Biomedical subjects
D R Gastfriend
Publications and source records attributed to D R Gastfriend.
Cocaine dependence with and without PTSD among subjects in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study.
OBJECTIVE: This study examined the prevalence of lifetime traumatic events and current symptoms of posttraumatic stress disorder (PTSD) among treatment-seeking cocaine-dependent outpatients and compared patients with and without PTSD on current substance use, psychopathology, and sociodemographic characteristics. METHOD: The subjects were 122 adult cocaine-dependent outpatients participating in a treatment outcome study of psychosocial therapy. In addition to standard self-report and interview measures of psychopathology and substance use, the subjects completed the Trauma History Questionnaire and the PTSD Checklist before entering treatment. RESULTS: These patients experienced a large number of lifetime traumatic events (mean = 5.7); men experienced more general disasters and crime-related traumas than women, and women experienced more physical and sexual abuse than men. According to self-report measures, 20.5% of the subjects currently met the DSM-III-R criteria for PTSD; the rate of PTSD was 30.2% among women and 15.2% among men. Patients with PTSD had significantly higher rates of co-occurring axis I and axis II disorders, interpersonal problems, medical problems, resistance to treatment, and psychopathology symptoms than patients without PTSD. Psychopathology symptoms represented the most consistent difference between the two groups and provided the best prediction of PTSD status in a logistic regression. However, the groups did not differ significantly in current substance use or sociodemographic characteristics. CONCLUSIONS: These findings underscore the value of screening substance abusers for PTSD, because it can identify a small but substantial number who might require additional treatment. Further studies of the relationship between PTSD and substance abuse appear warranted.
The Addiction Severity Index as a screen for trauma and posttraumatic stress disorder.
OBJECTIVE: The Addiction Severity Index (ASI) includes items to assess patients' history of trauma (physical or sexual). The goal of this study was to assess the sensitivity and specificity of those questions in relation to the Trauma History Questionnaire (THQ), a more thorough measure of lifetime trauma and, in addition, to an actual posttraumatic stress disorder (PTSD) diagnosis. METHOD: At the start of treatment cocaine dependent outpatients (N = 110, 65.5% male) were assessed on the ASI, the THQ and a PTSD symptom checklist as part of a multisite clinical trial. RESULTS: Specificity of the ASI questions was higher than sensitivity for both sexual trauma (specificity = .96, sensitivity = .46) and physical trauma (specificity = .71, sensitivity = .50), while for PTSD the sensitivity of the ASI (.91) was higher than its specificity (.43). Other findings indicated that patients were more likely to report trauma on the THQ than on the ASI (which may be due to the self-report format of the THQ); that the ASI was better at assessing sexual than assessing physical trauma; and that the higher the number of ASI trauma items endorsed, the more likely was the PTSD diagnosis. Finally, PTSD patients had greater severity than non-PTSD patients on other ASI items (e.g., psychological severity, need for treatment). CONCLUSIONS: The ASI trauma questions show stronger utility as a screen for PTSD than for trauma. Results of the study are discussed in light of ways to modify the ASI to screen more accurately for trauma, clinical implications, and limitations of the study method.
The National Institute on Drug Abuse Collaborative Cocaine Treatment Study. Rationale and methods.
The National Institute on Drug Abuse Collaborative Cocaine Treatment Study is a large, multisite psychotherapy clinical trial for outpatients who meet the DSM-IV criteria for cocaine dependence. For 480 randomized patients, the outcomes of 4 treatments are compared for an 18-month period. All treatments include group drug counseling. One treatment also adds cognitive therapy, one adds supportive-expressive psychodynamic therapy, and one adds individual drug counseling; one consists of group drug counseling alone. In addition, 2 specific interaction hypotheses, one involving psychiatric severity and the other involving degree of antisocial personality characteristics, are being tested. This article describes the main aims of the project, the background and rationale for the study design, the rationale for the choice of treatments and patient population, and a brief description of the research plan.
Treatment matching. Theoretic basis and practical implications.
An extensive knowledge base supports the development of treatment matching methods for alcohol and other drug abuse. Many matching variables have been identified that relate to specific modalities of treatment and to specific levels of care. Physicians and other providers can use many putative matching variables to address patients' substance use problems on a highly individualized basis. These variables include demographic factors (age, gender, culture), typology and severity (age of onset; severity of intoxication; withdrawal; quantity, recency, frequency of substance use), intrapersonal characteristics (psychiatric diagnosis, cognitive function, self-efficacy, stage of change), and interpersonal function (social stability). The evolution of formal criteria for patient placement such as the ASAM criteria is a beneficial, adaptive process that is underway in numerous states, managed care entities, professional provider societies, and provider groups. Currently, matching approaches rely more heavily on consensus recommendations than on empiric matching data. The technology for conducting psychosocial treatment matching studies is rapidly increasing in sophistication. Although predictive validity has not yet been fully demonstrated on a large, multisite basis, the national research portfolio on treatment matching is expanding in size and complexity. This is an essential public health need, given dramatic cost pressures, if addiction services are to continue to grow in quality and availability.
Acute effects of cocaine on human brain activity and emotion.
We investigated brain circuitry mediating cocaine-induced euphoria and craving using functional MRI (fMRI). During double-blind cocaine (0.6 mg/kg) and saline infusions in cocaine-dependent subjects, the entire brain was imaged for 5 min before and 13 min after infusion while subjects rated scales for rush, high, low, and craving. Cocaine induced focal signal increases in nucleus accumbens/subcallosal cortex (NAc/SCC), caudate, putamen, basal forebrain, thalamus, insula, hippocampus, parahippocampal gyrus, cingulate, lateral prefrontal and temporal cortices, parietal cortex, striate/extrastriate cortices, ventral tegmentum, and pons and produced signal decreases in amygdala, temporal pole, and medial frontal cortex. Saline produced few positive or negative activations, which were localized to lateral prefrontal cortex and temporo-occipital cortex. Subjects who underwent repeat studies showed good replication of the regional fMRI activation pattern following cocaine and saline infusions, with activations on saline retest that might reflect expectancy. Brain regions that exhibited early and short duration signal maxima showed a higher correlation with rush ratings. These included the ventral tegmentum, pons, basal forebrain, caudate, cingulate, and most regions of lateral prefrontal cortex. In contrast, regions that demonstrated early but sustained signal maxima were more correlated with craving than with rush ratings; such regions included the NAc/SCC, right parahippocampal gyrus, and some regions of lateral prefrontal cortex. Sustained negative signal change was noted in the amygdala, which correlated with craving ratings. Our data demonstrate the ability of fMRI to map dynamic patterns of brain activation following cocaine infusion in cocaine-dependent subjects and provide evidence of dynamically changing brain networks associated with cocaine-induced euphoria and cocaine-induced craving.
A measure of readiness for substance abuse treatment. Psychometric properties of the RAATE-R interview.
The Recovery Attitude and Treatment Evaluator-Research (RAATE-R) scale is a structured interview that assesses readiness for substance abuse treatment in five subscales: resistance to treatment, resistance to continuing care, bio-medical acuity, psychological acuity, and environmental/ social problems. Psychometric properties, based on an interrater reliability analysis of 23 raters and administration of the scale to 116 cocaine-dependent outpatients, included high interrater reliability, high internal consistency, independence of subscales, and a factor structure that partially supports the scale's original design. The authors discuss limitations of these conclusions and the lack of concurrent validity with a self-report measure of therapy readiness.
The effect of anonymous vs. nonanonymous rating conditions on patient satisfaction and motivation ratings in a population of substance abuse patients.
Patient self-report in evaluations involving alcohol and other drug abuse has generally been found to be reliable and valid. However, little is known about the variables associated with greater or lesser degrees of reliability and validity. This study was conducted to determine how motivation and satisfaction ratings obtained under anonymous conditions would compare with ratings obtained under nonanonymous conditions. Over the course of 12 months, 1397 subjects in the Boston Target Cities Project were assigned to either confidential or fully anonymous data collection procedures in an interrupted time-series design. Anonymity had either no effect on ratings or accounted for < 1% of the variance. Satisfaction and motivation ratings obtained under confidential conditions are probably as reliable and valid as ratings obtained under fully anonymous conditions.
Nitric oxide-induced motor neuron disease in a patient with alcoholism.
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The glutamatergic basis of human alcoholism.
OBJECTIVE: Although alcoholism is one of the most common psychiatric diagnoses, understanding of its pathophysiology remains poor. Accumulating evidence suggests that neurophysiological and pathological effects of ethanol are mediated to a considerable extent through the glutamatergic system. This article reviews the evidence of ethanol's effects on glutamatergic transmission and proposes a glutamatergic basis for alcoholism. METHOD: The information was derived from original research. The authors located more than 100 articles from psychiatry and neuroscience journals that related ethanol to glutamatergic transmission. They critically reviewed the neurobiology of the glutamatergic system in alcoholism and synthesized a unifying glutamatergic theory. RESULTS: Acute effects of ethanol disrupt glutamatergic neurotransmission by inhibiting the response of the N-methyl-D-aspartate (NMDA) receptor. Prolonged inhibition of the NMDA receptor by ethanol results in development of supersensitivity; acute removal of ethanol causes marked augmentation of activity of postsynaptic neurons, such as those in the noradrenergic system, and, in the extreme, glutamate-induced excitotoxicity. Neurobiological effects of alcoholism, such as intoxication, withdrawal seizures, delirium tremens, Wernicke-Korsakoff syndrome, and fetal alcohol syndrome, can be understood as a spectrum of consequences of ethanol's effect on the glutamatergic system. CONCLUSIONS: A host of findings support the hypothesis that the unifying mechanism of action of ethanol in interference with glutamatergic neurotransmission, especially through the NMDA receptor. Alcoholism may be considered another member of the expanding family of glutamate-related neuropsychiatric disorders. These insights should increase understanding of the biologic vulnerabilities leading to ethanol abuse and dependence and aid development of more effective pharmacologic interventions.
A pilot study of factors associated with resilience to substance abuse in adolescent sons of alcoholic fathers.
This pilot study evaluated the association between substance abuse outcome and putative protective factors in sons of alcoholic fathers. A battery of questionnaires was anonymously self-administered to 24 sons of alcoholic fathers ages 16-19 years to identify relationships between alcohol and/or drug abuse and factors hypothesized to be related to parental alcoholism. Of the 24 subjects, 13 were categorized through self-identification and self-report screening measures as having alcohol and/or drug problems and 11 were categorized as not having substance abuse problems. Boys without substance problems: (1) had significantly higher maternal occupational status (p = .01); (2) experienced more good life events (p < .001), and (3) had a more internally oriented locus of control (p < .001). Good events and internal locus of control were highly correlated with each other (r = .620, p < .01). The fact that these preliminary findings are consistent with other literature despite marked methodologic and sample differences indicates that these putative components of resilience are robust and deserve further study towards improved substance abuse prevention in those at high risk.
Buprenorphine effects on morphine- and cocaine-induced subjective responses by drug-dependent men.
The effects of daily buprenorphine treatment (4 or 8 mg/day, sublingual) on reports of subjective effects after single intravenous doses of morphine (10 mg), cocaine (30 mg), and saline placebo were studied on an inpatient clinical research ward in 26 men concurrently dependent on opioids and cocaine (DSM-III-R). Latency to detection and certainty of a drug effect, as well as drug quality (intensity, euphoria, and dysphoria), were studied before and after 10 to 12 days of buprenorphine maintenance. Saline was accurately identified by all 26 patients during the drugfree baseline and by 25 patients during buprenorphine maintenance conditions. All patients accurately identified morphine during the drugfree period before treatment with buprenorphine, but 18 (69%) of 26 patients were unable to detect morphine during buprenorphine maintenance and 2 misidentified morphine as cocaine. Six men (23%) accurately identified morphine and reported that the intensity and quality of morphine's effects were equivalent to drugfree conditions. Cocaine levels in plasma 5 minutes after intravenous cocaine injection were equivalent before and during buprenorphine treatment and averaged 282.8 +/- 43.6 and 295.2 +/- 28.8 ng/ml during 4 and 8 mg/day of buprenorphine maintenance, respectively. All patients accurately identified cocaine before and during buprenorphine maintenance, and there were no significant changes in latency to detection and certainty of a drug effect or reports of cocaine-induced intensity or euphoria during buprenorphine treatment. The concordance between responses to morphine and cocaine during inpatient buprenorphine maintenance and drug use during the first 4 weeks of outpatient buprenorphine treatment was also examined in 16 men. The effects of buprenorphine on individual responses to an acute intravenous dose of morphine or cocaine during the inpatient study did not reliably predict the frequency of heroin or cocaine self-administration during the first 4 weeks of daily outpatient buprenorphine maintenance.
Pharmacotherapy of psychiatric syndromes with comorbid chemical dependence.
Because of the paucity of research on the pharmacotherapy of psychiatric syndromes with comorbid psychoactive substance use disorders, treatment guidelines are primarily drawn from general principles of clinical psychopharmacology and the addictive disease model. Effective treatment requires the determination of a discrete psychiatric diagnosis or working differential, consideration of the range of drug effects as they vary over time, and awareness of potential pharmacologic interactions between medication and alcohol or drug use. Either nonspecific prescribing or failure to treat may result in protracted dysfunction, relapse, or medical morbidity and mortality. Pharmacotherapy may also determine whether treatment results in mere abstinence vs. recovery from addictive disease. Primary emphasis on non-pharmacologic strategies and the use of a formal treatment contract increase the likelihood of successful pharmacotherapy outcome.
Acute distress after switch from Norpramin to generic desipramine.
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Adjunctive buspirone in benzodiazepine treatment of four patients with panic disorder.
Four patients with panic disorder whose panic attacks responded to benzodiazepine treatment but who suffered persistent anxiety improved after addition of buspirone. Despite its lack of antipanic effect, buspirone may offer an adjunctive benefit when added to benzodiazepines in panic disorder.
Adjunct low dose lithium carbonate in treatment-resistant depression: a placebo-controlled study.
Resistance to antidepressant therapy is a common clinical problem in the treatment of affective disorders. Adjunctive low dose lithium is a promising strategy based on biochemical models and encouraging clinical trials. After a mean duration of 9.2 months of conventional therapy, 16 healthy patients with treatment-resistant depression were treated for a minimum of 2 weeks with either adjunctive lithium or placebo using a double-blind design. We found no difference between the two groups in rate or degree of response. The two most dramatic responses occurred in patients treated with placebo, although 50% of patients treated with lithium had at least a partial response. The number of patients studied was clearly inadequate to avoid a type 2 error. The cumulative response rate reported in the literature of greater than 60%, however, suggests that lithium is indeed an effective adjunct in some patients with treatment-resistant depression. Our patients differed from those in other studies in that they were treated with a lower dose of lithium, the duration of conventional antidepressant therapy was longer, and, finally, they were less depressed and possibly depressed for a longer period. These differences may explain the comparable lithium and placebo responses in this study.
An Intelligent Display System for psychiatric education in primary care.
We have shown how new concepts for displaying knowledge and data may overcome some of the limitations of existing decisionmaking and educational aids and how they may improve psychiatric diagnosis and education. Elsewhere, we illustrated how these concepts can also be applied in redesigning ordinary textbooks in many other areas of medicine. Using such ideas to simplify decisionmaking without oversimplifying and without reducing physician participation may help us to cope with the enormous growth of information and knowledge. This is a problem common to many areas of medicine, one that demands new ways of thinking about how to simplify educational methods.
Orthostatic hypotension and antidepressant pharmacotherapy.
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