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A novel highly effective treatment of interstitial cystitis causing chronic pelvic pain of bladder origin: case reports.

PURPOSE: To determine if a very effective therapy for idiopathic orthostatic cyclic edema--dextroamphetamine sulfate--would alleviate symptoms of chonic pelvic pain of bladder origin/interstitial cystitis. METHODS: Two women with interstitial cystitis that had been refractory to various therapies were treated with dextroamphetamine sulfate (20 mg/day) without any other treatment. The diagnosis of idiopathic edema was made by abnormal water load test and interstitial cystitis diagnosed by elevated scores on the pelvic pain and urgency and frequency symptom scale. RESULTS: Both patients quickly improved their bladder symptoms and all pain and urgency was gone within a week. The interstitial cystitis remained in remission as long as the women stayed on their medication. One woman proved Koch's postulates by stopping the medication because of forgetting it and symptoms resumed quickly only to disappear again upon resuming therapy. CONCLUSIONS: Dextroamphetamine sulfate can be a very effective therapy for recalcitrant cases of interstitial cystitis. Prospective placebo controlled studies are needed to determine what percentage of patients with this debilitating condition have concomitant idiopathic edema as determined by abnormal water load test and how well a larger series will respond to this novel therapy.

Adult↗

Acute psychostimulant challenge in primary obsessive-compulsive disorder.

The effects of acute oral administration of methylphenidate 40 mg versus dextroamphetamine 30 mg versus matched placebo were compared in 11 patients with primary obsessive-compulsive disorder. Dextroamphetamine but not methylphenidate had a significantly greater antiobsessive-compulsive effect as measured by the Comprehensive Psychiatric Rating Scale--Obsessive-Compulsive Subscale, as compared with placebo. This effect appeared unrelated to their effect on depression although a differential effect of the two psychostimulants on anxiety was observed. Although both these stimulants affect serotonin, the differences noted between dextroamphetamine and methylphenidate suggest that catecholamines may be implicated in the pathophysiology of obsessive-compulsive disorder.

Adult↗

Effects of fluoxetine on mood and immune status in depressed patients with HIV illness.

BACKGROUND: When present, depression in the context of human immunodeficiency virus (HIV) illness not only detracts from quality of remaining life but may interfere with motivation to obtain good medical care as well, thus directly influencing life's duration. This study was undertaken to assess the efficacy of fluoxetine in treating depression occurring in the context of HIV illness and to assess effects, if any, of fluoxetine on immune status (T-cell subsets). METHOD: Patients had originally participated in a double-blind, placebo-controlled, 6-week study of imipramine. Imipramine nonresponders or relapsers and side effect dropouts were offered open treatment with fluoxetine for 12 weeks. Adjunctive dextroamphetamine was prescribed if the treating psychiatrist considered it clinically indicated. Eligibility criteria for the original study included a DSM-III-R diagnosis of major depression, dysthymia, or both. Concurrent HIV medications were permitted. RESULTS: Measures included the clinician-rated Hamilton Rating Scale for Depression and Clinical Global Impressions Scale, and patient-rated Brief Symptom Inventory and Beck Hopelessness Scale. Of the 23 patients receiving only fluoxetine, 83% (N = 19) were classified as responders. Of the 7 (30%) who also received adjunctive dextroamphetamine, all responded. Patients with CD4 cell counts under 200/cu mm did as well as others. CD4 cell count was not influenced by duration of treatment with fluoxetine; the average decline was that expected due to the passage of time alone. Side effects were mild and relatively infrequent. CONCLUSION: In this open treatment study, fluoxetine alone and fluoxetine plus dextroamphetamine were found to be effective treatments for patients with HIV illness and Axis I depression, regardless of the initial level of immune deficiency or number or type of HIV medications used concurrently. No negative effects on immune status were observed.

Acquired Immunodeficiency Syndrome↗

Efficacy of a mixed amphetamine salts compound in adults with attention-deficit/hyperactivity disorder.

BACKGROUND: We report on a controlled trial of a mixed amphetamine salts compound (Adderall, dextroamphetamine sulfate, dextro-, levoamphetamine sulfate, dextroamphetamine aspartate, levoamphetamine aspartate, and dextroamphetamine saccharate) in the treatment of adult attention-deficit/hyperactivity disorder (ADHD). METHODS: This was a 7-week, randomized, double-blind, placebo-controlled, crossover study of Adderall in 27 well-characterized adults satisfying full DSM-IV criteria for ADHD of childhood onset and persistent symptoms into adulthood. Medication was titrated up to 30 mg twice a day. Outcome measures included the ADHD Rating Scale and the Clinical Global Impression Score. Comorbid psychiatric disorders were assessed to test for potential effects on treatment outcome. RESULTS: Treatment with Adderall at an average oral dose of 54 mg (administered in 2 daily doses) was effective and well tolerated. Drug-specific improvement in ADHD symptoms was highly significant overall (42% decrease on the ADHD Rating Scale, P<.001), and sufficiently robust to be detectable in a parallel groups comparison restricted to the first 3 weeks of the protocol (P<.001). The percentage of subjects who improved (reduction in the ADHD rating scale of > or =30%) was significantly higher with Adderall treatment than with a placebo (70% vs 7%; P =.001). CONCLUSIONS: Adderall was effective and well tolerated in the short-term treatment of adults with ADHD. More work is needed to evaluate the long-term effects of Adderall, or other amphetamine compounds, in the treatment of adults with ADHD.

Adult↗

A randomized comparison of the effect of two diuretics, a converting enzyme inhibitor, and a sympathomimetic amine on weight loss in diet-refractory patients.

We hypothesized that women refractory to dietary weight loss may have a type of idiopathic edema. In a study of 200 women, we compared four drugs, used previously for treating idiopathic edema, to determine their efficacy in causing weight reduction. After 6 months of treatment, the percentage of treated groups losing at least 10% of baseline weight was 6% for hydrochlorothiazide, 8% for spironolactone, 68% for dextroamphetamine sulfate, and 4% for captopril. The percentage losing >20% and >30% of baseline weight in the same treatment groups was 28% and 10% for dextroamphetamine therapy but 0% for the other three groups. Of the women who failed to lose weight with one of the nonamphetamine therapies during the first 6 months, 132 were then treated with dextroamphetamine; 68% lost =10% of their baseline weight, and 30% and 7% of patients lost =20% and =30%, respectively. With use of the classic definition of idiopathic orthostatic edema (urinary output of <55% of ingested water load in 4 hours), only 58 of the 200 study patients had this diagnosis; however, 144 patients excreted <75% of the load. Comparison of the efficacy of amphetamine therapy in patients with <75% versus =75% urinary excretion showed 120 of 131 (92%) lost =10% in the former category versus only 4 of 51 (8%) in the latter. Of the 58 patients who excreted <55% of the water load, 52 (90%) lost =10% of baseline weight with amphetamine therapy. The patients noted no effects of therapy on dietary consumption. The responsiveness of the patients to amphetamine therapy during the second 6-month period despite failing to lose weight with the three other therapies suggests that no inadvertent bias was present in the randomization process. Thus, the results suggest that some women who are recalcitrant to dietary weight loss may have a mild type of water retention that is refractory to diuretics but responsive to amphetamines.

Clinical Trial↗

Attention-deficit hyperactivity disorder.

The epidemiology, etiology, pathogenesis, clinical presentation, diagnostic criteria, and clinical course of attention-deficit hyperactivity disorder (ADHD) are described and the role of pharmacotherapy in the management of this disorder is discussed. ADHD is a behavioral disorder of unknown etiology characterized by inattention, impulsiveness, and hyperactivity. The behavior, which may be manifest at home, at school, or in social situations, is generally worse in settings requiring sustained attention; as a result, academic underachievement is frequently an associated problem. Although the onset usually occurs before the age of four years, ADHD is most commonly diagnosed when the child enters school. It is up to six times more common in boys than in girls. Nearly one third of all children with ADHD continue to show symptoms of the disorder in adulthood. While many questions about the pathophysiology of ADHD remain unanswered and a cure has not yet been found, pharmacotherapy can effectively control the symptoms of the disorder in most patients. Three psychostimulant medications--dextroamphetamine sulfate, methylphenidate hydrochloride, and pemoline--are considered the drugs of first choice for management of the behavioral manifestations of ADHD. Dextroamphetamine and methylphenidate are equally effective in improving the symptoms of ADHD. Pemoline, a newer agent, may be tried in patients who cannot tolerate or do not respond to these two first-line agents. Common adverse effects associated with stimulant medications include anorexia, insomnia, stomach pain, and weight loss; these are generally transient and decrease with time. Imipramine hydrochloride and desipramine hydrochloride are less effective and may produce more serious adverse effects than the psychostimulants and are therefore considered second-line agents for the treatment of ADHD. Dextroamphetamine sulfate, methylphenidate hydrochloride, and pemoline have been shown to effectively control the behavioral symptoms of ADHD. For maximum impact, pharmacotherapy should be accompanied by behavioral, educational, and psychosocial intervention.

Attention Deficit Disorder with Hyperactivity↗

Methysergide in the treatment of narcolepsy.

Five patients with narcolepsy (four with the allied symptom of cataplexy) were treated with the serotonin antagonist methysergide. All patients had as good control of their sleep attacks while on methysergide therapy as on a control period of dextroamphetamine therapy. The cataplexy was less well controlled by methysergide than by dextroamphetamine, but improved when compared to a period without medication. Two patients developed severe calf claudication while on methysergide.

Adult↗

Cardiovascular and subjective effects of intravenous cocaine administration in humans.

Nine volunteer subjects were tested with intravenously administered cocaine hydrochloride in doses ranging from 4 to 32 mg, as well as 10 mg of dextroamphetamine sulfate. Measures of cardiovascular and subjective effects were made. Generally parallel dose-effect functions were obtained for heart rate, blood pressure, Addiction Research Center Inventory scores, Profile of Mood Scales, and subject ratings. A substantial effect on each of these variables was recorded after 8 mg of cocaine. The increase continued and peaked at approximately 16 mg after which it usually leveled off. Ten milligrams of dextroamphetamine generally had an effect comparable to 8 to 16 mg of cocaine.

Adult↗

Treatment of hyperactive children with monoamine oxidase inhibitors. I. Clinical efficacy.

Fourteen boys (mean age, 9.2 +/- 1.5 years) with Attention Deficit Disorder (ADD) With Hyperactivity were treated with dextroamphetamine sulfate or a monoamine oxidase inhibitor (MAOI) (six received clorgyline, eight received tranylcypromine sulfate) for four weeks each in a double-blind, cross-over study that included a two-week placebo washout between active drug periods. The MAOIs had immediate, clinically significant benefit and were clinically indistinguishable from dextroamphetamine. Most children responded to both stimulant and MAOI. These findings of equivalent efficacy of MAOIs in ADD are in contrast to our previous studies with neurotransmitter system selective agents, which showed only weak effects, and suggest that multiple neurotransmitter alterations may be required for stimulant drug effects in ADD. The immediate response to MAOIs indicates a different mechanism from that mediating antidepressant effect. The MAOIs may be useful alternate treatments in selected cases of ADD.

Attention Deficit Disorder with Hyperactivity↗

Single-tablet enantiomeric purity assay of amphetamine by rotation enhancement.

Enhancement of the optical rotation of dextroamphetamine by production of an optically active chromophore through reaction with 1-fluoro-2,4-dinitrobenzene to give alpha-methPYL-N-(2,4-dinitrophenyl)-beta-phenylethylamine is reported. This reaction forms the basis of an assay for both the content and optical purity of dextroamphetamine sulfate at single-dose levels (5 mg). Results of assays of standard solutions and of commercial tablets demonstrate the suitability of the method for the determination of enantiomeric purity and amphetamine content.

Dextroamphetamine↗

Motor/vocal tics and compulsive behaviors on stimulant drugs: is there a common vulnerability?

The occurrence of abnormal movements or perserverative/compulsive behaviors was noted in 34 (76%) of a group of 45 hyperactive boys during a double-blind crossover treatment trial of methylphenidate and dextroamphetamine given in a wide range of doses. These adverse effects were often subtle and transient, and they usually occurred only on one drug. There was only one case where treatment was discontinued due to the severity of the tic the subject developed during his initial treatment phase. Dextroamphetamine tended to produce more compulsive behaviors, which were also more likely to resemble clinical obsessive-compulsive disorder (OCD), than did methylphenidate. Abnormal movements and compulsive behaviors tended to co-occur on methylphenidate only; no general "Tourette-OCD diathesis" was found for this population.

Attention Deficit Disorder with Hyperactivity↗

The bioavailability of intranasal and smoked methamphetamine.

BACKGROUND: Patients in harm-reduction treatment programs are switching from intravenous to other routes of methamphetamine (INN, metamfetamine) administration to avoid risks associated with needle use. Relatively little has been reported about the bioavailability of methamphetamine when smoked or used intranasally. METHODS: Eight experienced methamphetamine users were administered smoked or intranasal methamphetamine concurrently with an intravenous dose of deuterium-labeled methamphetamine. Plasma and urine concentrations were measured for calculation of bioavailability and other pharmacokinetic parameters by noncompartmental methods. RESULTS: Methamphetamine was well absorbed after smoking or intranasal administration, with bioavailabilities of 79% after intranasal administration and 67% of the estimated delivered dose or 37.4% of the absolute (pipe) dose after smoking. Maximum methamphetamine concentrations occurred at 2.7 and 2.5 hours after intranasal and smoked doses. The elimination half-life was similar for intravenous (11.4 hours), intranasal (10.7 hours), and smoked (10.7 hours) methamphetamine. Clearance (272 mL x h(-1) x kg(-1)), steady-state volume of distribution (4.2 L/kg), and mean residence time (16 hours) of the intravenous dose were similar to previously reported values. Dextroamphetamine (INN, dexamfetamine) half-life (all routes) was 16.2 hours. Methamphetamine and dextroamphetamine renal clearances (all routes) were about 100 and 1100 mL x h(-1) x kg(-1), respectively. CONCLUSIONS: Intranasal and smoked methamphetamine are well absorbed. Although intranasal or smoked routes may decrease the risk of transmission of blood-borne diseases, exposure to methamphetamine and the possibility of drug-related complications remain substantial.

Administration, Inhalation↗

Defining the boundaries of atypical depression: evidence from the HPA axis supports course of illness distinctions.

BACKGROUND: Treatment outcome and brain laterality differ between early onset (<20 years) chronically (no well-being >2 months) depressed patients with atypical features (early/chronic atypical) and those with either later onset or less chronic illness (late/nonchronic atypical). Because hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been hypothesized to distinguish atypical depression from melancholia, we examined whether HPA measures would also differentiate these two groups of depressed patients with atypical features. METHODS: Three-hour afternoon cortisol levels, stimulation of cortisol by afternoon dextroamphetamine, and suppression of cortisol by dexamethasone were investigated in 85 depressed patients with atypical features. The latter group was divided into early/chronic atypical and late/nonchronic atypical based on chart review of course of illness. RESULTS: Patients with early/chronic atypical had significantly lower mean 3 h afternoon cortisol levels (N=21) and 4:00 p.m. post-dexamethasone cortisol levels (N=20) than did those with late/nonchronic atypical (N=43 with afternoon cortisol; N=26 with post-dexamethasone cortisol). Post-dextroamphetamine cortisol levels were numerically higher in the early/chronic atypical group (N=15 vs. 19), but this failed to reach conventional significance (0.05<p<0.1). Arbitrary categorical distinctions of normal and abnormal did not separate these groups on any of the tests. LIMITATIONS: Lack of demonstrated reliability of the chart review and retrospective determination of atypical features and course of illness limit the generalizability of these findings. CONCLUSIONS: These HPA data are consistent with earlier treatment and brain laterality findings that course of illness distinguishes biologically distinct groups within depressed patients with atypical features. The DSM should consider adding course of illness requirements to its criteria for atypical features.

Adult↗

A comparative analysis of standard and alternative antidepressants in the treatment of human immunodeficiency virus patients.

Our research group has conducted clinical trials of standard (imipramine, fluoxetine, and sertraline) and alternative antidepressants (dextroamphetamine and testosterone replacement therapy) in the treatment of clinical depression among patients with human immunodeficiency virus (HIV) illness. This report presents secondary analyses of data pooled from these trials with the purpose of comparing the antidepressant efficacy of these various agents. In all trials, a DSM-III-R depressive disorder was the primary criterion for study entry, and each treatment resulted in significant improvement after both 2 and 6 weeks of treatment according to the Hamilton Depression Rating Scale (HDRS). Response rates for standard antidepressants ranged from 70% to 74%, with similar, high response rates found in trials of dextroamphetamine (93%) and testosterone (81%). The response rate of each active drug treatment was superior to that of placebo (33%). Each treatment was well-tolerated in terms of side effects, and there was essentially no effect of any treatment on CD4 cell count. Differences in trial design, entrance criteria, and measurements require that caution be used in interpreting these results; nonetheless, each of the five treatments studied demonstrated strong efficacy and possessed relatively unique benefits, providing health care providers with valuable treatment options in addressing individual needs of patients.

1-Naphthylamine↗

Stimulant medication therapy in the treatment of children with attention deficit hyperactivity disorder.

Despite the tremendous research advances that have increased our knowledge regarding the pharmacodynamics, clinical pharmacology, pharmacokinetics, and adverse effects of stimulant medications in the treatment of children with ADHD, our knowledge is yet incomplete. Perhaps the most central unresolved issue concerns our understanding of the pathogenesis, pathophysiology, and diagnosis of ADHD. This review has touched briefly on the controversy and confusion surrounding this issue. Although our understanding of the use of stimulant medications in this disorder is similarly incomplete, a review of the literature does allow certain conclusions to be made that are helpful to the practitioner. 1. Stimulant medications are an effective treatment modality for most children with ADHD. Short-term efficacy is well documented, and long-term outcome may be improved when stimulants are used with other therapeutic strategies. Stimulants in and of themselves are not a panacea. 2. It is impossible to predict which children will have a favorable response to stimulant medications and which children may have a placebo response. The use of individual single-blind medication trials is a practical solution to this problem and should be considered for all children who are candidates for stimulant therapy as a means for preventing overuse or inappropriate use of these medications. 3. The precise mechanism of action of stimulants is not yet completely understood, but stimulants appear to exert their therapeutic effects through their influence on multiple neurotransmitters in the catecholamine, dopamine, norepinephrine axis in the central nervous system. 4. The three major stimulants--methylphenidate, dextroamphetamine, and pemoline--appear to be equally efficacious, although methylphenidate has emerged as the most commonly used and most studied drug. Because of its potential for causing liver toxicity, pemoline has remained a second-line medication. 5. The three major stimulants appear to have somewhat different mechanisms of action so that failure of a patient to respond to one medication does not mean that he or she will not respond to another. 6. The recommended starting doses for the stimulants are 0.3 mg per kg of methylphenidate, 0.15 mg per kg of dextroamphetamine, and 37.5 mg of pemoline. There is a great deal of individual variability in dose response, so doses must be titrated for optimal effects in each child. Sustained release preparations are much more expensive than regular preparations and may be less effective. 7. There is no evidence that stimulants have any effect on ultimate adult height. 8. Although relatively uncommon, motor tics have been observed in children on stimulants, and all children on stimulants need to be carefully monitored for the development of tics. (ABSTRACT TRUNCATED AT 250 WORDS)

Attention Deficit Disorder with Hyperactivity↗

Effects of acute stimulant medication on cerebral metabolism in adults with hyperactivity.

Recent work in our laboratory has demonstrated both global and regional reductions in cerebral glucose metabolism in adult subjects with attention-deficit hyperactivity disorder (ADHD). The purpose of the present study was to examine the effects of an acute dose of stimulant medication on cerebral metabolism in adults with ADHD using positron emission tomography with fluorodeoxyglucose-18 as the tracer. Each subject underwent scanning twice, once off-drug and again after receiving a single oral dose of either dextroamphetamine (0.25 mg/kg) or methylphenidate (0.35 mg/kg). Subjects completed behavioral self-report measures before and after the scan and performed an auditory continuous performance task during the tracer uptake period. Neither drug changed global metabolism. Both drugs increased systolic blood pressure, and dextroamphetamine improved performance on the auditory attention task. Each stimulant produced a differential pattern of increases and decreases in regional metabolism throughout the regions of interest that were sampled. Rather than increasing glucose utilization in specific brain regions with lowered metabolic rates in adults with ADHD, stimulants may act by altering glucose use throughout the brain.

Adult↗

Relative efficacy of drugs for the treatment of sleepiness in narcolepsy.

A survey was conducted on 10 polysomnographic studies on the pharmacologic treatment of the sleepiness of narcolepsy. Three studies employed the MSLT and 7 employed the MWT as their polygraphic measure of sleep tendency. Statistically and clinically significant therapeutic changes were apparent for pemoline, modafinil, dextroamphetamine and methylphenidate. Codeine, ritanserin and protriptyline did show statistically significant effects. The common feature among the drugs that did produce clinically significant improvements seems to be facilitatory action on central catecholaminergic transmission. Within this group of drugs, only methylphenidate and dextroamphetamine brought MWT sleep latencies to approximately 70% of normal levels.

Adult↗

Opioid peptides, adrenocorticotrophic hormone, and idiopathic (orthostatic) edema.

The effect of dextroamphetamine sulfate (Dexedrine) on plasma opioid peptides, hormones, and other metabolites was studied in eight female subjects with idiopathic (orthostatic) edema and five healthy females. All subjects were given 20 mg of dextroamphetamine sulfate, a drug widely used in the treatment of this disorder, and blood samples were collected before and 30, 60, and 90 minutes after treatment. Patients with idiopathic (orthostatic) edema had significantly lower plasma sodium levels but higher blood urea nitrogen, aldosterone, and renin levels. D-amphetamine decreased aldosterone and renin levels in both groups. Plasma adrenocorticotropin levels were lower whereas met-enkephalin levels were higher in idiopathic (orthostatic) edema subjects compared to control subjects. D-amphetamine had no significant effect on plasma beta-endorphin, adrenocorticotrophic hormone, or enkephalins. Our data indicate that opioid peptides, especially enkephalins, and adrenocorticotrophic hormone may be involved in the pathogenesis of idiopathic (orthostatic) edema syndrome, but they seem uninvolved in the aldosterone- and renin-lowering action of amphetamine. It is possible that amphetamine is acting further down the chain, either directly on the adrenal and kidney or the microvasculature, rather than at hypothalamus-pituitary axis.

Adrenocorticotropic Hormone↗