.

Seven patients with AIDS-related cognitive and emotional deficits had neuropsychologic testing and then were treated with methylphenidate or dextroamphetamine in individualized doses. Three patients showed marked functional improvement and 5 of the 7 became more spontaneous, reactive, and animated. Additional neuropsychologic testing showed statistically significant improvement in a subset of tests; however, scores did not return to baseline in tests done after the treatment was discontinued for 1-3 days.

Acquired Immunodeficiency Syndrome↗

Single- and multiple-dose pharmacokinetics of an oral mixed amphetamine salts extended-release formulation in adults.

OBJECTIVES: Assess the bioavailability of mixed amphetamine salts extended-release (MAS XR) 30-mg capsules and the dose proportionality of pharmacokinetic measures for MAS XR 20, 40, and 60 mg. METHODS: Study A, an open-label single-period study, and Study B, a randomized, open-label, three-way crossover study, were conducted in healthy adults in a clinical research unit. In Study A, 20 subjects received a single MAS XR 30-mg capsule by mouth daily for 7 days. In Study B, 12 subjects received single oral doses of MAS XR 20, 40, and 60 mg separated by 7-14-day washout periods. FINDINGS: Plasma dextroamphetamine (d-amphetamine) and levoamphetamine (l-amphetamine) concentrations were measured using a validated LC-MS/MS method. In Study A, a 3:1 ratio of d-amphetamine to l-amphetamine was observed for AUC0-inf and Cmax. Tmax was 4.2 and 4.3 hours for d-amphetamine to l-amphetamine, respectively. In Study B, for d- and l-amphetamine, statistically significant differences were observed for AUC0-t, AUC0-inf, and Cmax between all doses; there was a linear relationship between pharmacokinetic variables and dose and Tmax was similar for each isomer (range: 4.5-5.3 hours) with all given MAS XR doses. CONCLUSION: The extent of exposure as assessed by mean AUC0-24 and Cmax reflected the 3:1 ratio of d-amphetamine to l-amphetamine in MAS XR 30-mg capsules. The pharmacokinetic profiles of MAS XR 20, 40, and 60 mg are dose proportional for the isomers.

Administration, Oral↗

Idiopathic orthostatic cyclic edema as a unique etiology for vasomotor flushing in a normal estrogenic woman with normal day 3 follicle stimulating hormone--case report.

PURPOSE: To describe a unique cause and therapy for vasomotor flushing. METHODS: Serum follicle stimulating hormone (FSH) and estradiol, renal and liver function studies and urinalysis were performed as well as a water load test. RESULTS: All laboratory tests were normal but the water load test showed inadequate four-hour urine excretion when she was erect but normal when supine. Complete relief from vasomotor symptoms occurred shortly after treatment with sympathomimetic amines. CONCLUSIONS: Idiopathic orthostatic cyclic edema can cause vasomotor flushing even with normal estrogen and serum FSH, and treatment of the edema state with the drug of choice dextroamphetamine sulfate can effectively control these symptoms.

Adult↗

The treatment of idiopathic edema, a cause of chronic pelvic pain in women: effectively controlled chronic refractory urticaria--case reports.

PURPOSE: To corroborate or refute a previous case report from 20 years ago whether treatment with sympathomimetic amines is effective in controlling chronic urticaria. METHODS: All cases of chronic urticaria in our reproductive endocrinology and infertility practice were identified. All four had been treated with dextroamphetamine sulfate. Quickness and duration of response were then determined. RESULTS: Four women were identified. All showed improvement within the first month. The marked improvement did not dissipate including two patients whose duration of improvement was 8.5 and 13 years, respectively. CONCLUSIONS: Gynecologists should consider idiopathic edema as an etiology when facing chronic pelvic pain and urticaria. Since allergists and dermatologists do not seem to be aware of this treatment option, the initiation of therapy may need to come from the gynecologist.

Chronic Disease↗

Psychostimulants for depression in the medically ill.

Medically ill patients who show signs of depression may have problems with traditional antidepressant therapy, because of the side effect profile and the delayed onset of action of these agents. Psychostimulants such as methylphenidate and dextroamphetamine are another treatment option. The beneficial effects of these drugs are usually noted within 36 hours, and drug habituation is generally not a problem. The primary obstacle to the use of these agents for depression in medically ill patients is the hesitancy of physicians to prescribe them.

Adult↗