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Effects of diphenylhydantoin on anxiety and hostility in institutionalized prisoners
Abstract
1.(1) In a double-blind, drug-placebo study, a group of 42 emotionally disturbed, male criminals incarcerated at a treatment center with an average age of 25 ± 6 and an average educational level of 8 ± 2, were randomly assigned for a 6-month period to 300 mg of diphenylhydantoin daily by mouth or to a placebo in the form of 24 mg of diphenylhydantoin daily.2.(2) Five-minute tape-recorded speech samples, elicited by standardized instructions to “talk about any interesting or dramatic life experiences,” were obtained before drug administration and for a 6-month period postdrug. The typescripts of these speech samples were blindly scored, by content analysis technicians unfamiliar with the purpose or nature of this study, for anxiety, total hostility outward, overt hostility outward, covert hostility outward, hostility inward, and ambivalent hostility according to the method of Gottschalk (Gottschalk and Gleser, 1969; Gottschalk et al., 1969).3.(3) There were no significant differences between the drug and placebo groups in the magnitude of these anxiety or hostility scores over the 6-month period, as assessed by comparison of the slopes for all the affect scores overtime.4.(4) These findings confirm the observations of several other investigators that diphenylhydantoin has a weak effect, if any, as an antianxiety or antihostility agent, even when administered over a 6-month period of time of a group of aggressive, antisocial, criminal offenders.5.(5) The relationship and relevance of scores of psychological states derived from the content analysis of speech to manifest behavior is dicussed.
... For nine of the papers (Bichescu, Neuner, Schauer, & Elbert, 2007;Bradley & Follingstad, 2003;Gottschalk, Covi, Uliana, & Bates, 1973;Hilkey, Wilhelm, & Horne, 1982;Maunder et al., 2009;Nguyen, 2005;Valentine & Smith, 2001;Wilson, 1990;Zlotnick, Johnson, & Najavits, 2009), the means, standard deviations, and number of individuals in the intervention and control groups necessary to calculate a Hedges g effect size were published, and therefore figures could be derived. Where an effect size was published, a re-calculation was made to ensure accuracy of figures, and if an alternative method of calculating effect sizes was given, a Hedges g calculation was undertaken providing all the summary statistics were available to do so. ...
... In total, 14 studies were included in the final review. Eleven of these were psychological interventions (Bichescu et al., 2007;Bradley & Follingstad, 2003;Gussak, 2007;Hilkey et al., 1982;Holt et al., 2009;Maunder et al., 2009;Nguyen, 2005;Richards et al., 2000;Valentine & Smith, 2001;Wilson, 1990;Zlotnick et al., 2009), two were pharmacological interventions (Brick et al., 1966;Gottschalk et al., 1973), and one was an exercise intervention (Cashin, Potter, Stevens, et al., 2008). Most of the studies were from the last decade, though one dated back as far as 1966. ...
... Phenytoin is an anticonvulsant medication that was used in the past to treat symptoms of anxiety and depression, though it is not licensed now for this indication. Phenytoin was found to reduce anxiety in a study of its use in emotionally disturbed male prisoners (Gottschalk et al., 1973). Anxiety levels were assessed using the Gottschalk-Gleser content analysis method (Gottschalk & Gleser, 1969). ...
There is a high prevalence of anxiety and depression in offender populations but with no recent systematic review of interventions to identify what is effective. This systematic review was undertaken to identify randomised controlled trials of pharmacological and non-pharmacological interventions in adult offenders in prison or community settings. A search of five databases identified 14 studies meeting inclusion criteria, which considered the impact of psychological interventions, pharmacological agents, or exercise on levels of depression and anxiety. A narrative synthesis was undertaken and Hedges g effect sizes calculated to allow comparison between studies. Effect sizes for depression interventions ranged from 0.17 to 1.41, for anxiety 0.61 to 0.71 and for posttraumatic stress disorder 0 to 1.41. Cognitive behavioural therapy interventions for the reduction of depression and anxiety in adult offenders appear effective in the short term, though a large-scale trial of sufficient duration is needed to confirm this finding.
... Content analysis scores obtained from previous studies (Gottschalk, 1976;Gottschalk et al., 1975;Gottschalk, Covi, Uliana, & Bates, 1973;Gottschalk, Hoigaard, Birch, & Rickels, 1976) were reexamined. ...
... The fifth group consisted of emotionally disturbed male criminal offenders (N = 44) imprisoned in Maryland's Patuxent Institution (Gottschalk, Covi, Uliana, & Bates, 1973) with an average age of 25.6 years (SD = 6.15) and average educational level of 8.25 years (SD = 1.90). These patients were classified as having psychiatric disorders on the basis of DSM-II criteria. ...
Used L. A. Gottschalk and G. C. Gleser's (1969) method of content analysis to examine 5-min samples of speech elicited from 6 different groups of Ss: 30 young normal men (mean age 25.7 yrs), 30 normative adults (aged 20–50 yrs), 30 normative schoolchildren (aged 6–26 yrs), 20 adults with psychoneuroses, 44 emotionally disturbed criminal offenders (mean age 25.6 yrs), and 22 acute schizophrenics (aged 21–55 yrs). Ss were given purposely ambiguous standardized instructions simulating the request to free-associate. Findings indicate that displacements and denials in mentally healthy individuals are more likely to function as coping mechanisms in contrast to their function as defenses or symptoms in mentally disordered people. No significant effects of sex, age, intelligence, or state of consciousness were found. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
... Angina pectoris [44] 1974 RCT, crossover, placebo 16 Schizophrenia [45] 1974 RCT, placebo 66 Anxiety, hostility [46] 1973 RCT, placebo 42 IBS [47] 1973 RCT, crossover 14 Psychoneurotism [48] 1972 RCT, comparator 80 Anxiety, anger, irritability [49] 1970 RCT, crossover 15 but has been found to be effective in many chronic pain states, such as neuropathic pain, menstrual pain and central neuropathic pain in multiple sclerosis, in chronic dermatitis and glaucoma. It has also found to be effective in a great variety of models: Alzheimer, Parkinson, depression, anxiety, renal inflammation, inflammatory bowel disorders and pelvic syndrome. ...
Phenytoin is an anti-epileptic drug that has been evaluated in a clinical setting for 80 years, and results show it has therapeutic potential beyond reduction of seizures. Research has identified neurological, psychiatric and non-CNS indications, such as wound healing, which are supported by pilot studies for phenytoin. Wound healing and aggression are the indications most frequently explored, and preliminary studies with phenytoin demonstrated reduced aggressive outbursts and aggression. We argue that aggression has great potential as an area for phenytoin repurposing, since the unmet need in aggression therapy is very high. Furthermore, especially 'dirty drugs' such as phenytoin, which have promiscuous targets and important physiological relevance seem to hold great promise for repositioning.
... 90 In men with a history of violating institutional discipline rules, treatment with phenytoin compared with active placebo did not affect anxiety. 92 Other interventions during imprisonment. Of 4 studies of other interventions during imprisonment (X. ...
We systematically reviewed randomized controlled trials of interventions to improve the health of people during imprisonment or in the year after release. We searched 14 biomedical and social science databases in 2014, and identified 95 studies.
Most studies involved only men or a majority of men (70/83 studies in which gender was specified); only 16 studies focused on adolescents. Most studies were conducted in the United States (n = 57). The risk of bias for outcomes in almost all studies was unclear or high (n = 91). In 59 studies, interventions led to improved mental health, substance use, infectious diseases, or health service utilization outcomes; in 42 of these studies, outcomes were measured in the community after release.
Improving the health of people who experience imprisonment requires knowledge generation and knowledge translation, including implementation of effective interventions.
... Phenytoin blocked the anxiety induced by the benzodiazepine antagonist Ro 5-4864 in healthy human subjects (File and Lister, 1983). Other studies have suggested efficacy in the treatment of PTSD (Bremner et al., 2004) anxiety (Jonas, 1969; Stephens and Shaffer, 1970) hostility (Resnich, 1967; Turner, 1967; Gottschalk et al., 1973) and depression (Overall et al., 1973). There are several limitations of the current study. ...
Phenytoin (Dilantin) is an anticonvulsant used in the treatment of epilepsy. It is believed to act by modulation of glutamatergic transmission. Because the neurobiology of post-traumatic stress disorder (PTSD) has been hypothesized to involve alterations in glutamatergic transmission with subsequention neurotoxicity, we assessed the effects of phenytoin on cognition and brain structure in PTSD patients. Phenytoin was administered in an open label fashion for 3 months to nine adult patients with PTSD related to a variety of traumas, including early abuse, combat and car accidents. Subjects underwent magnetic resonance imaging for measurement of whole brain and hippocampal volume, and neuropsychological testing of memory and cognition, before and after treatment. Phenytoin treatment resulted in a significant 6% increase in right brain volume (p < 0.05). Increased hippocampal volume was correlated with reductions in symptom severity as measured by the Clinician Administered PTSD Scale and improvements in executive function as measured by the Trails test. However, treatment associated improvements in memory and cognition did not achieve statistical significance. These findings suggest that phenytoin treatment may be associated with changes in brain structure in patients with PTSD.
Background:
Antisocial personality disorder (AsPD) is associated with rule-breaking, criminality, substance use, unemployment, relationship difficulties, and premature death. Certain types of medication (drugs) may help people with AsPD. This review updates a previous Cochrane review, published in 2010.
Objectives:
To assess the benefits and adverse effects of pharmacological interventions for adults with AsPD.
Search methods:
We searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers up to 5 September 2019. We also checked reference lists and contacted study authors to identify studies.
Selection criteria:
Randomised controlled trials in which adults (age 18 years and over) with a diagnosis of AsPD or dissocial personality disorder were allocated to a pharmacological intervention or placebo control condition.
Data collection and analysis:
Four authors independently selected studies and extracted data. We assessed risk of bias and created 'Summary of findings tables' and assessed the certainty of the evidence using the GRADE framework. The primary outcomes were: aggression; reconviction; global state/global functioning; social functioning; and adverse events.
Main results:
We included 11 studies (three new to this update), involving 416 participants with AsPD. Most studies (10/11) were conducted in North America. Seven studies were conducted exclusively in an outpatient setting, one in an inpatient setting, and one in prison; two studies used multiple settings. The average age of participants ranged from 28.6 years to 45.1 years (overall mean age 39.6 years). Participants were predominantly (90%) male. Study duration ranged from 6 to 24 weeks, with no follow-up period. Data were available from only four studies involving 274 participants with AsPD. All the available data came from unreplicated, single reports, and did not allow independent statistical analysis to be conducted. Many review findings were limited to descriptive summaries based on analyses carried out and reported by the trial investigators. No study set out to recruit participants on the basis of having AsPD; many participants presented primarily with substance abuse problems. The studies reported on four primary outcomes and six secondary outcomes. Primary outcomes were aggression (six studies) global/state functioning (three studies), social functioning (one study), and adverse events (seven studies). Secondary outcomes were leaving the study early (eight studies), substance misuse (five studies), employment status (one study), impulsivity (one study), anger (three studies), and mental state (three studies). No study reported data on the primary outcome of reconviction or the secondary outcomes of quality of life, engagement with services, satisfaction with treatment, housing/accommodation status, economic outcomes or prison/service outcomes. Eleven different drugs were compared with placebo, but data for AsPD participants were only available for five comparisons. Three classes of drug were represented: antiepileptic; antidepressant; and dopamine agonist (anti-Parkinsonian) drugs. We considered selection bias to be unclear in 8/11 studies, attrition bias to be high in 7/11 studies, and performance bias to be low in 7/11 studies. Using GRADE, we rated the certainty of evidence for each outcome in this review as very low, meaning that we have very little confidence in the effect estimates reported. Phenytoin (antiepileptic) versus placebo One study (60 participants) reported very low-certainty evidence that phenytoin (300 mg/day), compared to placebo, may reduce the mean frequency of aggressive acts per week (phenytoin mean = 0.33, no standard deviation (SD) reported; placebo mean = 0.51, no SD reported) in male prisoners with aggression (skewed data) at endpoint (six weeks). The same study (60 participants) reported no evidence of difference between phenytoin and placebo in the number of participants reporting the adverse event of nausea during week one (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.06 to 16.76; very low-certainty evidence). The study authors also reported that no important side effects were detectable via blood cell counts or liver enzyme tests (very low-certainty evidence). The study did not measure reconviction, global/state functioning or social functioning. Desipramine (antidepressant) versus placebo One study (29 participants) reported no evidence of a difference between desipramine (250 to 300 mg/day) and placebo on mean social functioning scores (desipramine = 0.19; placebo = 0.21), assessed with the family-social domain of the Addiction Severity Index (scores range from zero to one, with higher values indicating worse social functioning), at endpoint (12 weeks) (very low-certainty evidence). Neither of the studies included in this comparison measured the other primary outcomes: aggression; reconviction; global/state functioning; or adverse events. Nortriptyline (antidepressant) versus placebo One study (20 participants) reported no evidence of a difference between nortriptyline (25 to 75 mg/day) and placebo on mean global state/functioning scores (nortriptyline = 0.3; placebo = 0.7), assessed with the Symptom Check List-90 (SCL-90) Global Severity Index (GSI; mean of subscale scores, ranging from zero to four, with higher scores indicating greater severity of symptoms), at endpoint (six months) in men with alcohol dependency (very low-certainty evidence). The study measured side effects but did not report data on adverse events for the AsPD subgroup. The study did not measure aggression, reconviction or social functioning. Bromocriptine (dopamine agonist) versus placebo One study (18 participants) reported no evidence of difference between bromocriptine (15 mg/day) and placebo on mean global state/functioning scores (bromocriptine = 0.4; placebo = 0.7), measured with the GSI of the SCL-90 at endpoint (six months) (very low-certainty evidence). The study did not provide data on adverse effects, but reported that 12 patients randomised to the bromocriptine group experienced severe side effects, five of whom dropped out of the study in the first two days due to nausea and severe flu-like symptoms (very low-certainty evidence). The study did not measure aggression, reconviction and social functioning. Amantadine (dopamine agonist) versus placebo The study in this comparison did not measure any of the primary outcomes.
Authors' conclusions:
The evidence summarised in this review is insufficient to draw any conclusion about the use of pharmacological interventions in the treatment of antisocial personality disorder. The evidence comes from single, unreplicated studies of mostly older medications. The studies also have methodological issues that severely limit the confidence we can draw from their results. Future studies should recruit participants on the basis of having AsPD, and use relevant outcome measures, including reconviction.
Since the time of Pavlov, scientists have attempted to replicate emotional illness in man with animal models. In the area of aggression, most researchers are familiar with experimental paradigms of isolation, footshock, and septal-lesion induced aggression in rats and muricidal rats. Animal models utilizing fighting fish or certain brain preparations of other animals have been described as means of studying aggression. All these analogs of aggression have provided valuable data in the field of pharmacology and neurophysiology. Parallels have been drawn between septal-induced aggression in animals and humans with certain forms of brain dysfunction. Here, the neurophysiology may be similar, but it is now well known that there are distinct and remarkable behavioral differences between such species as cats, dogs, rats, and men with regard to the psychological effects obtained from lesions and stimulations of the same cortical areas. Analogies have been drawn between footshock or isolation-induced aggression in rats and hyperirritable states in humans ranging from hyperkinetic syndromes to the hypervigilant states accompanying paranoid or paranoid psychotic states.
In The Measurement of Psychological States Through the Content Analysis of Verbal Behavior [1], authors Gottschalk and Gleser thoroughly discussed the theoretical bases for qualifying and quantifying psychological states through content analysis of speech. They outlined their theoretical approaches to content analysis in general, the method of eliciting verbal behavior, and the effect of the method of elicitation used on the data obtained, assessing intensity, scale development, and validation. While providing a detailed description of their theories concerning the measurement of anxiety, hostility, and social alienation/personal disorganization, they also supplied guidelines on how to develop procedures for measuring other psychological states from verbal samples.
This chapter discusses the association between drugs and human aggression, laboratory studies of human aggression, and effects of drugs on human aggression under laboratory conditions. It argues that methodological difficulties often prevent unequivocal interpretations of the outcomes of pharmacological treatments of aggression. Conducting well-designed placebo-controlled studies in an inpatient setting is difficult, as drugfree washout periods may be unsafe for both patients and staff. Thus, it is clinically difficult to assess whether a reduction in aggression is a specific effect of the pharmacological agent or of nonspecific effects of medications such as neuroleptics and benzodiazepines commonly used for the management of specific Axis I and Axis II disorders. Nonpharmacological factors, such as the therapeutic milieu, can affect treatment outcome and should be considered when evaluating the efficacy of a pharmacotherapeutic intervention for aggression.
Reviews the literature on the pharmacologic treatment of aggressive behavior (AB) that is frequently encountered in patients with underlying disorders such as brain injury, schizophrenia, manic depressive disorder, and personality disorders. It is argued that many studies evaluating pharmacologic treatments of AB have methodological problems. The use and extent of effectiveness of various types of drugs (e.g., anticonvulsants, lithium carbonate, antipsychotics, sedatives and hypnotics, beta blockers) are discussed. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Whether defense mechanisms may serve as markers of increased vulnerability or resistance to illness is an issue that merits being more clearly and definitively addressed and investigated. Anna Freud (1936/1946) focused on defense mechanisms as tools used to relieve anxiety and their presence might, hence, be seen as clues to some underlying psychopathological process. The ways in which defense mechanisms function to influence the course of illness have been rarely studied. On the other hand, hope is a state or trait that has been examined over many years in empirical studies to determine whether it is capable of influencing the onset or course of illness. French (1952) and Frank (1968) regarded hope as a personal incentive toward encouraging a person to cope better with inner psychological conflicts. Perley, Winget, and Placci (1971) found that elevated hopefulness predicted patients who followed up recommendations that they seek psychiatric treatment. Gottschalk, Kunkel, Wohl, Saenger, and Winget (1960) found that hope scores derived from verbal samples predicted the duration of survival of patients with terminal cancer receiving irradiation treatment. Gottschalk, Mayerson, and Gottlieb (1967) and Gottschalk, Fox, and Bates (1973), moreover, found that high measures of hopefulness pointed to relatively favorable outcome in psychotherapy. Udelman and Udelman (1986) reported a significant correlation between hope scores and indicarors of immune competence, namely mitogenic stimulation by concanavalin A and percentage of B cells.
Antisocial personality disorder (AsPD) is associated with a wide range of disturbance including persistent rule-breaking, criminality, substance misuse, unemployment, homelessness and relationship difficulties.
To evaluate the potential beneficial and adverse effects of pharmacological interventions for people with AsPD.
We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library 2009, Issue 3), MEDLINE (1950 to September 2009), EMBASE (1980 to 2009, week 37), CINAHL (1982 to September 2009), PsycINFO (1872 to September 2009) , ASSIA (1987 to September 2009) , BIOSIS (1985 to September 2009), COPAC (September 2009), National Criminal Justice Reference Service Abstracts (1970 to July 2008), Sociological Abstracts (1963 to September 2009), ISI-Proceedings (1981 to September 2009), Science Citation Index (1981 to September 2009), Social Science Citation Index (1981 to September 2009), SIGLE (1980 to April 2006), Dissertation Abstracts (September 2009), ZETOC (September 2009) and the metaRegister of Controlled Trials (September 2009).
Controlled trials in which participants with AsPD were randomly allocated to a pharmacological intervention and a placebo control condition. Two trials comparing one drug against another without a placebo control are reported separately.
Three review authors independently selected studies. Two review authors independently extracted data. We calculated mean differences, with odds ratios for dichotomous data.
Eight studies met the inclusion criteria involving 394 participants with AsPD. Data were available from four studies involving 274 participants with AsPD. No study set out to recruit participants solely on the basis of having AsPD, and in only one study was the sample entirely of AsPD participants. Eight different drugs were examined in eight studies. Study quality was relatively poor. Inadequate reporting meant the data available were generally insufficient to allow any independent statistical analysis. The findings are limited to descriptive summaries based on analyses carried out and reported by the trial investigators. All the available data were derived from unreplicated single reports. Only three drugs (nortriptyline, bromocriptine, phenytoin) were effective compared to placebo in terms of improvement in at least one outcome. Nortriptyline was reported in one study as superior for men with alcohol dependency on mean number of drinking days and on alcohol dependence, but not for severity of alcohol misuse or on the patient's or clinician's rating of drinking. In the same study, both nortriptyline and bromocriptine were reported as superior to placebo on anxiety on one scale but not on another. In one study, phenytoin was reported as superior to placebo on the frequency and intensity of aggressive acts in male prisoners with impulsive (but not premeditated) aggression. In the remaining two studies, both amantadine and desipramine were not superior to placebo for adults with opioid and cocaine dependence, and desipramine was not superior to placebo for men with cocaine dependence.
The body of evidence summarised in this review is insufficient to allow any conclusion to be drawn about the use of pharmacological interventions in the treatment of antisocial personality disorder.
Background:
Aggression is a major public health issue and is integral to several mental health disorders. Antiepileptic drugs may reduce aggression by acting on the central nervous system to reduce neuronal hyper-excitability associated with aggression.
Objectives:
To evaluate the efficacy of antiepileptic drugs in reducing aggression and associated impulsivity.
Search strategy:
We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, metaRegister of Controlled Trials (mRCT) and ClinicalTrials.gov to April 2009. We also searched Cochrane Schizophrenia Group's register of trials on aggression, National Research Record and handsearched for studies.
Selection criteria:
Prospective, placebo-controlled trials of antiepileptic drugs taken regularly by individuals with recurrent aggression to reduce the frequency or intensity of aggressive outbursts.
Data collection and analysis:
Three authors independently selected studies and two authors independently extracted data. We calculated standardised mean differences (SMDs), with odds ratios (ORs) for dichotomous data.
Main results:
Fourteen studies with data from 672 participants met the inclusion criteria. Five different antiepileptic drugs were examined. Sodium valproate/divalproex was superior to placebo for outpatient men with recurrent impulsive aggression, for impulsively aggressive adults with cluster B personality disorders, and for youths with conduct disorder, but not for children and adolescents with pervasive developmental disorder. Carbamazepine was superior to placebo in reducing acts of self-directed aggression in women with borderline personality disorder, but not in children with conduct disorder. Oxcarbazepine was superior to placebo for verbal aggression and aggression against objects in adult outpatients. Phenytoin was superior to placebo on the frequency of aggressive acts in male prisoners and in outpatient men including those with personality disorder, but not on the frequency of 'behavioral incidents' in delinquent boys.
Authors' conclusions:
The authors consider that the body of evidence summarised in this review is insufficient to allow any firm conclusion to be drawn about the use of antiepileptic medication in the treatment of aggression and associated impulsivity. Four antiepileptics (valproate/divalproex, carbamazepine, oxcarbazepine and phenytoin) were effective, compared to placebo, in reducing aggression in at least one study, although for three drugs (valproate, carbamazepine and phenytoin) at least one other study showed no statistically significant difference between treatment and control conditions. Side effects were more commonly noted for the intervention group although adverse effects were not well reported. Absence of information does not necessarily mean that the treatment is safe, nor that the potential gains from the medication necessarily balance the risk of an adverse event occurring. Further research is needed.
Violence is a symptom of an underlying mental state such as a psychosis, a characterological problem, or brain dysfunction. Thus drugs used to treat aggression in man exert effects by their specific pharmacological actions (e.g., antipsychotic, anticonvulsant). Most literature to date has dealt with animals and human models of aggression and lacks conceptual clarity. Aggression differs from depression, a coherent clinical entity, in its etiological diversity and its paroxysmal or impulsive basis, and this may account for the relationship seen in literature linking violence to epilepsy; yet literature on anticonvulsants is equivocal with regard to beneficial effects on aggression. Lithium has been shown to have positive effects, although its mode of action is unclear. A variety of antipsychotic agents and minor tranquilizers have been mentioned. Central nervous system stimulants have been found useful to treat hyperkinetic syndromes in both children and adults where aggression is a symptom. Hormonal agents are discussed. Drug treatment of aggression should not obscure the need for verbal therapies, and social and environmental factors should always be regarded.
A substantial body of research with both animals and humans demonstrates that pharmacologic modulation of three neurotransmitter systems (the GABAergic, the noradrenergic, and the serotonergic) and electrical stimulation of regions of the brain produce marked alterations in aggressive and violent behavior. The author reviews this research and uses case reports to illustrate how it has been applied in the development of a rational pharmacotherapy for violent patients. Four basic principles of clinical application that can enhance trials of pharmacologic treatment of the violent patient are identified. Evidence suggests that behavioral and social learning approaches to the treatment of violence can be more effective when administered after the patient has been stabilized through pharmacologic interventions.
Reliable and valid measurement of affects, emotions, and moods has posed a problem for psychiatric and psychophysiological research as the demand has grown for more sensitive, precise, and objective assessment methods than the methods of clinical impressionistic evaluation. There are 3 major methods in current use for assessing these psychological variables: self report scales, behavioral rating scales, and the content analysis of verbal behavior. Self report inventories give an individual an opportunity to describe his subjective state, and their major advantage is that what the person is actually experiencing may not be correctly perceived by external observers. Disadvantages of the self report method include the possibility that the subject may malinger or fake or may not be in good communication with his own feelings so that he gives a distorted report about them. Psychiatric rating scales have the advantage of putting a trained observer to the task of assessment, and the clinician rater has the option of using a broad range of behavioral and affective cues, verbal and nonverbal, in following this method. But since such raters are not free from systematic distortion and thorough familiarity with the subject of observation is infrequent, all relevant information to make a valid assessment is often not available. Moreover, different interviews may evoke varying emotional responses from the same person. Objective content analysis of verbal behavior can avoid most of the shortcomings of the self report and observer rating methods, so long as reasonably standardized procedures are used for eliciting verbal behavior and other key features of scientific methodology are followed. A disadvantage of the content analysis method is that it is time consuming and requires training and quality checks to carry out accurate content analysis coding. On the other hand, reliable and valid measurement procedures in all fields of research take time and care. A brief review is provided of the variety of findings and applications of the content analysis method of measuring feeling states, and these applications include the research areas of psychotherapy, psychophysiology, and neuropsychopharmacology.
Studies of the effects of phenytoin on aggression have produced equivocal results primarily because of a lack of (1) common objective criterion measures of aggressive acts across studies; (2) rigorous inclusion and exclusion criteria for selecting subjects; and (3) a nosologic basis for classifying different types of aggression. The current study was designed to remedy these deficiencies. Aggression was defined using a nosology that defines three types of aggression: (1) medically related; (2) premeditated; and (3) impulsive. The purpose of this study was to test the hypothesis that phenytoin will decrease impulsive aggressive acts but not have a significant influence on 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. The study used a double-blind, placebo-controlled, crossover design. As hypothesized, phenytoin (200 mg a.m. and 100 mg p.m.) significantly reduced impulsive aggressive acts but not premeditated aggressive acts. Event-related potentials (ERPs) measured information processing in the cortex during drug/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. There were no significant changes in P300 ERP waveforms between drug/placebo conditions among nonimpulsive aggressive subjects.
This article aims to answer the question whether developing technology is now capable of measuring objectively and accurately the effects of psychoactive pharmacological agents by means of computerized assessments of psychological states and traits through the analysis of content and form of people's speech. At the present time, psychopharmacological researchers involved in clinical trials rely on DSM-IV criteria and standardized self-report measures and observer rating scales to assess psychoactive drug effects. Attention is drawn to the potentially unrecognized measurement errors and relatively low interrater reliability by these methods--for example, all raters are not free of observer bias and every subject administered a drug is not equally and accurately well-informed about the self. The computerized content analysis methods tend to avoid these biases and measurement errors. A review is provided describing the Gottschalk-Gleser method of measuring psychobiological dimensions from the form and content of short (usually five-minute) speech samples of verbal behavior, generally elicited by standardized and purposely ambiguous instructions to talk about any interesting or dramatic personal life experiences. Norms have been obtained by this method of speech elicitation, adjusted for age, sex and educational level. Sections are provided covering cross-cultural and language validation research on the Gottschalk-Gleser content analysis method, the influence of medical or psychiatric illness as well as psychoactive drugs on verbal content analysis-derived scores, and the research carried out for more than 20 years computerizing this content analysis procedure through the development of artificial intelligence software enabling these measurements to be done from typescripts of speech samples on computer diskettes. A brief review deals with the general applications of this method of measurement to basic and clinical psychiatry, psychosomatic medicine, neuropsychology, the diagnostic process in a psychiatry outpatient clinic, children's mental health problems, dream research, and assessment of mental processes during PET scanning of the brain. This is followed by a review of the applications of this method of content analysis of speech to neuropsychopharmacological testing of antianxiety, antidepressive, antipsychotic, and other psychoactive drugs, as well as to pharmacokinetic variables and clinical response. This method is now in the process of being used in clinical trials in psychopharmacology and is recommended for more extensive use in this research area.
Phenytoin is an anticonvulsant used in the treatment of epilepsy. Its mechanism of action is incompletely understood but most likely involves modulation of glutamatergic transmission. The neurobiology of posttraumatic stress disorder (PTSD) has been hypothesized to involve, at least in part, alterations in glutamatergic transmission in the hippocampus and possibly other brain regions. The purpose of this study was to assess the effects of phenytoin on symptoms of PTSD.
Phenytoin was administered in an open-label fashion for 3 months to 9 adult male and female patients with DSM-IV PTSD related to a variety of traumas including childhood abuse, combat, and car accidents. Dosage was adjusted to maintain the therapeutic blood levels used in the treatment of epilepsy. Subjects were assessed before, during, and after treatment for PTSD with standardized dimensional measures of disease severity including the Clinician Administered PTSD Scale (CAPS), the Hamilton Rating Scale for Depression (HAM-D), and the Hamilton Rating Scale for Anxiety (HAM-A). Data were collected from November 2001 through June 2003.
Phenytoin treatment resulted in a significant decrease in PTSD symptoms as measured with the CAPS (mean score = 65 pretreatment vs. 38 posttreatment) with reductions in each of the symptom clusters of intrusions, avoidance, and hyperarousal (p < .05). There were no significant decreases in symptoms of depression severity as measured with the HAM-D or anxiety severity as measured with the HAM-A.
These findings suggest that phenytoin may be efficacious in the treatment of PTSD, possibly mediated through its antiglutamatergic effects. Randomized, controlled, double-blind clinical trials are indicated to further evaluate this medication in the treatment of PTSD.
To assess the potential role of newer antiepileptic drugs (AEDs) in the management of agitation/aggression in patients with dementia or developmental disability.
A MEDLINE/PUBMED search (1986-May 2007) was conducted to identify pertinent English language studies of six newer AEDs, as well as carbamazepine and valproate, in the management of agitation/aggression.
All studies evaluating any aspect of management of agitation/aggression, emphasizing those associated with dementia or developmental disability.
Pharmacotherapy of agitation/aggression in these two patient groups remains an underexplored area. Carbamazepine and valproate have a reasonable, readily available evidence base, and preliminary recommendations regarding their use in these two patient groups. The most published data with newer AEDs involve gabapentin, followed by topiramate. Even so, the literature regarding newer AEDs is modest in volume.
Based on current data, gabapentin, oxcarbazepine, and topiramate are qualitatively similar in efficacy to carbamazepine/valproate in the management of agitation/aggression. However, studies-to-date in this field have had, in the main, numerous design flaws. In considering use of newer AEDs, the clinician needs to be aware of potential adverse events that are unique to these agents or infrequently seen with older AEDs (e.g., hyponatremia with oxcarbazepine, and acute myopia and angleclosure glaucoma, urinary tract stones, and cognition difficulties with topiramate). In addition, there is an extensive literature documenting that newer AEDs can precipitate new-onset or worsen existing behavioral disorders, including agitation/aggression.
Examined the relationship between kinetic behavior, defined by a scoring system of object- and body-focused hand movements, and direction of verbal aggression. Motor behavior and concomitant verbal samples were scored from videotaped interview segments of 24 female college students. Intercorrelational analysis revealed that object-focused movements were related to overt hostility (r = .49) and that this relationship varied with subcategories of such movements: for speech primacy, r = .49; for representational, r = .36; and for nonrepresentational motor primacy movements, r = .09. Body-focused movements were related to covert hostility (r = .53) and specifically to hand-to-hand motions (r = .52). Analysis of peak-trough periods within interviews revealed significant covariations between movements and forms of hostility. Qualitative clause-by-clause analysis elucidated the nature of the movement-hostility contiguity. Results are interpreted in terms of the differential role of object- and body-focused movements in the encoding of affect. (25 ref.) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Not only is dilantin an anticonvulsant but it is capable of producing distinct changes of mood. Unlike bromides and phenobarbital, in most instances dilantin has a striking effect on psychic equivalents.¹ Blair, Bailey and McGregor² gave special attention to this action and reported that most of their epileptic patients became "more cheerful and congenial, less quarrelsome and complaining, and more easily managed." There is evidence that this effect of dilantin is independent of a decrease in the number of convulsions, whereas improvement in intelligence and performance tests seems to parallel the reduction in the number of convulsions. Ross and Jackson,³ who differentiated carefully between the effect of treatment on psychometric rating and that on conduct, mentioned a patient whose seizures were controlled by dilantin and who also exhibited remarkable improvement in behavior; when dilantin was withdrawn, he had no recurrence of convulsions, but he returned fully to
The purpose of this study was to test the efficacy of a method of assessing the subjective and behavioral effects of psychoactive drugs in the human subject. The method involves the psycholinguistic analysis of short samples of the subject’s speech.Method and Procedure
A brief summary of our method of eliciting and analyzing verbal productions will be given here; details of our method are available elsewhere.4-6Subjects are asked by the observer to talk about any interesting or dramatic personal life experience for a five-minute period, during which time the observer indicates he will not reply to any questions until the time period is over. The verbalizations are recorded on a tape recorder, and the material is transcribed by a secretary. The typed copy is the only material that is analyzed. The verbal analysis includes an analysis at the level of word types, according to a grammatical
In previous publications, we have described scales developed to assess the relative magnitude of various labile psychologic states from small samples of speech. The speech samples, usually obtained in units of five minutes, have been elicited by standardized instructions designed to encourage subjects to associate freely. In these other reports, we have discussed reliability and validity studies on an anxiety scale18 and a schizophrenic scale of social alienation and personal disorganization.21,25,26Using the same raw data, namely speech, and the same general techniques of analyzing and scoring verbal content, we have devised scales for measuring three kinds of hostility, classified principally on the basis of direction: hostility directed outwards, ambivalently directed hostility, and hostility directed inwards. This paper will give, in detail, our working concepts of these hostility measures, and it will summarize reliability and validity studies of our method of measuring these
Forty-three delinquent boys were randomly assigned to double-blind treatment with diphenylhydantoin sodium, methylphenidate, or placebo for two weeks. Ratings of symptoms by cottage parents and teachers, a measure of frustration, the Porteus Mazes, and an interview were used to assess the effects of the treatments. None of the measures showed effects attributable to the drugs, and subjective reports tended to show negative effects of the active drugs. The danger of random assignment studies was demonstrated, however, by the fact that the more disturbed children were assigned by chance to the placebo group. The lack of severe symptomatology, the short period of treatment, and the heterogeneous nature of the sample were considered as possible explanations of the apparent lack of beneficial effects of the two drugs.
THE PRESENT STUDY investigated the effects of diphenylhydantoin (Dilantin) as an agent for mitigating disruptive behavior in a sample of male juvenile delinquents. Neither a sedative nor a central nervous system depressant, diphenylhydantoin acts as an anticonvulsant by reducing the seizure process and limiting the development of maximal seizure activity. The drug serves to stabilize the threshold of nerve cells against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing the membrane sodium gradient. Neuropharmacologically, this threshold-stabilizing action occurs through a decrease in the intracellular concentration of sodium in brain cells, in cardiac muscle, and perhaps universally in excitable membranes.1 Hypothetically, such active extrusion of sodium results from metabolic stimulation of the "sodium pump."
A partial review of the literature on the use of diphenylhydantoin with nonepileptic populations strongly suggests that the drug may have some efficacy in curbing
Six adult male former drug users were given single 100-mg doses of meperidine by the intramuscular route and an additional six were administered 100-mg doses by the oral route in a single-blind situation. Anxiety and hostility were measured by speech-content analysis before and after drug administration and correlated with plasma concentrations of meperidine. Significant decreases in anxiety and outward overt hostility scores occurred 1 to 1.5 hr postdrug when plasma meperidine concentrations were high, with return of these affect scores toward predrug values at 6 hr when plasma concentrations of meperidine were falling. Meperidine was found to resemble sedative-hypnotics in its effects on anxiety and hostility. Significant correlations were noted between plasma meperidine concentration and decrease in anxiety and hostility inward scores. The findings are consistent with the hypothesis that narcotic abuse is enhanced through the psychological effects of these drugs.
In a six-week double-blind cross-over study, DPH, 100 mg, t.i.d., was found to be markedly more effective than DPH, 5 mg, t.i.d., used as a placebo, in reducing symptoms relating to anger, irritability, impatience, and anxiety. The psychoactive properties of DPH were demonstrated by both self-ratings and physician ratings of change. Improvement when changing from 5 mg to 100 mg was matched by worsening when changing from 100 mg to 5 mg. Patients in the controlled study were selected on the basis of the presence of symptoms of anger, irritability, and anxiety, a social class more typical of private patients than clinic patients, and a Barron Ego Strength score of 40 or above. No undesirable side effects were encountered.
This study is a double-blind comparison of the clinical effects of diphenylhydantoin (DPH) and phenobarbital among 80 adult psychoneurotic, non-epileptic outpatients. Patients were assigned at random to eight weeks of treatment with DPH 300 mg or phenobarbital 90 mg daily. During this time, patients were followed in brief bi-weekly interviews by one of two treating psychiatrists.
At each visit, the patient's clinical condition was evaluated by the patient's ratings of distress on a factored list of 65 common psychoneurotic symptoms, on a mood adjective checklist, on the Psychiatric Evaluation Profile and on a global scale of change, and by the doctor's ratings on several global scales of change. Each criterion was analyzed with respect to initial score, medication, doctor and the medication by doctor interaction. The one doctor's patients responded better than the other doctor's patients.
The results suggested that DPH and phenobarbital in the doses employed had similar effects on psychoneurotic symptoms. More extensive analyses of one patient rating and one doctor rating were performed to look for characteristics of the patient or the treatment situation that might affect medication responses. No useful predictors of differential response to the two medications appeared. Patients with brief illnesses, no prior psychiatric care and no previous phenothiazines or antidepressants responded better than their counterparts to both medications.
Some patients who terminated prematurely reported very marked improvement—even more than most patients who completed the prescribed course of treatment. This observation challenges the usual assumption that drop-outs represent treatment failures. The equivocal results with regard to medication effects point up the potential value of studies designed to produce dose-response information.
1.(1) This was a double-blind, drug-placebo, cross-over study examining the effects on several psychological states of a single oral dose of chlordiazepoxide (25 mg) on 18 chronically anxious subjects.2.(2) Plasma levels of chlordiazepoxide ranged from 0.26 to 1.63 μg/ml. These plasma levels were not correlated with the time interval between ingestion of the drug and time of drawing the blood sample for chlordiazepoxide determination (average time interval 92 minutes, range 60 to 145 minutes), nor with body weight or sex.3.(3) Anxiety, hostility outward, and ambivalent hostility scores tended to decrease (p < 0.10) over the 50-minute observation period of this study when subjects were on chlordiazepoxide as compared to a placebo. But a statistically significant decrease in anxiety scores (p < 0.025) during this time period occurred only in those 11 subjects whose chlordiazepoxide plasma levels exceeded 0.70 μg/ml. The decrease in hostility outward, hostility inward, and ambivalent hostility scores, when these subjects were on chlordiazepoxide, did not reach a convincing level of significance.4.(4) Chlordiazepoxide plasma levels of all 18 subjects correlated with scores on anxiety (− 0.26), ambivalent hostility (− 0.42) and achievement strivings (− 0.31). Chlordiazepoxide blood levels of the 11 subjects whose levels exceeded 0.70 μg/ml also correlated with hostility outward scores (0.82) and hostility inward scores (− 0.47).5.(5) Implications of these findings are discussed as well as directions for future research.
To examine the diagnostic and therapeutic significance of the EEG pattern called 14 and 6 per second positive spiking, when it occurs in patients with behavior disorders, the authors studied 78 adolescent and young adult inpatients. Although they did find some support for their hypothesis that positive spiking might be regarded as a neurophysiological handicap which varies as a function of the patient's environment, they conclude that further investigation is warranted.
In the following article, symptom-rating scales are critically examined from the standpoint of factors that relate to the reliability of distinctions generated by the scales, the objectivity of these distinctions, and their validity. Although the commentary is specific, it is intended to be general in its relevance and should be of interest not only to those who construct and use symptom-rating scales but also to those who read the literature in which the results of rating scales are offered as a primary datum.
A study is described illustrating the use, in neuropsychopharmacologic studies, of an objective measure of psychological states, such as anxiety, through the content analysis of 5 minute samples of speech. In this report, the psychoactive drug tested was a new benzodiazepine, lorazepam. It was found to exert significant antianxiety effects (p < 0.05) as measured by the content analysis method when administered parenterally at a dosage of 5.0 mg. compared to anxiety changes occurring after no drug or 3.0 mg. of lorazepam. Interesting physiological changes in relation to drug dose and anxiety inhibition were followed and are also reported.
Assigned adult criminal offenders to 3 drug groups in order to assess the effect on achievement strivings as measured by the Gottschalk-Gleser Achievement Strivings Scale. 16 Ss received 15 mg. of an amphetamine, 7 received 50 mg. chlorpromazine, and 14 received a placebo. Achievement striving scores were taken prior to the administration of drugs and again at 2- and 4-hr postdrug periods. Results indicate a significant increase in achievement strivings on the 1st postdrug testing for the amphetamine group when compared to the placebo group. This difference disappeared by the 2nd postdrug testing. There was no significant difference between chlorpromazine and placebo groups on either of the postdrug administrations. (15 ref.) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
THIS REPORT presents the findings with respect to differential changes in affect accompanying the administration of chlordiazepoxide (Librium) as compared to a placebo in a sample of juvenile delinquent boys. The data were obtained in conjunction with a study of elctrodermal activity recorded under basal and mild stress conditions. On the basis of reports in the literature7,11-13 and our own studies with other psychoactive drugs4,16 it was hypothesized that anxiety-fear would be reduced following administration of the active drug and that there might also be an accompanying reduction in "hostility outward" as measured by the verbal behavior sampling procedure.
Method
The subjects in this study were 46 male white adolescents, 14 to 16 years of age, who were incarcerated in a juvenile detention center for asocial or delinquent behavior. The boys were newly admitted inmates, none of whom displayed severe
Seventy-four hospitalized chronic schizophrenic patients, who were able to cooperate with testing and interview procedures, were studied for eight weeks to sequentially evaluate the effect of withdrawal and readministration of phenothiazine medication. The patients, Caucasians of both sexes, in the age range 24–54, had been on some one phenothiazine derivative for at least the previous six months. For the first four weeks all patients were on placebo, while during the next four weeks half were on placebo and half were on thioridazine.
STUDIED THE VALUE OF DIPHENYLHYDANTOIN (DPH) IN NONEPILEPTIC DISORDERS OF THOUGHT AND MOOD. SS WERE 72 PATIENTS WITH VARYING DEGREES OF EMOTIONAL AND BEHAVIORAL DISORDERS SEEN DURING 18 MO. OF A PSYCHIATRIC PRACTICE. 86% SHOWED SOME DEGREE OF IMPROVEMENT THOUGHT TO BE DRUG RELATED. IMPROVEMENT WAS RECORDED WITH ANGER, IRRITABILITY, TENSION, SLEEP DISTURBANCES, MILD OR ACUTE SITUATIONAL DEPRESSION, RUMINATIONS, PHOBIAS, SHAME AND WITHDRAWAL BUT NOT RELATED TO DIAGNOSTIC CATEGORY, CONCEPTUAL CAPACITY, INSTITUTE FOR PERSONALITY AND ABILITY TESTING, 16 PF, OR ANXIETY SCALES, AGE, SEX, OR EEG FINDING. THE IMPROVEMENT WAS USUALLY SUBTLE AND INSIDIOUS, EGO-SYNTONIC WITH NO SENSE OF INTOXICATION, SEDATION, OR STIMULATION. IT IS HYPOTHESIZED THAT DPH RESTORES TO NORMAL ANY CELL WITH DEFECTIVE SODIUM PUMP AND THAT SUCH CELLS MAY OCCUR IN THE CNS OF PERSONS SUFFERING FORM "FUNCTIONAL" NERVOUS DISORDERS. (43 REF.) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
In an experimental study of the pathologic psychophysiology of essential hyper- tension, measurements of anxiety and hostility levels of 12 hypertensive women were observed over two 3-week periods; during these time periods the women re- ceived either hydrochlorothiazide (25-50 mg.) or a placebo. Significant positive correlations occurred between hostility inward levels and average systolic and diastolic blood pressures. Significant negative correlations occurred between hostility outward levels and blood pressure. These and other significant psychophysiologic correlations disappeared completely when the sub- jects were taking hydrochlorothiazide. Furthermore, no significant changes in anxiety or hostility levels occurred while the women were taking hydrochloro- thiazide, even though there were significant decreases in blood pressure during this time. A HIS is A REPORT of a method of explor- were two principal aims in this study, ing certain aspects of psychophysiologic One was to determine what psychophys- relations in essential hypertension. There iologic relations could be found between blood pressure variables and the magni- From the Departments of Psychiatry and tude of various affects, such as anxiety
I. Introduction
The responsiveness of the cardiovascular system to stress and emotional arousal has been a well-known phenomenon since the classic researches of Cannon. Subsequent studies tended to view stress as a nonspecific threat and did not relate physiological responses to a particular affect evoked or investigate the personalized meanings of the stimulus to the subject. Later researches have indicated that physiological responses could be understood better in terms of the relevance of the stress to the individual.25 Yet, even here little attention has been paid to the specific quality and quantity of the concomitant affective state.The present study attempts to clarify relationships between specific affective and physiological responses to psychological stress, utilizing quantitative estimates of each. Our major focus is on anger, especially suppressed anger, and on the relation of these feeling states to blood pressure and heart rate. A technique
A controlled study of the effect of diphenylhydantoin (DPH) on dangerous antisocial recidivists. I. Effects on aggressive behavior
- Covi
The use of content analysis of short samples of speech for preliminary investigation of psychoactive drugs: effect of lorazepam on anxiety scores
- Gottschalk
Effectiveness of diphenylhydantoin in management of non-epileptic psychomotor excitement-states
- Freyhan
Relationship of thioridazine plasma concentrations, after single oral dose of 4 mg/kg, to clinical response in acute schizophrenic patients
- Gottschalk