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Clinical observations on the use of meprobamate in dental procedures
Pharmacology and Therapeutics CLINICAL OBSERVATIONS ON THE USE OF MEPROBAMATE IN DENTAL PROCEDURES LEO LUND, D.M.D., AND:J. M.
ANHOLM,
D.D.S., CORVALLIS,ORE.
ERVOUSNESS and acute apprehension are probably the most common emotional problems encountered in dental patients. Although especially troublesome among children, such disturbances occur in all age groups. They often prevent a satisfactory doctor-patient relationship, hindering skillful performance of oral operations, and retard normal adjustment in the postsurgical period, especially in prosthetic cases. The patient who is accustoming himself to dentures must expect a certain amount of temporary sensitiveness of the oral tissues ; however, additional difficulties often complicate the situation. For example, although the actual soreness may be moderate, the mechanical irritation caused during the first few days by every movement os the jaw and the keen embarrassment experienced by patients with more than usually acute emotional sensibilities may build up an unbearable state of tension, leading to irritability and impaired efficiency in daily work. The highly nervous patient with low tolerance for discomfort is therefore often impelled to make unnecessarily frequent office calls for adjustments, and in some cases there may ultimately be unwarranted dissatisfaction with the services provided by the dentist. Until recently the barbiturates, with all the attendant risks of respiratory, circulatory, and central nervous system depression, toxicity, and habituation, were the only recourse, in dentistry as well as in medicine, for control of apprehension and noncooperation. On introduction of the so-called tranquilizers, the interest of the dental profession was directed to the possibility that such compounds might be used to aid management of refractory patients. Meprobamate* (2-methyl-2-n-propyl-1, 3-propanediol dicarbamate), a nonbarbiturate interneuronal blocking agent described ~ as "entirely unrelated to anything heretofore used," has been demonstrated 2 as the most satisfactory of a series o~ 2, 2-disubstituted-1, 3-propanediol compounds. In studies 3 carried out in monkeys, the substance produced dramatic changes in behavior, causing the animals to lose their natural fear and hostility and to become tame and friendly. Competent investigators ~, 4, 5 have shown that the compound possesses definite relaxant properties which relieve both psychic stress and
N
*Meprobamate is available as Equanil from Wyeth Laboratories. 1281
1282
LUND
AND
ANHOLM
O.S., O. M., & O. P. December, 1957
muscular spasm without significant effect on the circulatory, respiratory, or other autonomic functions. B e r g e r 3 has reported t h a t the compound almost immediately controls the " i r r a t i o n a l fears and vague sense of d r e a d " typical of the anxiety state; he found nleprobamate more effective than the barbiturates for alleviation of emotional tension. Selling Gr e p o r t e d that twenty-seven of twenty-nine patients suffering from anxiety and fear showed definite improvement as a result of medication with meprobamate, and a series of electromyographic studies by Dickel and assoelates 7 demonstrated an increase in neuromuscular relaxation after t r e a t m e n t with the compound without hindrance to the daily activities of tile patient. In clinical studies of both museuloskeletal s and central nervous system disabilities,S, 9 Gillette found that meprobamate exerts a direct physical relaxant action as well as tranquilization of the emotions. The only side effect that occurs with any degree of f r e q u e n c y is drowsiness,3, s which is most likely to appear in children and in patients on high dosage and which usually subsides on continuance of medication for about one week. A small percentage of allergic manifestations have been reported b y some investigators, 3, c,, 8 ranging from mild skin rash to syncope, but, as pointed out b y Pelner, ~~ there is h a r d l y a potent drug on the m a r k e t that does not induce side reactions in a few patients. Subacutc and chronic toxicologic studies 2, 4, 1~ of meprobamatc have indic;~ted a v e r y low toxicity (the compound is a p p r o x i m a t e l y one-fifth as toxic as the barbiturates). Selling 6 has reported two cases of deliberate overdosagc in which one patient, a 107-pound female, ingested fifty tablets and the other, a male, swallowed 100 tablets in a twentyfour-hour period. Both recovered with no adverse effects. The findings in these and other studies % ~, 6, ;, suggested that meprobamate would be a safe and hclpful a d j u n c t to specific t r e a t m e n t in dental as well as medical practice. An investigation was planned, therefore, to determine the value of the compound in two phases of dentistry: (1) premedication for general dental procedures and (2) for relief of nervous tension and consequent reduction of discomfort during the difficult period of a d j u s t m e n t to the wearing of dental prostheses. The total series, representing as n e a r l y as possible a true cross section of average dental practice, included fifty-three private patients subjected to 174 surgical t r e a t m e n t s upon the mouth. Premedication for General Dental Procedures Thirty-nine patients (twenty-four females and fifteen males) received meprobamate prior to the performance of extractions, restorations, or both (Table I). All were selected for p r e t r e a t m e n t medication on the basis of their apprehension and intractability. Most had previously been u n d e r t r e a t m e n t b y us at r e g u l a r intervals, and their histories of resistance and noncooperation were a m a t t e r of record ; difficulties in management were therefore expected in all cases.
Volume l0
Number 12
USE OF MEPROBAMATE
IN DENTAL
1283
PROCEDURES
Thirteen were children 2 to 4 years old. All were frightened and unmanageable; one was e x t r e m e l y allergic, and had a d i e t a r y deficiency and a h e a r t murmur. TABLE I. D E N T A L SURGERY PERFORMED ON F O R T Y - T w o PATIENTS W H O
I~ECEIVED
MEPROBAI~ATE IN PREI~EDICATION
GROUP
P r e m e d i c a t i o n f o r d e n t a l surgery P r e m e d i c a t i o a f o r extraction, with immediate fitting of dentures
EXTRACTIONS ONLY
RESTORATIONS ONLY
EXTRACTIONS AND RESTORATIONS
TOTAL
8
20
11
39
3
3 42
Eleven were of grade school age. F o u r of these were k n o w n problem children : one was hysterical and of subnormal mentality, one had been u n d e r psychiatric treatment to reduce his fear of noise, the third was a neurotic, and the f o u r t h had so severe a behavior problem t h a t several other dentists had refused to t r e a t him. Nine were adolescents, of whom one was so apprehensive t h a t it was impossible to p e r f o r m the required s u r g e r y without premedication. There were six adults, 20 to 40 years old, of whom all were e x t r e m e l y nervous and one was mentally deficient. D o s e . - - T h e dosage varied according to the intensity of the emotional distress of the patient. Seventeen received 400 rag. the night before and 400 mg. one to two hours before operation the following morning. F o u r patients, scheduled for operation in the afternoon, received 400 rag. the night before, the n e x t morning on arising, and again one h o u r before the procedure. One 3 89 child received doses of 200 rag. (one-half tablet) on the same schedule. F o r sixteen patients 400 mg. one h o u r before operation sufficed, and one patient received a second dose of 400 rag. one-half hour before the scheduled surgical treatment. F o r small children the tablets were crushed and administered in jam, jelly, orange juice, or honey. Seven patients were subjected to one surgical t r e a t m e n t only, twenty-five received two to six treatments, and seven received eight to fifteen treatments. F o r patients on whom a series of procedures were to be performed, we usually prescribed twelve tablets, which was enough in most cases to supply the anticipated m a x i m u m needs of the patient for premedication. The degree of relaxation a p p a r e n t in the behavior of the patient and the cooperativeness which he showed in his approach to s u r g e r y were evaluated as objectively as possible. I f he had been a patient in the past, his response a f t e r medication was compared to previous records of his behavior w i t h o u t such t r e a t m e n t . Our clinical impressions of the results of medication were t a b u l a t e d as "excellent," "good," " f a i r , " and "none."
1284
LUND
AND
ANHOLM
O.S., O. M., & 0. P. December, 1957
Response was considered "excellent" when the patient showed a complete change in attitude. His fear, pallor, rapid pulse, and uncooperative attitude gave way to a state of relaxed friendliness, enabling rapid, efficient completion of all necessary phases of dental service. The result was considered "good" if there was a marked improvement in patient cooperation, so that he permitted all necessary services, but not all apprehension was eliminated. " F a i r " indicated a change for the better but left much to be desired. These cases were few. In no instance was there any physical resistance to treatment. Some adults in this group showed retention of anxiety, as indicated by surliness. It was impossible to ascertain whether these patients wer'e taking the suggested dosage of naeprobanaate.
Adjunctive Therapy in Dental Prosthesis At the beginning of the study, meprobanaate was administered to patients fitted with prostheses only when they began to exhibit signs of nervous tension. Later the medication became a routine part of the management of each case. A total of fourteen patients (nine females and five males) were fitted with dental prostheses. Nine were adults 23 to 65 years of age. Five were adolescents, aged 14 to 19 years. Nine of the series were fitted with dentures immediately after extraction. Three of these, all adults, were exceedingly tense, one being a known neurotic. One of the three had required two extractions; one, six extractions with three sutures; and the third, twelve extractions. In preparation for extraction these three patients also received three 400 nag. doses of naeprobanaate in premeditation on the schedule previously described (Table I). We made it a practice, on fitting the prostheses, to prescribe fifty tablets of 400 nag. naeprobanaate, since we found that this was the average total dose required to ease the patient through the adjustment period. The usual daily dosage schedule consisted of 400 nag. three times daily, and 400 rag. at bedtime, if needed, throughout the first week. In the second week the close was reduced to 400 mg. twice daily, and thereafter 400 nag. was to be taken as needed, bl most cases medication was continued for about three weeks, for a total of fortyeight to fifty tablets. The response was judged according to the subjective observations reported by the patient and our own clinical impressions of his emotional status during office calls.
Results Premedication in Dental Proeedures.--Results appeared most satisfactory on the three-tablet schedule (400 nag. the night before, on arising, and one hour before operation). Of the thirty-nine patients treated, thirty-two (82 per cent), including the boy who was refused treatment elsewhere because of his unmanageability and s.ev.erM other problem children, submitted to treatment in a manner that
Volume I0 Number 12
USE OF M E P R O B A M A T E I N D E N T A L P R O C E D U R E S
1285
could be considered good to excellent. In several of this group, who had been extremely uncooperative and difficult to handle during previous procedures, the improvement in behavior was actually dramatic. The response in the remainder was rated as fair, with the exception of one patient, the mentally deficient adult, who showed no benefit. It is doubtful that she took the medication at all. Only one patient, a small child, offered any resistance to swallowing the dose. Adjunctive Therapy in Dental Prosthesis.--Control of nervous tension and irritability was impressive. The relief obtained was rated as good to excellent in 93 per cent (all but one). No patient complained of embarrassment, which so often is a source of unhappiness to the sensitive person newly fitted with dentures. The one patient, a 17-year-old girl, in whom the result was unsatisfactory was fitted with immediate upper and partial lower dentures and is currently under treatment. She remains uncooperative, however, and is suspected of omitting the medication. The three who had received meprobamate preliminary to extraction and immediate fitting of dentures approached surgery in an adequately relaxed state and had an excellent result throughout the adjustment period. One patient, who worked in a candy store and was trying to adhere to an obesity diet, had less difficulty in controlling her food intake during meprobamate medication. Used in premedication, the compound did not interfere with the efficiency of the anesthestics or with other medications required. There was no evidence of potentiation of the anesthesia or of additive effects. Drowsiness occurred in a few of the smaller children (2 to 6 years old), which was an advantage, and was present to a slight degree in an adolescent and one adult, but caused no inconvenience.
Summary and Conclusions A total of fifty-three private patients subjected to 174 dental procedures received meprobamate (1) as premedication (thirty-nine patients) and (2) for relief of nervous tension during adjustment to the wearing of dental prostheses (fourteen patients). Three of the latter group also received premedication before extraction, with immediate fitting of dentures. Thirty-three of the total series were children or adolescents. All were apprehensive and uncooperative, and most had a history of intractability under treatment. Dosage for premedication varied with the intensity of the emotional stress of the individual patient. Best results in premedication were obtained with the three-dose schedule--400 rag. the night before, the next morning on arising, and again one hour before operation. The improvement in behavior and in submission to treatment after medication was good to excellent in 82 per cent. Used as an adjunct to dental prosthesis, meprobamate was administered usually in doses of 400 rag. three or four times daily in the first week after fitting of the dentures, twice daily in the second week, and thereafter as
1286
LUND AND ANHOLM
O.S., O. M.. &0. P. December. 19~7
needed, for a total dose of forty-eight to fifty tablets t h r o u g h o u t the adjustment period. Control of nervous tension and irritability was good to excellent in all but one case (93 per cent). Drowsiness occurred in a few of the smaller children, one adolescent, and one adult, but caused no inconvenience. No other side effect was observed. Meprobamate is a valuable a d j u n c t to dental practice.
References 1. Borrus, J-. C.: Study of Effect of ~Iiltown (2-methyl-2-n-propyl-1, 3-propanediol dlcarbamate) on Psychiatric States, 5. A. M. A. 157: 1596-1598, 1955. 2. Berger, F. M.: The Pharmacological Properties of 2-methyl-2-n-propyl-1, 3-propanediol dicarbamate (Miltown), a New Interneuronal Blocking Agent, J. Pharmacol. & Exper. Therap. 119.: 413-423, 1954. 3. Berger, F. M.: Meprobamate, Its Pharmacologic Properties and Clinical Uses, Internat. Rec. Med. 169: 184-196, 1956. 4. Hendley, C. D., Lynes, T. E., and Berger, F. M.: Effect of 2-methyl-2-n-propyl-1, 3-propanediol dicarbamate (Miltown) on Central Nervous System, Prec. Soc. Exper. Biol. & Med. 87: 60.~-610, 1954. 5. Lemere, F.: New Tranquilizing Drugs, Northwest Med. 54: 1098-1100, 1955. 6. Selling, L. S.: Clinical Study of a New Tranquilizing Drug, Use of Miltown (2-methyl2-n-propyl-1, 8-propanediol dicarbamate), J. A. M. A. 157: 1594-1596, 1955. 7. Dickel, H. A., Dixon, H. H., Wood, J., and Shanklin, I. G. : Electromyographic Studies on Patients Treated With Meprobamate, West. J. Surg. 64: 197-201, 1956. 8. Gillette, I-L E.: Relaxant Effects of l~eprobamate in Disabilities Resulting From Musculoskeletal and Central Nervous System Disorders: Clinical Observation of 55 Cases, Internat. Rec. Med. 169: 453-468, 1956. 9. Gillette, H. E.: Effect of Meprobamate on Cerebral Palsy: Electromyographic Studies on Patients With Pyramidal or Extrapyramidal Lesions (Read before the Conference on ~deprobamate and Other Agents Used in Mental Disturbances, The New York Academy of Sciences, Sections on Biology and Psychology, New York, Oct. 18-19, 1956), Ann. New York Acad. Sc. 67: 859-872, 1957. 10. Pelner, L.: Meprobamate, 5. A. M. h. 161: 644, 1956. 11. Ludwig, B. J., and Piech, E. C.: Some Anticonvulsant Agents Derived From 1,3propanediols, J. Am. Chem. Soc. 73: 5779-5781, 1951. 9 HouT BLDG.
ANHOLM,
D.D.S., CORVALLIS,ORE.
ERVOUSNESS and acute apprehension are probably the most common emotional problems encountered in dental patients. Although especially troublesome among children, such disturbances occur in all age groups. They often prevent a satisfactory doctor-patient relationship, hindering skillful performance of oral operations, and retard normal adjustment in the postsurgical period, especially in prosthetic cases. The patient who is accustoming himself to dentures must expect a certain amount of temporary sensitiveness of the oral tissues ; however, additional difficulties often complicate the situation. For example, although the actual soreness may be moderate, the mechanical irritation caused during the first few days by every movement os the jaw and the keen embarrassment experienced by patients with more than usually acute emotional sensibilities may build up an unbearable state of tension, leading to irritability and impaired efficiency in daily work. The highly nervous patient with low tolerance for discomfort is therefore often impelled to make unnecessarily frequent office calls for adjustments, and in some cases there may ultimately be unwarranted dissatisfaction with the services provided by the dentist. Until recently the barbiturates, with all the attendant risks of respiratory, circulatory, and central nervous system depression, toxicity, and habituation, were the only recourse, in dentistry as well as in medicine, for control of apprehension and noncooperation. On introduction of the so-called tranquilizers, the interest of the dental profession was directed to the possibility that such compounds might be used to aid management of refractory patients. Meprobamate* (2-methyl-2-n-propyl-1, 3-propanediol dicarbamate), a nonbarbiturate interneuronal blocking agent described ~ as "entirely unrelated to anything heretofore used," has been demonstrated 2 as the most satisfactory of a series o~ 2, 2-disubstituted-1, 3-propanediol compounds. In studies 3 carried out in monkeys, the substance produced dramatic changes in behavior, causing the animals to lose their natural fear and hostility and to become tame and friendly. Competent investigators ~, 4, 5 have shown that the compound possesses definite relaxant properties which relieve both psychic stress and
N
*Meprobamate is available as Equanil from Wyeth Laboratories. 1281
1282
LUND
AND
ANHOLM
O.S., O. M., & O. P. December, 1957
muscular spasm without significant effect on the circulatory, respiratory, or other autonomic functions. B e r g e r 3 has reported t h a t the compound almost immediately controls the " i r r a t i o n a l fears and vague sense of d r e a d " typical of the anxiety state; he found nleprobamate more effective than the barbiturates for alleviation of emotional tension. Selling Gr e p o r t e d that twenty-seven of twenty-nine patients suffering from anxiety and fear showed definite improvement as a result of medication with meprobamate, and a series of electromyographic studies by Dickel and assoelates 7 demonstrated an increase in neuromuscular relaxation after t r e a t m e n t with the compound without hindrance to the daily activities of tile patient. In clinical studies of both museuloskeletal s and central nervous system disabilities,S, 9 Gillette found that meprobamate exerts a direct physical relaxant action as well as tranquilization of the emotions. The only side effect that occurs with any degree of f r e q u e n c y is drowsiness,3, s which is most likely to appear in children and in patients on high dosage and which usually subsides on continuance of medication for about one week. A small percentage of allergic manifestations have been reported b y some investigators, 3, c,, 8 ranging from mild skin rash to syncope, but, as pointed out b y Pelner, ~~ there is h a r d l y a potent drug on the m a r k e t that does not induce side reactions in a few patients. Subacutc and chronic toxicologic studies 2, 4, 1~ of meprobamatc have indic;~ted a v e r y low toxicity (the compound is a p p r o x i m a t e l y one-fifth as toxic as the barbiturates). Selling 6 has reported two cases of deliberate overdosagc in which one patient, a 107-pound female, ingested fifty tablets and the other, a male, swallowed 100 tablets in a twentyfour-hour period. Both recovered with no adverse effects. The findings in these and other studies % ~, 6, ;, suggested that meprobamate would be a safe and hclpful a d j u n c t to specific t r e a t m e n t in dental as well as medical practice. An investigation was planned, therefore, to determine the value of the compound in two phases of dentistry: (1) premedication for general dental procedures and (2) for relief of nervous tension and consequent reduction of discomfort during the difficult period of a d j u s t m e n t to the wearing of dental prostheses. The total series, representing as n e a r l y as possible a true cross section of average dental practice, included fifty-three private patients subjected to 174 surgical t r e a t m e n t s upon the mouth. Premedication for General Dental Procedures Thirty-nine patients (twenty-four females and fifteen males) received meprobamate prior to the performance of extractions, restorations, or both (Table I). All were selected for p r e t r e a t m e n t medication on the basis of their apprehension and intractability. Most had previously been u n d e r t r e a t m e n t b y us at r e g u l a r intervals, and their histories of resistance and noncooperation were a m a t t e r of record ; difficulties in management were therefore expected in all cases.
Volume l0
Number 12
USE OF MEPROBAMATE
IN DENTAL
1283
PROCEDURES
Thirteen were children 2 to 4 years old. All were frightened and unmanageable; one was e x t r e m e l y allergic, and had a d i e t a r y deficiency and a h e a r t murmur. TABLE I. D E N T A L SURGERY PERFORMED ON F O R T Y - T w o PATIENTS W H O
I~ECEIVED
MEPROBAI~ATE IN PREI~EDICATION
GROUP
P r e m e d i c a t i o n f o r d e n t a l surgery P r e m e d i c a t i o a f o r extraction, with immediate fitting of dentures
EXTRACTIONS ONLY
RESTORATIONS ONLY
EXTRACTIONS AND RESTORATIONS
TOTAL
8
20
11
39
3
3 42
Eleven were of grade school age. F o u r of these were k n o w n problem children : one was hysterical and of subnormal mentality, one had been u n d e r psychiatric treatment to reduce his fear of noise, the third was a neurotic, and the f o u r t h had so severe a behavior problem t h a t several other dentists had refused to t r e a t him. Nine were adolescents, of whom one was so apprehensive t h a t it was impossible to p e r f o r m the required s u r g e r y without premedication. There were six adults, 20 to 40 years old, of whom all were e x t r e m e l y nervous and one was mentally deficient. D o s e . - - T h e dosage varied according to the intensity of the emotional distress of the patient. Seventeen received 400 rag. the night before and 400 mg. one to two hours before operation the following morning. F o u r patients, scheduled for operation in the afternoon, received 400 rag. the night before, the n e x t morning on arising, and again one h o u r before the procedure. One 3 89 child received doses of 200 rag. (one-half tablet) on the same schedule. F o r sixteen patients 400 mg. one h o u r before operation sufficed, and one patient received a second dose of 400 rag. one-half hour before the scheduled surgical treatment. F o r small children the tablets were crushed and administered in jam, jelly, orange juice, or honey. Seven patients were subjected to one surgical t r e a t m e n t only, twenty-five received two to six treatments, and seven received eight to fifteen treatments. F o r patients on whom a series of procedures were to be performed, we usually prescribed twelve tablets, which was enough in most cases to supply the anticipated m a x i m u m needs of the patient for premedication. The degree of relaxation a p p a r e n t in the behavior of the patient and the cooperativeness which he showed in his approach to s u r g e r y were evaluated as objectively as possible. I f he had been a patient in the past, his response a f t e r medication was compared to previous records of his behavior w i t h o u t such t r e a t m e n t . Our clinical impressions of the results of medication were t a b u l a t e d as "excellent," "good," " f a i r , " and "none."
1284
LUND
AND
ANHOLM
O.S., O. M., & 0. P. December, 1957
Response was considered "excellent" when the patient showed a complete change in attitude. His fear, pallor, rapid pulse, and uncooperative attitude gave way to a state of relaxed friendliness, enabling rapid, efficient completion of all necessary phases of dental service. The result was considered "good" if there was a marked improvement in patient cooperation, so that he permitted all necessary services, but not all apprehension was eliminated. " F a i r " indicated a change for the better but left much to be desired. These cases were few. In no instance was there any physical resistance to treatment. Some adults in this group showed retention of anxiety, as indicated by surliness. It was impossible to ascertain whether these patients wer'e taking the suggested dosage of naeprobanaate.
Adjunctive Therapy in Dental Prosthesis At the beginning of the study, meprobanaate was administered to patients fitted with prostheses only when they began to exhibit signs of nervous tension. Later the medication became a routine part of the management of each case. A total of fourteen patients (nine females and five males) were fitted with dental prostheses. Nine were adults 23 to 65 years of age. Five were adolescents, aged 14 to 19 years. Nine of the series were fitted with dentures immediately after extraction. Three of these, all adults, were exceedingly tense, one being a known neurotic. One of the three had required two extractions; one, six extractions with three sutures; and the third, twelve extractions. In preparation for extraction these three patients also received three 400 nag. doses of naeprobanaate in premeditation on the schedule previously described (Table I). We made it a practice, on fitting the prostheses, to prescribe fifty tablets of 400 nag. naeprobanaate, since we found that this was the average total dose required to ease the patient through the adjustment period. The usual daily dosage schedule consisted of 400 nag. three times daily, and 400 rag. at bedtime, if needed, throughout the first week. In the second week the close was reduced to 400 mg. twice daily, and thereafter 400 nag. was to be taken as needed, bl most cases medication was continued for about three weeks, for a total of fortyeight to fifty tablets. The response was judged according to the subjective observations reported by the patient and our own clinical impressions of his emotional status during office calls.
Results Premedication in Dental Proeedures.--Results appeared most satisfactory on the three-tablet schedule (400 nag. the night before, on arising, and one hour before operation). Of the thirty-nine patients treated, thirty-two (82 per cent), including the boy who was refused treatment elsewhere because of his unmanageability and s.ev.erM other problem children, submitted to treatment in a manner that
Volume I0 Number 12
USE OF M E P R O B A M A T E I N D E N T A L P R O C E D U R E S
1285
could be considered good to excellent. In several of this group, who had been extremely uncooperative and difficult to handle during previous procedures, the improvement in behavior was actually dramatic. The response in the remainder was rated as fair, with the exception of one patient, the mentally deficient adult, who showed no benefit. It is doubtful that she took the medication at all. Only one patient, a small child, offered any resistance to swallowing the dose. Adjunctive Therapy in Dental Prosthesis.--Control of nervous tension and irritability was impressive. The relief obtained was rated as good to excellent in 93 per cent (all but one). No patient complained of embarrassment, which so often is a source of unhappiness to the sensitive person newly fitted with dentures. The one patient, a 17-year-old girl, in whom the result was unsatisfactory was fitted with immediate upper and partial lower dentures and is currently under treatment. She remains uncooperative, however, and is suspected of omitting the medication. The three who had received meprobamate preliminary to extraction and immediate fitting of dentures approached surgery in an adequately relaxed state and had an excellent result throughout the adjustment period. One patient, who worked in a candy store and was trying to adhere to an obesity diet, had less difficulty in controlling her food intake during meprobamate medication. Used in premedication, the compound did not interfere with the efficiency of the anesthestics or with other medications required. There was no evidence of potentiation of the anesthesia or of additive effects. Drowsiness occurred in a few of the smaller children (2 to 6 years old), which was an advantage, and was present to a slight degree in an adolescent and one adult, but caused no inconvenience.
Summary and Conclusions A total of fifty-three private patients subjected to 174 dental procedures received meprobamate (1) as premedication (thirty-nine patients) and (2) for relief of nervous tension during adjustment to the wearing of dental prostheses (fourteen patients). Three of the latter group also received premedication before extraction, with immediate fitting of dentures. Thirty-three of the total series were children or adolescents. All were apprehensive and uncooperative, and most had a history of intractability under treatment. Dosage for premedication varied with the intensity of the emotional stress of the individual patient. Best results in premedication were obtained with the three-dose schedule--400 rag. the night before, the next morning on arising, and again one hour before operation. The improvement in behavior and in submission to treatment after medication was good to excellent in 82 per cent. Used as an adjunct to dental prosthesis, meprobamate was administered usually in doses of 400 rag. three or four times daily in the first week after fitting of the dentures, twice daily in the second week, and thereafter as
1286
LUND AND ANHOLM
O.S., O. M.. &0. P. December. 19~7
needed, for a total dose of forty-eight to fifty tablets t h r o u g h o u t the adjustment period. Control of nervous tension and irritability was good to excellent in all but one case (93 per cent). Drowsiness occurred in a few of the smaller children, one adolescent, and one adult, but caused no inconvenience. No other side effect was observed. Meprobamate is a valuable a d j u n c t to dental practice.
References 1. Borrus, J-. C.: Study of Effect of ~Iiltown (2-methyl-2-n-propyl-1, 3-propanediol dlcarbamate) on Psychiatric States, 5. A. M. A. 157: 1596-1598, 1955. 2. Berger, F. M.: The Pharmacological Properties of 2-methyl-2-n-propyl-1, 3-propanediol dicarbamate (Miltown), a New Interneuronal Blocking Agent, J. Pharmacol. & Exper. Therap. 119.: 413-423, 1954. 3. Berger, F. M.: Meprobamate, Its Pharmacologic Properties and Clinical Uses, Internat. Rec. Med. 169: 184-196, 1956. 4. Hendley, C. D., Lynes, T. E., and Berger, F. M.: Effect of 2-methyl-2-n-propyl-1, 3-propanediol dicarbamate (Miltown) on Central Nervous System, Prec. Soc. Exper. Biol. & Med. 87: 60.~-610, 1954. 5. Lemere, F.: New Tranquilizing Drugs, Northwest Med. 54: 1098-1100, 1955. 6. Selling, L. S.: Clinical Study of a New Tranquilizing Drug, Use of Miltown (2-methyl2-n-propyl-1, 8-propanediol dicarbamate), J. A. M. A. 157: 1594-1596, 1955. 7. Dickel, H. A., Dixon, H. H., Wood, J., and Shanklin, I. G. : Electromyographic Studies on Patients Treated With Meprobamate, West. J. Surg. 64: 197-201, 1956. 8. Gillette, I-L E.: Relaxant Effects of l~eprobamate in Disabilities Resulting From Musculoskeletal and Central Nervous System Disorders: Clinical Observation of 55 Cases, Internat. Rec. Med. 169: 453-468, 1956. 9. Gillette, H. E.: Effect of Meprobamate on Cerebral Palsy: Electromyographic Studies on Patients With Pyramidal or Extrapyramidal Lesions (Read before the Conference on ~deprobamate and Other Agents Used in Mental Disturbances, The New York Academy of Sciences, Sections on Biology and Psychology, New York, Oct. 18-19, 1956), Ann. New York Acad. Sc. 67: 859-872, 1957. 10. Pelner, L.: Meprobamate, 5. A. M. h. 161: 644, 1956. 11. Ludwig, B. J., and Piech, E. C.: Some Anticonvulsant Agents Derived From 1,3propanediols, J. Am. Chem. Soc. 73: 5779-5781, 1951. 9 HouT BLDG.