Benefits In Non-Epileptics

Lindsley and Henry, Psychosomatic Medicine (1942),225 in an early study, observed that problem children given PHT showed behavioral improvement.

225. Lindsley, D. B. and Henry, C. E., The effect of drugs on behavior and the electroencephalograms of children with behavior disorders, Psychosom. Med., 4: 140-149, 1942.

Brown and Solomon, American Journal of Psychiatry (1942),38 reported that delinquent boys committed to a state training school showed important behavioral improvement on PHT therapy. Improvement was seen in a reduction in extreme hyperactivity, excitability and temper “flare-ups” and in attention span and more efficient work patterns.

38. Brown, W. T. and Solomon, C. I., Delinquency and the electroencephalograph, Amer. J. Psychiat., 98: 499-503, 1942.

Silverman, Criminal Psychopathology (1944),716 in what appears to be the first reported study on the use of PHT in prisoners, found PHT to be superior to all other agents tested. The study was done with sixty-four prisoners at the Medical Center for Federal Prisoners, Springfield, Missouri. Improvements were noted in sleep, sense of well-being and cooperativeness. These observations were made in a double-blind crossover study with placebo.

716. Silverman, D., The electroencephalograph and therapy of criminal psychopaths, Criminal Psychopathology, 5: 439-457, 1944.

Bodkin, American Journal of Digestive Diseases (1945),25 reporting on his ten years of successful treatment of pruritus ani with PHT, noted that all the patients had one thing in common—they were highly nervous.  (See Pruritus Ani)

25. Bodkin, L. G., Oral therapy for pruritus ani, Amer. J. Dig. Dis., 12: 255-257, 1945.

Goodwin, Journal of the National Proctologic Association (1946),127 reporting the successful treatment of patients with pruritus ani with PHT, agreed with Bodkin25 that nervousness was a factor common in the vast majority of these patients. (See Pruritus Ani)

127. Goodwin, F. B., Oral therapy in anogenital pruritus, J. Nat. Proct. Assn., 18: 84-87, 1946.
25. Bodkin, L. G., Oral therapy for pruritus ani, Amer. J. Dig. Dis., 12: 255-257, 1945.

Walker and Kirkpatrick, American Journal of Psychiatry (1947),373 treated ten behavior problem children with abnormal EEG findings with PHT. None of the children had clinical evidence of seizures, and physical and neurological examinations were all negative. All of these children showed definite clinical improvement under PHT treatment.

373. Walker, C. F. and Kirkpatrick, B. B., Dilantin treatment for behavior problem children with abnormal electroencephalograms, Amer. J. Psychiat., 103: 484-492, 1947.

Fabrykant and Pacella, Annals of Internal Medicine (1948),92 in discussing the effects of PHT in labile diabetes, noted that PHT alleviated anxiety, nervous tension and irritability. In addition, the ability to concentrate and to work increased and the patients exhibited a general feeling of well-being.

92. Fabrykant, M. and Pacella, B. L., Labile diabetes: electroencephalographic status and effect of anticonvulsive therapy, Ann. Intern. Med., 29: 860-877, 1948.

Zimmerman, New York State Journal of Medicine (1956),395 gave PHT to a group of two hundred children having severe behavior disorders. Improvement was seen in 70% of the cases. The use of PHT resulted in reduced excitability, less severe and less frequent temper tantrums, reduced hyperactivity and distractibility, fewer fears, and less tendency to go out of contact.

395. Zimmerman, F. T., Explosive behavior anomalies in children on an epileptic basis, New York J. Med., 56: 2537-2543, 1956.

Chao, Sexton and Davis, Journal of Pediatrics (1964),51 conducted an extensive study of 535 children classified as having convulsive equivalent syndrome characterized by autonomic disturbances and dysfunction in behavior and communication. A majority of these patients had 14- and 6-EEG patterns. PHT was used alone with 296 of these children and in combination with other drugs in 117 children.The symptoms benefited included headache, abdominal pain, vasomotor disturbances, nausea, dizziness or syncope, fever and/or chills, shortness of breath, eye pain, photophobia, sweating, weakness, pain in extremities and chest pain. Behavioral and emotional problems, retardation, school problems in non-retarded, sleep disturbances, speech problems and neurological deficits also responded to treatment. The response was rapid and often striking.

51. Chao, D., Sexton, J. A., and Davis, S. D., Convulsive equivalent syndrome of childhood, J. Pediat, 64: 499-508, 1964.

Jonas (1965),432 in his book Ictal and Subictal Neurosis, based on observations of 162 patients over a twelve-year period, found PHT of benefit in a wide range of nonconvulsive disorders. Among the symptoms which the author noted were helped by PHT were anxiety, depression, agitation, irritability, violence, headache, sleep disturbances, abdominal symptoms, sexual disturbances, hypochondria, visual and auditory phenomena and body image distortion.

432. Jonas, A. D., Ictal and subictal neurosis, C. C. Thomas, Springfield, Ill., 1965.

Lynk and Amidon, Michigan Medicine (1965),576 studied the effect of medication with severely disturbed delinquents under court jurisdiction. The number of patients who received PHT (out of a total of 125) was not given.They found that some of the children with borderline EEGs but no epilepsy had markedly aggressive behavior. These children responded to PHT when no other drug seemed to help.

576. Lynk, S. M. and Amidon, E., Chemotherapy with delinquents, Mich. Med., 762-766, Oct., 1965.

Dreyfus (1966),707 reported on “The Beneficial Effects of PHT on the Nervous System of Nonepileptics—As Experienced and Observed in Others by a Layman.” The author observed that multiple simultaneous thoughts as well as obsessive and preoccupied thinking were relieved by PHT. Coincident with this, marked improvements were noted in symptoms of anger and related conditions of impatience, irritability, agitation and impulsiveness. Also, there was marked improvement in symptoms of fear and the related emotions such as worry, pessimism, anxiety, apprehensiveness and depression. He noted that the ability to fall asleep more promptly and to sleep more soundly, without nightmares, occurred in the majority of cases. However, with a minority who slept excessively (so-called avoidance sleep) duration of sleep tended to be beneficially reduced. Based on his observations, the author formed the impression that excessive bioelectrical activity in the nervous system causes unfavorable emotional responses, anger and fear being chief among them. PHT corrects this excessive bioelectrical activity, causing excessive anger and fear to be eliminated.

707. Dreyfus, J. J. Jr., The beneficial effects of diphenylhydantoin on the nervous systems of nonepileptics-as experienced and observed in others by a layman. Presented at the Amer. College of Neuropsychopharmacology, Dec. 7, 1966, Dreyfus Medical Foundation, 1966.

Rossi, New York State Journal of Medicine (1967),314 stated that PHT is clinically effective in impulsivity and behavior in hyperactive children and particularly effective in controlling nightmares.

314. Rossi, A. O., Psychoneurologically impaired child: community mental health clinic approach, New York J. Med., 67: 902-912, 1967.

Resnick, International Journal of Neuropsychiatry (1967),297 reported a double-blind controlled study with crossover and placebo involving eleven inmates at a prison, selected from a group of forty-two volunteers. The entire study (Resnick and Dreyfus, 1966)704 was recorded on tape. The beneficial effects of PHT were reported in connection with overthinking, anger and fear, tension, irritability and hostility. There was marked improvement in ability to concentrate and in sleep problems. Improvement was also observed in headaches, gastrointestinal disturbances and, in one case, phantom limb pain. Subsequently similar observations were made at a reformatory in six juvenile delinquents ranging in age from twelve to fifteen. With the administration of 100 mg PHT daily, prompt relief in anger and fear was noted and clearly expressed in marked diminution in fighting by five of the boys. The sixth boy, who was withdrawn and passive, became more outgoing, talkative and had an occasional fight. General improvements in overthinking, tension, impatience, impulsiveness, irritability, anger, fear, sleep difficulties and headaches were also observed.

297. Resnick, O., The psychoactive properties of diphenylhydantoin: experiences with prisoners and juvenile delinquents, Int. J. Neuropsychiat. 3: S30-S48, 1967.
704. Resnick, O. and Dreyfus, J. J., Jr., Worcester County Jail study: Beneficial effects of DPH on the nervous systems of nonepileptics (condensed), Dreyfus Medical Foundation, 1966.

Turner, International Journal of Neuropsychiatry (1967),364 studied the effect of PHT on patients seen in psychiatric practice during an eighteen-month period. They suffered from a wide variety of emotional and behavioral disorders. Forty-six of fifty-six neurotic patients improved. Improvement was observed in relation to anger, irritability, tension, sleep disturbances, ruminations, anxiety, depression, feelings of guilt and withdrawal, regardless of diagnostic category or EEG findings. Because of the lack of sedation or stimulation, the author suggested that PHT might be called a normalizer.

364. Turner, W. J., The usefulness of diphenylhydantoin in treatment of non-epileptic emotional disorders, Int. J. Neuropsychiat., 3: suppl. 2, S8-S20, 1967.

Jonas, International Journal of Neuropsychiatry (1967),181 found that over half of 211 patients seen in general psychiatric practice had a therapeutic response to PHT, ranging from reduction to complete reversal of symptoms in the following conditions: anxiety and tension states, reactive depressions, certain cognitive disturbances, obsessive-compulsive manifestations, hypochondria, psychopathy, obesity, and addiction to alcohol and to cigarette smoking. Many patients reported favorable reactions within one hour after intake of PHT. The author suggested that the action of PHT placed it in a category separate from the tranquilizers or stimulants and agreed with Turner 364 that the term normalizer seemed appropriate.

181. Jonas, A. D., The diagnostic and therapeutic use of diphenylhydantoin in the subictal state and non-epileptic dysphoria, Int. J. Neuropsychiat., 3: S21 -S29, 1967.
364. Turner, W. J., The usefulness of diphenylhydantoin in treatment of non-epileptic emotional disorders, Int. J. Neuropsychiat., 3: suppl. 2, S8-S20, 1967.

Ayd, International Drug Therapy Newsletter (1967),538 in a summary of the clinical psychopharmacological value of PHT entitled “New Uses for an Old Drug,” pointed out the effectiveness of PHT for psychic overactivity, distractibility, short attention span, irritability, impulsiveness, insomnia and behavioral disorders in children.

538. Ayd, F. J., Jr., New uses for an old drug, Intern. Drug Ther. Newsletter, 2: 1-2, Jan., 1967.

Itil, Rizzo and Shapiro, Diseases of the Nervous System (1967),178 studied the effect of PHT, combined with thioridazine, on twenty behaviorally disturbed children and adolescents. Eleven patients had personality disorders; five schizophrenic reactions; and four chronic brain syndrome, two with convulsions. These patients showed low frustration tolerance, hyperactivity and restlessness, aggressive destructive behavior, impulsiveness, poor school or work performance, antisocial acts, sexual acting out, irritability and stubbornness. After three months of treatment, fifteen of the twenty patients showed moderate to marked improvement and fourteen of them were discharged.

178. Itil, T. M., Rizzo, A. E., and Shapiro, D. M., Study of behavior and EEG correlation during treatment of disturbed children, Dis. Nerv. Syst., 28: 731-736, 1967.

Tec, American Journal of Psychiatry (1968),355 reviewed his fifteen years’ experience with PHT in the treatment of behavior disorders in children. The author reported that PHT improved disruptive behavior in the large majority of the children seen during that period and emphasized that PHT often helped when the phenothiazines and amphetamines failed.

355. Tec, L., Efficacy of diphenylhydantoin in childhood psychiatric disorders, Amer. J. Psychiat., 124: 156-157, 1968.

Boelhouwer, Henry and Glueck, American Journal of Psychiatry (1968),27 in a double-blind study with crossover features and placebo, reported that PHT alone or in combination with thioridazine (Mellaril) was effective at a statistically significant level in a group of seventy-eight patients, ranging in age from fourteen to thirty. Forty-seven of these patients showed 14- and 6-per second positive spiking, whereas no such abnormality was present in thirty-one. The thirty-one patients without EEG abnormality responded best to PHT alone. The positive spike group responded better to PHT in combination with thioridazine than to either drug alone. Significant changes were observed for the following factors with PHT alone: disturbance of affect, lack of social conformity, lack of insight, hostile aggressive behavior, dissociative tendency, thinking disorder, self-destructive tendency, and guilty self-concept. In addition to the above, significant changes were observed for the following factors with PHT and Mellaril combined: overt anxiety symptoms, dissociative concern, paranoid thinking, and depression.

27. Boelhouwer, C., Henry, C. E., and Glueck, B. C., Positive spiking: a double blind control study on its significance in behavior disorders, both diagnostically and therapeutically, Amer. J. Psychiat., 125: 473-481, 1968.

Baldwin, Maryland Medical Journal (1969),706 reported on the treatment with PHT of behavior disorders in children (see also Baldwin and Kenny, 1966).8  The most consistent complaint was hyperactivity. Other important problems were temper tantrums or rage reactions, impulsive behavior and social adaptation. Attention span was short and concentration poor. Of 300 cases treated during a six-month period, it was found that 109 had improved so markedly that they were able to return to school. Of the 109 who showed marked improvement, 78 had received PHT—48 of them had behavior problems not associated with seizures.

706. Baldwin, R. W., Behavior disorders in children, Maryland Med. J., 18: 68-71, 1969.
 8. Baldwin, R. W. and Kenny, T. J., Medical treatment of behavior disorders, Learning Disabilities, J. Hellmuth, Ed., 2: 313-327, Special Child Publications of The Seattle Seguin School, Inc., Seattle, 1966.

Case, Rickels and Bazilian, American Journal of Psychiatry (1969),46 reported that anxious-neurotic psychiatric clinic outpatients were treated over a four-week period with PHT (100 mg twice daily). While some improvement was observed in this patient group, no statistically significant difference was noted between the PHT and a comparable placebo group. However, the authors reported an interesting finding, namely, “a paucity of side effects in the PHT-treated group (only one patient reported mild dizziness), while our placebo control group had the usual variety of side effects . . . in twelve of the twenty patients.” If the only variable in these two groups was that one took PHT and one took placebo, then the probability that PHT was effective in preventing the placebo “side effects” in these anxious-neurotic patients was at the level of significance of p<0.001.

46. Case, W. G., Rickels, K., and Bazilian, S., Diphenylhydantoin in neurotic anxiety, Amer. J.,Psychiat., 126: 254-255, 1969.

Stephens and Shaffer, Psychopharmacologia (1970),700 in a double-blind study with thirty adult outpatients, found PHT to be markedly effective in reducing symptoms relating to anger, irritability, impatience and anxiety. The therapeutic effectiveness of PHT was demonstrated at statistically high levels by both self-ratings and physician ratings of change. This double-blind study was done on a crossover basis with placebo. The dosage of PHT was 100 mg t.i.d. When compared to placebo, such standard scale factors as “anger,” “furious,” and “impatience” improved with PHT at p levels between 0.01 and 0.001. Standard scale factors of  “worried,” and “angry” improved at levels of p<0.01. Factors of “tension,” “grouchy,” “ready for a fight,” “nervous,” “nervousness and shakiness,” “trembling,” and “quarrelsomeness improved at levels of p<0.05. In the crossover analysis, PHT improved “tension,” “worried,” “uncertain about things,” “resentful,” “bad tempered,” “angry,” “impatience,” and global change rated by patient all at the level of p<0.01; PHT improved “bewildered,” “nervous,” “ready for a fight,” “confused,” “anxious,” “irritability,” “quarrelsomeness,” “heart pounding,” “temper outbursts,” “trembling,” “nervousness and shakiness,” all at levels of p<0.05; and the factors of “furious,” “grouchy,” and global change rated by physician all were improved by PHT at levels of p<0.001. The patients’ feelings of tranquility, composure, relaxation, optimism and cheerfulness also showed statistically significant improvement with PHT. No undesirable side effects were encountered.

700. Stephens, J. H. and Shaffer, J. W., A controlled study of the effects of diphenylhydantoin on anxiety, irritability, and anger in neurotic outpatients, Psychopharmacologia, 17: 169-181, 1970.

Looker and Conners, Archives of General Psychiatry (1970),1304 conducted a double-blind study with PHT on seventeen subjects, ranging in age from five to fourteen years, who had periodic episodes of misbehavior. Although no statistically significant group changes were attributable to drug effect, it was the impression of the authors that among the patients “there were some who responded rather dramatically.” The authors also reported on three children in whom PHT had a marked effect in the treatment of severe temper tantrums. In each case the response to PHT was prompt. The children were followed-up six months later and the marked improvement had persisted. In two of the cases, when the parents forgot to give PHT, deterioration was noted within two days. This deterioration was promptly corrected with PHT.

1304. Looker, A. and Conners, C. K., Diphenylhydantoin in children with severe temper tantrums, Arch. Gen. Psychiat., 23: 80-89, 1970.

Goldberg and Kurland, Journal of Nervous and Mental Diseases (1970),713 in a double-blind study, reported the effectiveness of PHT on the emotional, cognitive and social behavior of forty-seven hospitalized retardates, ages nine to fourteen. Patients treated with PHT showed strong improvement in ability to maintain attention, in self-control, and in improved interpersonal relationships with adults. There was marked improvement in logical thinking, and decreased temper outbursts, impulsivity and aggression. There were also trends toward increased ability to concentrate and better visual-motor organization. The effective dose of PHT was 100 mg twice daily. Neither toxicity nor side effects were observed.

713. Goldberg, J. and Kurland, A. A., Dilantin treatment of hospitalized cultural-familial retardates, J. Nerv. Ment. Dis., 150: 133-137, 1970.

Daniel, Geriatrics (1970),938 states that symptoms of confusion, which are so common in the aged, often are caused by underlying physical illness, frequently cardiac and respiratory disorders resulting in cerebral hypoxia. He states that PHT is therapeutically useful in this group, yet it is often overlooked. (This discussion of PHT by Daniel is part of a larger study of other substances entitled, “Psychiatric drug use and abuse in the aged.” For other work on the effect of PHT in cerebral blood flow and hypoxia, see Refs. 790, 1216, 1560, 2142, 2768. See also Anti-Anoxic Effects of PHT, Basic Mechanisms of Action.) Among the symptoms of confusion so common in the aged are: disorientation; lack of attention and concentration; fluctuation in state of consciousness; memory loss, particularly of current events; and impairment of conventional judgment. The author states that although problems of insufficient cerebral blood flow are well known in the aged, direct measurement of cerebral blood flow is difficult. However, the author states that symptoms of insufficient cerebral blood flow are identifiable clinically. Among these symptoms are irritability, restlessness, mental confusion and sometimes severe depression. The author notes that after a cerebrovascular accident the patient often has paresthesias and tingling. He states that PHT not only frequently gives relief from the paresthesias, but that mental symptoms also improve.  (See Cerebral)

938. Daniel, R., Psychiatric drug use and abuse in the aged, Geriatrics, 144-156, January, 1970.
 790. Baldy-Moulinier, M., Cerebral blood flow and membrane ionic pump, Europ. Neurol., 6: 107-113, 1971/72.
1216. Kennedy, C., Anderson, W., and Sokoloff, L., Cerebral blood flow in epileptic children during the interseizure period, Neurology, 8: 100-105, 1958.
1560. Slosberg, P. S., Medical therapy for the cerebrovascular insufficiencies; eight years’ experience, Mt. Sinai Med. J., 37: 692-698, 1970.
2142. Aldrete, J.A., Romo-Salas, F., Mazzia, V.D.B. and Tan, S.L., Phenytoin for brain resuscitation after cardiac arrest, Critical Care Medicine, 9(6): 474-7, 1981.
2768. Massei, R., DeSilva, E., Grosso, P., Robbiati, B. R., Infuso, L., Ravagnati, L., Altamura, C. A., Cerebral protection with diphenylhydantoin during disobliterating surgery of the sovra-aortic branches, J. Neurosurg. Sci., 27(2): 107-10, 1983.

Bozza, in a detailed paper presented at the Fourth Italian National Congress of Child Neuropsychiatry (1971),863 reports on an individual basis on twenty-one slightly brain damaged retarded children who were observed for periods of from twelve to thirty-six months. In most of the cases PHT was tried. The author concludes that PHT and vitamins materially improved the expected intellectual growth rate of these retarded children. (See also Refs. 8, 355, 373, 1626.)

863. Bozza, G. A., Normalization of intellectual development in the slightly brain-damaged, retarded child, Paper presented at the 4th Italian National Congress on Child Neuropsychiatry, Genoa, 1971.
8. Baldwin, R. W. and Kenny, T. J., Medical treatment of behavior disorders, Learning Disabilities, J. Helimuth, Ed., 2: 313-327, Special Child Publications of The Seattle Seguin School, Inc., Seattle, 1966.
355. Tec, L., Efficacy of diphenylhydantoin in childhood psychiatric disorders, Amer. J. Psychiat ., 124: 156-157, 1968.
373. Walker, C. F. and Kirkpatrick, B. B., Dilantin treatment for behavior problem children with abnormal electroencephalograms, Amer. J. Psychiat., 103: 484-492, 1947.
1626. Turner, W. J., Dilantin effect on emotionally disturbed children, Drugs and Cerebral Function, 99-102, Smith, W. L., Ed., Charles C Thomas, 1970.

Alvarez, in a book titled Nerves in Collision (1972),761 reviews his twenty-five years’ experience in the use of PHT for a wide variety of disorders. In his book, Alvarez reports on the successful use of PHT in the treatment of anxiety, nervousness, tension, fear, nightmares, depression, rage, violent outbursts, confusion, fatigue (extreme), abdominal pain, alcoholism, anorexia nervosa, bed wetting, blackouts, dizzy spells, head pain, involuntary movements, migraine-like headaches. (See also Ref. 4.)

761. Alvarez, W. C., Nerves in collision, Pyramid House, New York, 1972.
4. Alvarez, W. C., “Why, that’s our Jimmy,” Mod. Med., 75-76, 1968.

Stephens and Shaffer, The Journal of Clinical Pharmacology (1973).1592 In an earlier paper700 the authors had reported on the successful treatment with PHT of thirty private psychiatric outpatients. This study had been done on a double-blind crossover basis. About two years later, ten of this group of patients participated in a double-blind study of PHT for four consecutive two-week periods. Consistent with the previous study, 100 mg t.i.d. of PHT proved significantly more effective than placebo in relieving symptoms of anxiety, anger and irritability as assessed both by self-ratings and physicians’ ratings of change.

1592. Stephens, J. H. and Shaffer, J. W., A controlled replication of the effectiveness of diphenylhydantoin in reducing irritability and anxiety in selected neurotic outpatients, J. Clin. Pharmacol., 13: 351-356, 1973.
700. Stephens, J. H. and Shaffer, J. W., A controlled study of the effects of diphenylhydantoin on anxiety, irritability, and anger in neurotic outpatients, Psychopharmacologia, 17: 169-181, 1970.

Brodsky, Zuniga, Casenas, Ernstoff and Sachdev, Psychiatric Journal of the University of Ottawa (1983),2357 describe a group of ten patients with recurrent anxiety. Eight responded to PHT alone. The ninth responded to a combination of PHT and clonazepam, and the tenth to carbamazepine. All patients had normal routine EEGS, but abnormal twenty-four-hour sleep-deprived EEGS. (See also Ref. 2356.)

2357. Brodsky, L., Zuniga, J. S., Casenas, E. R., Ernstoff, R., Sachdev, H. S., Refractory anxiety: a masked epileptiform disorder?, Psychiatr. J. Univ. Ottawa, 8: 42-5, 1983.

2356. Brodsky, L., Shah, A., Casenas, E., Two distinct “paradoxical” reactions to neuroleptics, Psychiatr. J. Univ. Ottawa, 9: 61-4, 1984.

De La Torre, Navarro and Aldrete, Current Therapeutic Research (1985),2437 reported a controlled study of eighty patients with irritable bowel syndrome. Forty patients received PHT (100 mg t.i.d.) and forty received conventional treatment which included either a tranquilizer or an antidepressant. In addition to greater relief of abdominal pain, diarrhea, constipation, nausea, vomiting and pyrosis, patients receiving PHT had a statistically significant greater number of complete remissions of depression, insomnia and anxiety than patients receiving conventional therapy.

2437. de la Torre, R., Navarro, J. L., Aldrete, J. A., Comparison between phenytoin and conventional treatment for irritable bowel syndrome, Curr. Ther. Res., 38(4): 661-9, 1985.

McNamara and Fogel, Journal of Neuropsychiatry (1990), 3102 present five case reports of patients who experienced recurrent panic attacks. These attacks usually began with feelings of unreality and anxiety and escalated into severe panic attacks that could last as long as fifteen minutes. Treatment with phenytoin alone (400-450 mg/day) or in combination with clonazepam (2 mg/day) led to complete cessation of these panic attacks for three of the patients. The other two patients did not receive phenytoin. The three phenytoin-treated patients had previously received other medications without complete relief. One patient had suffered from these attacks for eighteen years.

3102. McNamara, M.E. and Fogel, B.S., Anticonvulsant-responsive panic attacks with temporal lobe EEG abnormalities, J. Neuropsych., 2(2): 193-196, 1990.

Fan, Zhang, Lu and Huang, National Workshop of Clinical Use of Phenytoin, Chengdu, China (1992), 3103 treated with phenytoin (300 - 400 mg/day, 2 - 3 times per day) 48 cases of depressive psychosis. There were 30 cases diagnosed as major depression and 18 cases diagnosed as dysphoria according to the DMS - III - R. The ages of the patients ranged between 22 and 63 years. The mean course of disease was 8.23 years and there was no epileptic history of abnormal phenomena of electroencephalogram. These patients were treated with phenytoin for one month; seventeen patients with sleep problems also took valium. A similar group of 37 patients with depression were treated with amitriptyline (100 - 300 mg/day). For the 48 cases treated with phenytoin, the effective rate was 66.67 %. Phenytoin therapy resulted in marked improvement for 17 cases and improvement for 15 cases and was ineffective for 16 cases. In control group treated with amitriptyline, there were 10 cases of marked improvement, and 11 cases of ineffective. The difference was not statistically significant (X2 = 0.065, p > 0.05), the average score of HDS before treatment was 22.5 and after treatment was 16.3. The authors found phenytoin was especially useful in emotional liability, poor contact, somatic complaints, anxiety, phobia and hypothymia.

3103. Fan, Z., Zhang, Z., Lu, G., and Huang, Z., The effects of phenytoin treated depressive psychosis, Presented at the National Workshop of Clinical Use of Phenytoin, Chengdu, China, 1992.

Yao, Zhang and Wang, Archives of Psychiatry (Shanghai) (1993), 3104 reported that PHT was effective as a treatment for the emotional and behavioral disturbances associated with Alzheimer's disease (AD). Fifteen male AD patients were administered PHT over a twelve-week period, 100 mg/day during the first 2 weeks; 200 mg/day from week 3 to 8; and 300 mg/day from 9-12 weeks. Symptoms of the disease including depression, anxiety and depression, markedly decreased (p < .001 compared to baseline) in 73% of the patients during the first two weeks of the study. Serum levels of 7.60 ± 2.74 µg/ml were correlated with the clinical benefits. Dosages of 300 mg/day were no more effective than 200 mg/day.

3104. Yao, D., Zhang, X., and Wang, B., Administration of phenytoin to treat the mental symptoms of Alzheimer's patients, Arch. Psychiatr. (Shanghai Psychiatry), 5(1): 38-40, 1993.

Liu, Wei, Liu, Ling, Lu and Wang, National Workshop of Clinical Use of Phenytoin, Chengdu, China (1995), 3105 conducted a double-blind, 8-week study of the effect of phenytoin on anxieties and neurotic depression. A total of 42 patients who met the diagnostic criteria of DSM-II-R and CCMD-2R were randomly assigned to 3 treatment groups. In group A (21 phenytoin-treated patients), there were 11 full remissions, 4 marked improvement, 2 improvement and 4 ineffective. In group B (13 benzodiazepine-treated patients), there were 5 full remissions, 2 marked improvement, 1 improvement and 5 ineffective. In group C (8 benzodiazepine plus tricyclic antidepressants-treated patients), there were 3 full remissions, 1 marked improvement, 1 improvement and 3 ineffective. The authors conclude that phenytoin was significantly more effective (p < 0.01).

3105. Liu, D., Wei, M., Liu, Y., Ling, J., Lu, Q., and Wang, J.T., A double-blind study of the effect of phenytoin on anxiety and neurotic depressions, Presented at the National Workshop of Clinical Use of Phenytoin, Chengdu, China, 1995.

Mishory, Yaroslavsky, Bersudsky and Belmaker, American Journal of Psychiatry (2000), 3106 compared the effectiveness of haloperidol plus phenytoin to that of haloperidol plus placebo in a five-week double-blind study in thirty-nine patients with either bipolar I disorder, manic type, or schizoaffective disorder, manic type. Patients who had undesirable side effects from, or inadequate response to, mood stabilizers (lithium, carbamazepine) used in previous episodes were included in the study.

Thirty of the thirty-nine patients completed at least three weeks of the study and 25 completed all five weeks. Mean phenytoin blood levels were 16.0 ± 7.4 µg/ml at week 3 and 21.4 ± 9.9 µg/ml at week 5. According to the authors' analysis, "Significantly more improvement (p values of the order of 0.03 at week 3 and 0.01 at week 5 on the Brief Psychiatric Rating Scale (BPRS) for the bipolar I patients, for example) was observed in the patients receiving phenytoin." The improvements in the BPRS and Clinical Global Impression (CGI) scales were statistically significant for bipolar I patients, but not the patients with schizoaffective disorder, although both groups of patients showed significant improvement on the Young Mania Rating Scale (for the two-way interaction of treatment and time, for example (p value 0.008 for all patients).

The authors note that the magnitude of the phenytoin-related therapeutic effect in both the bipolar manic and schizoaffective manic patients is comparable to that seen with carbamazepine in other studies of similar patients conducted by them. They recommend further study of phenytoin's therapeutic potential as both an add-on and a primary medication in these disorders.

3106. Mishory, A.,Yaroslavsky, Y., Bersudsky, Y., and Belmaker, R.H., Phenytoin as an antimanic anticonvulsant: a controlled study, Am. J. Psychiatry, 157(3): 463-465, 2000.

Brown, Stuard, Liggin, Hukovic, Frol, Dhanani, Khan, Jeffress, Larkin, McEwen, et. al., Biological Psychiatry (2005), 3107 in a placebo-controlled study, treated a group of 39 patients with pulmonary or rheumatologic illnesses who were scheduled to receive a course of corticosteroids, with either phenytoin or placebo in order to examine PHT's ability to prevent mood and memory changes secondary to corticosteroid treatment. Mood was assessed at baseline and after 7 days of treatment using the Young Mania Rating Scale and Activation (ACT) subscale of the Internal State Scale and declarative memory using the Rey Auditory Verbal Learning Test (RAVLT). The 22 phenytoin-treated patients (300 mg/day) showed significantly smaller increases on the ACT than the placebo-treated group, while the 2 groups did not differ significantly in their ability to prevent changes in declarative memory.

3107.Brown, E.S., Stuard, G., Liggin, J.D.M., Hukovic, N., Frol, A., Dhanani, N., Khan, D.A., Jeffress, J., Larkin, G.L., McEwen, B.S., et. al., Effect of phenytoin on mood and declarative memory during prescription corticosteroid therapy, Biol. Psychiatry, 57:543-548, 2005.

See also Ref.

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3109. Huang, M. and Ling, X., A controlled study of the effects of phenytoin on anxiety, West China Med. J. , 7(4): 407-408, 1992.

3110. Greist, J.H., Current use of carbamazepine and other anticonvulsants as lithium alternatives in bipolar disorders, Int. Clin. Psychopharmacol. , 5: 15-26, 1990.

3111. Keck, P.E. and McElroy, S.L., Anticonvulsants in the treatment of rapid-cycling bipolar disorder, Use of Anticonvulsants in Psychiatry: Recent Advances, 115-125, McElroy, S.L. and Pope, H.G., Eds., Oxford Health Care, Inc., Clifton, NJ, 1988.

3112. Post, R.M. and Ubde, T.W., Refractory manias and alternatives to lithium treatment, Depression and Mania, 410-438, Georgotas, A., et al, Eds., Elsevier, NY, 1988.

3113. Delucchi, G.A. and Calabrese, J.R., Anticonvulsants for treatment of manic depression, Cleve. Clin. J. Med. , 56: 756-761, 1989.

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