Howard M. Rhoades

Impulsivity and history of drug dependence

Impulsivity was contrasted between 32 subjects with a history of drug-dependence (DRUG+) and 26 subjects with no drug use history (DRUG-) using both behavioral and self-report measures. The hypothesis was that the DRUG+ group would be more impulsive than the DRUG- group. Subjects in the DRUG+ group self-reported more of a tendency toward impulsivity than the DRUG- group in the situations posed in questionnaires. In the behavioural paradigm involving a choice between a smaller intermediate reward and a larger but delayed reward, DRUG+ subjects selected the impulsive option more often, but these differences were not significant. The DRUG+ and DRUG- groups did differ on the mean delay interval for the larger reward, indicating less ability to tolerate longer delays for the larger reward. A frequency distribution of delay intervals for the larger reward indicated that DRUG+ subjects were more likely to maintain very short intervals and less likely to maintain longer intervals.

Dextroamphetamine for cocaine-dependence treatment : A double-blind randomized clinical trial

A properly implemented agonist treatment regimen should improve retention and reduce illicit drug use. Cocaine-dependent subjects (N = 128) were enrolled in a 12-week randomized, double-blind, placebo-controlled trial. In the multistage dosing design, subjects initially received placebo (PBO) or 15 to 30 mg of dextroamphetamine sulfate, sustained-release capsules. At week 5, the dose doubled to 30 mg or 60 mg for active groups. Subjects attended the clinic twice a week, provided urine samples, obtained medication, and had one behavioral therapy session a week. Retention was best for the 15-to 30-mg group, whereas the proportion of benzoylecgonine-positive urine screens was, from lowest to highest, 30 to 60 mg, 15 to 30 mg, and PBO at study end. Dosing must be refined. The results provide support for additional examination of the agonist model in psychostimulantdependence treatment.

Cognitive Behavior Therapy for Generalized Anxiety Disorder Among Older Adults in Primary Care: A Randomized Clinical Trial

CONTEXT Cognitive behavior therapy (CBT) can be effective for late-life generalized anxiety disorder (GAD), but only pilot studies have been conducted in primary care, where older adults most often seek treatment. OBJECTIVE To examine effects of CBT relative to enhanced usual care (EUC) in older adults with GAD in primary care. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial recruiting 134 older adults (mean age, 66.9 years) from March 2004 to August 2006 in 2 primary care settings. Treatment was provided for 3 months; assessments were conducted at baseline, posttreatment (3 months), and over 12 months of follow-up, with assessments at 6, 9, 12, and 15 months. INTERVENTION Cognitive behavior therapy (n = 70) conducted in the primary care clinics. Treatment included education and awareness, motivational interviewing, relaxation training, cognitive therapy, exposure, problem-solving skills training, and behavioral sleep management. Patients assigned to receive EUC (n = 64) received biweekly telephone calls to ensure patient safety and provide minimal support. MAIN OUTCOME MEASURES Primary outcomes included worry severity (Penn State Worry Questionnaire) and GAD severity (GAD Severity Scale). Secondary outcomes included anxiety ratings (Hamilton Anxiety Rating Scale, Beck Anxiety Inventory), coexistent depressive symptoms (Beck Depression Inventory II), and physical/mental health quality of life (12-Item Short Form Health Survey). RESULTS Cognitive behavior therapy compared with EUC significantly improved worry severity (45.6 [95% confidence interval {CI}, 43.4-47.8] vs 54.4 [95% CI, 51.4-57.3], respectively; P < .001), depressive symptoms (10.2 [95% CI, 8.5-11.9] vs 12.8 [95% CI, 10.5-15.1], P = .02), and general mental health (49.6 [95% CI, 47.4-51.8] vs 45.3 [95% CI, 42.6-47.9], P = .008). There was no difference in GAD severity in patients receiving CBT vs those receiving EUC (8.6 [95% CI, 7.7-9.5] vs 9.9 [95% CI, 8.7-11.1], P = .19). In intention-to-treat analyses, response rates defined according to worry severity were higher following CBT compared with EUC at 3 months (40.0% [28/70] vs 21.9% [14/64], P = .02). CONCLUSIONS Compared with EUC, CBT resulted in greater improvement in worry severity, depressive symptoms, and general mental health for older patients with GAD in primary care. However, a measure of GAD severity did not indicate greater improvement with CBT. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00308724.

Psychometric properties of the Depression Anxiety and Stress Scale-21 in older primary care patients

The Depression Anxiety Stress Scale (DASS) was designed to efficiently measure the core symptoms of anxiety and depression and has demonstrated positive psychometric properties in adult samples of anxiety and depression patients and student samples. Despite these findings, the psychometric properties of the DASS remain untested in older adults, for whom the identification of efficient measures of these constructs is especially important. To determine the psychometric properties of the DASS 21-item version in older adults, we analyzed data from 222 medical patients seeking treatment to manage worry. Consistent with younger samples, a three-factor structure best fit the data. Results also indicated good internal consistency, excellent convergent validity, and good discriminative validity, especially for the Depression scale. Receiver operating curve analyses indicated that the DASS-21 predicted the diagnostic presence of generalized anxiety disorder and depression as well as other commonly used measures. These data suggest that the DASS may be used with older adults in lieu of multiple scales designed to measure similar constructs, thereby reducing participant burden and facilitating assessment in settings with limited assessment resources.

Motivational interviewing with cocaine-dependent patients: A pilot study

A brief motivational interviewing (MI) intervention was evaluated within the context of an outpatient, cocaine-detoxification program. MI was hypothesized to assist patients in completing the detoxification program and to improve outcomes during subsequent treatment. Participants (N = 105) were randomly assigned to MI or to detox-only conditions. Results indicated that although participants completed the detoxification program at equal rates, completers who received MI increased use of behavioral coping strategies and had fewer cocaine-positive urine samples on beginning the primary treatment. MI patients with lower initial motivation were more likely to complete detoxification.

Fluoxetine is ineffective for treatment of cocaine dependence or concurrent opiate and cocaine dependence: Two placebo-controlled, double-blind trials

Cocaine dependence has proved difficult to treat, whether occurring alone or in combination with opiate dependence. No medication has been demonstrated to be uniquely effective. Fluoxetine was examined as a candidate in two randomized, double-blind, placebo-controlled trials, one with cocaine-dependent patients (study 1) and the other with patients both cocaine and opiate dependent (study 2). It was selected for known specific action, antidepressant effects, minimum side effects, and data showing reduced cocaine effect and self-administration. Clinic visit frequency requirement, a variable with implications for treatment and cost, was also examined in study 1. A total of 228 patients in study 1 and 21 patients in study 2 completed consent and intake procedures. Patients with serious medical or DSM-III-R diagnoses other than cocaine dependence (study 1) or opiate and cocaine dependence (study 2) were excluded. Study 1 patients were assigned to one of two visit frequency schedules (2 or 5 days/week) and one of three medication doses (0, 20, or 40 mg of fluoxetine/day). Study 2 patients received placebo or 20 mg of fluoxetine and 65 to 80 mg of methadone and attended the clinic 5 days/week. All patients participated in individual therapy sessions. Urine screens were conducted twice weekly. A fluoxetine dose response relationship emerged in study 1 for retention with groups from best to worst being placebo, 20 mg, and 40 mg. Dose effect order was the same for both visit conditions. Cocaine use persisted in all groups. The two visits/week condition was correlated with better retention than the five visits/week condition. A significant interaction emerged between intake urine and visit frequency; patients with benzoylecognine screens at intake used cocaine significantly less in the 5 days/week condition, while exhibiting no reduction in the 2 days/week condition. Patients cocaine positive at intake were better retained with infrequent visits. In study 2, a transient reduction in benzoylecognine-positive drug screens emerged for the fluoxetine group. These complementary studies demonstrate that fluoxetine is ineffective in reducing cocaine use or craving. Study 1 also points to setting conditions modulating treatment outcome.

Effects of Language and Ethnic Status on Reliability and Validity of the Center for Epidemiologic Studies-depression Scale with Psychiatric Patients

Data from 562 psychiatric patients were analyzed to assess the effects of ethnic status (Anglo/Mexican origin) and language (English/Spanish) on the reliability and validity of the Center for Epidemiologic Studies-Depression Scale. The results indicate no systematic variation in either reliability (test-retest, internal consistency), dimensionality, or ability of the CES-D Scale to detect clinical depression among Anglos or persons of Mexican origin classified according to language use as Spanish dominant, English dominant, or bilingual. However, the data indicate that this particular screening instrument does not adequately discriminate between patients with clinical depression and those without depression. These results corroborate several recent studies that question the utility of the CES-D Scale as a depression screening instrument. Taken together, the available evidence suggests that the ability of the CES-D Scale to detect major depression is so limited that further use of the instrument as a screening scale would seem unwarranted, at least in treatment settings.

Agonist-Like or Antagonist-Like Treatment for Cocaine Dependence with Methadone for Heroin Dependence: Two Double-Blind Randomized Clinical Trials

Concurrent abuse of cocaine and heroin is a common problem. Methadone is effective for opioid dependence. The question arises as to whether combining agonist-like or antagonist-like medication for cocaine with methadone for opioid dependence might be efficacious. Two parallel studies were conducted. One examined sustained release d-amphetamine and the other risperidone for cocaine dependence, each in combination with methadone. In total, 240 subjects (120/study) were recruited, who were both cocaine and heroin dependent and not currently receiving medication. All provided consent. Both studies were carried out for 26 weeks, randomized, double-blind and placebo controlled. Study I compared sustained release d-amphetamine (escalating 15–30 or 30–60 mg) and placebo. Study II examined risperidone (2 or 4 mg) and placebo. All subjects underwent methadone induction and were stabilized at 1.1 mg/kg. Subjects attended clinic twice/week, provided urine samples, obtained medication take-home doses for intervening days, and completed self-report measures. Each had one behavioral therapy session/week. In Study I, reduction in cocaine use was significant for the 30/60 mg dose compared to the 15/30 mg and placebo. Opioid use was reduced in all groups with a trend toward greater reduction in the 30/60 mg d-amphetamine group. In Study II, methadone reduced illicit opioid use but cocaine use did not change in the risperidone or placebo groups. There were no adverse medication interactions in either study. The results provide support for the agonist-like (d-amphetamine) model in cocaine dependence treatment but not for antagonist-like (risperidone) treatment. They coincide with our previous reports of amphetamine or risperidone administered singly in cocaine-dependent individuals.

Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy

We measured CBF and the CMRglc in normal controls and in patients with severe liver disease and evidence for minimal hepatic encephalopathy using positron emission tomography. Regions were defined in frontal, temporal, parietal, and visual cortex; the thalamus; the caudate; the cerebellum; and the white matter along with a whole-slice value obtained at the level of the thalamus. There was no difference in whole-slice CBF and CMRglc values. Individual regional values were normalized to the whole-slice value and subjected to a two-way repeated measures analysis of variance. When normalized CBF and CMRglc values for regions were compared between groups, significant differences were demonstrated (F = 5.650, p = 0.00014 and F = 4.58, p = 0.0073, respectively). These pattern differences were due to higher CBF and CMRglc in the cerebellum, thalamus, and caudate in patients and lower values in the cortex. Standardized coefficients extracted from a discriminant function analysis permitted correct group assignment for 95.5% of the CBF studies and for 92.9% of the CMRglc studies. The similarity of the altered pattern of cerebral metabolism and flow in our patients to that seen in rats subjected to portacaval shunts or ammonia infusions suggests that this toxin may alter flow and metabolism and that this, in turn, causes the clinical expression of encephalopathy.

Relationships among laboratory and psychometric measures of impulsivity: Implications in substance abuse and dependence.

Objectives Problems with impulsive behavior are a key feature in substance use disorders. Many studies have examined this relationship, but methods used to measure impulsivity have varied greatly. The present study used a multimethod approach to determine relationships using both laboratory and psychometric measures of impulsivity commonly employed in the behavioral and health sciences. Methods Thirty-two adult male subjects participated for 5 days, completing psychometric instruments on day 1 and behavioral tests in counterbalanced order on days 2–5. Results Correlations between the behavioral and psychometric measures were uniformly low. Correlations within the psychometric instruments were consistently high. Principal components analysis revealed that the behavioral measures loaded into separate factors of response inhibition tasks and delay of reward tasks. Psychometric measures loaded into a single factor. Conclusions Results are discussed in terms of how studies of impulsivity might be interpreted based upon the tasks used, and how these interpretations may subsequently guide theory and measurement in substance abuse and dependence.