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Many of the studies of the effects of PHT for epileptics and non-epileptics have reported PHT useful for anger and related symptoms. Expressions used are aggressive behavior, anger, hostile, temper tantrums, impulsivity, rage, assaultive behavior and violent behavior. The following studies have their main focus on violence.
Maletsky, Medical Times (1972),1329 states that it is currently fashionable to ascribe the roots of violence to social ills. The role of brain dysfunction has been relatively neglected until recently. The author reports on a study of twenty-two patients with the syndrome referred to as episodic dyscontrol. In describing this syndrome he states that the subjects usually have a history of hyper-activity and poor school performance as children, aggression toward other children and animals and fire-setting. Truancy and petty stealing frequently lead them to grand larceny, assault and battery and even murder. Other typical symptoms are traffic violations and recklessness. The author states that central to this dyscontrol syndrome is the “storm of violence.” Upon minimal or even no provocation these patients lose control, wrecking property and directing violence against anyone in their way. Twenty-two patients with episodic dyscontrol were treated with PHT. Tabulation of the results of this treatment was based on the author’s observations and on reports of relatives and friends of the patient. The author pointed out that the patients had all been through futile trials with other drugs. Nineteen of the patients achieved a result equal to or better than “good response.” Fifteen of these achieved an excellent response with virtually complete absence of attacks. This response usually occurred within the first two weeks. Data collected at twelve months showed that all cases responding to PHT remained free of violent outbreaks.All of the patients said they had not lost the ability to feel anger, but they were better able to control its escalation.
1329. Maletzky, B. M., Treatable violence, Med. Times, 100: 74-79, 1972.
Maletsky and Klotter, Diseases of the Nervous System (1974),1328 in a controlled study, found PHT significantly effective (p<.0l) in twenty-two patients with episodic dyscontrol syndrome. The authors state that this study, with placebo, confirms the earlier work of Maletsky in which he found PHT highly effective in the treatment of this syndrome. As a result of these studies, the authors conclude that PHT should be tried in patients with episodic dyscontrol.
1328. Maletzky, B. M. and Klotter, J., Episodic dyscontrol: A controlled replication, Dis. Nerv. Syst., 35: 175-179, 1974.
Diamond and Yaryura-Tobias, Paper presented at the Fifth World Congress of Psychiatry (1971),961 found PHT effective in the treatment of violent and aggressive behavior in schizophrenics. Twenty-two patients were studied. With PHT, in doses up to 300 mg a day, violent behavior was well controlled in all cases, eleven with excellent results and seven with moderate results. The authors state that all therapeutic methods used by the patients prior to PHT administration were ineffective.
961. Diamond, B. and Yaryura-Tobias, J. A., The use of diphenylhydantoin in non-epileptic psychotics, V World Congress of Psychiatry, 1971.
Soloman and Kleeman, California Medicine (1971),1569 in reporting seven cases of episodic dyscontrol syndrome, comment separately on the only two in which PHT was given. In both cases the patient’s behavior was markedly improved. In a case detailed, a thirty-nine-year-old woman entered the hospital because of repeated attacks of uncontrolled behavior. Without warning, she would be assailed by intense feelings of either rage or sexual excitement. Tranquilizing medication proved ineffective. PHT caused a remarkable improvement in this patient’s behavior.
1569. Solomon, P. and Kleeman, S. T., Medical aspects of violence, Calif. Med., 114: 19-24, 1971.
Bach-Y-Rita, Lion, Climent and Ervin, American Journal of Psychiatry (1971),787 reported that in the course of two years they had seen 130 patients with assaultive and destructive behavior. PHT was found useful whether or not EEG abnormalities were found.
787. Bach-Y-Rita, G., Lion, J. R., Climent, C. E., and Ervin, F. R., Episodic dyscontrol: A study of 130 violent patients, Amer. J. Psychiat., 127: 49-54, 1971.
Barratt, Shappell and Brandt, Society for Neuroscience Abstracts (1988),3116 as part of their continuing evaluation of phenytoin's effects on impulsivity and cognitive functioning, extended their earlier study of phenytoin's effect on early and late cortical event-related potentials while subjects watched light flashes at three intensities. In the present study, using two PHT dosages (100 mg and 200 mg), 22 subjects performed two additional tasks (oddball and go/no-go). Although at both doses, PHT's effects on event-related potentials were consistent with their earlier work, (see Ref. 11767) the 200 mg dosage of PHT had more generalized cortical effects. The authors conclude that their results are consistent with the hypothesis that phenytoin modulates cognition by acting on frontal cortical areas during information processing.
3116. Barratt, E.S., Shappell, S.A., and Brandt, M.E., Effects of acute phenytoin on cortical event-related potentials, Soc. Neurosci. Abstr., 14(PT 2): 1105, 1988.
Barratt, Kent, Bryant, Felthous and Stanford, Society for Neuroscience Abstracts (1991), 3117. in a double-blind crossover study, administered phenytoin (300 mg/day) or a placebo for 6 weeks each to 20 prisoners with a history of aggressive behavior which the investigators have hypothesized is related to poor impulse control. The authors recorded event-related potentials ERP's) during several tasks including an "off-target" task designed to study impulsiveness. ERP results were compared in the prisoners to those obtained in medical students (N = 20) and adult controls (N = 20). Topographical and related statistical data analyses were performed. In the prisoners, phenytoin significantly changed cortical ERP's toward a more normal profile. PHT significantly reduced the frontal lobe activity and diffuse right hemisphere activity and led to a better-focused posterior late positive component (LPC). Placebo had no such effects. In contrast to medical students and adult controls, the prisoners had well-defined frontal lobe activity and diffuse right hemisphere positivity during the window for the LPC (250-600 ms) in the baseline recordings. The authors conclude that these data are consistent with the hypothesis that impulsiveness is a frontal lobe function (with involvement of the right hemisphere).
Ed. Note: Phenytoin's ability to produce a more normal ERP profile is consistent with the behavioral data obtained by the same investigators. (See Ref. 3117.)
3117. Barratt, E.S., Kent, T., Bryant, S., Felthous, A., and Stanford, M., Phenytoin improves brain functions among impulsive aggressive prisoners, Soc. Neurosci. Abstr.,16(PT 1): 141, 1990.
Barratt, Kent, Bryant and Felthous, Journal of Clinical Psycho-pharmacology (1991), 3118. studied the effects of phenytoin on the aggressive behavior and mood of thirteen inmates in a maximum-security prison. In a randomized, double-blind, crossover study, placebo, PHT 100 mg/day and PHT 300 mg/day were each given for four weeks with an intervening one week washout period. Phenytoin at a 300 mg/day dosage significantly reduced aggressive behavior (p < 0.001 by Wilcoxon's signed ranks test) and improved tension-anxiety and depression-dejection. Interestingly, neither phenytoin at 100 mg/day nor placebo effected significant changes in behavior or mood. Behavioral control was improved, but anger-hostility was not changed by phenytoin.
3118. Barratt, E.S., Kent, T.A., Bryant, S.G., and Felthous, A.R., A controlled trial of phenytoin in impulsive aggression, J. Clin. Psychopharmacology, 11(6): 388-389, 1991.
Barratt, Kent and Stanford, 3rd International Brain Research Organization World Congress of Neuroscience, Montreal, Canada (1991), 3119reported their evaluation of the basis for phenytoin's reduction of impulsive aggressive behaviors. The authors made a detailed analysis of event-related potentials (ERP's) recorded during their "oddball" test paradigm in prisoners (20), medical students (20) and matched controls (20). The prisoner's baseline ERP's were significantly different from those of the controls at parietal sites and in the relationship of parietal to frontal lobe activity at 250-600 ms. The prisoners had significantly less independence of cortical functioning between these sites. For these prisoners, phenytoin (300 mg/day) had a significant positive effect on parietal lobe functioning increasing the independence of the parietal lobe-frontal lobe activity.
3119. Barratt, E.S., Kent, T., and Stanford, M., The effects of phenytoin on event-related potentials among impulsive aggressive prisoners, Presented at the 3rd International Brain Research Organization World Congress of Neuroscience, Montreal, Canada, 342, ABS P53.10, 1991.
Barratt and Kent, XVIIIth Collegium International Neuropsychopharmacolicum Congress, Nice, France (1992), 3120conducted a study to test the hypothesis that PHT would significantly effect parietal-frontal lobe interactions during information processing. In a double-blind, placebo controlled crossover design, PHT (300 mg/day) was administered to 33 prisoners for six weeks. PHT had two major effects: (1) increased the independence of parietal-frontal lobe interactions; (2) produced a gradient of increased cortical negativity starting in the frontal lobes and diminishing posteriorly. The results indicate that PHT has a generalized effect on frontal lobe electrical activity that is not reflected in significant changes at specific electrode sites. PHT does effect the relationship of frontal lobe activity with other cortical sites as reflected in topographical maps.
3120. Barratt, E.S. and Kent, T., The effects of phenytoin (PHT) on frontal and parietal event-related potentials(ERPs) among impulsive aggressive prisoners, Presented at the XVIIIth Collegium International Neuropsychopharmacolicum Congress, Nice, France, 1992.
Zhou, National Workshop of Clinical Use of Phenytoin, Chengdu, China (1995), 3121 conducted a double-blind, controlled study of 26 psychiatric patients with assaultive and destructive behavior. Group A (5 patients) was given placebo, group B (15 patients) was given PHT1 (phenytoin manufactured in the US), and group C (6 patients) was given PHT2 (phenytoin made in China). The dosage was 300 - 600 mg/day. Before and after treatment, the authors used the Modified Overt Aggression Scale (MOAS) to measure the severity of aggressive behavior and the Brief Psychiatric Rating Scale (BPRS) to rate mental status. The response rate in group B (80%) was better than in group C (33.3%) and group A (0%) (p < 0.01). MOAS average scores were lower after treatment than before in group B (p < 0.01). BPRS scores for group B patients indicated a decrease in hospitality (p < 0.01). The scores for patients in groups A and C were unchanged. There were no reports of serious side effects.
3121. Zhou, J., The use of diphenylhydantoin in psychotic patients with aggressive behavior, Presented at the National Workshop of Clinical Use of Phenytoin, Chengdu, China, 1995.
Barratt, Stanford, Felthous and Kent, Journal Clinical Psychopharmacology (1997), 3122 report a randomized double-blind, placebo-controlled study designed to test the hypothesis that phenytoin will decrease impulsive-aggressive acts, but not premeditated aggressive acts. Sixty inmates were divided into two groups on the basis of committing primarily impulsive aggressive acts or premeditated aggressive acts while in prison. Medical aggression was ruled out by subject selection. As hypothesized, phenytoin (200 mg each morning and 100 mg in the afternoon/evening) significantly reduced the frequency (71%) and intensity (60%) of impulsive aggressive acts, but not those of premeditated aggressive acts.
Event-related potentials (ERPs) measured information processing in the cortex during drug and placebo conditions. The amplitudes of P300 ERP waveforms among impulsive-aggressive subjects were increased significantly during the phenytoin condition, but not during the placebo condition or in non-impulsive aggressive subjects. The authors conclude "It is probable that the use of medications, such as phenytoin, that are free of dependence risk and are relatively inexpensive can make a dramatic impact on violence in prisons."
3122. Barratt, E.S., Stanford, M.S., Felthous, A.R., and Kent, T.A., The effects of phenytoin on impulsive and premeditated aggression: a controlled study, J. Clin. Psychopharmacology, 17(5): 341-349, 1997.
Houston, Mathias, Johnston, Villemarette-Pittman and Stanford, Psychophysiology, (2000), 3123conducted a study on the behavioral and physiological effects of PHT in impulsive aggression. In a double-blind crossover procedure, twenty-six male participants were randomly administered 300 mg of PHT or placebo each day for six weeks. At the end of the six weeks, participants underwent a two-week placebo washout period. After the washout period, participants underwent treatment in reverse order for another six weeks. Statistical analysis indicated that impulsive-aggressive outbursts among patients recorded during PHT administration were significantly reduced as compared to the patients under baseline (p <.01) and placebo (p <.05) administration. In addition, the statistically significant decreases in self-reported anxiety, depression, anger and hostility during PHT administration provided positive support for the drug's use in these populations. Finally, the study showed the favorable effects of PHT on sensory processing in impulsive aggression.
3123. Houston, R.J., Mathias, C.W., Johnston, M.S., Villemarette-Pittman, N., and Stanford, M.S., The effect of phenytoin on mid-latency evoked potentials in impulsive aggression, Psychophysiology, abs 37(S49), 2000.
Stanford, Helfritz, Conklin, Villemarette-Pittman, Greve, Adams and Houston, Experimental and Clinical Psychopharmacology, (2005), 3124compared the behavioral effects of 3 anticonvulsants in impulsive aggression men in a double-blind, placebo-controlled, parallel groups designed study. Participants were randomly assigned to 1 of 4 6-week treatments: phenytoin (n=7), carbamazepine (n=7), valproate (n=7), or placebo (n=8). All 3 treatment groups showed a significant reduction in impulsive aggression compared to placebo, however, the treatment effect during carbamezepine administration was slightly delayed compared to phenytoin and valproate.
3124. Stanford M.S., Helfritz, L.E., Conklin, S.M., Villemarette-Pittman, N.R., Greve, K.W., Adams, D., and Houston, R.J., A comparison of anticonvulsants in the treatment of impulsive aggression, Exp. Clin. Psychopharmacology, 13(1):72-77, 2005.
See also Ref.
3125. Barratt, E.S., Felthous, A., Kent, T., Liebman, M.J., and Coates, D.D., Criterion measures of aggression - impulsive versus premeditated aggression, The Science, Treatment, and Prevention of Antisocial Behavior: Application to the Criminal Justice System, 41-4-18, Fishbein, D.H., Ed., Civic Research Institute, Kingston, NY, 2000.
3126. Barratt, E.S. and Slaughter, L., Defining, measuring, predicting impulsive aggression: a heuristic model, Behav. Sci. Law,16(3):285-302, 1998.
3127. Barratt, E.S., Stanford, M.S., Dowdy, L., Liebman, M.J., and Kent, T.A., Impulsive and premeditated aggression: A factor analysis of self-reported acts, Psychiatry Res., 86(2): 163-173, 1999.
3128. Barratt, E.S., Impulsiveness and aggression, Violence and Mental Disorder: Developments in Risk Assessment, 61-79, Monahan, J. and Steadman, H.J., Eds., University of Chicago, Chicago, IL, 1994.
3129. Johnson, G.F., Psychopharmacology of aggression, Limbic Epilepsy and the Dyscontrol Syndrome, Proceedings of the First International Symposium on Limbic Epilepsy and the Dyscontrol Syndrome, Sydney, Australia, 207-18, Girgis, M. and Kiloh, L.G., Eds., Elsevier/North-Holland Biomedical Press, Amsterdam, 1980
3130. Maletzky, B.M., Treatable violence, Med. Times, 100(10): 74-9, 1972.
3131. Barratt, E.S., The use of anticonvulsants in aggression and violence, Psychopharmacol. Bull., 29(1): 75-81, 1993.