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PubMed1990

Challenging the amphetamine challenge test: report of an antidepressant treatment study.

The primary goal of this study was to determine whether the amphetamine challenge test (ACT) response, as measured by a subjective rating scale, the How I Feel Scale (HIF), could predict antidepressant treatment outcome. Following a 1-day non-blind ACT with dextroamphetamine (d-AMPH), patients were treated double-blind for 6 weeks with either desipramine, alprazolam, or a desipramine-alprazolam combination. Regression (true score) analyses were carried out on pre- and post-ACT HIF scores and on baseline and end of study Hamilton Depression Rating Scale (HDRS) scores to determine the magnitudes of improvement measured in response to the ACT and antidepressant treatment, respectively. Regression analyses were performed on the residuals (true scores of improvement) to determine the best fitting (linear) prediction equation. Improvement in the HIF total score predicted HDRS improvement for the whole sample. Possible sources of error contributing to the outcome are identified and the results are discussed in relation to previous clinical investigations of the potential usefulness of the ACT as a predictor of antidepressant response.

Adult↗
PubMed1993

The amphetamine challenge test correlates with affective lability in healthy volunteers.

The personality dimension of mood lability may be reflected in the mood response to the amphetamine challenge test. To test this hypothesis, the investigators acutely administered oral dextroamphetamine or placebo in a double-blind fashion to 11 normal control subjects who were free of any psychiatric disorders. Increased scores on interview and self-report measures of mood change during the challenge test, particularly increases in depression and anxiety, positively correlated with scores on the Affective Lability Scale, a measure of the lifetime personality trait of mood lability. These findings suggest that a dysphoric response to amphetamine is a marker for affective lability and that it may be useful to study this trait in patients with personality disorders.

Adult↗
PubMed1991

Effects of antihistaminics on locomotor activity in mice. Comparison with opiate and amphetamine-induced hyperactivity.

1. Three histamine H1-receptor antagonists (tripelennamine, diphenhydramine and cyclizine) and two H2-receptor antagonists (ranitidine and cimetidine)--1 and 10 mg/kg--were tested alone or in combination with the opioid partial agonist buprenorphine (1 mg/kg), the opioid antagonist naloxone (1 mg/kg) or dextroamphetamine (3 mg/kg) on locomotor activity in mice. 2. All three H1-antihistaminics tested and the H2-antihistaminic, cimetidine, enhance locomotor activity in a dose-dependent manner. 3. Furthermore, tripelennamine, diphenhydramine, cyclizine, ranitidine and cimetidine potentiate the buprenorphine-induced hyperactivity. 4. Previous administration of naloxone blocks the tripelennamine- and diphenhydramine-induced hyperactivity. 5. On the other hand, none of antihistaminics tested modifies the amphetamine-induced locomotor stimulation. 6. These results suggest that H1- and H2-receptor antagonists effects on locomotor behavior in mice may be related with opioid mechanisms, but not with amphetamine mechanisms.

Animals↗
PubMed1982

Behavioral, biochemical and neuroendocrine responses to amphetamine in normal twins and 'well-state' bipolar patients.

An i.v. injection of dextroamphetamine (0.3 mgm/kg) was given to 13 pairs of normal monozygotic twins, three pairs of normal dizygotic twins and 11 patients with bipolar affective disorder in remission and off medications. Behavioral excitation in response to amphetamine was highly correlated in monozygotic twins; it was predicted by the baseline variables of high plasma MHPG, low serum prolactin and low pulse; it correlated with a rise in cortisol; and it was not correlated with plasma amphetamine level. Pre-infusion baseline MHPG and growth hormone and prolactin responses to amphetamine also were concordant in twins. Plasma amphetamine level, pulse and blood pressure and cortisol responses were not concordant, suggesting significant environmental influences. Haloperidol pretreatment in one pair of twins abolished the excitation response but did not reduce increases in cortisol and growth hormone. This suggests a role for dopamine in the excitation response but predominant serotonergic and noradrenergic mediation of the hormonal responses. None of the responses or baseline measures distinguished patients from controls. Thus, no consistently altered sensitivity to monoaminergic stimulation by amphetamine in bipolar affective disorder was demonstrated in this study. This is one of the first reports of familial (possibly genetic) variation in a psychostimulant drug response in man. The responses identified as concordant may be useful in characterizing other pathologic conditions.

Adolescent↗
PubMed1981

Auditory cue preceding intracranial stimulation induces event-related potential in rat frontal cortex: alterations by amphetamine.

Slow potential (SP) responses to a click followed by rewarding stimulation of the medial forebrain bundle (MFB) were recorded from the frontal cortex of rats with permanently implanted electrodes. Trials were presented at variable intervals and the final interval between the click and MFB stimulation was 2 seconds. Negative SP responses developed rapidly with training, as the interstimulus interval was gradually increased from 0.5 sec to 2 sec. No decrement of the SP response was observed during recording sessions consisting of more than 300 trials. The SP responses remained stable over several weeks of recording. Dextroamphetamine produced a dose-related depression of the SP responses. Since the effect of amphetamine in this study was similar to the effect in studies using food reinforcement, the results suggest that amphetamine-induced depression of event-related slow potentials in rat frontal cortex is not dependent on the type reinforcement. Advantages of the use of intracranial stimulation as reinforcement for event-related potential studies are discussed.

Acoustic Stimulation↗
PubMed1996

Cerebrospinal fluid homovanillic acid predicts behavioral response to stimulants in 45 boys with attention deficit/hyperactivity disorder.

Central dopaminergic activity has been assumed to play a role in the efficacy of stimulant drugs in attention deficit/hyperactivity disorder (ADHD), although supporting evidence has been scant. This study examined baseline cerebrospinal fluid (CSF) of boys with ADHD in relation to response to three different stimulant drugs. Forty five boys with DSM-III-R-diagnosed ADHD had a lumbar puncture before double-blind trials of methylphenidate, dextroamphetamine, and placebo. Sixteen also received pemoline as part of a subsequent open trial. Stepwise linear regressions determined significant predictors of drug response. Our prior report of a positive significant correlation between CSF homovanillic acid (HVA) and ratings of hyperactivity on placebo was replicated in a new sample of 20 boys. After baseline symptom severity, CSF HVA was the best predictor of stimulant drug response, with significant independent contribution to four of the ten measures of hyperactivity that changed significantly with medication. Higher HVA predicted better drug response, and lower HVA was associated with worsening on some measures. This supports the mediating role of central dopaminergic activity in stimulant drug efficacy in childhood hyperactivity.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Amphetamine modulates human incentive processing.

Research suggests that psychostimulants can physiologically alter dopamine kinetics in the ventral striatum (VS) and psychologically enhance mood and attention. Using event-related functional magnetic resonance imaging (fMRI), we conducted a within-subject, double-blind, placebo (PLAC)-controlled study of the effects of oral dextroamphetamine (AMPH, 0.25 mg/kg) treatment on brain activity and affect during incentive processing. In two counterbalanced scanning sessions 60-180 min after ingesting AMPH or PLAC, 8 healthy volunteers played a game involving anticipation and receipt of monetary gains and losses. Group and volume of interest analyses suggested that by enhancing tonic over phasic activation, AMPH treatment "equalized" levels of VS activity and positive arousal during anticipation of both gain and loss. These findings suggest that therapeutic effects of amphetamine on incentive processing may involve reducing the difference between anticipation of gains and losses.

Adult↗
PubMed1999

Amphetamine disrupts P50 suppression in normal subjects.

BACKGROUND: P50 suppression is viewed as an operational measure of sensory "gating" that is reduced in patients with schizophrenia and their family members. Previous reports have demonstrated that neural gating is regulated by monoaminergic tone in rodent models of P50 suppression. METHODS: In this study, 11 healthy subjects participated in P50 event-related potential recordings at baseline and after either oral administration of dextroamphetamine (.3 mg/kg) or placebo, to determine if the administration of a monoaminergic agonist produces P50 suppression deficits similar to those observed in patients with schizophrenia. RESULTS: As hypothesized, amphetamine disrupted the suppression of the P50 event-related potential. There was a statistically significant decrement in P50 suppression during the amphetamine challenge condition (t10 = 3.15, p < .01, mean difference = -44.1%, d = -2.5) relative to the baseline P50 condition. A comparison of P50 suppression in the placebo and amphetamine conditions (both after a baseline recording session) revealed a significant amphetamine-induced disruption of P50 suppression (t6 = 3.71, p < .01, mean difference = -54.4%, d = -3.14). CONCLUSIONS: The biochemical alterations associated with an amphetamine-induced disruption of P50 suppression in this study may be related to the pathophysiology of P50 suppression deficits in schizophrenia. The findings are consistent with several careful examinations of suppression deficits in rodent models that have identified the monoaminergic regulation of P50 suppression. These data indicate that amphetamine induces a disruption of P50 suppression in normal subjects.

Adrenergic Agents↗
PubMed1999

Effects of lithium and amphetamine on inositol metabolism in the human brain as measured by 1H and 31P MRS.

BACKGROUND: The clinical effectiveness of lithium may be due to its decreasing the intracellular concentration of myo-inositol and increasing that of its inositol monophosphate precursors, which is known as the inositol depletion hypothesis. METHODS: Magnetic resonance spectroscopy (MRS) was used to measure the concentration of both myo-inositol (1H MRS) and phosphomonoesters (PME) [31P MRS], in healthy volunteers in a double-blind placebo-controlled study. MRS measurements were made at baseline, again on the 7th day of lithium (1200 mg, n = 10) or placebo (n = 6) administration, and again on day 8, 2 hours following oral administration of 20 mg dextroamphetamine to stimulate the phosphoinositol (PI) cycle. RESULTS: Subjects who received lithium showed a greater increase in PME ratios in response to amphetamine administration than did placebo-treated subjects. CONCLUSIONS: The present results support the hypothesis that lithium administration blocks the conversion of inositol monophosphates to myo-inositol, and that this effect is especially apparent following PI cycle stimulation. The effects of lithium treatment on myo-inositol in healthy volunteers in vivo are uncertain, and may have to await improvements in the ability to measure myo-inositol in the brain.

Adolescent↗
PubMed1975

Growth rebound after termination of stimulant drugs.

To explore further the report of an accelerated weight gain following termination of treatment with a stimulant drug, 66 biannual growth measurements were obtained from 1970 to 1973 on hyperactive schoolchildren who were receiving medication. All received either dextroamphetamine or methylphenidate during the school year; some also received it during the summer. The data revealed that those whose stimulant medication was terminated at the start of summer subsequently grew in weight and height at a significantly greater rate than those who continued to receive medication from June to September. In fact, discontinuance of the medication resulted in a growth rebound for this period which was 15-68% above the age-expected increment.

Adolescent↗
PubMed1991

Psychostimulants for secondary depression in medical illness.

The hospital charts of 198 patients with acute medical or surgical illnesses who had been treated with either dextroamphetamine or methylphenidate for secondary depression during a 5-year period at the Massachusetts General Hospital were examined. Eighty-two percent of patients showed improvement following psychostimulant treatment. Seventy percent of all patients demonstrated marked or moderate improvement in depressive symptoms. No significant differences in efficacy between the two psychostimulants or across diagnostic categories for depression were observed. Patients improved quickly, usually within the first 2 days of treatment. Adverse reactions necessitating the termination of psychostimulant treatment occurred in 10% of trials. Anorexia was not observed as a side effect of treatment.

Adult↗
PubMedDate not supplied

Psychostimulants for depression in hospitalized cancer patients.

The hospital charts of 59 hospitalized oncology patients who had been treated with either dextroamphetamine or methylphenidate for depression during a 5-year period at the Massachusetts General Hospital were examined. Eighty-three percent of the patients showed at least some improvement following psychostimulant treatment. Seventy-three percent of all patients demonstrated marked or moderate depressive symptom improvement. No significant differences in efficacy were noted between the two psychostimulants, or across psychiatric diagnostic categories for depression. The patients improved quickly, usually within the first 2 days of treatment. Ten percent of the patients experienced adverse reactions warranting discontinuation of the psychostimulants. Fifty-four percent of all patients had some appetite improvement. Anorexia was not observed as a treatment side effect. The authors conclude that psychostimulants are an effective and safe method of treatment for the depressed oncology patient.

Adult↗
PubMed1978

Ritalin, Benzedrine and Dexedrine do not transform F 1706 rat cells.

Ritalin (methylphenidate hydrochloride), Benzedrine (amphetamine sulfate), and Dexedrine (dextroamphetamine sulfate) were examined for oncogenicity using a serial line of Fischer rat embryo cells, which was previously shown to be a sensitive and accurate indicator of chemicals carcinogenic for rodents. At the concentrations tested, none of the 3 drugs induced transformation in Fischer rat embryo cells.

Amphetamine↗
PubMedDate not supplied

A review of fatigue in people with HIV infection.

Fatigue is often cited by clinicians as a debilitating symptom suffered by the many who are infected with HIV. This article provides a review of HIV-related fatigue, including research on possible physiological causes such as anemia, CD4 count, impaired liver function, impaired thyroid function, and cortisol abnormalities. Psychological causes of fatigue, particularly depression, are reviewed as well. Measurement issues, such as the use of inappropriate tools, the problem of measuring the presence or absence of fatigue, and the use of tools developed for other groups of patients, are reviewed. The need for a comprehensive fatigue tool that is appropriate for people with HIV is discussed. Current treatment research, including thyroid replacement, hyperbaric oxygen, and dextroamphetamine, is presented. Finally, the implications for further research, including the need for qualitative studies to learn more about the phenomenon, develop an instrument to measure fatigue, and examine variables together to get a complete picture of this complex concept, are reviewed.

CD4 Lymphocyte Count↗
PubMed2003

Efficacy and safety of modafinil for improving daytime wakefulness in patients treated previously with psychostimulants.

OBJECTIVES: To assess the efficacy and safety of modafinil for improving wakefulness in narcolepsy patients treated previously with psychostimulants. BACKGROUND: Modafinil has become a standard therapy for improving daytime wakefulness in narcolepsy patients and may be a useful therapeutic alternative to psychostimulants used to improve waking function in other medical conditions. Modafinil is chemically dissimilar to and has a pharmacological profile that differs from the psychostimulants. Modafinil has a low abuse potential and is well tolerated. METHODS: Patients (N=151) with narcolepsy who had been unsatisfactorily treated with dextroamphetamine (N=48), methylphenidate (N=66), or pemoline (N=37) were enrolled in this 6-week, open-label, multicenter study. Following a 2-week washout period, patients received modafinil once daily (Week 1, 200 mg; Weeks 2-6, 200 or 400 mg). Efficacy was evaluated at Weeks 1, 2, and 6 using the Epworth Sleepiness Scale and the Clinical Global Impression of Change. Adverse events were monitored throughout the study. RESULTS: Treatment with modafinil improved daytime wakefulness versus baseline regardless of which psychostimulant was taken previously. Mean ESS scores were improved after 1 week of treatment with modafinil. Improvements were maintained throughout the 6 weeks of treatment (all P<0.001 versus baseline after washout). At Week 6, 79% of all patients were considered to be clinically improved relative to post-washout baseline. The most frequent adverse events were headache, nausea, and insomnia; the majority of adverse events were mild or moderate in nature. Approximately 70% of patients were receiving 400 mg of modafinil once daily at the end of the study. CONCLUSION: During this 6-week, open-label study, modafinil was an effective and well-tolerated treatment for improving daytime wakefulness in narcolepsy patients previously treated with psychostimulants.

Adolescent↗
PubMed2000

Medium-term outcomes are comparable with short-term outcomes in children with attention deficit hyperactivity disorder treated with stimulant medication.

OBJECTIVE: To compare the short- and medium-term effects of psychostimulant medication in children with attention deficit hyperactivity disorder (ADHD). METHODS: Seventy-three children with ADHD participated in a double-blind crossover study of dextroamphetamine (DEX) and methylphenidate (MPH; results previously reported). At the completion of this study, subjects continued to take the preferred stimulant. Subjects were restudied 6-9 months later. The principal outcome measures were the Revised Conners' Parent and Teacher Rating Scales. RESULTS: Fifty-three families (73%) returned the follow-up surveys. At 6-9 months, mean T scores were still significantly lower than the mean at baseline for all factors of both the CPRS-R and CTRS-R (P < 0.01). There were no statistically significant differences between scores at 6-9 months and scores at the completion of the corresponding medication period in the crossover trial. CONCLUSIONS: After 6-9 months treatment with stimulant medication, ratings remained significantly better than at baseline. This suggests that the early benefits of stimulants are sustained for at least 6 months.

Adolescent↗
PubMedDate not supplied

Emergence of tics in children with attention deficit hyperactivity disorder treated with stimulant medications.

The emergence of tics in children treated with stimulant medication for attention deficit hyperactivity disorder (ADHD) was investigated. A retrospective chart review of the medical records of 555 subjects was performed to examine the emergence of tics in relation to treatment with a stimulant medication, dosage, duration of treatment, and age of subjects. A total of 7.8% of the subjects treated with stimulants developed tics: 8.3% of subjects treated with methylphenidate, 6.3% with dextroamphetamine, and 7.7% with pemoline. The subjects who developed tics were significantly younger than those who did not. Subjects treated with higher doses of stimulant medication were not more likely to develop tics. While the emergence of tics was common, these subjects may have developed tics irrespective of stimulant medication. Controversy remains as to the long-term risk of tics in relation to stimulant medication and to appropriate practice should tics emerge during the course of stimulant medication treatment.

Attention Deficit Disorder with Hyperactivity↗
PubMed1978

A multidimensional test approach for the description of the CNS activity of drugs in human pharmacology.

In a double-blind cross-over trial ten healthy male volunteers were administered placebo as well as one representative of each of the four hypothetical psychotropic drug classes, antipsychotics, antidepressants, anxiolytics, and psychostimulants. The drugs were: 75 mg of chlorpromazine, 75 mg of amitriptyline, 10 mg of diazepam and 18 mg of dextroamphetamine sulfate. The effects of the compounds were assessed by pharmaco EEG, an adjective checklist, and a battery of psychological performance tests. The results demonstrate that the test model differentiates well between sedative and stimulatory drug effects. In addition, this multidimensional test approach discriminates adequately the effects of the various sedative drugs. The advantages and limitations of multidimensional test approaches for the description of psychotropic drugs along with the importance of employing such an approach for the development of psychotropic drugs are discussed.

Adult↗