Coping methods and reasons for not drinking.

Methods for coping with stress and reasons for not drinking were examined among abstinent alcoholics to determine whether change occurred with length of sobriety. Results showed that 1) alcoholics with briefer abstinence relied more heavily on coping methods, 2) alcoholics relied less on negative than positive coping methods regardless of length of sobriety, and 3) the number and types of reasons for not drinking did not vary with length of sobriety, rather, several positive reasons for not drinking continued as motivators. Concerning coping methods, the authors speculate that as alcoholics remain sober longer, coping methods become less important or automatic and less conscious.

Ethnicity and antipsychotic response.

OBJECTIVE: To review the data generated by studies examining interethnic/racial differences in response to antipsychotics. DATA SOURCES: A MEDLINE search (1966-1996) identified all articles examining differences in antipsychotic response among Caucasians, Asians, Hispanics, and African-Americans, as well as articles evaluating postulated mechanisms for these differences. STUDY SELECTION: All abstracts, studies, and review articles were evaluated. DATA SYNTHESIS: Ethnic/racial differences in response to antipsychotic medications have been reported and may be due to genetics, kinetic variations, dietary or environmental factors, or variations in the prescribing practices of clinicians. Studies suggest that Asians may respond to lower doses of antipsychotics due to pharmacokinetic and pharmacodynamic differences. Research relevant to African-Americans is limited, but some studies suggest that differences in this group may be due to clinician biases and prescribing practices, rather than to pharmacokinetic or pharmacodynamic variability. CONCLUSIONS: Future research directed at validating the hypotheses that different ethnic/racial groups show variations in response to antipsychotics should focus on homogeneous ethnic groups, use recent advances in pharmacogenetic testing, and control for such variables as observer bias, gender, disease chronicity, dietary and environmental factors, and exposure to enzyme-inducing and -inhibiting agents. Clinicians should be aware that potential interethnic/racial differences in pharmacodynamics and pharmacokinetics may exist that can alter response to antipsychotics.

Assessing the neuropsychological profile of stable schizophrenic outpatients.

In an administration of the Computerized Neuropsychological Test Battery (CNTB), stable schizophrenic outpatients (n = 26) showed significant impairment (P < 0.05) relative to normal control subjects (n = 28) in overall function and measures of verbal learning. Except on tests of motor speed, the performance profile of schizophrenic patients was similar to that of elderly normal control subjects (n = 33). This profile of deficits is consistent with findings of other investigators in similar patient populations. In addition to displaying sensitivity to the mild impairments found in outpatients, the CNTB showed high test-retest reliability (r = 0.76, P < 0.0001). It should be useful for evaluating cognitive impairment in clinical trials of prospective treatments.

Placebo response in anxiety disorders.

OBJECTIVE: To review literature on placebo response in anxiety, to discuss sources and levels of placebo response in various anxiety disorders, and to suggest methods to prevent high placebo response rates in clinical research trials. DATA SOURCE: Data from scientific literature were identified using a MEDLINE search, and were extracted and summarized for this review. STUDY SELECTION: Representative findings were selected from clinical and epidemiologic studies, review articles, letters to the editor, book chapters, and proceedings. DATA EXTRACTION: Data from English-language reports of studies on humans were included. Only the most representative conclusions drawn from review articles were used. DATA SYNTHESIS: Anxiety disorders in general are thought to be extremely susceptible to a variety of influences, including patient characteristics and environmental variables. Reported placebo response levels in clinical studies of anxiolytics for generalized anxiety disorder and panic disorder vary widely, with a tendency to be rather high, although studies in social phobia and obsessive compulsive disorder appear to have consistently low placebo response rates. Comparisons of anxiety studies with studies of other indications, such as depression, show similar overall placebo response rates. To determine efficacy, drug response rates and placebo response rates must be clearly differentiated. CONCLUSIONS: Examination of the literature suggests that placebo response rates in studies of anxiolytics are influences by a number of factors, including both endogenous and exogenous variables. High placebo response rates may mask true drug response rates and may result from poor study design or lack of procedural standardization. The use of certain design methods may help to prevent high placebo response rates in anxiolytic clinical trials.

Effect of the ACE inhibitor ceronapril on cerebral blood flow in hypertensive patients.

OBJECTIVE: To assess the effect of the angiotensin-converting enzyme inhibitor ceronapril on cerebral blood flow (CBF) in patients with moderate hypertension. DESIGN: Patients received chlorthalidone 25 mg for 4 weeks, and if diastolic blood pressure remained in the range of 100-115 mm Hg, they were given titrated doses of ceronapril (10-40 mg/d based on blood pressure response) in addition to chlorthalidone for 9 weeks. SETTING: Outpatient research clinic. SUBJECTS: Eligible patients had moderate essential hypertension (diastolic blood pressure 100-115 mm Hg) assessed when the patients were receiving no medications. Thirteen patients were entered into the study; 1 withdrew for reasons unrelated to the study drug. Twelve patients (11 men, 1 woman; mean age 52 y) completed the study. INTERVENTION: Ceronapril, given with chlorthalidone. MAIN OUTCOME MEASURES: CBF measurements were taken at the start and end of ceronapril therapy using intravenous 133Xe; blood pressures were determined weekly. RESULTS: Mean arterial blood pressure decreased from 130 +/- 4 to 120 +/- 7 mm Hg after 4 weeks of chlorthalidone administration, and fell further to 108 +/- 8 mm Hg after an additional 9 weeks of combined chlorthalidone-ceronapril therapy (p < 0.05). CBF fell from 44 +/- 15 to 34 +/- 5 mL/min/100 g during the 9 weeks of combined therapy (p = 0.05). No adverse effects consistent with decreased CBF were observed. The decrease in CBF was not linearly correlated with the change in systemic blood pressure, but was strongly correlated (r = -0.937; p < 0.001) with the initial CBF. CONCLUSIONS: The decrease in mean arterial blood pressure was not associated with a decrease in CBF. Patients with high CBF may be predisposed to a decrease in CBF when treated with ceronapril and chlorthalidone.

Cholinergic rebound and rapid onset psychosis following abrupt clozapine withdrawal.

Following the conduct of a 28-day inpatient bioequivalence study of clozapine in schizophrenia patients, withdrawal effects after abrupt discontinuation from clozapine were assessed. Thirty patients who met DSM-III-R criteria for schizophrenia, residual type, or schizophrenia in remission were enrolled in the study. Patients were evaluated for symptoms of withdrawal effects for 7 days after clozapine 200 mg/day was abruptly withdrawn. Of 28 patients who completed the study, 11 had no withdrawal symptoms; 12 had mild withdrawal adverse events of agitation, headache, or nausea; four patients experienced moderate withdrawal adverse events of nausea, vomiting, or diarrhea; and one patient experienced a rapid-onset psychotic episode requiring hospitalization. Cholinergic rebound is a likely explanation for the mild to moderate withdrawal symptoms and is easily treated with an anticholinergic agent. Mesolimbic supersensitivity, as well as specific properties of clozapine, are discussed as likely causes for rapidonset psychosis. Our findings are consistent with previous reports of withdrawal reactions associated with clozapine, further reminding clinicians to monitor patients closely following abrupt discontinuation of clozapine.

Abstinence, reasons for not drinking, and life satisfaction.

This study examines the reasons given for not drinking by abstinent alcoholics with varying lengths of sobriety. A Reasons for Not Drinking Scale is tested, as well as the Purpose in Life Questionnaire and Life Satisfaction Scale. Subjects are 60 males from a VA population. Results show that subjects with less education and those treated in a detoxification setting are more likely to endorse negative reasons for not drinking. Individuals with short and long abstinence have a higher level of life "dissatisfaction" than those with moderate periods of abstinence. The study suggests that purpose in life, life satisfaction, and reasons for not drinking are important measures of progress in treatment and movement through phases of recovery.

Idioventricular rhythm: hypervagotonia associated with placebo.

We report a case of hypervagotonia manifested by idioventricular rhythm in a healthy, athletic man who participated in a Phase I study of an investigational calcium-channel blocker. Upon breaking the study's double-blind study code, it was discovered that the subject had received placebo. We discuss this unusual finding and the implications of including athletic subjects in safety/tolerance studies.

Transnasal butorphanol: a new method for pain relief in post-cesarean section pain.

This study was undertaken to evaluate the efficacy and the safety of transnasal butorphanol (TNB) compared to intravenous butorphanol (IVB) in 186 patients experiencing moderate to severe post-cesarean section pain. Patients were randomly assigned to five groups in a double-blind fashion: Group I (n = 37) received 2 mg IVB, Group II (n = 38) 2 mg TNB, Group III (n = 36) 1 mg TNB followed by a repeat dose of 1 mg TNB at 60 min, Group IV (n = 38) 0.5 mg TNB followed by a repeat dose of 0.5 mg at 60 min, and Group V (n = 37) received placebo. All administrations were double dummy. Pain intensity and relief were noted and the incidence of side effects was recorded. Remedication with the same study drug was allowed up to 72 h. Onset of analgesia was more rapid in the 2 mg IV group compared to the three TN groups: 5 min vs 15 min, respectively. However, the 2 mg and the 1-1 mg TN groups had a longer duration of analgesia, approximately 4.5 h, compared to 3.0 h for the 2 mg IV group (P less than 0.05). Somnolence was dose related and was the most frequent side effect, and was less frequent when the TN dose was divided into 2 doses administered 1 h apart. Multiple doses of TNB and IVB were safe and clinically acceptable up to 3 days at all doses studied. There were no incidences of nasal mucosa irritation, or cardiovascular or respiratory depression. It is concluded that transnasal butorphanol represents a safe and effective alternative to injectable butorphanol for post-cesarean section pain and offers a better and longer duration of analgesia compared to IV butorphanol. The optimum dose seems to be 2 mg TN butorphanol and it is tolerated better when divided into 1 mg increments, given 1 h apart.

Ipsapirone: evidence for efficacy in depression.

Sixty-five inpatients of a psychosomatic hospital in the Federal Republic of Germany with the diagnosis of anxiety neurosis (n = 31) or neurotic depression (n = 34) as defined by the International Classification of Disease (ICD-9), were randomized to a 4-week course of ipsapirone at 7.5 mg t.i.d. or placebo in a prospective, double-blind clinical trial to assess safety, tolerability, and efficacy. This article reports the efficacy results for those patients with the diagnosis of neurotic depression. The primary efficacy variable for patients with neurotic depression was the change from baseline in the Hamilton Rating Scale for Depression (HAM-D) at 4 weeks of treatment. Considering all of the randomized patients with neurotic depression (n = 34, the intent-to-treat population), the mean change from baseline in the HAM-D at Week 4 (observed cases) was -13.13 +/- 6.06 (n = 16) for the ipsapirone group, and -3.19 +/- 5.99 (n = 16) for the placebo group (p less than .001). A parallel analysis of the change from baseline in the Core Depression score of the HAM-D (defined as the sum of items 1, 2, 3, 7, and 8) also showed a significant treatment difference (p less than .01). Results were similar for the intent-to-treat population, last observation carried forward. Safety and tolerability were evaluated for all study patients independent of diagnosis. Treatment-emergent events (n = 65) were reported by 76 percent of patients treated with ipsapirone (n = 33) and by 38 percent of patients treated with placebo (n = 32).(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of panic and phobic disorders.

The clinical features, pathophysiology, and treatment of panic and phobic disorders are reviewed. Evidence from genetic, epidemiological, biological, and pharmacological studies suggests that phobic and panic disorders differ from other psychiatric illnesses. Dysfunction of the autonomic nervous system, causing excessive release of norepinephrine from the locus ceruleus, is implicated in the pathophysiology of these disorders. Overstimulation of the locus ceruleus by yohimbine, sodium lactate, and carbon dioxide can cause feelings of panic and anxiety in both patients with panic disorder and control subjects. Currently, excessive activity of the locus ceruleus is the only comprehensive neuroanatomic and physiological hypothesis for the etiology of panic disorder. Tricyclic antidepressant agents (TCAs), monoamine oxidase inhibitors (MAOIs), anxiolytic agents, and adrenergic agents all have been used to treat phobic and panic disorders. TCAs and the benzodiazepines, particularly alprazolam, are the drugs most commonly chosen for therapy. If these agents are ineffective, an MAOI or combination therapy can be tried. MAOIs are second-line agents for many patients because of toxicity and dietary limitations. Whether they are more effective than other agents requires further study. Panic and phobic disorders and depression have in common many properties of a dysregulated system; an improved understanding of the pathophysiology of panic and phobic disorders should lead to the development of more effective treatment strategies.

Deterrence of drunk driving in Massachusetts: criminal justice system impacts.

This paper examines the extent to which a "toughened" drunk driving law in Massachusetts has deterred drunk driving and the law's impact on criminal justice system operations. Included are analyses of pre- to postlaw trends in: alcohol-related highway fatalities and arrests, drunk driving arraignments and convictions, and jail sentences served by drunk driving offenders. Many of the positive trends found since the implementation of the law (increased arrests, reduced fatalities, and increased conviction rates) actually began before the law took effect. Moreover, the law has exacerbated existing problems in the criminal justice system such as overcrowded jails.

The employee as client: perceptions of a work-based alcohol treatment program.

The clients' reports provide invaluable insights into the EAP in which they participated. Overall, they reaffirmed the viability of occupational alcoholism programs as an effective intervention in problem drinking. They did raise serious questions about the fit between the theoretical expectations of EAPs and actual practice. They felt work performance problems were poorly documented and therefore were not used in the confrontation-referral process. As a consequence, early problem identification, seen as one of the major advantages of occupational intervention, does not seem to take place. Most of the clients felt they were referred only after long periods of problem drinking. While the reports of the clients represent an insider's view of the EAP, an obvious question that arises is how valid are their reports? Precisely because they are the targets of the EAP activity and because their problem drinking is generally seen as deviant behavior, their reports may be clouded by fear, rationalization, attempts to please others in the work organization and endless other personal concerns. The validity of self-reports are always difficult to assess. The usual precautions were taken in collecting the data, including assurance of confidentiality, voluntary participation in the study, assurance that the research team was independent of any work-related interest group and the use of neutral grounds for data collection. While all of these add some measure of confidence to the reports, they do not constitute guarantees of validity. Another source of evidence for validity is corroborating evidence.(ABSTRACT TRUNCATED AT 250 WORDS)