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PubMed1999

Context-dependent, neural system-specific neurophysiological concomitants of ageing: mapping PET correlates during cognitive activation.

We used PET to explore the neurophysiological changes that accompany cognitive disability in ageing, with a focus on the frontal lobe. Absolute regional cerebral blood flow (rCBF) was measured in 41 healthy volunteers, evenly distributed across an age range of 18-80 years, during two task paradigms: (i) the Wisconsin Card Sorting Test (WCST), which depends heavily on working memory and is particularly sensitive to dysfunction of the dorsolateral prefrontal cortex (DLPFC); and (ii) Raven's Progressive Matrices (RPM), which may also have a working memory component, but depends more on visuo-spatial processing and is most sensitive to dysfunction of postrolandic regions. We used voxel-wise correlational mapping to determine age-related changes in WCST and RPM activation and developed a method to quantitate and localize statistical differences between the correlation maps for the two task paradigms. Because both WCST and RPM performance declined with age, as expected, correlational analyses were performed with and without partialling out the effect of task performance. Task-specific reductions of rCBF activation with age were found in the DLPFC during the WCST and in portions of the inferolateral temporal cortex involved in visuo-spatial processing during the RPM. We also found reduced ability to suppress rCBF in the right hippocampal region during the WCST and in mesial and polar portions of the prefrontal cortex during both task conditions. Task-dependent alterations with age in the relationship between the DLPFC and the hippocampus were also documented; because the collective pattern of changes in the hippocampal-DLPFC relationship with ageing was opposite to that seen in a previous study using dextroamphetamine, we postulated a dopaminergic mechanism. These results indicate that, despite some cognitive overlap between the two tasks and the age-related cognitive decline in both, many of the changes in rCBF activation with age were task-specific, reflecting functional alteration of the different neural circuits normally engaged by young subjects during the WCST and RPM. Reduced activation of areas critical for task performance (i.e. the DLPFC during the WCST and posterior visual association areas of the inferolateral temporal cortex during the RPM), in conjunction with the inability to suppress areas normally not involved in task performance (i.e. the left hippocampal region during the WCST and mesial polar prefrontal cortex during both the WCST and RPM), suggest that, overall, reduced ability to focus neural activity may be impaired in older subjects. The context dependency of the age-related changes is most consistent with systems failure and disordered connectivity.

Adolescent↗
PubMed1988

Studies of autonomic psychophysiology and attention in schizophrenia.

Research from this laboratory over the years has found a rather consistent pattern of high baseline levels of many (but not all) indices of autonomic activity, slow adaptation, and attenuated autonomic reactivity to significant stimuli and situations in schizophrenia and that this pattern may be related to prognosis. Our studies have also shown that qualitatively similar changes occur in healthy subjects after a dose of dextroamphetamine and that certain aspects of the pattern are exaggerated in schizophrenic patients with cortical atrophy. It is hypothesized that there are specific autonomic markers for the two syndromes of schizophrenia defined by positive and negative symptoms which reflect distinct biological mechanisms. Current research seeks to determine the biological and symptomatic correlates of autonomic activity, to establish the specificity of certain autonomic markers to schizophrenia versus other major diagnoses, and to study the mechanisms and improve the assessment of attentional deficits in schizophrenia.

Arousal↗
PubMed1995

Bupropion versus methylphenidate in the treatment of attention-deficit hyperactivity disorder.

OBJECTIVE: In the treatment of attention-deficit hyperactivity disorder (ADHD), the efficacy of the tricyclic antidepressants and monoamine oxidase inhibitor antidepressants has been compared with that of both placebo and the stimulants (methylphenidate and/or dextroamphetamine). However, the effectiveness of bupropion has been contrasted only with placebo. The primary aim of this study was to contrast the efficacy of bupropion with that of methylphenidate in the treatment of ADHD. METHOD: A double-blind, crossover design was used in this study. After a 14-day medication washout period, 15 ADHD subjects (7 to 17 years old) were randomized to either methylphenidate or bupropion for 6 weeks, washed out for an additional 2 weeks, and then "crossed over" to the other drug. Methylphenidate was titrated to the maximum effective dose of 0.4 to 1.3 mg/kg per day (mean 0.7 mg/kg per day) and bupropion was titrated to an effective dose ranging from 1.4 to 5.7 mg/kg per day (mean 3.3 mg/kg per day). RESULTS: Both methylphenidate and bupropion produced significantly greater (p < .001) and equivalent improvement on the Iowa-Conners Teacher's Rating Scale according to both the subjects' parents and teachers. The same pattern of improvement was also noted for improvement on the Clinical Global Impression Scale, Kagan's Matching Familiar Figures Test, Continuous Performance Test, Children's Depression Inventory, Children's Manifest Anxiety Scale, and Rey Auditory-Verbal Learning Test. CONCLUSIONS: In this double-blind, crossover trial, bupropion and methylphenidate were both effective and did not differ in their overall efficacy as treatments for ADHD.

Adolescent↗
PubMed2001

Summary of the practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults.

This practice parameter describes treatment with stimulant medication. It uses an evidence-based medicine approach derived from a detailed literature review and expert consultation. Stimulant medications in clinical use include methylphenidate, dextroamphetamine, mixed salts of amphetamine, and pemoline. They carry U.S. Food and Drug Administration indications for the treatment of attention-deficit hyperactivity disorder.

Adolescent↗
PubMed2002

Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults.

This practice parameter describes treatment with stimulant medication. It uses an evidence-based medicine approach derived from a detailed literature review and expert consultation. Stimulant medications in clinical use include methylphenidate, dextroamphetamine, mixed-salts amphetamine, and pemoline. It carries FDA indications for treatment of attention-deficit/hyperactivity disorder and narcolepsy.

Adolescent↗
PubMed1999

Cerebral functional magnetic resonance imaging activation modulated by a single dose of the monoamine neurotransmission enhancers fluoxetine and fenozolone during hand sensorimotor tasks.

Fluoxetine inhibits the reuptake of serotonin, and dextroamphetamine enhances presynaptic release of monoamines. Although the excitatory effect of both noradrenaline and dopamine on motor behavior generally is accepted, the role of serotonin on motor output is under debate. In the current investigation, the authors evidenced a putative role of monoamines and, more specifically, of serotonin in the regulation of cerebral motor activity in healthy subjects. The effects on cerebral motor activity of a single dose of fluoxetine (20 mg), an inhibitor of serotonin reuptake, and fenozolone (20 mg/50 kg), an amphetamine-like drug, were assessed by functional magnetic resonance imaging. Subjects performed sensorimotor tasks with the right hand. Functional magnetic resonance imaging studies were performed in two sessions on two different days. The first session, with two scan experiments separated by 5 hours without any drug administration, served as time-effect control. A second, similar session but with drug administration after the first scan assessed drug effects. A large increase in evoked signal intensity occurred in the ipsilateral cerebellum, and a parallel, large reduction occurred in primary and secondary motor cortices (P < 10(-3)). These results are consistent with the known effects of habituation. Both drugs elicited comparable effects, that is, a more focused activation in the contralateral sensorimotor area, a greater involvement of posterior supplementary motor area, and a widespread decrease of bilateral cerebellar activation (P < 10(-3)). The authors demonstrated for the first time that cerebral motor activity can be modulated by a single dose of fluoxetine or fenozolone in healthy subjects. Drug effects demonstrated a direct or indirect involvement of monoamines and serotonin in the facilitation of cerebral motor activity.

Adult↗
PubMed2003

Pharmacokinetics of SLI381 (ADDERALL XR), an extended-release formulation of Adderall.

OBJECTIVE: To assess the pharmacokinetic (PK) properties of a single daily dose of Adderall (mixed amphetamine salts) and the extended-release formulation, SLI381 (ADDERALL XR), in pediatric attention-deficit/hyperactivity disorder (ADHD). METHOD: Fifty-one children (aged 6-12 years) with ADHD participated in a 6-week, seven-visit, PK and pharmacodynamic study. PK sampling occurred during visit 1 and again at visit 7. At visit 1, subjects received an initial oral dose of SLI381, 20 mg. At visit 7 subjects completed 1 week of medication treatment following random assignment to once-daily orally dosed SLI381 10 mg, 20 mg, or 30 mg; Adderall 10 mg; or placebo. RESULTS: PK parameters evidenced substantial intersubject variability (coefficients of variation = 28-56%). Time to maximum concentration (Tmax) for SLI381 versus Adderall showed average increases of 3.0 hours for dextroamphetamine (t = -2.35, p = .04, df = 8.6) and 3.2 hours for levoamphetamine (t = -2.39, p = .04, df = 9.2). The d- and l-isomer concentrations were highly correlated and approximated a 3:1 ratio. CONCLUSIONS: SLI381 showed extended Tmax values compared with Adderall and appears suitable for once-daily dosing. Intersubject variability underscores the need for individual dose titration.

Amphetamines↗
PubMed1988

Khat-induced hypnagogic hallucinations.

Khat is a plant whose leaves are chewed for their stimulating effect. This effect is attributed to cathinone, an alkaloid identical to dextroamphetamine. Khat chewing is widespread among eastern African and Yemenite populations and is believed to be innocuous. Our experience shows, however, that a substantial number of chronic khat chewers experience persistent hypnagogic hallucinations - a symptom that has not yet been described. Three vignettes illustrates this phenomena, which often interferes with psychiatric diagnosis. Different explanatory models are discussed, among them chronic suppression of REM sleep.

Adjustment Disorders↗
PubMed1971

Associations between drugs administered during pregnancy and congenital abnormalities of the fetus.

In a retrospective study to compare the drug consumption during pregnancy of mothers of infants with congenital abnormalities and of those without, over 97% of 1,369 mothers took prescribed drugs and 65% self-administered drugs. Significantly more mothers of infants with congenital abnormalities took aspirin, antacids, dextroamphetamine, phenobarbitone, sodium amytal, other barbiturates, cough medicines, iron, sulphonamides, and nicotinamide than mothers in the control group. However, most mothers taking analgesics, antacids, appetite suppressants, barbiturates, cough medicines, iron, sulphonamides, and vitamins produced normal infants. Any teratogenic effect of these drugs is therefore one of low potency. On the other hand, deficiencies such as those of ascorbic acid and folic acid may have a teratogenic effect. There is need for caution in presuming teratogenic effects on the basis of the associations shown here. During pregnancy, however, it would appear wise to avoid the administration of any drug which carries a suspicion of teratogenicity unless that drug is specifically indicated, and self-medication with common household remedies such as aspirin and antacids should be avoided. These recommendations would also apply to any woman of childbearing age in whom conception is likely.

Abnormalities, Drug-Induced↗
PubMed1998

Psychopharmacologic treatment of acquired attention disorders in children with brain injury.

This investigation examined the efficacy of psychostimulant therapy in alleviating neurobehavioral dysfunction attendant to pediatric brain injury. The most commonly reported neurobehavioral sequelae associated with head injury in the pediatric population involve deficits along the attentional matrix. This is also the most common objectively documented neurobehavioral finding among children as well as adults. There are several investigations in the adult literature which have employed the use of psychostimulants in treating both psychiatric and neuropsychological residua associated with head injury. Overall, the results of these studies are equivocal, but suggest a beneficial impact on general functioning. The present prospective investigation utilized a double-blind, placebo-controlled, cross-over experimental design to examine the efficacy of methylphenidate in treating children with acquired attentional disorders secondary to brain injury. A cohort of 14 children with varying degrees of head injury were recruited for participation. As expected, differences between drug and placebo conditions uniformly achieved statistical significance. Additionally, there were no differences in performance between baseline and placebo conditions on neurobehavioral tasks of attention and concentration. Current findings suggest that methylphenidate (and probably other psychostimulants such as Cylert, Adderal, Wellbutrin and dextroamphetamine sulfate) is an extremely effective agent in treating attentional disorders secondary to brain injury in children.

Adolescent↗
PubMed1981

Acute effects of caffeine in normal prepubertal boys.

A recent study demonstrated that dextroamphetamine has an effect in normal prepubertal boys similar to that seen in hyperactive children. The purpose of the present study was to see whether the effects of caffeine are similar to those of amphetamine in normal children. The authors observed 19 prepubertal boys following administration of a single dose of placebo, 3 mg/kg of caffeine, and 10 mg/kg of caffeine in a double-blind, crossover design. Caffeine produced increased vigilance and decreased reaction time, as does amphetamine. Unlike amphetamine, however, the higher dose of caffeine did not have a motor calming effect but increased motor activity. Separate biological systems, therefore, may be differentially affected by the two substances.

Attention↗
PubMed1998

Pharmacotherapy of adolescent attention deficit hyperactivity disorder: challenges, choices and caveats.

A recent increase in stimulant treatment of adolescents with attention deficit hyperactivity disorder (ADHD) has been documented. Challenges in treating adolescent ADHD with methylphenidate or dextroamphetamine include compliance with frequent dosing, abuse potential and wear-off or rebound effects. Co-morbid anxiety, occurring in at least 30 percent of ADHD youths, is associated with lower rate of response to stimulants. The effective alternatives, tricyclic antidepressants or pemoline, are each associated with rare but serious toxicity. Bupropion has recently proven effective in controlled trials. Other noradrenergic or dopamine-enhancing agents such as venlafaxine and nicotine show some benefit in open trials. The need for more options in pharmacotherapy of ADHD is evidenced by rapid adoption in clinical practice of alternative and adjunctive medication despite lack of controlled research on efficacy and safety. The indications for long-term stimulant treatment of ADHD present some controversy, and highlight a need for more research on safety and efficacy through the lifespan. Thresholds for diagnosis are much lower with DSM than with ICD, and thresholds for treatment are contentious, given the performance-enhancing effects of stimulants in normal students. The endpoint for treatment is unclear, as stimulants are also effective in adult ADHD. Based on short- and intermediate-term studies to date, stimulant medication is clearly more efficacious than cognitive and behavioral strategies for the symptoms of ADHD. Longer term research is needed to determine whether sustained stimulant therapy will reduce the adverse emotional, behavioral and academic consequences of inattention and impulsivity in adolescents and adults.

Adolescent↗
PubMedDate not supplied

Abuse of prescription medicines in southwestern France.

BACKGROUND: Few quantitative data are available concerning abuse of medicine in the general population, although dependence on prescription medicines involves a significant proportion of the population. Falsified prescription forms can be used as an indicator of abuse. METHODS: Community pharmacists in a representative network were asked to report any falsified prescription form presented over a 1-year period. Sales data were used to express results as abuse rate and abuse rate ratio. RESULTS: Two-thirds of the 130 pharmacies in the network reported at least 1 falsified prescription. The reported incidence of falsified prescriptions was 2.3 per 10 000 inhabitants. A total of 392 falsified prescription forms was collected. The abuse rate ratios were 171 (95% CI 140 to 210) for dextroamphetamine-phenobarbital in combination, 168 (95% CI 131 to 216) for fenozolone, 67 (95% CI 53 to 84) for buprenorphine, and 40.5 (95% CI 33 to 50) for clobenzorex. CONCLUSIONS: These results show the efficiency of a method for detecting falsified prescriptions forms using community pharmacists. The abuse of medicines already known for their addictive potential can be estimated and alerts can also be detected.

Crime↗
PubMed2000

Pharmacologic treatment of cognitive deficits and hypersexuality due to "shaken-baby syndrome".

OBJECTIVE: To describe the clinical effects of amantadine and propranolol in an agitated pediatric patient with cognitive deficits, hyperactivity, and hypersexualism secondary to "shaken-baby syndrome." BACKGROUND: Patients with shaken-baby syndrome can present with cognitive and behavioral impairments. CASE: A 9-year-old girl presented with cognitive impairments secondary to shaken-baby syndrome at 3 weeks of age. She was receiving many medications, including dextroamphetamine, methylphenidate, and clonidine, that were not effective in improving her cognitive status or decreasing her hypersexuality. She was weaned from stimulants and clonidine and prescribed amantadine 100 mg bid with improvement of attention, concentration, and cognition, although hypersexuality remained. She was then started on propranolol 10 mg tid and a gradual increase to 40 mg tid with amelioration of hypersexuality and hyperactivity and no unwanted effects noted. Self-weaning of propranolol was associated with the return of hypersexuality. The combination of amantadine and propranolol led to improvement of cognition and behavior, especially intellectual functioning and appropriate socialization with peers, respectively. CONCLUSION: Cognitive deficits and hypersexuality with hyperactive features due to shaken-baby syndrome may respond to the drug regimen of amantadine and propranolol.

Adrenergic beta-Antagonists↗
PubMed1996

Sensitivity and specificity of QEEG in children with attention deficit or specific developmental learning disorders.

The sensitivity and specificity of QEEG-based discriminant functions were evaluated in populations of children diagnosed with specific developmental learning disorders and those with attention deficit disorders. Both populations of children could be distinguished from each other, and from the normal population, with high levels of accuracy. Pretreatment QEEG could be utilized to distinguish ADD/ADHD children who responded to dextroamphetamine from those who responded to methylphenidate, again with high levels of accuracy. This paper provides a replication of all presented discriminant functions, and should provide the research basis for the generalized utilization of QEEG in the initial evaluation of children with learning and/or attention disorders.

Adolescent↗
PubMed1999

Amphetamines to counteract opioid-induced sedation.

OBJECTIVE: To describe the data regarding the use of amphetamines and amphetamine derivatives to counteract opioid-induced sedation. SUMMARY: Sedation is a major dose-limiting adverse effect of opioid therapy for many patients. Several reports have evaluated the use of amphetamines and amphetamine derivatives, such as mazindol, dextroamphetamine, and methylphenidate, to counteract opioid-induced sedation, with limited results. CONCLUSIONS: General use of amphetamines for the treatment of opioid-induced sedation is not recommended. However, these agents may be effective for certain patients who experience dose-limiting sedation with opioids and have exhausted all other options available to manage this adverse effect More research is needed to identify appropriate candidates for therapy, the preferred amphetamine, and the optimal dose.

Amphetamines↗
PubMed2005

Safety, efficacy and extended duration of action of mixed amphetamine salts extended-release capsules for the treatment of ADHD.

Stimulant medications have proven to be effective in reducing the core symptoms of hyperactivity, impulsivity and inattention and are considered the first line of therapy for patients with attention-deficit/hyperactivity disorder (ADHD). Mixed amphetamine salts extended-release capsules (MAS XR; Adderall XR, Shire Pharmaceuticals Group) include immediate-release pellets of mixed amphetamine salts that release the first half of the dose upon ingestion and delayed-release pellets that begin to release active drug approximately 4 h later. The MAS XR capsule contains the same 3:1 ratio of dextroamphetamine to levoamphetamine as do mixed amphetamine salts immediate-release tablets (MAS IR; Adderall), Shire Pharmaceuticals Group), and the bioavailability and pharmacokinetic profiles of MAS XR 20 mg are comparable to those with MAS IR 10 mg b.i.d. MAS XR has a rapid onset of action--within 1.5 h--and provides 12 h coverage. The efficacy, safety and extended duration of action of MAS XR have been established through clinical studies in school-age children, adolescents and adults.

Amphetamines↗
PubMed2004

Drug treatment of poststroke aphasia.

Impairment of language function (aphasia) is one of the most common neurological symptoms after stroke. Approximately one in every three patients who have an acute stroke will suffer from aphasia. The estimated incidence and prevalence of stroke in Western Europe is 140 and 800 per 100,000 of the population. Aphasia often results in significant disability and handicap. It is a major obstacle for patients to live independently in the community. When recovery from aphasia occurs, it is usually incomplete and patients are rarely able to return to full employment and other social activities. Currently, the main treatment for aphasia is conventional speech and language therapy. However, the effectiveness of this intervention has not been conclusively demonstrated and empirical observations suggest that spontaneous biological recovery may explain most of the improvement in language function that occurs in aphasics. The generally poor prognosis of the severe forms of poststroke language impairment (Broca, Wernicke and global aphasia), coupled with the limited effectiveness of conventional speech and language therapy has stimulated the search for other treatments that may be used in conjunction with speech and language therapy, including the use of various drugs. Dopamine agonists, piracetam (Nootropil), amphetamines, and more recently donepezil (Aricept), have been used in the treatment of aphasia in both the acute and chronic phase. The justification for the use of drugs in the treatment of aphasia is based on two types of evidence. Some drugs, such as dextroamphetamine (Dexedrine), improve attention span and enhance learning and memory. Learning is an essential mechanism for the acquisition of new motor and cognitive skills, and hence, for recovery from aphasia. Second, laboratory and clinical data suggest that drug treatment may partially restore the metabolic function in the ischemic zone that surrounds the brain lesion and also has a neuroprotective effect following acute brain damage. An example of this is the nootropic agent piracetam. Extensive animal studies have demonstrated the beneficial effects of this and other drugs on neural plasticity, but data on humans are still sparse. This review provides a critical analysis of the current evidence of the effectiveness of these drugs in the treatment of acute and chronic aphasia.

Amphetamine↗