Comparison of outcomes for clients in randomized versus open trials of treatment for alcohol use disorders.

OBJECTIVE: There has been continuing concern that clients who accept randomization into a controlled trial may not be representative of those in noncontrolled trials or ordinary treatment situations. However, it is not possible to test the impact of randomization through a randomized trial. Two parallel studies conducted at the same treatment facility provided an opportunity for a quasi-experimental study to evaluate whether participation in a controlled trial itself affects treatment outcome. METHOD: Two concomitant samples of clients were enrolled during overlapping recruitment periods: one (n = 226) into a randomized clinical trial (RCT) and the other (n = 122) offered treatment as usual (non-RCT). Both samples were given extensive baseline and follow-up assessment. RESULTS: Baseline assessment indicated demographic similarity of the two samples, with somewhat higher problem severity in the non-RCT sample, consistent with the RCT selection criteria. Client retention in treatment was somewhat comparable, and follow-up rates exceeded 90% in both studies. Overall outcomes did not differ for the RCT and non-RCT samples. CONCLUSIONS: It appeared that clients enrolled into an RCT did not differ from those receiving ordinary treatment. Retention was similarly high in both studies, clients completed a comparable number of outpatient sessions, and the number of informal treatment sessions attended during the 6 months of follow-up was comparable. There are some aspects of this study that limit the ability to draw firmer conclusions but despite some pretreatment differences, participation in the RCT did not itself exert an apparent effect on aggregate treatment outcomes.

Constituents of craving in a clinical alcohol sample.

PURPOSE: Craving describes a subjective state, and it remains unclear what people mean when they use the term. However, as with many other subjective states, craving should be able to be described by those who experience it. METHODS: To try to understand the descriptors and constituents of craving, 213 clients appearing for treatment for alcohol use disorders were asked to rate the frequency of the occurrence over the past 30 days of a number of events and states that have been historically regarded as part of craving. These clients were also asked to rate the frequency with which they had experienced craving and urges over the same period. Using discriminant function analysis (DFA), some states were elucidated that separated those who reported craving from those who did not. RESULTS AND IMPLICATIONS: Those who reported craving consistently reported the occurrence of more dysphoric states, more of certain physical feelings associated with thoughts of alcohol, more thoughts of alcohol, and desiring alcohol when confronted with environmental cues. Such descriptions may aid in establishing reliable criteria for understanding the constituents of craving.

The topography of relapse in clinical samples.

In two clinical samples, alcohol consumption, other drug use, and tobacco use were measured at approximately 6 months following admission of individuals into treatment. Using only the alcohol consumption variables, cluster analyses with several different solutions consistently identified abstinent, moderate, and unremitted groups. With the addition of tobacco and other drug use, analyses identified a largely abstinent group, a drug use group that did not drink, a heavy drinking group that did not use other drugs, and a group using both alcohol and other drugs, indicating the need for broad definitions of relapse. All solutions distinguished clusters of tobacco users and nonusers in remission from alcohol and other drug use, and tobacco users and nonusers tended to be differentiated among those continuing to drink or use other drugs, suggesting that the presence or absence of tobacco use marks different outcome groups. Generally speaking, clustering methods using complete and average linkage as agglomeration measures with cosine similarity as a proximity measure produced the most consistent clusters and the most clinically interpretable results.

Comparison of treatment utilization and outcome for Hispanics and non-Hispanic whites.

OBJECTIVE: To examine the use of formal alcohol treatment and Alcoholics Anonymous (AA) by Hispanics and non-Hispanic whites, and to compare ethnic groups on posttreatment functioning. METHOD: Data from a publicly funded substance abuse treatment center in New Mexico were used to investigate possible differences between Hispanic (n = 46) and non-Hispanic white (n = 62) men (n = 76) and women (n = 32) on percent days alcohol therapy and AA attendance for 6 months after study recruitment. RESULTS: Hispanic clients were more often male (80% vs 63%), had fewer years of education (mean = 11.6 vs 12.6) and were less likely to live alone (7% vs 29%) than were non-Hispanic white clients. The heavy drinking (drinks per drinking day mean = 16.7; standard drink units in prior 90 days mean = 941.00) and few abstinent days (mean = 0.44) that characterized both groups at intake improved over time with Hispanics engaging in more formal alcohol therapy sessions but attending fewer AA meetings than non-Hispanic whites over the course of 6 months of follow-up. Attendance at treatment and AA were separately associated with decreased intensity and quantity of alcohol use, but not abstinent days, for both ethnic groups. CONCLUSIONS: Hispanic and non-Hispanic white clients used somewhat different treatment strategies to deal with alcohol-related problems, these paths, however, ultimately resulted in similar posttreatment drinking outcomes (frequency, intensity and quantity of alcohol consumption).

Relapse research and the Reasons for Drinking Questionnaire: a factor analysis of Marlatt's relapse taxonomy.

A factor analysis (n = 183) of Marlatt's relapse taxonomy as assessed by the Reasons for Drinking Questionnaire (RFDQ) (see Appendix I, this article) was conducted using a heterogeneous alcohol treatment sample. Results indicated that the predominant factor was negative emotions. The second factor consisted of social pressure and positive emotions, and a third factor consisted of physical withdrawal, wanting to get high, testing control, substance cues and urges to drink. Each of the 13 categories in the Marlatt taxonomy loaded on one of the three factors. Scores on the first factor for the first and second lapses were correlated. The same held true for the other two factors. The negative emotions factor was positively related to blood alcohol level on the first day of the lapse, the lapse duration (in days), and occurrence of a second lapse (even when controlling for alcohol dependence). The negative emotions factor in turn was related to client reports of alcohol dependence, trait anger, and depression (all positively). Women scored higher on the first factor, and men scored higher on the second factor. The third factor was inversely related to the number of days of abstinence preceding the lapse. Taken together, these analyses, illustrate that different precipitants occur together, suggesting that clients might productively be trained in the use of specific relevant coping skills to address potential relapse precipitants. Focusing on the third RFDQ factor may be particularly important in the early stages of abstinence. The importance of anger and depression management during alcohol treatment is also highlighted by these results.

What predicts relapse? Prospective testing of antecedent models.

Predictors of relapse to drinking were examined in a clinical sample of 122 individuals seeking outpatient treatment for alcohol problems. Drinking status and a variety of predictor variables were measured every two months for one year following presentation for treatment. In addition to pretreatment characteristics, potential antecedents of relapse were assessed at each point within five domains: (1) the occurrence of negative life events; (2) cognitive appraisal variables including self-efficacy, alcohol expectancies, and motivation for change; (3) client coping resources; (4) craving experiences; and (5) affective/mood status. Although the occurrence of adverse life events did not predict 6-month relapse, all other domains singly accounted for significant variance in drinking outcomes. Proximal antecedents (from the prior 2-month interval) significantly and substantially improved predictive power over that achieved from pretreatment characteristics alone. When analyzed jointly, these predictors accounted for a majority of variance in 6-month relapse status. A prospective test supported Marlatt's developmental model of relapse, pointing to two client factors as optimally predictive of resumed drinking: lack of coping skills and belief in the disease model of alcoholism.

Screening for childhood physical and sexual abuse among outpatient substance abusers.

Research demonstrates that substance-abusing individuals report substantially higher rates of childhood sexual and physical abuse than the general population. This study sought to test a method of identifying substance-abusing clients with histories of childhood sexual and/or physical abuse and to explore the differences between those reporting childhood abuse and those not. Files of substance abusing clients from two distinct time periods were examined for reports of childhood abuse. At Time 1 (n = 399) clients were not systematically asked about experiences of childhood abuse, and at Time 2 (n = 305) clients were routinely asked about this issue. Results indicate that significantly more male and female clients disclosed childhood abuse at Time 2. Additionally, male clients reporting childhood abuse appeared more distressed than those not reporting abuse; female clients reporting childhood abuse did not appear more distressed than their counterparts.

Alcohol measuring scales may influence conclusions about the role of alcohol in human immunodeficiency virus (HIV) risk and progression to acquired immunodeficiency syndrome (AIDS).

In an effort to clarify the role of alcohol in human immunodeficiency virus (HIV) risk and progression to acquired immunodeficiency syndrome (AIDS), the author reviewed the method of measuring alcohol consumption across 10 studies published from 1986 through 1990. When the reports in which the association between alcohol and HIV has been evaluated in at-risk groups are compared, the role of alcohol remains unclear. Although there are fewer reports available for analysis, the role of alcohol in the progression of the disease to AIDS has been consistent in indicating that there is no effect of alcohol use. However, the research in both of these areas has utilized different methods to measure alcohol use. There are data relevant to the association between alcohol and HIV that indicate that the estimate of alcohol use is at least partially dependent on the type of measuring instrument used. The application of different measures of alcohol use may have led to different conclusions regarding the role of alcohol in HIV. With regard to the role of alcohol in the progression of the disease to AIDS, even in the consistent findings that alcohol does not lead to progression of the disease to AIDS, a more sensitive measure of alcohol use might yield different results.

Norepinephrine and brain damage: alpha noradrenergic pharmacology alters functional recovery after cortical trauma.

The goal of these experiments was to evaluate the effects of some drugs affecting noradrenergic (NE) synaptic transmission, commonly prescribed following stroke or traumatic brain injury, on functional recovery. Measurement of recovery from a transient hemiplegia produced by a traumatic unilateral focal contusion in sensorimotor cortex (SMCX) of rats was used to assess the effects of chronic haloperidol (HAL) treatment begun early (1 day) or late (18 days to recovered animals) after injury. Additionally, using the same model, the effects of a single administration of drugs with selective action at NE receptors were also evaluated early or late (30 days) after injury. These drugs were: phenoxybenzamine (PBZ), an alpha 1-NE antagonist; prazosin (PRAZ), an alpha 1-NE antagonist; yohimbine (YOH), an alpha 2-NE antagonist; propranolol (PROP), a beta 1- and 2-NE receptor antagonist; methoxymine (METHOX), an alpha 1-NE agonist; and clonidine (CLON), an alpha 2-NE agonist. The data indicate that drugs with antagonistic effects at alpha 1 NE receptors, including HAL and PRAZ but not PROP, administered early after SMCX contusion retard locomotor recovery. Beneficial effects of enhancing NE transmission by METHOX or YOH were not observed. In animals recovered from beam walk (BW) deficits, a single administration of PBZ or PRAZ (alpha 1 NE antagonists) or CLON (alpha 2 NE agonist) transiently reinstated hemiplegic symptoms. The nonspecific beta NE receptor antagonist PROP had no effect in recovered animals. A single dose of HAL had no effect in recovered animals, but a BW deficit transiently developed in some animals following chronic treatment. The data are discussed with reference to drug contraindications noted in clinical studies of recovery from poststroke aphasia and cognition in demented patients with degenerative brain disease.

Mechanisms of general anesthesia: brain regional responses to baclofen.

The GABAB agonist baclofen is reported to produce general anesthesia when administered either centrally into the lateral ventricles of rats or peripherally to mice. Previously we demonstrated that beta-endorphin given intracerebrally produces anesthesia in rats, a response localized to sites in or adjacent to the inferior third and fourth ventricles. In order to compare the anatomical localization of these two anesthetic responses, we administered baclofen into the inferior or superior lateral or third ventricles, the aqueduct, or fourth ventricle in rats. Although 10 micrograms baclofen infusions into several regions caused loss of the righting reflex, in no case did animals exhibit an unconscious state which satisfied strict criteria of anesthesia. Infusions of 20 micrograms into the inferior third and fourth ventricles elicited seizures followed by a postictal depression. Although unresponsive to some stimuli, these animals showed no impairment in the corneal reflex. Since this dose was often lethal, higher doses not tested. Baclofen, given to mice intraperitoneally at doses of 25, 50, or 75 mg/kg, failed to elicit strictly defined anesthesia, although, to varying degrees, animals exhibited analgesia, loss of the righting reflex, and loss of behavioral responses to loud sounds. Animals continued to show motor responses when handled and retained corneal reflexes. Baclofen does not evoke an unconscious anesthetic state when administered centrally or systemically, emphasizing the need for strict criteria to define general anesthesia and to categorize drugs that promote this state.

Adenosine analogs inhibit gastric acid secretion.

The potencies with which four adenosine deaminase-resistant analogs of adenosine affected the volume, pH and acid output of basal gastric acid secretions were examined in unanesthetized rats with chronic indwelling gastric cannulas. All four adenosine receptor agonists, R-phenylisopropyladenosine (R-PIA), S-phenylisopropyladenosine (S-PIA), N-ethylcarboxamide adenosine (NECA), and 2-chloroadenosine (CADO) significantly decreased gastric acid output in a dose-dependent manner. The rank order of potency was NECA, R-PIA greater than CADO greater than S-PIA. NECA and R-PIA were approximately equipotent in reducing gastric acid output. The levels of gastric acid output tended to increase at the lowest doses of the agonists. NECA decreased the volume of gastric secretion, whereas R-PIA had no effect on volume, but significantly increased the pH of the secretions. Valid measurements of pH in NECA-treated rats were not always obtainable because of near total inhibition of gastric secretions. S-PIA did not significantly affect volume, but increased pH at the higher doses tested. CADO decreased volume, but did not affect pH. These results indicate that adenosine analogs regulate not only the hydrogen ion concentration, but also the volume of gastric secretions.

Inhibitors of histidine decarboxylase decrease basal gastric acid secretion in the rat.

We examined the ability of two specific inhibitors of histidine decarboxylase, (s)-alpha-fluoromethylhistidine (FMHd) and (s)-alpha-fluoromethylhistamine (FMHm), to inhibit basal gastric acid secretion. The two highest doses of FMHd administered, 50 and 100 mg/kg, decreased basal gastric acid secretion and total secretion volume but did not affect intraluminal pH. FMHm decreased gastric acid secretion, raised intraluminal pH, and to a lesser degree decreased total secretion volume. Neither compound changed the severity of gastric ulcers produced by cold restraint stress.

Central effects of adenosine analogs on stress-induced gastric ulcer formation.

Rats subjected to restraint stress developed gastric lesions that could be reduced by R-phenylisopropyladenosine (R-PIA) administered intracerebroventricularly. This protective effect was reversed by 8-sulfophenyltheophylline given centrally, and by peripherally administered 8-phenyltheophylline. These results suggest that central adenosine receptors mediate the effect. In subsequent studies it was found that if the absolute level of ulcer formation in control rats was low, R-PIA had no ulcer protective effect. Thus, although it appears that adenosine receptors are important in attenuating pathological gastric responses to stress, this attenuation seems to be dependent on the level of ulcer formation in control animals.

Modulation of gastric acid secretion by adenosine in conscious rats.

Basal (nonstimulated) gastric acid output was determined in conscious rats fitted with indwelling gastric cannulae. The adenosine deaminase resistant analog of adenosine, R-phenylisopropyladenosine, elevated intraluminal pH beyond 7.0 and decreased gastric acid secretion when given at doses of 0.10 or 1.0 mg/kg, while S-phenylisopropyladenosine at similar doses did not affect either gastric acid output or pH. The potent adenosine receptor antagonist, 8-phenyltheophylline, given at doses of 0.1, 1.0, and 2.5 mg/kg augmented gastric acid output and, at doses of 0.01, 0.1, 1.0, and 2.5 mg/kg, blocked the acid-reducing effect of R-phenylisopropyladenosine (0.1 mg/kg). These data suggest that adenosine systems may be important regulators of gastric function.