Biomedical subjects
Publications and source records attributed to F W Reimherr.
To elucidate the role of catecholamines in attention deficit disorder, the authors conducted an open 8-week trial of L-tyrosine in 12 adults with attention deficit disorder, residual type. Eight showed marked to moderate clinical response in 2 weeks; at 6 weeks these eight developed tolerance, suggesting that L-tyrosine is not useful in attention deficit disorder, residual type.
Alterations in serotonin metabolism may be an important factor in the etiology and treatment of depression. In this regard, 5-hydroxytryptophan (5-HTP), a serotonin precursor, has been given to patients with depression. Although a review of these studies suggests that 5-HTP possesses antidepressant properties, additional trials are clearly indicated. Following a discussion of the pharmacology of 5-HTP, the authors highlight adverse effects associated with its administration to depressed patients, neurologic subjects, and normal individuals. Relatively few adverse effects are associated with its use in the treatment of depressed patients.
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Nineteen patients meeting the criteria for attention deficit disorder, residual type (adult hyperactivity), were given a 2-week double-blind crossover of DL-phenylalanine versus placebo. Thirteen subjects completed the study; the mean global rating of improvement approached significance as compared with placebo. A significant improvement was noted on mood and mood lability. The phenylalanine responders were then continued on open drug, but lost all positive benefits within 3 months. A later open trial of L-phenylalanine produced no clinical effect.
Thirty-seven adult patients meeting the Utah criteria for attention deficit disorder, residual type, were entered into a double-blind crossover trial of methylphenidate and placebo. A moderate-to-marked therapeutic response occurred in 21 (57%) of the patients while receiving methylphenidate and in four (11%) while receiving placebo, a highly significant difference statistically and clinically. The responding patients showed significant improvement in the following areas: attentional difficulty, motor overactivity, affective lability, and impulsivity. The diagnosis of attention deficit disorder, residual type, should be considered in patients with prominent complaints of impulsivity, restlessness, emotional lability, and hot temper who do not suffer from schizophrenia or major mood disorder and do not have symptoms of schizotypal or borderline personality disorders.
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Following the hypothesis that attention deficit disorder in adults (attention deficit disorder, residual type; ADD, RT), as well as in children, is associated with decreased central dopaminergic activity, the authors measured lumbar cerebrospinal fluid monoamine metabolites in a group of adults with ADD, RT and matched control subjects. Patients were then entered into a double-blind, placebo-controlled trial of methylphenidate. It was predicted that the patients would have lower levels of homovanillic acid (HVA), the major dopamine metabolite in humans. Patients who had a significant response to methylphenidate showed a trend in this direction. Nonresponding patients had significantly higher levels of HVA than controls.
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Twenty-two patients who met the Utah criteria for attention deficit disorder, residual type (hyperactivity, minimal brain dysfunction in adults) received an open trial of pargyline (Eutonyl). Of these 22 patients, 13 (59%) showed a moderate to marked therapeutic response. Clinically useful features of pargyline in the treatment of attention deficit disorder, residual type are that its duration of action is greater than 24 hours and that it has not been abused. Pargyline inhibits monoamine oxidase, type B, and its therapeutic efficacy is compatible with the hypothesis that decreased phenethylaminergic function, dopaminergic function, or both play a role in the etiology of the disorder.
The authors assessed the prevalence of attention deficit disorder, residual type, in a population of young adult male alcoholic patients in two residential alcohol treatment programs. They found the prevalence of the disorder in this sample to be 33% and hypothesize that attention deficit disorder in childhood (and adulthood) may be associated with an increased risk for the development of alcoholism. If substantiated, this finding could be of theoretical and therapeutic importance.
This study replicated an earlier one dealing with the diagnosis and treatment of attention deficit disorder (ADD, or minimal brain dysfunction) in adults. Subjects who met provisional operational criteria for adult ADD were entered in a random-assignment, parallel, double-blind trial of placebo and pemoline, a noneuphorigenic psychostimulant drug effective in children with ADD. There was improvement in both the pemoline group and the placebo group, but the difference in improvement was not statistically significant. When the analyses were confined to that subgroup of patients whose parents had described them in the 95th percentile of childhood "hyperactivity" or when the hyperactivity score was partialled out statistically, pemoline was demonstrably more effective than placebo. Revised operational criteria for adult ADD are proposed.
MBD has long been considered a childhood disorders. Recent research suggests that in some it persists into adult life and that at least one form is a consequence of reduced activity of dopaminergic systems in the brain. To test this hypothesis, three adults with "presumptive" MBD were given L-dopa plus carbidopa. Although overall this combination was less effective than stimulant medication, all the patients showed an initial response, and in one patient L-dopa seemed to potentiate the effect of methylphenidate. The authors point out that various dopamine agonists have different effects and that the possible potentiation effect is consistent with a dopaminergic hypothesis.
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Minimal brain dysfunction (MBD) has long been considered a disorder limited to childhood. A number of longitudinal and adoption studies suggest that MBD may persist into adult life where its existence is concealed by the application of a variety of diagnostic labels. In order to test the hypothesis that MBD does persist into adulthood, 15 putative MBD adults were identified on the basis of current MBD-like complaints, self-description of MBD characteristics in childhood, and a parental rating (on a standardized form) of "hyperactivity" in childhood. Eleven of the 15 subjects were given a double-blind trial of methylphenidate hydrochloride, and all 15 were given an open trial of pemoline, imipramine hydrochloride, or amitryptiline hydrochloride. Eight of the 11 showed a significant response to the double-blind trial of methylphenidate. Of the 15, eight showed a good response to stimulants or tricyclic antidepressants, two showed a moderately favorable response, and five were unresponsive to drug therapy.
This multicenter, randomized, double-masked, placebo-controlled, parallel-group study compared the antidepressant efficacy and safety of bupropion sustained-release (SR) tablets (150 mg QD or 150 mg BID) with placebo in outpatients with moderate-to-severe depression. The study consisted of a 1-week placebo phase followed by 8 weeks of active treatment with bupropion SR 150 mg/d (150 mg QD, n = 121) or 300 mg/d (150 mg BID, n = 120) or placebo (n = 121). Efficacy was measured by changes in scores on the 17-item Hamilton Rating Scale for Depression (HAM-D) and the Clinical Global Impressions for Severity of Illness (CGI-S) and Clinical Global Impressions for Improvement of Illness (CGI-I) scales. Safety was monitored by regular assessment of vital signs and adverse events as well as by pretreatment and posttreatment physical and clinical laboratory examinations. By day 56, both bupropion SR treatments were more effective in relieving the symptoms of depression than was placebo. Compared with those receiving placebo, patients in the bupropion SR 150- and 300-mg/d groups had significantly reduced symptoms by treatment day 56, as measured on the 17-item HAM-D, CGI-S, and CGI-I scales (P < 0.05). Bupropion SR was well tolerated, with no serious adverse events reported by bupropion-treated patients; 95% of all reported adverse events were of mild or moderate intensity. No clinically significant changes in vital signs, laboratory test results, or physical findings were observed. A greater mean weight loss was observed at the end of treatment in both the bupropion SR 150-mg (0.5 kg) and bupropion SR 300-mg (1.0 kg) group compared with placebo (0.2 kg). We found that bupropion SR 150 mg administered either once or twice daily was more effective than placebo in treating depression and that once-daily dosing appears to be at least as effective as twice-daily dosing. Should this prove true, depressed patients may be able to benefit from the convenience and improved tolerability associated with once-daily dosing.