Sleep Disorders

Many of the preceding studies emphasize the benefits of PHT in sleep (see Refs. 4, 51, 297, 314, 364, 538, 704, 707, 713, 716, 761, 1841, 2037), but few studies have been done on sleep disturbances alone. However, reports are consistent that people fall asleep more easily, sleep longer, and are less troubled with unpleasant dreams and nightmares. A less common sleep disturbance, too much sleep (avoidance sleep), is also reported helped by PHT.

4. Alvarez, W. C., “Why, that’s our Jimmy,” Mod. Med., 75-76, 1968.
51. Chao, D., Sexton, J. A., and Davis, S. D., Convulsive equivalent syndrome of childhood, J. Pediat, 64: 499-508, 1964.
297. Resnick, O., The psychoactive properties of diphenylhydantoin: experiences with prisoners and juvenile delinquents, Int. J. Neuropsychiat. 3: S30-S48, 1967.
314. Rossi, A. O., Psychoneurologically impaired child: community mental health clinic approach, New York J. Med., 67: 902-912, 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.
538. Ayd, F. J., Jr., New uses for an old drug, Intern. Drug Ther. Newsletter, 2: 1-2, Jan., 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.
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.
713. Goldberg, J. and Kurland, A. A., Dilantin treatment of hospitalized cultural-familial retardates, J. Nerv. Ment. Dis., 150: 133-137, 1970.
716. Silverman, D., The electroencephalograph and therapy of criminal psychopaths, Criminal Psychopathology, 5: 439-457, 1944.
761. Alvarez, W. C., Nerves in collision, Pyramid House, New York, 1972.
1841. Fukuyama, Y., Ochiai, Y., Hayakawa, T. and Miyagawa, F., Overnight sleep EEG and cerebrospinal fluid monoamines in seizures induced by movement, Neuropadiatrie, 10(2): 138-49, 1979.
2037. Rau, J. H. and Green, R. S., Compulsive eating: a neuropsychologic approach to certain eating disorders, Compr. Psychiat., 16: 223-31, 1975.

Bjerk and Hornisher, Electroencephalography and Clinical Neurophysiology (1958),835 refer to generalities in the literature that anticonvulsants are not effective for narcolepsy. The authors present a case, which they consider typical narcolepsy, that showed excellent response to treatment with PHT. The patient, a thirty-seven-year-old female, had overpowering attacks of sleep and other typical symptoms of narcolepsy. On 100 mg of PHT t.i.d. the patient’s symptoms left her on the seventh day. The improvement was marked by a complete loss of symptoms, appetite improved and the patient said that she had not felt so well in a long time. When the patient stopped taking the medication, the symptoms recurred.

835. Bjerk, E. M. and Hornisher, J. J., Narcolepsy: a case report and a rebuttal, Electroenceph. Clin. Neurophysiol., 10: 550-552, 1958.

Zung, Psychophysiology (1968),397 studied the effect of PHT on sleep. Ten adults, between the ages of twenty and forty-six, were studied with all-night EEG and electrooculogram recordings. With PHT the time spent in REM sleep was significantly decreased compared to control. Non-REM (deeper) sleep was increased.

397. Zung, W. W. K., Effect of diphenylhydantoin on the sleep-dream cycle: an EEG study in normal adults, Psychophysiology, 5: 206, 1968.

Boller, Wright, Cavalieri and Mitsumoto, Neurology (1975),1753 reported the complete relief with PHT in a sixty-five-year-old man from paroxysmal nightmares, a sequel to a stroke. These nightmare-like episodes gradually increased in frequency (twenty per day) to a point where the patient had to be hospitalized. During an episode the patient would suddenly bolt upright, pace around with a terrified expression on his face, and shout in a dysarthric voice. At times he related fright visions. PHT was given, with a loading dose of 300 mg intravenously, followed by 900 mg orally over the next twenty-four hours. Thereafter the patient received daily doses of 300 mg/day. The episodes ceased and the patient remained symptom-free when followed up six months later.

1753. Boller, F., Wright, D. G., Cavalieri, R. and Mitsumoto, H., Paroxysmal “nightmares,” Neurology, 25: 1026-28, 1975.

Pedley and Guilleminault, Annals of Neurology (1977),2014 described six patients, between the ages of seventeen and thirty-two years, who had been experiencing unusual sleepwalking episodes characterized by screaming or unintelligible vocalizations, complex and often violent automatisms, and ambulation. All patients were treated with either phenytoin or carbamazepine, with cessation of the abnormal behavior during follow-up periods ranging from nine to forty-eight months.

2014. Pedley, T. A. and Guilleminault, C., Episodic nocturnal wanderings responsive to anticonvulsant drug therapy, Ann. Neurol., 2(l): 30-5, 1977.

Fukuyama, Ochiai, Hayakawa and Miyagawa, Neuropadiatrie (1979),1841 describe the successful use of PHT in treating an eight-year-old male with choreoathetoid activity. In addition to eliminating the abnormal movements, behavior improvements were noted, and the patient’s sleep patterns were improved. Sleep patterns were evaluated before and after PHT. Increase in sleep time, decrease in number of stages, and disappearance of interrupting awakening were noted.

1841. Fukuyama, Y., Ochiai, Y., Hayakawa, T. and Miyagawa, F., Overnight sleep EEG and cerebrospinal fluid monoamines in seizures induced by movement, Neuropadiatrie, 10(2): 138-49, 1979.

Wolf, Roder-Wanner and Brede, Epilepsia (1984),3080 studied polygraphic (EEG, EOG or electrooculogram, ECG and respiration) sleep patterns in forty untreated epileptic patients. They compared phenobarbital and PHT in a randomized crossover design. With both phenobarbital and PHT sleep onset came sooner, but with PHT light sleep was decreased and deep sleep increased. The authors state, “The decrease of light sleep to the benefit of deep sleep, together with the rapid sleep onset, make PHT look like an excellent sleeping medication.” In addition, they comment that few patients report sleep “hangovers” with PHT.

See also Refs. 2626, 2858, 2967, 2986.

3080. Wolf, P., Roder-Wanner, U. U., Brede, M., Influence of therapeutic phenobarbital and phenytoin medication on the polygraphic sleep of patients with epilepsy, Epilepsia, 25(4); 467-75, 1984.
2626. Johnson, L. C., Effects of anticonvulsant medication on sleep patterns, Sleep and Epilepsy, Sterman, M. B., Shouse, M. N., Passouant, P., Eds., Academic Press, New York, 381-94, 1982.
2858. Perez-Ruvalcabaga, J. A., Quintero-Perez, N. P., Campa-Uribe, G., Chapa-Alvarez, R., Rodriquez-Noriega, E., The multiple uses of phenytoin in a general hospital setting, Eur. J. Clin. Invest., 14: 37, 1984.
2967. Snyder, C. H., Epileptic equivalents in children, Pediatrics, 21: 308-18, 1958.
2986. Striano, S., Meo, R., Bilo, L., Vitolo, S., Sleep apnea syndrome in Thomsen’s disease. A case report, Electroencephalogr. Clin. Neurophysiol., 56: 323-5, 1983.

Roder-Wanner, Noachtar and Wolf , Acta Neurologica Scandinavica (1987), 3154 report on a prospective longitudinal study of alterations in polygraphic sleep associated with PHT monotherapy for epilepsy. Forty un-medicated, newly admitted patients with various types of epilepsy, in need of anti-epileptic drug treatment, entered the study. In a crossover design, PHT and phenobarbital were administered to each patient in random sequence, and sleep was registered polygraphically while sleep recordings were evaluated. PHT administration levels started at 50 mg and phenobarbital at 100mg, which were eventually raised with the intent of reaching levels of 10-20 µg/ml of PHT and 15-30 µg/ml of phenobarbital. Final results of the study found a significant reduction of sleep latency associated with PHT administration, especially in the first few weeks of treatment.

3154. Roder-Wanner, U.U.,Noachtar, S., and Wolf, P., Response of polygraphic sleep to phenytoin treatment for epilepsy. A longitudinal study of immediate, short- and long-term effects, Acta. Neurol. Scand., 76: 157-67, 1987.

Wolf, Advances in Epileptology (1987), 3155 conducted a series of prospective polygraphic studies of the sleep of un-medicated patients and their response to some major antiepileptic drugs. One study compared PHT and phenobarbital in the short-term effects of 31 patients who fell asleep more rapidly than others. Researchers found a decrease in the percentage of sleep stages 1 and 2 but an increase in the percentage of deep non-rapid-eye-movement (NREM) sleep while REM sleep did not change. Duration of deep sleep increased significantly in the third, fourth, and fifth REM cycles. The third REM cycle was the most affected one, with significant changes of every single NREM sleep stage. Therefore, the usual sleep structure seemed to be leveled by PHT. In terms of long-term effects, PHT monotherapy was assessed in 12 patients when maintained for 6 months or longer. Results indicated a reversal of most short-term effects (all NREM stages and the structural parameters, especially concerning the third REM cycle.) Compared with baseline nights, the only persistent change was a reduction of sleep latency.

Researchers concluded that among other anti-epileptic drugs tested, PHT has specific effects on sleep in respect to sleep stages, time of maximal influence to the distribution of sleep stages through the night sleep and to the complex matters of sleep structure and sleep quality.

3155. Wolf, P., Influence of antiepileptic drugs on sleep, in: Advances in Epileptology, Vol 16, Wolf, P., et al, eds.,Raven Press, New York, 733-7, 1987.

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