US3864489A - Treatment of hyperkinetic conditions with caffeine - Google Patents

Abstract

The conditions of hyperkinesis are alleviated by administering an effective amount of caffeine to subjects exhibiting such conditions.

Description

United States Patent Biscardi Feb. 4, 1975 TREATMENT OF HYPERKINETIC CONDITIONS WITH CAFFEINE [56] References Cited [75] Inventor: Salvatore F. Biscardi, Cornwall, OTHER PUBLICATIONS Grollman, Pharmacology & Therapeutics, 6th Ed. [73] Assignee: General Foods Corporation, White Plains, NY. Primary Examiner-Stanley J. Friedman [22] Filed 1974 Attorney, Agent, or Firm-Bruno P. Struzzi; Daniel J. [21] Appl. No.: 435,902 Donovan; William J. Speranza Related U.S. Application Data [63] Continuation of Ser. No. 236,239, March 20, 1972, [57] ABSTRACT abandoned. The conditions of hyperkinesis are alleviated by administering an effective amount of caffeine to subjects [52] U.S. Cl. 424/253 exhibiting such conditions. [51] Int. Cl A6lk 27/00 [58] Field of Search 424/253 4 Drawmgs I TREATMENT OF HYPERKINETIC CONDITIONS WITH CAFFEINE This is a continuation, of application Ser. No. 236,239, filed Mar. 20, 1972, now abandoned.

BACKGROUND OF THE INVENTION This invention relates to the treatment of conditions associated with the hyperkinetic syndrome and more particularly to the treatment of the conditions of hyperkinesis and other behavioral disorders interrelated with such conditions.

The hyperkinetic syndrome is due to minimal brain damage which may result from a variety of causes during the prenatal period, childbirth or early infancy. Children exhibiting such symptoms are generally hyper-active, and have short attention spans. Their actions are often considered irrelevant and without clear direction. The restlessness, impulsiveness and garrulousness of these children disrupts discipline both in the home and in the classroom, and they are often regarded by their peers and by adults as spoiled, ill-mannered, and uncoordinated. Although the hyperkinetic child is often of average or above average intellegence, he is usually below average in schoolwork performance, because of poor concentration and impaired motor memory and speech functions.

Hyperkinesis is a nervous system disorder in children and adolescents which is estimated to effect about 4 percent of the school population. It is a sub-group of the learning disorders in children, problems which may effect over of the school population. A condition which is closely interrelated with such behavioral problems is dyslexia, attributed more specifically to reading disorders in children.

The conditions of hyperkinesis are also generally recognized as one of the important neurological dysfunctions associated with cerebral palsied children. Research has shown that alleviating hyperkinetic behavior in cerebral palsied children has an extremely beneficial effect by allowing the child to overcome these behavior symptoms that may interfer with his ability to accept therapy.

Therapy in alleviating hyperkinetic conditions in children is aimed at controlling motor hyper-activity which results in improvement in attention, memory, perception and coordination. Surprisingly, however, sedative drugs have been found to be ineffective in calming these children and, in fact, actually cause extreme agitation in hyperkinetic children. Quite to the contrary, stimulant drugs such as amphetamines, have been found to be effective in producing a calming effect in nearly 85 percent of these patients. In the treatment of cerebral palsied children, the use of amphetamines have been shown also to be effective, primarily due to its ability to alleviate conditions of the hyperkinetic impulse disorder.

The amphetamines and other stimulants used currently in the treatment of hyperkinetic condition, however, have appreciable undesirable side effects. Almost percent of children treated with such stimulants demonstrate anorexia, irritability and insomnia. Further, the underlying fears associated with the use of drugs such as amphetamines has generally hampered their effectiveness in the treatment of disorders in children.

It would be desirable, then, to achieve a calming effect in hyperkinetic patients through the use of a compound which does not produce any undesirable amphetamine-like side effects.

SUMMARY OF THE INVENTION It has been found that the administration of effective amounts of caffeine to a patient displaying hyperkinetic conditions or the related conditions of dyslexia is effective in alleviating such conditions and does not produce any appreciable undesirable side effects at the dosage levels at which it is effective.

DETAILED DESCRIPTION OF THE INVENTION As mentioned above, amphetamines. stimulant drugs, which one would normally predict would increase hyper-activity have been found to result in a calming effect in hyperkinetic children. Theories advanced to explain this result generally hold that hyperkinetic children have a defect in the pathways for sensory input into the brain. The children then are hyperactive to increase the number of sensory stimuli produced, and, therefore, to increase to higher levels the number ofsensory stimuli reaching the brain. Amphetamines increase the neural activity so that more experienced stimuli are actually perceived and less hyperactivity is necessary to produce higher levels of stimuli reaching the brain.

In order to determine the effectiveness of therapy in alleviating conditions of hyperkinesis in children, tests are normally conducted to measure the activity of a hyperkinetic child his concentration, and his response to stimuli as measured by electroencephalogram techniques.

A clinical investigation was undertaken to determine the effect of caffeine treatment on patients exhibiting hyperkinetic conditions and to evaluate the treatment for undesirable side effects. The subjects for this study were seventeen children previously diagnosed as being hyperkinetic. Their ages ranged from 8 years to 11 years. All subjects received three treatments, in counter-balanced order: placebo (control), a low dose of caffeine, and a high dose of caffeine. The low dose was approximately 3 mg/kg, and the high dose was approximately 6 mg/kg. The actual dosage ranged from to mg. per subject. The mean weight of the subjects was 28.5 kg.

The children tested were randomly assigned to six possible orders of the three treatments. The children received the coded tablets, double-blind, one hour before the start of testing which lasted for approximately one hour.

The following tests were administered in a fixed order:

1. Continuous Performance Test.

This ten-minute test required the child'to monitor a display of five buttons, four of which present two patterns (horizontal or vertical stripe) in two colors (red or blue). The display changes every 1.6 seconds, and the child presses a center buttonwhenever he sees the red-vertical appear. The target item appears about fifty times, and there a total of 300 trials. Errors of omission and errors of commission are recorded automatically on counters.

The mean errors of commission and omission for the three treatments are shown in Table l.

The figures presented in Table I represent statistically analyzed averages of the fixed orders of treatment. As can be seen from the figures, the high dose treatment produced the fewest errors of commission, that is, the fewest number of errors caused by the child pressing the button when in fact the red vertical had not appeared, and also produced the fewest errors of omission, that is, errors caused by the child not pressing the button when a red vertical had appeared. The placebo condition, as can be seen from Table I, produced the highest number of errors of both omission and commission, with a low dose of caffeine intermediate. Since the hyperkinetic child often displays poor concentration and impaired motor functions, the results of the continuous performance test indicate a significant beneficial effect through the use of caffeine. Further, the test indicates that the effects obtained appear to be dose related.

2. Activity Measurement.

While the child is taking the continuous performance test he sits in a chair which records activity (seat movement. seat rotation, or foot movement). The sum of these measures of fidgeting constitute an overall measure of activity, the results of which are shown in Table ll.

The results of Table ll again indicate a beneficial effect in the reduction of hyper-activity through the use of caffeine. The highest activity is seen to occur for the placebo treatment, and the lowest for the highdose of' caffeine. 3. Visual Cortical Evoked Response.

This is the measure of responses, as measured on an electroencephalogram (EEG), obtained from left and right occipital, and left and right parietal areas of the scalp. Experiments have shown that deflectionin the EEG and also the amplitude of certain of the waves recorded are indicative of increased activity normally found in hyperkinetic children. The stimuli to which responses were averaged consisted of flashes presented at 1.6 second intervals. Randomly interpersed with the bright flashes were dim flashes to which the subject had to respond by pressing a telegraph key. Analysis of the wave forms recorded on the EEG showed that large positive peaks normally found in the hyperkinetic children are significantly smaller when 'the children are treated with caffeine. Again, the effect appears to be dose related in that the high dose of caffeine produced the smallest possible peaks and the low dose intermediate between those obtained for the placebo and the high dose.

At the close of the testing period the children were found to have suffered no adverse effects from the caffeine treatment as indicated both by self and parental reports.

The overall results of the tests indicate a beneficial effect on the treatment of the hyperkinetic syndrome through drug therapy employing caffeine. As previously mentioned, this finding is useful in treating children whose problems are solely hyperkinetic activity or its related reading disorder, dyslexia, and also for treatment ofthe hyperkinetic conditions found to be prominent in more complex behavioral disorders such as cerebral palsy.

Administration to the subject of an amount of caffeine effective to allay hyperkinetic conditions may be accomplished in a variety of methods. The caffeine may be incorporated within an edible, inert pharmaceutical carrier, or may be incorporated directly into a foodstuff. Preferably, the foodstuff should be one which is readily acceptable to children and which does not mask the effects of the caffeine treatment. Examples of such foodstuffs would be beverages or beverage mixes, cereal, candy, confectionaries, and the like. The foodstuffs are formulated such that the amount of caffeine within the foodstuff is sufficient for administering the required amount of caffeine which is effective in alleviating hyperkinetic conditions. Thus, for example, a beverage drink may be prepared such that ingestion ofa normal amount of the drink, say 8 ounces, provides an amount of caffeine effective to alleviate the hyperkinetic conditions.

The amount of caffeine administered is that amount which is effective to produce the desired alleviation of hyperkinetic conditions in subjects exhibiting such conditions. The administration is generally as needed. A preferred level for administering caffeine is amounts of at least about 3 mg/kg of body weight of the subject.

Experimentation has shown that the effects imparted by the caffeine are dose related, and, therefore, upper limits on the dosage amount of caffeine employed are subject solely to considerations of the appearance of side effects in the subject. As previously mentioned, dosage levels of 6 mg/kg have been found to be effective without producing any appreciable undesirable side effects.

We Claim:

1. A method of alleviating hyperkinetic conditions, comprising orally administering to a subject exhibiting said conditions a dosage amount of caffeine effective to alleviate said conditions.

2. The method according to claim 1 wherein said dosage amount of caffeine is from about three milligrams to about six milligrams for each kilogram of body weight of said subject.

3. The method of claim 2 wherein said dosage amount of caffeine is incorporated within an edible, inert pharmaceutical carrier.

4. The method of claim 2 wherein said dosage amount of caffeine is added to a foodstuff.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3, 864,489 Dated February 4, 197,5

Inventoflg) Salvatore F. Biscardi It: is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

In column 3, Table I, opposite "Placebo" and under heading "Errors of Commission," change "16.523" to 16.528

Signed and sealed this 15th day of July 1975.

(SEAL) Attest:

C. MARSHALL DANN RUTH C. MASON Commissioner of Patents Attesting Officer and Trademarks

Claims (8)

1. A METHOD OF ALLEVIATING HYPERKINETIC CONDITIONS, COMPRISING ORALLY ADMINISTERING TO A SUBJECT EXHIBITING SAID CONDITIONS A DOSAGE AMOUNT OF CAFFEINE EFFECTIVE TO ALLEVIATE SAID CONDITIONS.

2. The method according to claim 1 wherein said dosage amount of caffeine is from about three milligrams to about six milligrams for each kilogram of body weight of said subject.

3. The method of claim 2 wherein said dosage amount of caffeine is incorporated within an edible, inert pharmaceutical carrier.

4. The method of claim 2 wherein said dosage amount of caffeine is added to a foodstuff.

5. A foodstuff containing an added amount of caffeine effective to alleviate hyperkinetic conditions in a subject exhibiting such conditions.

6. A foodstuff according to claim 5 wherein said amount of caffeine in said foodstuff is sufficient for administering to said subject about three milligrams to about six milligrams of caffeine for each kilogram of body weight of said subject.

7. The foodstuff of claim 6 wherein said foodstuff is selected from the group consisting of cereals and beverages.

8. The foodstuff of claim 5 wherein said foodstuff is selected from the group consisting of cereals and beverages.