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PubMed1991

CNS stimulant potentiation of monoamine oxidase inhibitors in treatment-refractory depression.

We report on our clinical experience with a combination of a CNS stimulant (either pemoline or dextroamphetamine) and a monoamine oxidase inhibitor (MAOI) for treating 32 depressed patients (mainly outpatients) refractory to standard antidepressant pharmacotherapy. This combination, though not approved by the FDA, appears to be safe and effective. Twenty-five (78%) of these patients experienced at least 6 months of symptom remission with a stimulant + MAOI combination. Many patients required adjunctive antidepressant treatment, including tricyclics and lithium. Side effects were not excessive, though 6 patients (3 unipolar and 3 bipolar) cycled to mania (N = 1) or hypomania (N = 5). None developed hypertensive crises. With properly motivated and complaint patients and careful clinical monitoring by the prescribing psychiatrist, stimulant potentiation of MAOIs may be a viable option for treatment-resistant depressed patients.

Bipolar Disorder↗
PubMed1991

The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia.

To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by 133Xe dynamic single-photon emission-computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated. Amphetamine produced a modest, nonsignificant, task-independent, global reduction in rCBF. However, the effect of amphetamine on task-dependent activation of rCBF (i.e., WCST minus control task) was striking. Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task, on amphetamine significant activation of the left dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean number of correct responses and the mean conceptual level increased (p less than 0.05) with amphetamine relative to placebo. In addition, with amphetamine, but not with placebo, a significant correlation (p = -0.71; p less than 0.05) emerged between activation of DLPFC rCBF and performance of the WCST task. These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity.

Adult↗
PubMed1989

Psychostimulant response in AIDS-related complex patients.

Methylphenidate or dextroamphetamine was used to treat 17 of 32 patients with AIDS-related complex who were referred for neuropsychiatric evaluation of symptoms representative of cognitive and/or affective dysfunction. All 17 patients were found to have some degree of cognitive impairment. Psychiatric diagnoses included organic mental disorder (8), adjustment disorder (5), and major depression (4). The 17 patients were receiving no other psychoactive or neurotoxic medications nor were they receiving concomitant investigational antiviral or chemotherapeutic agents. Clinical response to psychostimulant therapy was rated using the Efficacy Index of the Clinical Global Impressions. Pharmacotherapy with either psychostimulant was clinically effective in improving affective parameters in 89.5% (15) of the 17 patients, with 79% (13) of the 17 achieving a moderate to marked response. No adverse side effects were encountered.

AIDS-Related Complex↗
PubMed1977

Nutrient intake and stimulant drugs in hyperactive children.

Recent studies have demonstrated suppressed growth of height and weight in children receiving stimulant drugs for hyperactivity. For approximately twelve months, growth data and food records were collected on two subjects receiving different types and dosages of stimulant drugs. The two cases demonstrated that dextroamphetamine levels of 10 mg. or more and methylphenidate levels of 30 mg. or more decreased caloric intake significantly. This decrease may be limiting for long-term growth. Both subjects had a variety of feeding problems due to poor appetite. Careful nutritional evaluation and planning are important to insure optimal energy and nutrient intake in these children receiving stimulant drugs.

Ascorbic Acid↗
PubMed1987

The effect of activity state upon the production of lethalities due to the inhalation of the toxic pyrolysis products of polyacrylonitrile.

Hydrogen cyanide is known to be produced upon the pyrolysis of the synthetic material polyacrylonitrile. Cyanide inhibits phosphorylation reactions, therefore, decreasing the amount of high energy bonds available for metabolic use. Since the energy requirements, as well as the respiratory minute volume, for an individual decrease with decreasing activity, it was of interest to investigate whether diminished physical activity would decrease the lethal potential of the pyrolysis products of polyacrylonitrile. In order to produce wide variations in physical activity, male ICR mice were pretreated with either 8.6 mg/kg dextroamphetamine sulfate ip 30 min prior to challenge, 75 mg/kg sodium pentobarbital ip 15 min prior to challenge, or 10 ml/kg of 70 proof ethyl alcohol ip 15 min prior to challenge. Control animals received injections of 10 ml/kg normal saline ip 15 min prior to challenge. Animals were subsequently challenged with the cooled/filtered smoke from the pyrolysis of polyacrylonitrile fibers at 660 C. Increased physical activity decreased the exposure time necessary to produce death. Animals pretreated with amphetamine appear to die more rapidly than control animals due to an increase in respiratory minute volume. Animals pretreated with sodium pentobarbital or ethanol appear to survive through long periods of exposure to the toxic gases due to both a decrease in minute volume and a decrease in energy utilization.

Acrylic Resins↗
PubMed1984

Sympathomimetic amines in the treatment of chronic urticaria: two case reports.

Two patients are presented whose chronic urticaria had previously failed to improve with antihistamine therapy or glucocorticoids. Both demonstrated marked improvement with dextroamphetamine sulfate. Both patients also had idiopathic orthostatic edema for which the treatment of choice is amphetamines. When treatment was discontinued the urticarial lesions returned, only to decrease significantly again when therapy was resumed. Whether the response to amphetamines in chronic urticaria is unique to patients with idiopathic orthostatic edema or will also prove to be effective in treating typical idiopathic urticaria will be determined by future research.

Adult↗
PubMed1984

Cisplatin-induced autonomic neuropathy.

A 57-year-old man with bronchogenic squamous cell carcinoma developed an autonomic neuropathy following treatment with a chemotherapy combination which included cisplatin. The autonomic neuropathy resolved following discontinuation of the cisplatin and treatment with dextroamphetamine. The following case represents a patient with bronchogenic carcinoma treated with cyclophosphamide, doxorubicin, and cisplatin, who developed a severe autonomic neuropathy following chemotherapy administration. This is the first report of cisplatin-associated autonomic neuropathy to appear in the literature.

Adult↗
PubMed1984

Carbamazepine-induced mania in two children: case report.

Carbamazepine-induced mania is described in two case reports of prepubertal boys, one of whom also developed manic symptoms after receiving imipramine and dextroamphetamine. The structural and chemical similarities between carbamazepine and polycyclic antidepressants are discussed and it is suggested that caution and close observation be employed when using carbamazepine to treat children who have been identified as being at risk for developing this adverse effect.

Age Factors↗
PubMedDate not supplied

Congenital behavioral effects in mature rats prenatally exposed to levo-alpha-acetylmethadol (LAAM).

Male and female rats exposed prenatally to LAAM (0.2 mg/kg maternal body weight per day, PO) or water were tested for congenital effects on their performance of various unconditioned and conditioned behaviors. No differences were found in neuromuscular development or in exploratory activity. Although they acquired and performed an autoshaped lever-touch response like controls, the LAAM rats responding under this paradigm were less affected by dextroamphetamine than were controls, suggesting an alteration in catecholamine neurotransmission in these subjects. Furthermore, when required to respond on a progressive fixed-ratio (FR) procedure, in which the response requirement for reinforcement was doubled each day from FR1 to a maximum of FR128, LAAM rats made more responses at the higher ratios than did controls. Although these data suggest that LAAM may be a behavioral of functional teratogen, the possibility that early postnatal toxicity or withdrawal are responsible for these findings is discussed.

Animals↗
PubMed1995

SPECT imaging of striatal dopamine release after amphetamine challenge.

UNLABELLED: This study assesses the feasibility of using SPECT to image intrasynaptic dopamine release in human striatum following dextroamphetamine sulfate (d-amphetamine) challenge testing. METHODS: A bolus plus constant infusion administration schedule of the D2 receptor radiotracer [123I]iodobenzamide ([123I]IBZM) was used to obtain a stable baseline for reliable quantitation of the d-amphetamine effect. Eight healthy subjects first underwent a controlled experiment to demonstrate that stable levels of striatal and occipital activities could be maintained from 150 to 420 min during programmed infusion of the tracer. Next, seven subjects underwent the experiment with d-amphetamine. The experimental conditions were identical except that 0.3 mg/kg amphetamine was injected intravenously at 240 min. The behavioral effects of d-amphetamine were measured by self-rating on the following analog scales: euphoria, alertness, restlessness and anxiety. RESULTS: The d-amphetamine injection induced a 15% +/- 4% (mean +/- s.d.) decrease in D2 receptor availability, measured as the specific-to-nonspecific equilibrium partition coefficient (V3"). The d-amphetamine injection induced marked increase in euphoria, alertness and restlessness scores. The intensity of these behavioral responses correlated with the decrease in D2 availability measured with SPECT. In contrast, the anxiety response was milder and not correlated with the decrease in D2 availability. CONCLUSION: These studies demonstrate the feasibility of using [123I]IBZM programmed infusion and SPECT imaging to measure endogenous dopamine release after d-amphetamine challenge and to study brain neurochemical correlates of emotions.

Adolescent↗
PubMed1993

Dissociation of the effects of alcohol and amphetamine on inert gas narcosis using reaction time and P300 latency.

Alcohol exacerbates and amphetamine ameliorates the slowing of reaction time (RT) produced by inert gas narcosis. The event-related brain potential P300 was used to determine whether these drug effects involve stimulus- or response-related processes, since P300 largely reflects the time to evaluate a stimulus while RT reflects this time plus the time to select and execute a response. Subjects breathed nitrous oxide (N2O) alone and in combination with ethyl alcohol or dextroamphetamine while responding to visually presented names that differed in probability (the oddball paradigm). N2O slowed P300, but this measure was comparatively insensitive to the exacerbation and amelioration that were indexed by RT. Relative to N2O alone, an RT-P300 difference was found for amphetamine + N2O but not for alcohol + N2O. We conclude that exacerbation involves both stimulus- and response-related processes but amelioration involves only the latter. This pattern of results can be explained by a model in which the drugs modulate slowing via the two energetical dimensions of arousal and activation, which influence stimulus- and response-related processes, respectively.

Action Potentials↗
PubMed1995

Sustaining helicopter pilot performance with Dexedrine during periods of sleep deprivation.

BACKGROUND: Around-the-clock operations often are mandated in combat, but while aircraft can function effectively throughout continuous 24-hour periods, aviators often cannot because of sleep loss. An efficacious countermeasure in sustained operations may be the administration of dextroamphetamine (Dexedrine). HYPOTHESIS: Dexedrine will effectively prevent many of the performance problems associated with sleep deprivation in helicopter pilots. METHODS: A placebo-controlled, double blind study was conducted. Six U.S. Army helicopter pilots completed five flights in a UH-60 simulator while their performance was evaluated. Immediately following each flight, data were collected on electroencephalographic (EEG) activity and subjective mood ratings. Testing sessions occurred at 0100, 0500, 0900, 1300, and 1700. One hour prior to each of the first three flights on drug-administration days, the aviators were given 10 mg of Dexedrine or placebo. RESULTS: Dexedrine, in comparison to placebo, improved aviator simulator control on descents, straight-and-levels, standard-rate turns, and a left-descending turn. Performance was facilitated most noticeably at 0500, 0900, and 1700 (after 22, 26, and 34 hours of continuous wakefulness). EEG and mood data showed that alertness was sustained significantly by Dexedrine--there was reduced slow-wave EEG activity and improved rating of vigor and fatigue. No adverse behavioral or physiological effects were observed. CONCLUSIONS: Dexedrine appears to be effective for sustaining helicopter pilot performance during short periods of sleep loss without producing adverse side effects.

Adult↗
PubMed1996

Predictors of weight loss in children with attention deficit hyperactivity disorder treated with stimulant medication.

OBJECTIVE: A retrospective study was undertaken to examine predictors of weight loss in children with attention deficit hyperactivity disorder (ADHD) treated with stimulant medication. DESIGN: Children diagnosed with ADHD and treated with methylphenidate hydrochloride (MPH) or dextroamphetamine sulfate (DEX) for at least 5 months were identified by retrospective chart review. Analyses were performed on 32 children (29 boys) treated with MPH and 28 children (25 boys) treated with DEX. Variables examined included pretreatment weight, pretreatment body mass index (BMI), duration of treatment, total daily dose, and weight-adjusted dose. RESULTS: The MPH-treated group was initially seen at a mean age (+/- standard deviation) of 7.5 years (+/- 2.1). Mean duration of follow-up was 11.2 months (+/- 3.8). Mean total daily dose was 25.5 mg (+/- 8.2) and mean weight-adjusted dose was 1.0 mg/kg/day (+/- .5). Mean change in weight as expressed in z scores was -0.4 SD (+/- .7). The DEX-treated group was initially seen at a mean age of 9.3 years (+/- 2.7). Mean duration of follow-up was 10.8 months (+/- 4.1). Mean total daily dose was 14.9 mg (+/- 8.2) and mean weight-adjusted dose was .5 mg/kg/day (+/- .3). Mean change in weight was -0.6 SD (+/- .6). Although the MPH group was younger than the DEX group, there were no between-group differences in weight or height either before treatment or at follow-up when adjusted for age and gender. Using linear regression analysis, significant correlations were found between pretreatment weight and change in weight for both the MPH-treated group (r = .63) and the DEX-treated group (r = .47). Stepwise multiple-regression analysis indicated that pretreatment age, weight-adjusted dose, and duration of follow-up did not significantly contribute to the variance in change of weight for either the MPH- or DEX-treated groups. To adjust for height, changes in BMI were also analyzed. For both medication groups, no differences were found between the heavier (BMI > or = 50%) and thinner (BMI < 50%) children in duration of follow-up, total daily dose, or weight-adjusted dose. When the medication groups were combined, a greater proportion of heavier children experienced a decrease relative to their predicted BMI compared with thinner children (80% vs 52%). Comparisons of mean BMI slopes revealed that the heavier group experienced an absolute decrease in their BMI (-.139) in contrast to the thinner group (+.014) (t = 2.70). CONCLUSIONS: Pretreatment weight, adjusted for age, gender, and height, is a significant predictor of weight loss in children with ADHD treated with either MPH or DEX. In contrast, pretreatment age, duration of treatment, and weight-adjusted dose were not found to be significant predictors.

Adolescent↗
PubMed1976

Hemodynamic effects of intra-arterial injection of drugs of abuse.

Acute vascular insufficiency following intra-arterial injection of a variety of drugs has been recognized for many years. The present study addresses the hypothesis that this vascular insufficiency may be due to vasospasm. Intra-arterial injections of logarithmic doses of drugs of abuse from the barbiturate, narcotic, non-narcotic analgesic, and amphetamine groups were studied in baboons. All drugs except amphetamine produced significant increases in femoral flow. Dextroamphetamine produced insignificant alteration in flow. Solid excipients, cornstarch, and talcum powder when injected intra-arterially decreased flow, and vascular obstruction was shown angiographically. These data suggest that vasospasm is not a primary response of intra-arterial injection of drugs of abuse.

Animals↗
PubMed1994

Therapy for attention-deficit hyperactivity disorder.

Attention-deficit hyperactivity disorder (ADHD) is a common, chronic neurological and behavioral syndrome in children, adolescents, and adults. Research studies carried out with subjects referred to specialists for treatment of ADHD have shown that methylphenidate hydrochloride improves behavior and academic performance in both children and adolescents, at least in the short term. Dextroamphetamine sulfate, pemoline, and desipramine hydrochloride are reasonable second choices for those patients who cannot tolerate or do not respond to methylphenidate. Cognitive-behavioral and family therapies, while intuitively appealing, appear to have weak effects and little empirical validation. The long-term outcome of ADHD as seen in primary care settings is not predictable.

Adolescent↗
PubMed1977

Immunoblastic lymphadenopathy. A report of two cases.

Two patients with immunoblastic lymphadenopathy had lymphadenopathy, hepatosplenomegaly, rash, dysproteinemia, constitutional symptoms, and typical morphologic findings or lymph node obliteration by immunoblasts and plasma cells, proliferation of aborizing vessels, and infiltration with amorphous, eosinophilic material. One patient had massive pulmonary infiltrates that responded to steroid therapy early in the course of the disease, but recurred and were found, at autopsy, to represent immunoblastic invasion of the lung. In both cases, a severe peripheral neuropathy developed during the course of the disease. One patient was addicted to dextroamphetamine for 20 years. Response to corticosteroids and cytotoxic therapy was initially rapid and complete, but refractoriness developed as seen in postmortem findings of extensive visceral involvement.

Aged↗
PubMedDate not supplied

Sonographic findings in methamphetamine-induced ischemic colitis.

Ischemic colitis is a clinicopathologic condition that commonly occurs in elderly patients with atherosclerotic disease or diabetes mellitus. Uncommon etiologies include vasculitis and use of drugs such as oral contraceptives, phenobarbital, nasal decongestants, dextroamphetamine, and cocaine. Recent studies have shown sonography and CT to be helpful in the evaluation of the colitides. We report the sonographic and CT findings in an unusual case of methamphetamine-induced ischemic colitis. Sonography and CT revealed diffuse thickening of the large bowel wall. Methamphetamine abuse should be considered in the differential diagnosis of the colitides, particularly in the setting of a young patient with a history of drug use and no other predisposing conditions.

Abdomen, Acute↗
PubMed1995

Absence of linkage of apparently single gene mediated ADHD with the human syntenic region of the mouse mutant Coloboma.

Attention deficit disorder (ADHD) is a complex biobehavioral phenotype which affects up to 8% of the general population and often impairs social, academic, and job performance. Its origins are heterogeneous, but a significant genetic component is suggested by family and twin studies. The murine strain, coloboma, displays a spontaneously hyperactive phenotype that is responsive to dextroamphetamine and has been proposed as a genetic model for ADHD. Coloboma is a semi-dominant mutation that is caused by a hemizygous deletion of the SNAP-25 and other genes on mouse chromosome 2q. To test the possibility that the human homolog of the mouse coloboma gene(s) could be responsible for ADHD, we have carried out linkage studies with polymorphic markers in the region syntenic to coloboma (20p11-p12). Five families in which the pattern of inheritance of ADHD appears to be autosomal dominant were studied. Segregation analysis of the traits studied suggested that the best fitting model was a sex-influenced, single gene, Mendelian pattern. Several genetic models were evaluated based on estimates of penetrance, phenocopy rate, and allele frequency derived from our patient population and those of other investigators. No significant linkage was detected between the disease locus and markers spanning this chromosome 20 interval.

Adolescent↗