Independent assessment of manic and depressive symptoms by self-rating. Scale characteristics and implications for the study of mania.

We report the reliability and validity of the Internal State Scale, a self-report instrument for the simultaneous assessment of severity of manic and depressive symptoms. The Internal State Scale consists of four empirically derived subscales: Activation, Well-Being, Perceived Conflict, and the Depression Index. All subscales had good internal consistency reliability. Activation subscale scores were significantly higher in manic patients than in depressed patients or control subjects, while Well-Being subscale scores were significantly lower and the Depression Index subscale scores were significantly higher in depressed patients than in the other two groups. Activation subscale scores were correlated specifically with clinician ratings of mania. Depression Index subscale scores were correlated specifically with clinician ratings of depression. Further evidence for the validity of the subscales of the Internal State Scale in reflecting manic or depressive symptoms came from discriminant function analysis in which these subscales assigned 88% of subjects to the correct diagnostic groups. In affectively ill patients who were studied in two or more mood states, Activation, Depression Index, and Well-Being subscale scores changed significantly in the predicted directions, while the same discriminant algorithm assigned 79% of mood states to the correct diagnostic category. Bimodal distribution of scores of manic patients on the Well-Being and Depression Index subscales substantiated earlier findings that euphoric mood is not an essential feature of mania. Based on findings from this and previous studies, the hypothesis is proposed that variables related to activation level, and not to mood state, constitute the core characteristics of the manic syndrome.

Antisocial personality disorder and psychopathy in cocaine-dependent women.

OBJECTIVE: The goal of this study was to examine the lifetime prevalence of antisocial personality disorder according to five diagnostic systems and the prevalence of psychopathy in a study group of women. The relationship between antisocial personality disorder and psychopathy was also examined. Finally, differences in treatment admission variables based on the presence or absence of antisocial personality disorder and/or psychopathy were evaluated. METHOD: Antisocial personality disorder was diagnosed in 137 treatment-seeking, cocaine-dependent women according to the Feighner criteria, Research Diagnostic Criteria (RDC), and DSM-III, DSM-III-R, and DSM-IV criteria. Psychopathy was assessed by the Revised Psychopathy Checklist. RESULTS: Rates of antisocial personality disorder varied from 76% according to the Feighner criteria to 11% for the RDC. Nineteen percent (N = 26) of the women scored in the moderate to high range on the Revised Psychopathy Checklist. All of these women were diagnosed with antisocial personality disorder according to DSM-III and Feighner criteria, but only 15 of the 26 were diagnosed according to DSM-III-R, 12 according to DSM-IV, and six with the RDC. Moderate levels of psychopathy were associated with a history of illegal activity at treatment admission, whereas antisocial personality disorder was not. CONCLUSIONS: There was relatively little diagnostic agreement between classification systems. This study indicates that antisocial personality disorder and psychopathy are not synonymous terms for the same disorder. Findings support a need to redefine antisocial personality disorder diagnostic criteria to make them gender neutral by including behaviors associated specifically with antisociality in women.

Assessment of object relations and reality testing in methadone patients.

OBJECTIVE: The authors studied methadone maintenance patients to determine the degree of their impairment in object relations and reality testing and the relationship of such impairment to comorbid axis I and axis II disorders. It was expected that deficits in object relations and, to a lesser degree, reality testing would be exhibited by the group as a whole and that they would be related to the presence of comorbid disorders. METHOD: The self-report Bell Object Relations Reality Testing Inventory was administered to 240 methadone maintenance patients. The subjects were first divided into groups on the basis of number of comorbid axis I disorders and then on the basis of number of comorbid axis II disorders. Finally, the subjects were placed into one of four groups on the basis of the combined presence or absence of axis I and axis II disorders. RESULTS: The methadone patients exhibited some specific impairments in object relations, but not in reality testing. Bell inventory scores did not significantly differ according to the number of comorbid axis I disorders, but they did significantly differ according to number of axis II disorders diagnosed. The scores were poorest for those with axis II disorders only, while subjects with only axis I disorders had scores similar to those with neither axis I nor II disorders. CONCLUSIONS: Comorbid axis II disorders, more than axis I disorders, may be associated with problems in object relations and reality testing in methadone patients.

Gender differences in diagnosing antisocial personality disorder in methadone patients.

OBJECTIVE: The goal of this study was to evaluate gender differences in the prevalence rates, short-term reliability, and internal consistency of the diagnosis of antisocial personality disorder for DSM-III-R, DSM-III, and Research Diagnostic Criteria (RDC). METHOD: A total of 37 men and 57 women methadone patients were diagnosed according to DSM-III-R, DSM-III, and RDC antisocial personality disorder criteria. RESULTS: The diagnostic rates, reliability, and internal consistency were lower for women than for men in all systems. DSM-III criteria resulted in the highest reliability for women, but for men, the DSM-III criteria were the least reliable. Examination of endorsement rates of individual antisocial personality disorder criteria revealed several significant gender differences on the majority of childhood criteria and on several adult criteria. Item-total correlations revealed that for women, the violent and aggressive childhood criteria in DSM-III-R that had not been included in DSM-III or RDC had a negative or no correlation to the assessment of antisocial personality disorder for women. CONCLUSIONS: The change in DSM-III-R from DSM-III childhood criteria appears to have resulted in a decrease in internal consistency and rates of antisocial personality disorder for women, but not for men. The results of this investigation indicate that the psychometric properties of the current antisocial personality disorder scales are weak for women, compared with men. To assess antisocial personality disorder in women it may be necessary to revise current, or develop new, diagnostic criteria.

Discovery of 1-[3-(aminomethyl)phenyl]-N-3-fluoro-2'-(methylsulfonyl)-[1,1'-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423), a highly potent, selective, and orally bioavailable inhibitor of blood coagulation factor Xa.

Factor Xa (fXa) plays a critical role in the coagulation cascade, serving as the point of convergence of the intrinsic and extrinsic pathways. Together with nonenzymatic cofactor Va and Ca2+ on the phospholipid surface of platelets or endothelial cells, factor Xa forms the prothrombinase complex, which is responsible for the proteolysis of prothrombin to catalytically active thrombin. Thrombin, in turn, catalyzes the cleavage of fibrinogen to fibrin, thus initiating a process that ultimately leads to clot formation. Recently, we reported on a series of isoxazoline and isoxazole monobasic noncovalent inhibitors of factor Xa which show good potency in animal models of thrombosis. In this paper, we wish to report on the optimization of the heterocyclic core, which ultimately led to the discovery of a novel pyrazole SN429 (2b; fXa K(i) = 13 pM). We also report on our efforts to improve the oral bioavailability and pharmacokinetic profile of this series while maintaining subnanomolar potency and in vitro selectivity. This was achieved by replacing the highly basic benzamidine P1 with a less basic benzylamine moiety. Further optimization of the pyrazole core substitution and the biphenyl P4 culminated in the discovery of DPC423 (17h), a highly potent, selective, and orally active factor Xa inhibitor which was chosen for clinical development.

Severity of dependence: data from the DSM-IV field trials.

The concept of a dependence syndrome with graded levels of severity was originally derived from work with alcoholics. The applicability and clinical utility of the dependence syndrome across a wider range of substances was examined as part of the DSM-IV field trials. When using a criterion count method to assess severity, it was found that persons cluster at different severity levels according to the drug on which they are dependent. Across all drug classes, severity correlated reasonably well with measures of quantity and frequency of use and with associated problems. The relationship between severity ratings and outcome was not tested, however data from other studies indicate that severity is only one of many factors that can influence outcome.

Development of the cocaine relapse interview: an initial report.

Although fine-grained analyses of circumstances surrounding relapses have been conducted with alcoholics, smokers and opiate users, there is comparatively little information about the relapse process in cocaine abusers. The Cocaine Relapse Interview (CRI) is a structured interview that gathers information on the onset, course and termination of cocaine relapse episodes. This article describes the development of the CRI and presents initial data on its reliability and validity. Sections of the CRI assess experiences on the day of the relapse, experiences during the week prior to the relapse, attributions for the relapse, experiences following initial use of cocaine and factors in terminating the relapse. Most of the subscales in each section of the CRI had adequate internal consistency and test-retest reliabilities. Validity studies indicated that most of the subscales that assess experiences prior to relapse differentiated relapsers from two control groups of non-relapsers, and that several subscales and individual items from the sections that assess experiences following initial use and factors in termination differentiated "lapsers" from "relapsers". Limitations of the CRI and recommendations for its use were also discussed.

The early course of change in methadone maintenance.

AIMS: This study examined the functional and substance use status of methadone maintenance (MM) patients at treatment entry and 2 and 7 months later. DESIGN: Two groups of subjects were identified for longitudinal follow-up, those in continuous MM treatment and those who left treatment. SETTING: The study was conducted at the Philadelphia Veterans Affairs Medical Center MM Program. PARTICIPANTS: Subjects were 157 men admitted to treatment. MEASUREMENTS: Change was evaluated using the Addiction Severity Index and urinalysis results. FINDINGS: Both groups of subjects reported significant reductions in drug use and increases in psychosocial functioning from admission to month 2, but demonstrated no significant changes from months 2 to 7. Subjects who left treatment, however, had more heroin use and criminal activity at all evaluation points than subjects who remained in treatment. Urinalysis data also suggested that subjects who left treatment were using drugs more frequently while in treatment than were those subjects who remained continuously enrolled in MM. Finally, subjects who left treatment spent more time in restricted environments (e.g. inpatient treatment, jail) at follow-up. CONCLUSIONS: Services may need to be enhanced to foster continuing progress in patients who remain in MM treatment and to retain those patients with more severe problems who leave treatment early.

The validity of the interviewer severity ratings in groups of ASI interviewers with varying training.

AIMS: This study evaluated the hypothesis that the subjective interviewer severity rating (ISR) summary indices of the intake Addiction Severity Index (ASI) of less trained interviewers are less valid than those of more highly trained interviewers. DESIGN: Baseline ASIs from three completed studies whose interviewers varied in degree of initial ASI training and subsequent quality assurance monitoring were examined. Associations between baseline ISRs and three other sets of ASI summary indices not based on interviewer ratings-composite scores, clinical indices and evaluation indices-were compared for three groups of interviewers with varying amounts of training. The assumption underlying these analyses was that more reliable ISRs, found in more trained interviewers, would be more highly associated with the other more objective indices. SETTING: Methadone maintenance patients in the Philadelphia and New York City areas. PARTICIPANTS: Thirty-five interviewers with the most intense training who administered 295 interviews; 10 interviewers with an intermediate level of training who administered 763 interviews; and eight identified (and other unidentified) least trained interviewers who administered a total of 276 interviews. Measurements and methods. Four sets of summary indices from the above ASIs. Both bivariate and multivariate analyses were performed. FINDINGS: The study found that the validity of the validity of ISRs was greater in more trained interviewers. CONCLUSIONS: Greater training and subsequent monitoring of ASI interviewers generally appears to be associated with increased ISR validity.

Group counseling versus individualized relapse prevention aftercare following intensive outpatient treatment for cocaine dependence: initial results.

Ninety-eight male cocaine-dependent patients who completed an intensive outpatient program (IOP) were randomly assigned to either standard group counseling (STND) or individualized relapse prevention (RP) aftercare. Heavier cocaine and alcohol use during IOP and low self-efficacy predicted more cocaine use during the treatment phase of the study, whereas lifetime diagnoses of alcohol dependence, major depression, and any anxiety disorder predicted less cocaine use. Rates of complete abstinence during the 6-month study period were higher in STND than RP, whereas RP was more effective in limiting the extent of cocaine use in those who used during Months 1-3. Matching analyses indicated patients who failed to achieve remission from cocaine dependence during IOP and those with a commitment to absolute abstinence did better in RP than in STND, whereas patients with other abstinence goals did better in STND than RP. Several differences in experiences before cocaine use and "near-miss" episodes were also identified.

Generality of Psychopathy Checklist-Revised factors over prisoners and substance-dependent patients.

The Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991) is an often-used device for assessment of adult antisociality. This research examined generalizability by replicating the 2-factor model for a sample of 326 male prisoners and assessing its congruence and relative reliability and specificity among 620 substance-dependent patients. Generality was assessed also across addiction subtypes (opioid, cocaine, and alcohol), age, gender, and ethnicity. The 2-factor model was found inappropriate for the substance-dependent samples, whereas a unidimensional model represented by the PCL-R total score was found generalizable across prison and substance-dependent samples.

Continuing care for cocaine dependence: comprehensive 2-year outcomes.

This report presents 2-year outcome data from an outpatient continuing care study in which cocaine-dependent patients (N = 132) were randomly assigned to either standard group counseling (STND) or individualized relapse prevention (RP). Data on cocaine outcomes during the 6-month treatment phase of the study were presented in an earlier report (J. R. McKay, A. I. Alterman, J. S. Cacciola, M. R. Rutherford, & C. P. O'Brien, 1997). In the present report, a continuing care condition main effect was obtained on only 1 of 8 outcome variables examined. However, patients who endorsed a goal of absolute abstinence on entering continuing care had better cocaine use outcomes in RP than in STND, whereas the opposite was the case for those with less stringent abstinence goals. In addition, patients with current cocaine or alcohol dependence on entering continuing care who received RP had better cocaine use outcomes in Months 1-6 and better alcohol use outcomes in Months 13-24 than those in STND.

A typology of antisociality in methadone patients.

Multistage cluster analyses with replications were used to sort score profiles of 252 methadone maintained men on 4 continuous measures of antisociality--childhood conduct disorder and adult antisocial personality disorder symptoms, the revised Psychopathy Checklist, and the Socialization scale of the California Psychological Inventory. The analysis yielded 6 replicable and temporally stable cluster groups varying in degree and pattern of antisociality. The groups were statistically compared on sets of external criterion variables--Addiction Severity Index measures of past and recent substance abuse and functioning and lifetime criminal history. Axis I and II symptomatology, anxiety and depression, object relations and reality testing, hostility, guilt, and machiavellianism. The expression of antisociality in the 6 groups and differences found among them on the external variables supported the validity of a more complex conceptualization of antisociality than is provided by antisocial personality disorder.

Relationships of personality disorders with problem severity in methadone patients.

The prevalence of DSM-III-R personality disorders were assessed in a sample of 179 male methadone maintained opiate addicts. The discriminant validity of three personality disorder (PD) groupings were compared with respect to Axis I disorders, functioning in a number of important life areas, risk for HIV infection, and social judgment/sensitivity. Results showed that a PD, regardless of the number or type, identified patients with more employment, family/social, and psychiatric problems, increased risk for HIV infection, and poor social judgment/sensitivity. Few differences were revealed when three clusters of PDs (Cluster A, B, and C) were compared. With few exceptions, subjects with antisocial PD were no worse off than those with any other PD with respect to current functioning.

The relationship of psychiatric comorbidity to treatment outcomes in methadone maintained patients.

The authors examined the relationship of comorbid non-substance use psychiatric disorders to preadmission problem status and treatment outcomes in 278 methadone maintenance patients. Recent admissions were assigned DSM-III-R Axis I and II diagnoses according to structured diagnostic interviews. The Addiction Severity Index was administered at admission to assess past and current substance use and psychosocial problems and again 7 months later. Treatment retention and month 7 drug urinalysis results were also obtained. Across substance use and psychosocial domains, participants showed significant and comparable levels of improvement regardless of comorbidity. Comorbid participants received more concurrent psychiatric treatment which may have accounted for the lack of differential improvement among groups. Nevertheless, psychiatric comorbidity was associated with poorer psychosocial and medical status at admission and follow-up and participants with the combination of Axis I and II comorbidity had the most severe problems. Admission and month 7 substance use were, for the most part, not related to psychiatric comorbidity, although there was a trend indicating more treatment attrition for participants with personality disorders.

Validity of the psychopathy checklist-revised in male methadone patients.

The psychopathy checklist-revised (PCL-R) has been shown to be reliable when used with male methadone patients, but validity has not been established in this population. This paper examines the PCL-R's validity in 251 male methadone patients. Correlations between the PCL-R and background variables, Axis I and Axis II disorders, and several self report measures of related constructs are evaluated. Correlations with Axis I disorders were low except for substance dependencies, but strong correlations between Cluster B personality disorders were found. Results provide evidence of construct validity for the PCL-R, particularly total and Factor 2 scores, in male methadone patients.

Validity of three measures of antisociality in predicting HIV risk behaviors in methadone-maintenance patients.

Most opiate users are injection drug users (IDUs). A significant percentage of IDUs have antisocial personality disorder (APD). APD has been found by some researchers to be an additional risk factor for human immunodeficiency virus (HIV) infection in IDUs. The present study evaluated the association of sociodemographic characteristics, substance abuse history, and several measures of antisociality including the DSM-III-R diagnosis made by the Personality Disorder Examination, the California Psychological Inventory-Socialization Scale, and Hare's Revised Psychopathy Checklist, to behaviors associated with HIV risk in 289 opiate-dependent methadone-maintained subjects. The presence of drug- and sex-related risky behaviors measured by the Risk Assessment Battery was predicted more consistently by measures of personality traits associated with antisociality than by a diagnosis of APD.

An examination of the cocaine relapse process.

Although empirical studies of the relapse process have been done with alcoholics, smokers, and opiate addicts, comparatively little information is available on the relapse process in cocaine abusers. This paper presents data from the Cocaine Relapse Interview (CRI), a structured interview that assesses factors associated with the onset, course, and termination of cocaine relapse episodes. In a sample of 95 cocaine dependent patients, the experiences that occurred with the greatest frequency immediately prior to relapse were wanting drugs, being alone, having money, and feeling extremely bored and lonely. Following the onset of the relapse, the most frequent experience was unpleasant affect, although positive reactions were also relatively common. The factors perceived as most important in terminating relapse were painful internal states, help-seeking behaviors, and other coping responses. Three types of relapse experiences, or pathways, were identified: (a) unpleasant affect--painful internal states prior to and throughout the relapse; (b) positive affect--positive affect and pleasant social experiences prior to relapse coupled with a relatively unproblematic course; and (c) sensation seeking--sensation seeking and interpersonal problems prior to relapse coupled with mixed emotional reactions and antisocial behavior during the relapse, and interpersonal problems at relapse termination.

Prediction of 7 months methadone maintenance treatment response by four measures of antisociality.

Zero-order correlational and simultaneous regression analyses were performed to ascertain the comparative validity of four measures of antisociality for predicting the initial 7 months treatment response of 193 male methadone maintenance (MM) patients. Predictor variables were the number of childhood conduct disorder (CD) behaviors, number of adult antisocial personality disorder (A-APD) behaviors, the revised Psychopathy Checklist (PCL-R) score and the revised California Psychological Inventory-Socialization (CPI-So) scale score. The outcome measures were completion/noncompletion of 7 months of treatment, percent positive during-treatment of cocaine, opiate and benzodiazepine urine toxicologies, and change from baseline to 7 months follow-up in seven Addiction severity index (ASI) composite scores (CSs). All four measures of antisociality were significantly correlated with treatment noncompletion, although only the PCL-R score was significant in the predictor model. The PCL-R predicted more positive cocaine urines. At the individual level, both PCL-R and CPI-So were associated with more positive benzodiazepine urines, but neither contributed a significant amount of variance when both were entered in the model. None of the predictors were significantly associated with self reported improvement in the CSs. The PCL-R and CPI-So were more successful in predicting outcomes than the two behavior-based measures.

The effectiveness of two intensities of psychosocial treatment for cocaine dependence.

Structured treatments for cocaine dependence have been shown to be effective despite high attrition rates. What is unclear is what level of treatment intensity is needed to improve and sustain patient outcomes, especially among low SES urban residents. This study evaluated whether there were differences between two levels of treatment intensities for cocaine dependence in reducing substance use and improving health and social indicators. Ninety-four cocaine dependent predominantly African-American male veterans were randomly assigned to either a 12 h/week day hospital program (DH12) or a 6 h/week outpatient program (OP6) and were evaluated at baseline, during treatment and at 4 and 7 months post-treatment. Both treatments stressed abstinence, behavior change and prosocial adjustment and only differed in level of treatment intensity. During treatment measures included urine toxicologies, program attendance, treatment completion and aftercare attendance. Participants reported a 52% reduction in days of cocaine use and experienced significant improvements in employment and psychiatric functioning at seven months post-treatment. However, there was no significant difference between the DH12 and OP6 programs in terms of abstinence during treatment, treatment completion, treatment or aftercare attendance or any Addiction Severity Index (ASI)-related variable assessing level of functioning at 4 and 7 months. While future research with a larger community-based sample that includes female clients is necessary, the current findings demonstrate that a 6 h/week program is just as effective and thus has a significant cost savings compared to a 12 h/week treatment modality for cocaine dependence.